Endemic and sporadic goiter .

Diffuse goiter with hyperthyroidism.

Inflammatory diseases of thyroid gland

DISEASES OF MAMMARY GLAND

 

 

 

Endemic goiter is the pathology of thyroid gland, which occurs in biogeochemical regions with iodine deficiency in environment (regional pathology).

Sporadic goiter is the disease of thyroid gland, which occurs in unendemic for goiter regions.

Anatomy(Fig.1;Fig.2;Fig.3.)

 

Fig.1.Anatomy of thyroid gland:

1 lobus pyramidalis gl. thyreoideae; 2 - lobus sinister gl. thyreoideae; 3 trachea; 4 isthmus gl. thyreoideae; 5 - lobus dexster gl. thyreoideae; 6 cartilago thyreoideae; 7 membrana hyothyreoideae; 8 os hyoides.

Video

 

Fig.2.Transversal section of the neck

on the thyroid gland level:

1 mm. sternohyoideus et sternothyreoideus; 2 m. sternocleidomastoideus; 3 m. omohyoideus; 4 - gl. parathyreoidea; 5 v. jugularis int.; 6 a. carotis communis i n. vagus; 7 nn. recurrentes ; 8 n. longus colli; 9 fascia praevertebralis; 10 - gl. parathyreoidea; 11 ; 12 capsula thyreoidea int.; 13 - capsula thyreoidea ext.; 14 platisma (by Welti).

 

Fig.3.Topography of recurrens nerve and art. thyreoidea inferior:

1 a. thyreoidea inf.; 2 - n. recurrens.

 

Etiology and pathogenesis

 

Except iodine deficiency, the goitrous endemia is contributed by excessive contents of calcium in environment, deficiency of bromine, poor sanitary and hygienic conditions. Decreased contents of cobalt, manganese, and zinc in environment also influence on expression of goitrous endemia. The lack of iodine in the organism blocks the synthesis of thyroid hormones. It results in hypersecretion of thyroidstimulating hormone of hypophysis, which in turn leads to hypertrophy and hyperplasia of thyroid epithelium that on initial stages can be compensated, but further transformed into the goiter.

The gravity of endemia is assessed by such indexes:

1)    relationship between men and women with goiter (if it approaches to 1, the endemia is more severe);

2)    predominance of the nodular form of goiter above its other forms;

3)    presence of cretinism;

4)    goiter in animals;

5)    a number of persons with thyroid hyperplasia.

Sporadic goiter arises from relative iodine deficiency, which results from disturbance of iodine ingestion, liver dysfunction.

 

Pathology

 

Macroscopically the goiter is divided onto diffuse, nodular and mixed. According to histological structure distinguished parenchymatous and colloid ones. Sometimes occur cystic transformation of the gland and calcification. The enlarged nodes may result in atrophy of adjacent tissues and organs. So, the advanced forms of goiter can cause compression of trachea and its softening (tracheomalacia). The sings of hyperthyroid transformation of euthyroid goiter include: the transformation of thyroid epithelium from squamous cell into cubic and cylindrical, presence of papillomatous overgrowth, agglomeration of lymphocytes, liquid vacuolated colloid.

 

Classification

 

According to the form of enlargement of thyroid gland distinguished:

1) diffuse goiter;

2) nodular goiter;

3) mixed goiter.

For determining of the degree of goiter used such scale:

0 - the thyroid gland is not palpated;

I - the isthmus of the gland is noticeable during swallowing and could be palpated;

II - entire gland is noticeable during swallowing and could be palpated;

III - the enlargement of gland results in evident thickening of neck ("a thick neck");

IV the gland considerably enlarged, and sharply deforms neck;

V - the enlargement reaches excessive size (goiter of major sizes).

According to the functional state of thyroid distinguished:

1) euthyroid goiter (normal function);

2) hyperthyroid goiter (excessive function);

3) hypothyroid (reduced function).

Diffuse enlargement of thyroid of I-II degrees without disturbances of function and nodular transformation referred to compensatory hyperplasia of the gland.

According to localization distinguished:

1) typical localization (anterior surface of neck);

2) retrosternal goiter;

3) ectopic goiter (goiter of the base of the tongue, intrathoracic goiter);

4) goiter of additional glands (aberrant goiter);

5) presternal goiter.

 

 

Symptomatology and clinical course

 

In the patients with endemic euthyroid goiter the clinical sings are basically caused by mechanical and reflex influence of enlarged thyroid gland on adjacent organs. Patients mainly complain of the presence of "tumour" and neck deformity. Sense of tightness in the neck, difficult breathing, swallowing, and also sudden attacks of cough (owing to compression of laryngeal nerves by goiter) trouble them. In case of great goiter (particularly retrosternal,) periodical dyspnea may develop (especially in the night), up to asphyxia, which is result of compression and inflection of trachea. Retrosternal goiter frequently accompanied with hoarseness, distended veins of face and neck.

The goiter with low thyroid function, as a rule, clinically manifests by general weakness, malaise, sleepiness, hypomnesia, chilliness, dry skin and edemas, particularly around eyes. Sometimes in such patients observed constipation.

The patients with hyperthyroid goiter complain of irritability, heartbeat, excessive sweating, and tremor of arms, sleeplessness, feeling of fever. Sometimes observed loss of weight, diarrhea. The thyroid hyperfunction in endemic goiter mainly slightly expressed, and not associated with exophthalmus.

Enlargement of thyroid gland in patients with endemic goiter mostly often has nodular or mixed character, and only in small number of the patients (mainly of younger age) observed diffuse enlargement of thyroid gland.

Nodular goiter is palpated as painless tumour with regular contours, smooth surface, not connected with adjacent tissues and displaced during swallowing. Such goiter is characterized by elastic or dense consistence. Long-term goiter leads to formation of fibrosis and calcification, it becomes solid, and tuberous.

The shape of diffuse goiter resembles the butterfly. It retains the contours, its surface is smooth, consistence mostly elastic, sometimes soft or dense. Mixed goiters combine manifestations of the nodular and diffuse one, however tactically, the mixed goiters refer to nodular group.

The separate nodes or entire goiter can partially or completely be displaced behind breastbone. Palpation of such goiter requires the special devices. The examination is performed when the patient is supine with the bolster under scapulas. During the procedure the patient must force by himself or cough, that causes the emergence of the upper pole or entire goiter above breastbone.

 

Variants of clinical course and complications

Features of the clinical course of endemic and sporadic goiter caused by its form (nodular, diffuse, mixed), degree of thyroid enlargement, character of functional state (euthyroid, hypothyroid, hyperthyroid), location (typical, retrosternal, ectopic, aberrant goiter), constitutional features of the patient, duration of the disease and character of previous treatment.

Complication: inflammation of the goitrous thyroid gland (strumitis), hemorrhage in the tissue of goiter, asphyxia, malignancy.

 

 

The diagnostic program

1.     Physical examination of the neck, palpation of thyroid gland(fig.4.).

2.     Sonography, computer tomography.

3.     Determining of thyroid function (serum hormones, serum iodine, and thyroid-iodine uptake)(Fig.5;Fig.6;Fig.7;Fig.8.).

4.     According to indications: X-radiography of the neck (calcification, ossified foci) with barium swallow (compression of esophagus, trachea, their shift, and deformity).

5.     Chest X-radiography, particularly of mediastinum, in two plains, pneumomediastinography (intrathoracic goiter).

6.     Puncture biopsy(Fig.9.)

Fig.4. Palpation of thyroid gland(right lobe)

 

 

 

 

Fig.5. Thyroid gland scanning

 

Fig.6. Scanogram of diffuse goiter

 

Fig.7. Scanogram of nodular goiter

 

Fig.8. Scanogram of mixed goiter

 

Fig.9. Endemic nontoxic goiter. Macro follicular

goiter with epithelium proliferation.

 

Differential diagnostics

 

Endemic and sporadic goiter requires the differential diagnostics with chronic autoimmune thyroiditis (Hashimoto's thyroiditis), Riedel's fibrous thyroiditis, neck cysts, lipomas and other tumours of the neck and mediastinum, malignant neoplasms of thyroid gland, metastases of tumours in cervical lymph nodes.

Hashimoto's thyroiditis is characterized by specific immunological indexes, diffuse density of thyroid, mosaic changes on sonogram and scintiscan, reducing of the goiter in response to prednisolone assay.

In case of Riedel's goiter the gland is tuberous, of woody consistency, quite often knitted with adjacent tissues (except skin).

The cysts, tumours of the neck, metastases in lymph nodes are well defined on sonograms, do not displace at swallowing and accumulate radioactive iodine.

The suspicion on thyroid cancer makes the necessity to carry out morphological verification by puncture biopsy with further cytological examination.

The manifestation of initial, vague and slightly expressed forms of thyrotoxicosis can resemble neuroses, rheumatic disease, tuberculosis, chroniosepsis, postcastrate syndrome, diencephalic lesions, and also malignant tumours. It particularly concerns those cases, when the enlargement of thyroid gland is slight or it is failed to detect.

All the mentioned diseases are characterized by palpitation, heart pain excessive sweating, subfebrile fever and loss of weight.

The acute development of thyrotoxicosis sometimes makes the necessity to rule out such acute infectious diseases, as dysentery, influenza or camp-fever.

The thyrotoxicosis with exophthalmos is necessary to differentiate with encephalitis, ophthalmopathy. Encephalitic exophthalmos is characterized by combination of looking upward paresis with diplopia, corneal ulceration, conjunctivitis, progressing, so-called malignant exophthalmos, which rather frequently can result in loss of eye. By the way, this type of exophthalmos is commonly unilateral.

Laboratory tests are important for differential diagnostics of thyrotoxicosis: detecting of thyroid hormones, serum protein-bounded iodine, thyroid-iodine uptake, biochemical, immunological investigations, sonography and scanning with the radioiodine or technetium.

In particularly severe cases it is advisable to apply trial antithyroid therapy.

 

Tactics and choice of treatment

 

Endemic goiter is the subject for treatment in all its forms and all stages of the development. The choice of treatment depends on type of the goiter (diffuse, nodular, mixed), degree of enlargement of the thyroid (I-V) and character of complications of the goiter (inflammation, hemorrhage, asphyxia, and malignancy).

Conservative treatment includes the drugs of inorganic iodine, thyroidine and pure hormonal drugs (thyroxine, triiodothyronine). Thyroxine is the most effective one. The iodine drugs less effective and frequently are the cause of secondary hyperthyroidism. The medicament treatment is administered in diffuse thyroid enlargement without sings of compression of neck organs. Polynodular goiter (particularly in elder women) sometimes complicated by malignancy and consequently, even if the sings of compression of neck organs and hyperthyroidism are absent, also treated by conservative agents. The important argument of medicament treatment is their often recurrences after operation.

The surgical approach in endemic and sporadic goiter are determined by their spread and character of the lesion. There used the principle that all transformed into the goiter parenchyma should be removed, and healthy preserved as much as possible.

The nodular and mixed form of the goiter, despite its function and size, is the subject for surgery. The hypothyroidism is not contraindication for operation, as the removal of the goiter results in functional normalization of unaltered, paranodular tissue. The operation, first of all, is indicated if present the sings of compression of neck organs, goiter of the major sizes, secondary hyperthyroidism and suspicion on malignancy. The goiter of additional thyroid glands (aberrant goiter) is the subject for obligatory surgical removal. The operation consists of removal of the aberrant gland with revision of the basic thyroid gland.

The intrathoracic goiter, which develops in retrosternal ectopy of thyroid gland, also requires obligatory surgical removal(Fig.10.). The best access is the longitudinal sternotomy. The cervical goiter is possible to remove by means of cervical access without the special technical efforts.

 

Fig.10. Scheme of goiter formation (retrosternal, intrathoracic)

 

In tongue ectopy if there are no severe disturbances of speech, swallow and breathe also possible observation and conservative treatment. Progressive growth of the goiter, presence of sings of compression, dysphagia, traumatic bleeding and suspicion on malignancy require the surgical treatment removal of the goiter mostly through a lateral pharyngeal incision.

The acute disturbance of breathing (asphyxia) requires performance of urgent operation.

The optimal method of anesthesia is the endotracheal narcosis. This method prevents mechanical asphyxia during operation resulting from compression or inflection of trachea at the moment of mobilization and drawing out of the goiter. The method permits to perform careful revision of entire gland and neck spaces, first of all retrosternal, retrotracheal, retroesophageal, where there can be separate thyroid nodes. It is necessary to consider a local anesthesia, and also other methods of general anesthesia as reserve.

For removal of goiter used transversal incision by Kocher in the inferior part of the neck above the sternoclavicular junctions. Operation on thyroid gland must begin from careful revision and intraoperative diagnostics that permits to choose the adequate operative tactics. Trachea must be mobilized by means of isthmus dissection. It permits better orientation in topographic situation caused by the goiter, and to perform tracheostomy at occurrence of asphyxia. Further isthmus and pyramidal lobe must be removed as the most dangerous as for relapse of the goiter.

The volume of thyroid resection in endemic and sporadic goiter is determined individually. The resection is performed subfascially that prevent the removal of parathyroid glands and trauma of laryngeal nerves. The node is necessary to eliminate together with paranodular tissue, as it is functionally failed. It is justified also by oncologic reasons. The operation of nodular enucleation is considered to be inadequate, thus never used. Meanwhile, in multinodular bilateral goiter, when practically entire thyroid gland is affected, it is necessary to eliminate separate nodes from healthy parenchyma, preserving its maximal amount, as the parenchyma is mainly disposed as lamina on their surface. This layer of parenchyma is necessary to dissect and draw aside by scissors out of node, having preserved its vascularization.(Fig.11-15.)

 

 

Fig.11. Operative incision

Fig.12. Prepararation of upper layers of the skin

 

 

Fig.13. Transversal section of prethyroid muscles

Fig.14. Sutures imposition and closing with thyroid stump

 

 

 

Fig.15.Sutures on prethyroid muscles

and drainage of operative wound

 

 

In endemic and sporadic goiter applied saving, extent and subtotal resection of the thyroid with obligatory indication of amount and site of leaving parenchyma.

For oncologic standpoint it is necessary in all cases to carry out intraoperative express cytology of the removed tissue.

For prophylaxis of goiter relapse after the operation necessary long-termed institution of thyroid hormones with the purpose to block thyroid stimulation by pituitary gland.

 

 

Diffuse goiter with hyperthyroidism

 

Diffuse goiter with hyperthyroidism (Grave's or Basedow's disease, thyrotoxicosis, hyperthyroidism) is severe autoimmune and neuroendocrine disease resulting from excessive secretion of thyroid hormones by diffuse-enlarged thyroid gland with lesion of all organs and systems of the body.

The diffuse goiter with hyperthyroidism (thyrotoxicosis) mostly occurs at women. In 5 % of persons with hyperthyroidism develop ophthalmopathy and pretibial myxedema.

 

Etiology and pathogenesis

 

The scientific investigation and clinical examination testify that the diffuse goiter with hyperthyroidism is autoimmune disease. This disease is commonly results from infections, intoxication, craniocerebral injury, dysfunction of other endocrine glands, first of all genital, acute and chronic mental disorder, sunstroke. The disease develops under the influence of these factors directly on generically predisposed to thyrotoxicosis organism.

 

 

 

Pathology

 

The thyroid gland is 2-5 times enlarged, moderately dense, on incision pulpy, sanguineous, of grey-pink color. Histologically revealed a polymorphism of follicles. Follicular epithelium is cylindrical with papillomatous growths. The colloid is eosinophilic, contains plenty of resorptive vacuoles. In interstitial space lot of lymphocytes, which form follicles. The severe form of thyrotoxicosis results in thyrotoxic heart, thyrotoxic liver cirrhosis, thyrotoxic ophthalmopathy, osteoporosis, and cachexia.

 

Classification

 

According to the clinical course distinguished mild, moderate and severe forms of the disease.

According to Milk's classification, there are four stages of hyperthyroidism.

I stage neurotic, onset of thyrotoxicosis, slight enlargement of thyroid gland.

II stage neurohormone, marked sings of thyrotoxicosis, the thyroid is noticeably enlarged in size.

III stage visceropathic, is characterized by a thyrotoxic lesion of viscera.

IV stage cachectic, is characterized by nonreversible dystrophy of organs and systems.

 

Symptomatology and clinical course

 

A diffuse toxic goiter affects practically all organs and systems and disturbs all types of metabolism. Except described in 1842 by Basedow classical triad (goiter, tachycardia and eye bulging), today is known about 70 signs, proper for thyrotoxicosis, which can be combined in three basic syndromes: hyperthyroidism, eye signs (ophthalmopathy) and lesion of skin (pretibial myxedema). By the may, the hyperthyroidism is the permanent phenomenon, and ophthalmopathy and pretibial myxedema occurs rather seldom (in 1-5 % of patients).

To initial sings of thyrotoxicosis can be regarded: general weakness, prompt fatigability, decreased work ability and muscular force, nervousness, irritability, sleeplessness, sweating and hyperemia of skin.

The basic signs of thyrotoxicosis are enlargement of thyroid gland (goiter), palpitation, exophthalmos, tremor and progressing loss of weight. (Fig. 16)

 

 

Fig.16. Thyrotoxicosis

 

 

The thyroid gland in the patients with thyrotoxicosis is diffuse enlarged and of moderate density. In some of them due to excessive blood supply it can pulsate. After long treatment by iodine the gland becomes dense and painless. Such long-term conservative treatment causes the development of sclerotic degenerative processes, sometimes with nodular transformation of the tissue, and the degree of thyroid enlargement frequently does not relate to the gravity of thyrotoxicosis.

Secretory activity of thyroid hyperplasia in the form of excessive releasing of its hormones (triiodothyronine and thyroxine) underlies the hyperthyroidism. The majority of effects of thyroid hyperfunction manifest through sympathetic nervous system: palpitation, tremor of fingers, tongue, and whole body (sign of "telegraphpole"), sweating. In the patients with thyrotoxicosis the protein, carbohydrate and lipid metabolism is elevated, which manifests by simultaneous excessive appetite and loss of weight.

The changes, which develop in organs of cardiovascular system and manifests by tachycardia, high systolic and low diastolic pressure, increase of pulse pressure and complete arrhythmia with the development of heart failure form a syndrome of thyrotoxic heart.

The excessive formation of heat owing to intensive metabolism, which results from the influence of thyroid hormones, leads to hyperthermal syndrome (feeling of fever, high body temperature). The sings of nervous dysfunction include irritability, anxiety, fear sensation, nervousness, sleeplessness, hyperactive tendon reflexes. The dysfunction of genitals manifests by oligo- or amenorrhea, and in the men by gynecomastia, which is the outcome of disturbed relation between estrogens and androgens. Thereafter libido and potency are reduced.

The thyrotoxicosis without treatment results in loss of weight, in advanced cases not only the subcutaneous fat disappears, but also a muscular tissue reduced, down to cachexia. Degenerative changes in muscles, and lesion of peripheral nervous system result in thyrotoxic myopathy.

In majority of patients develop characteristic eye signs. The predominant one is the exophthalmos. By the way, eye bulging, which occurs in 50 % of cases, frequently can be the initial manifestation of the disease, assigned by patient. Three types exophthalmos are distinguished: slight (14-17 mm), moderate (17-20 mm) and considerable (more than 20 mm). The exophthalmos in thyrotoxicosis is symmetric, the eye trophic and movements of does not disturbed. Except exophthalmos, there are lot of other eye signs observed in the patients with thyrotoxicosis.

        Graefe's sign the upper lid lag when the patient looks downward;

        Stellwag's sign infrequent winking;

        Mebius' sign a weakness of convergence;

        Dalrymple's sign - wide palpebral fissure;

        Kocher's sign retraction of the upper eyelid at prompt change of view.

The eye signs of diffuse toxic goiter are necessary to differentiate from ophthalmopathy (malignant exophthalmos), which observed approximately in 5 % of the patients with thyrotoxicosis. Such exophthalmos simultaneously associated with pain in the eyeballs, gritty sensation and eyewatering. Also detected lid edema, ocular injection. In considerable ophthalmopathy the eyeballs bulge from orbits, eyelids and conjunctiva are swollen, with sings of inflammation. It can result in keratitis with corneal ulceration, which finally can lead to blindness. The high orbital pressure caused by lymphoid infiltration, accumulation of fluid and edema of retroorbital tissues result in not only eye bulging exophthalmoses, but also compression of optic nerve and loss of sight. It is necessary also to specify that the ophthalmopathy in thyrotoxicosis, as a rule, develops on the background of encephalopathy and has an autoimmune genesis. (Fig.17.)

 

Fig.17. Exophthalmoses

 

Pretibial myxedema arises on the anterior surface of lower legs. The skin becomes dense, thickened, of purple-red color, and hair follicles jut out of its surface.

Thyroid hypersecretion also negatively influences on the liver parenchyma. In severe cases it can result in toxic hepatitis, jaundice and further hepatargy. It is necessary to consider the toxic hepatitis in such patients unfavorable as for prognosis.

Under the direct cytotoxic influence of thyroid hormones on intestinal mucosa suppressed its enzymatic function that leads to intestinal hyperkinesis and osmotic diarrhea thyrotoxic enteric syndrome. It is accompanied by gluco- and mineralocorticoid dysfunction of suprarenal gland, and leukopenia, granulocytosis and lymphocytosis in blood.

 

Variants of clinical course and complications

 

In clinical course of thyrotoxicosis distinguished the mild, moderate and severe forms.

The mild form of thyrotoxicosis is characterized by following signs: pulse 100 beat/min, loss of weight approximately 3-5 kg, slight sweating, eye signs absent or slightly expressed, normal arterial pressure, basal metabolism to +30 %, elevated thyroid-iodine uptake, and the maximum of iodine accumulation, which exceeds 30 % is detected after 24 hours.

The moderate gravity of the disease manifests by expressed symptomatology: loss of weight to 8-10 kg, tachycardia 101-120 beat/min, systolic pressure is elevated, and diastolic decreased or normal. Frequently observed exophthalmos, basal metabolism +31-50 %, thyroid-iodine uptake has been excessive since first hours.

The severe form of thyrotoxicosis is characterized by the sharply expressed symptomatology, which is caused by considerable visceral dysfunction. The pulse rate in such patients exceeds 120 per minute, and complete arrhythmia develops. Tremor and profuse sweating sharply expressed, pulse pressure considerably elevated circulatory failure and ophthalmopathy frequently observed. The loss of weight can overtop 10 kg, basal metabolism more than +50 %, the maximum of radioactive iodine accumulation detected in 4-6 hours after taking of isotope, and decreasing of accumulation curve exceed 24 hours.

According to the clinical course two forms of thyrotoxicosis distinguished: ) thyrotoxicosis with slow development; ) acute form of diffuse toxic goiter, which is characterized by an acute onset and prompt, sometimes within several hours, development. The acute thyrotoxicosis seldom occurs and in most cases ends lethally from thyrotoxic coma.

The clinics of acute thyrotoxicosis develop within some hours or days. Thus the thyroid gland is not enlarged, high temperature, vomiting, diarrhea, sharp loss of weight are observed.

The special forms of thyrotoxicosis include the thyrotoxicosis in childhood, in pregnant, in climacteric women, and people of the elderly age.

Among complications during the course of disease the most dangerous for the life is thyroid storm. It is observed in 0,02-0,05 % of the patients and develops, mainly, as the outcome of the lesion of provoking factor. Among them considered trauma (surgical intervention on thyroid gland or other organs), harsh palpation of the gland, mental trauma, emotional stress, infections, pregnancy, labors and radioiodine therapy.

 

The diagnostic program

 

1.     Clinical examination, examination, palpation, auscultation of thyroid gland.

2.     Detecting of basal metabolism, serum lipids, ECG.

3.     Detecting of thyroid hormone concentration (common free thyroxine 4, common free triiodothyronine 3), serum iodine-binding globulin, serum thyroidstimulating hormone of hypophysis.

4.     Determining of thyroidstimulating antibodies immunoglobulins, antithyroid antibodies.

5.     Sonography of thyroid gland.

 

Differential diagnostics

 

The manifestation of initial, vague and slightly expressed forms of thyrotoxicosis can resemble neuroses, rheumatic disease, tuberculosis, chroniosepsis, postcastrate syndrome, diencephalic lesions, and also malignant tumours. It particularly concerns those cases, when the enlargement of thyroid gland is slight or it is failed to detect.

All the mentioned diseases are characterized by palpitation, heart pain excessive sweating, subfebrile fever and loss of weight.

The acute development of thyrotoxicosis sometimes makes the necessity to rule out such acute infectious diseases, as dysentery, influenza or camp-fever.

The thyrotoxicosis with exophthalmos is necessary to differentiate with encephalitis, ophthalmopathy. Encephalitic exophthalmos is characterized by combination of looking upward paresis with diplopia, corneal ulceration, conjunctivitis, progressing, so-called malignant exophthalmos, which rather frequently can result in loss of eye. By the way, this type of exophthalmos is commonly unilateral.

Laboratory tests are important for differential diagnostics of thyrotoxicosis: detecting of thyroid hormones, serum protein-bounded iodine, thyroid-iodine uptake, biochemical, immunological investigations, sonography and scanning with the radioiodine or technetium.

In particularly severe cases it is advisable to apply trial antithyroid therapy.

 

Tactics and choice of treatment

 

The thyrotoxicosis revealed for the first time, and also its severe and moderate forms require institutional treatment. Three methods of treatment of thyrotoxicosis are commonly employed: ) antithyroid drugs; b) treatment by radioactive iodine; c) surgery.

The antithyroid drug therapy of the patients with thyrotoxicosis, first of all, should be directed to ameliorate hyperthyroidism. This is gained by the usage of iodine and thyrostatic agents, particularly mercasolil synthetic antithyroid drug. In severe cases the treatment begins from 45-60 mg (9-12 tablets) per day, in the moderate form from 30 mg (6 tablets), in mild from 15 mg (3 tablets) per day. The maximal initial dose ordered within 2-4 weeks to gain expressed clinical relief of the disease (decrease of irritability, normalization of pulse rate, increase of weight). After that, if the state of the patient gradually improves, the dosage is reduced every 3-4 weeks by 1-2 tablets per day to supportive dose (1 or 1/2 tablets per day during 2-3 months). Commonly, the course of the treatment by mercasolil should be lasted for 1-1,5 years. Among complications, which can arise during the treatment, it is necessary to mention leukopenia, agranulocytosis and allergy.

In case of allergic response to mercasolil or development of complications used a reserve drug lithium carbonate.

Such long conservative treatment of thyrotoxicosis is desirable in those patients, who gained euthyoidism in 1-3 months, that is the gradual reduce of goiter and eye signs. If during the treatment periodically exacerbation occurs, which manifests by thyroid enlargement, development of encephalopathy, activation of ophthalmopathy the surgery is indicated.

More recent studies showed that the treatment by radioactive iodine is a radical method of therapy of thyrotoxicosis. The radioactive iodine, which deposits in thyroid gland, irradiating its parenchyma, results in destruction of the active thyrocytes with their further replacement by connective tissue (bloodless thyroidectomy). The standard dosage is 0,1 mCi per gram of thyroid tissue, and it can be introduced at one time or partly.

Nevertheless such therapy has series of essential drawbacks. The lack of precise methods of determining the weight of the gland results in miscalculations at selection of total dose of the isotope. It is also impossible to exclude the harmful influence of the isotope on the genetic kettle of the patient. Almost in 70 % of the patients the hypothyroidism develops after the treatment by radioactive iodine and there is a potential threat of the development of radioactive thyroid cancer. That's why the indication for application of this method rather restricted.

The treatment by radioactive iodine is commonly indicated for the patients with thyrotoxicosis after 40, with recurrent thyrotoxicosis, and after operations particularly, in combination with severe concomitant diseases and in case of refuse of surgery. It is not justified at young age, pregnancy and during lactation, thyrotoxic multinodular adenoma, expressed leukopenia, and kidney dysfunction or at severe acute thyrotoxicosis.

Sometimes introduction of radioactive iodine can cause the exacerbation of thyrotoxicosis, up to the development of thyroid storm. Thus, before administration of the radioactive iodine, particularly in patient with severe form of thyrotoxicosis in order to relieve thyrotoxicosis it is necessary to institute antithyroid drugs.

The surgical method of treatment is considered to be radical and the most effective. The operation almost always allows to liquidate the manifestations of hyperthyroidism together with its morphological base. The efficiency of this method in the specialized clinics reaches 95-97 %.

The indications for surgery include thyrotoxicosis of moderate gravity when the conservative treatment is inefficient during 2-3 months, severe forms of thyrotoxicosis, goiter of IV-V degree despite the gravity of thyrotoxicosis, and also nodular transformation of toxic goiter.

The surgical method is not recommended for the patients with thyrotoxicosis with severe concomitant diseases and dysfunction of vital systems.

The obligatory requirement of successful surgery of the patients with thyrotoxicosis is the careful preoperative preparation, which goal is the liquidation or decreasing of hyperthyroidism, that achievement of euthyroid state. Preoperative preparation should be complex, pathogenically proved and individual.

The appropriate place in preoperative period should possess psychological preparation. The patients stay in chambers together with patients recovering after operation. In severe form of thyrotoxicosis a strict bed regime is ordered. The diet should be high-caloric, rich with proteins, vitamins. The patient must take antithyroid drugs under the control of general blood analysis. To prevent leukopenia and agranulocytosis instituted leukopoetic agents. Besides antithyroid therapy, are advisable reserpin that characterized by hypotensive, sedative and antithyroid activity, beta-blockers and tranquilizers for decreasing stimulation of CNS.

In severe form of thyrotoxicosis, at presence of hypoproteinemia is advisable the intravenous infusion of protein substitute solutions (albumin, protein, plasma). With the purpose of detoxycation applied neohaemodes, neocompensan. For exhausted patients beside high-caloric diet applied parenteral infusion of glucose, intralipid, amino acids and vitamins, particularly of B-group. The patient with sings of heart failure simultaneously should take cardiac glycosides and other cardiac agents. One of the measures in preoperative preparation is the regulation of reduced function of suprarenal glands. Glycocorticoids (hydrocortisone etc.) administered in daily dosage of 25-50 mg 2-3 times per day during 3-4 days before the operation and 2-3 days after it. Preoperative preparation should also include regulation of hemostatic dysfunction (vicasol, aethamsylat, dicynon, inhibitors of proteases).

The preoperative preparation is considered to be sufficient, if the state of the patient is regarded to euthyroid or approximate to it. It is testified by normalization of pulse (90-80 per minute), increase of weight on 3-5 kg, liquidation of nervousness and irritability, disappearance of tremor, regulation of function of cardiovascular system, liver, suprarenal glands, CNS and basal metabolism.

Anesthesia. The method of choice is endotracheal narcosis.

Operation. The most effective and rational surgery approach for thyrotoxicosis is the subtotal subfascial resection of the thyroid (O.V.Nickolayev, 1951) or thyroidectomy. The main difference of this procedure is the refuse of ligation of thyroid vessels before they enter the gland and subfascial resection of the gland. The goal of this technique is to gain bloodless and atraumatic procedure of operation, to prevent damage (removal) of parathyroid glands and laryngeal nerves. This procedure also favors the formation of a gland stumps in the site of parathyroid glands and passage of recurrent nerves. The volume of resection and, consequently, the size of the gland stamp must be based on the account of gravity of thyrotoxicosis, age of the patient, duration of the disease, previous treatment, morphology of the organ and immune state of the patient. (Fig.18)

 

Fig.18. Subtotal resection of thyroid gland by Welti

It is generally accepted, that the more severe the form of thyrotoxicosis, more young the patient, more short duration of the disease, more intensive vascularization, more dark color of the gland, the smaller tissue remnant is necessary to leave (mainly less 6 g, on 1-3 g from each side). Morphologically in such patients revealed hyperfunctional type of histogram and autoimmune processes on initial stage of the development.

The elderly age of the patients with long conservative treatment, reduced blood supply of the gland, expressed plasmolymphatic infiltration of the tissue requires to leave greater thyroid remnant (6-10 g). Morphologically in such patients detected regenerate type of histogram.

Sometimes a long anamnesis and conservative treatment, in association with expressed sclerosis of the gland or its nodular or cystic transformation requires performing of thyroidectomy.

Postoperative period. The clinical course of early postoperative period in the patients undergone the operation mainly depends both on quality of preoperative preparation, and on technique of the surgical intervention. In some patients, particularly with severe form of thyrotoxicosis, during first days after the operation it is possible to observe exacerbation of thyrotoxicosis postoperative thyrotoxic response.

There are three degrees of postoperative thyrotoxic response: mild, moderate gravity and severe.

Characteristic sings of mild degree is the tachycardia up to 120 per minute, fever as high as 38, satisfactory state of the patient, tachypnea.

The moderate gravity of thyrotoxic response manifests by mild psychomotor excitement. They complain of general weakness, headache, fever sensation, rapid pulse to 120-140 per minute (rhythmic, tense), sometimes extrasystole. Temperature raises as high as 38,5-39. Characteristic the considerable sweating, tachypnea, superficial sleep.

Severe degree of thyrotoxic response is characterized by expressed psychomotor excitement. The patients are restless, frequently change positions in the bed, they complain of considerable sweating, permanent fever sensation and expressed tremor. Hyperemia of the face, pulsate vessels of the neck and cyanosis of leaps are evident. The pulse rate usually exceeds 140 per minute, irregular and soft. The breathing is superficial. Body temperature is 39-40. The sleeplessness in such patients is almost impossible to liquidate by hypnotic and narcotics agents.

 

Complication of a postoperative period

 

1. Thyroid storm is the severe complication of postoperative period in the patients with thyrotoxicosis (thyrotoxic crisis, acute postoperative thyrotoxicosis). The crisis develops mainly on the second or third day after the operation. If is failed to liquidate it in a day after the onset, the patient can die.

The clinical development of such crisis is acute or fulminant. It manifests by excitement, up to psychosis and coma, motor disorders, tachycardia (pulse rate 150-200 per minute), complete arrhythmia, fever as high as 40 and more, hyperemia of the face, neck, limbs, cyanosis, extremely sweating, diarrhea.

Pathogenically thyroid storm is caused by excessive releasing of thyroid hormones. It can arise as the result of rough palpation of the thyroid, treatment by antithyroid drugs, radioactive iodine, infections and traumas.

The crisis requires an urgent and complex treatment. Infusion therapy includes transfusion of haemodes, solutions of glucose with vitamins, plasma, and albumin. Major doses of glycocorticoids, narcotics, neuroleptanalgesia are instituted. Also desirable administration of sedative antihistamine drugs, adrenergic blockers, cardiac glycosides, oxygenotherapy, hypothermia, particularly on regions of major vessels, medical narcosis, extracorporal method of detoxycation.

The prophylaxis of thyroid storm suggests an adequate preoperative preparation in order to gain euthyroid state of the patient, and also atraumatic performance of surgical intervention.

2. The damage of laryngeal nerves is the severe complication of operations on thyroid gland. Thus the paralysis of laryngeal nerves can be unilateral or bilateral, temporary or permanent. The basic causes of the paralysis: cutting off the nerve, its crushing or ligating, distention or compression. It is also necessary to specify that the bilateral injury of inferior laryngeal nerves is particularly dangerous.

The prophylaxis of the damages of laryngeal nerves basically consists of careful technique of subfascial resection of thyroid gland. It is always necessary gently manipulate in the region of inferior poles and "dangerous zone". The hemostasis in order to obtain "dry" operative wound should be carried out only under the visual control.

The development of asphyxia requires an urgent intubation of trachea, or tracheostomy.

3. Asphyxia. It is caused, except bilateral injury of inferior laryngeal nerves, by the damage of trachea, tracheomalacia, laryngeal edema or inflection of trachea.

The tracheal wall injuries must be sutured by atraumatic needle with further muscular plastics. Tracheomalacia requires supporting sutures on trachea or application of prosthetics from synthetic material. Sometimes it is necessary to perform temporary tracheostomy.

4. Air embolism. The cause of this infrequent complication is the entering of air in the neck veins owing to suctional activity of chest and negative venous pressure. The prophylaxis of such complications consists of clamping of veins before cutting.

5. Parathyroid tetany is a difficult postoperative complication, which is hardly to undergo rehabilitation. The basic cause parathyroid tetany is the removal of parathyroid glands together with thyroid tissue. Besides it can result from impaired blood supply of the glands after the operation. The tetany develops on the base of mineral metabolism disorders, first of all, extremely reduced serum calcium (less 2,5 mEq/l)

It manifests by acute attack of wide-spread or localized cramps of separate groups of muscles of the upper or lower limbs. The most dangerous in this plan is the development of laryngospasm or tonic contraction of diaphragm.

Early clinical manifestation of parathyroid tetany is the Chvostek's signs (percussion near mandible angle causes muscular contractions of the face), Ttrousseau (occurrence of paresthesias and the sign of "obstetrician's" hand" after applying of tourniquet on brachium.

The treatment of parathyroid tetany consists of prompt administration of calcium agents. The usage of parathormone in complex with vitamin D is usually beneficial. Simultaneously with conservative treatment also performed transplantation of bony tissue.

The careful technique of subfascial resection of thyroid gland prevents the damage of parathyroid glands (except cases of their thyroid ectopy).

6. Bleeding. The cause of intra- and postoperative bleedings is insufficient mechanical hemostasis.

The postoperative bleedings are observed within first hours after operation as the result of unreliable hemostasis or slipping of ligature from vessels. Bleedings are clinically characterized by the prompt enlargement of swelling in the region of neck, considerable sopping of bandage by blood. Meanwhile, the patients complain of feeling of tightness in the neck, fear, tachycardia, cyanosis and dyspnea. The treatment of this complication is only surgical. The goal consists of complete disclosure and revision of the wound, carrying out of careful hemostasis.

The prophylaxis of postoperative bleeding includes a complex of measures, the most important of which is a subfascial technique of thyroid resection, careful reliable hemostasis and anatomic operating. The special attention is necessary to pay on lateral thyroid veins (Kocher's veins), which are short and empty directly into interior jugular vein. If the vessels are sclerosed, fragile and easily broken, they should be tied at once after cutting, instead of leaving on clamps up to the end of gland removal.

The damage of larynx, esophagus, major vessels of neck, lymph duct and pleura very seldom occurs. The laryngeal defects are sewed up with further covering by muscles. The esophageal wound is sewed up tightly, and feeding of the patient during 7 days is carried out through the tube.

 

 

 

 

 

Inflammatory diseases of thyroid gland

 

PURULENT THYROIDITIS

 

The purulent thyroiditis is a suppurative septic lesion of thyroid parenchyma. There are also cases of purulent inflammation goitrous thyroid gland acute purulent strumitis.

 

Etiology and pathogenesis

 

The purulent thyroiditis arises owing to invasion of the thyroid by bacterial infection which spreads by hematogenous or lymphogenous way. The infecting agent most often represented by pyogenic streptococcus or staphylococcus aureus.

 

Pathology

 

Morphologically according to the character of inflammation distinguished the plain and specific thyroiditis, according to the course acute, subacute and chronic.

The acute thyroiditis mainly develops in one lobe. Histologically revealed formation of the necrotic foci, hemorrhages, leukocytic infiltration of stroma with admixture of lymphocytes and macrophages.

The subacute thyroiditis (de Kerven) is histologically represented by the developments granulomatous inflammation. The stroma is commonly infiltrated by lymphocytes, leukocytes and large cells, which remind the cells of foreign bodies.

The chronic thyroiditis can manifest in the form of Hashimoto's and Riedel's goiter or specific thyroiditis caused by tuberculosis, lues or actinomycosis.

Hashimoto's goiter is characterized by predominant lymphocytic infiltration with formation follicles (lymphocytic goiter). Riedel's goiter ("iron goiter, fibrous thyroiditis) is represented by growth of fibrous tissue.

In specific thyroidites revealed specific granulomas.

 

Classification

 

Distinguished acute purulent thyroiditis as diseases, which arise in unaltered thyroid gland, and acute purulent strumitis the lesion of the goitrous transformed thyroid gland.

 

Symptomatology and clinical course

 

The onset of the disease is usually acute. It manifests by spontaneous sharp pain in the region of the neck, which amplifies at movements, speech and swallowing, fever, chills, weakness, sweating and tachycardia. On examination it is possible to note local reddening and swelling. Palpation reveals tissue tension, thyroid enlargement, density, with fluctuation in the site of lesion. In blood observed neutrophil leukocytosis and increased erythrocyte sedimentation rate.

 

Variants of clinical course and complications

 

The clinical course of the disease is characterized by the sings of purulent septic pathology of the neck. The process spreads outside the thyroid. Late diagnostics and inappropriate treatment result in discharge of the abscess outside, development of neck phlegmon, mediastinitis and sepsis. Nevertheless, in general, the outcome is favorable, on the site of abscess replaced by fibrous tissue, and the function of gland tends to norm.

 

The manifestation of initial, vague and slightly expressed forms of thyrotoxicosis can resemble neuroses, rheumatic disease, tuberculosis, chroniosepsis, postcastrate syndrome, diencephalic lesions, and also malignant tumours. It particularly concerns those cases, when the enlargement of thyroid gland is slight or it is failed to detect.

All the mentioned diseases are characterized by palpitation, heart pain excessive sweating, subfebrile fever and loss of weight.

The acute development of thyrotoxicosis sometimes makes the necessity to rule out such acute infectious diseases, as dysentery, influenza or camp-fever.

The thyrotoxicosis with exophthalmos is necessary to differentiate with encephalitis, ophthalmopathy. Encephalitic exophthalmos is characterized by combination of looking upward paresis with diplopia, corneal ulceration, conjunctivitis, progressing, so-called malignant exophthalmos, which rather frequently can result in loss of eye. By the way, this type of exophthalmos is commonly unilateral.

Laboratory tests are important for differential diagnostics of thyrotoxicosis: detecting of thyroid hormones, serum protein-bounded iodine, thyroid-iodine uptake, biochemical, immunological investigations, sonography and scanning with the radioiodine or technetium.

In particularly severe cases it is advisable to apply trial antithyroid therapy.

 

The diagnostic program

 

1.     Clinical examination, palpation.

2.     General blood analysis.

3.     Sonography of thyroid gland.

4.     Diagnostic puncture of thyroid gland.

5.     Bacteriological investigation of exudate.

 

The purulent thyroidites must be differentiated from simple thyroiditis and strumitis. The stormy course and transformation of plane inflammation into purulent that detected clinically, and by means of diagnostic puncture (purulent exudate) distinguish acute thyroiditis from the other inflammatory processes in thyroid gland.

 

Tactics and choice of treatment

 

Diagnostic puncture is necessary in order to confirm the diagnosis. If present fluctuation and purulent exudate it is necessary to carry out surgical management (drainage of suppurative focus). Such patients require antibiotics, analgesics, antiinflammatory and sedative agents.

 

 

Autoimmune thyroiditis

Autoimmune (lymphomatous) thyroiditis is the disease described by Hashimoto in 1912. In most cases it occurs in women of age 40-50.

 

Etiology and pathogenesis

 

The basic etiologic factor in the development of autoimmune thyroiditis is the release and entering of thyroid antigens into the blood as the result of inflammatory processes and traumas combined with surgical operations on thyroid gland. It has been found the presence of antibodies to thyroglobulins, colloidal component of thyroid gland and microsomal fraction. However the presence of antithyroid antibodies not always results in the damage of the thyroid. The cytotoxic properties of these antibodies manifest only after their interaction with -lymphocytes and HLA antigens.

 

Pathology

 

The histological sign of autoimmune thyroiditis is the diffuse or focal thyroid infiltration by lymphocytes and plasma cells, which results in destruction of follicles and their basal membranes. Further thyroid tissue is replaced by connecting that leads to the focal fibrosis, which resemble nodes.

 

Classification

 

Distinguished diffuse and focal, and also hypertrophic and atrophic form of autoimmune thyroiditis.

 

Symptomatology and clinical course

 

Hashimoto's thyroiditis is characterized by the slow growth of goiter, the thyroid density, and gradual hypothyroidism. Besides develops the symptomatology, resulting from compression of organs and tissues of the neck by goiter. The patients complain of enlargement of thyroid gland, sense of tightness in the neck, difficult swallowing and breathing, pain in the region of gland and general weakness.

Enlargement of the thyroid is symmetric, it, as a rule, of dense consistence, and on palpation detected its nodular character. During pressing on one of the lobe of thyroid gland the elevation of contrlateral lobe is observed (the sign of "swing").

 

Variants of clinical course and complications

 

Autoimmune thyroiditis is characterized by the development of hypothyroidism. Nevertheless there are also atypical clinical forms of the disease: autoimmune thyroiditis with thyrotoxicosis (Hashitoxicosis) with gradual transferring into hypothyroidism, lesion of one lobe with clinical course according to the nodular type of euthyroid or hypothyroid goiter. The autoimmune thyroiditis can arise in thyroid stump after surgery for different forms of goiter. The combination of autoimmune thyroiditis with thyroid adenoma or cancer and its transferring into chronic rarely occur.

Autoimmune thyroiditis can complicated with hypothyroidism, compression of neck organs, in some cases - malignancy.

 

The diagnostic program

 

1.     Clinical examination of the patient (palpation of thyroid gland).

2.     Detecting of thyroid hormone concentration and thyrotropin.

3.     Sonography of thyroid gland.

4.     Detecting of antibodies to different thyroid components.

5.     Biopsy of thyroid gland.

 

Fig.19. Hashimoto's thyroiditis sonography picture

 

 

Differential diagnostics

 

It should be carried out with endemic and sporadic goiter, Riedel's fibrous goiter and thyroid cancer.

Symmetric enlargement of thyroid gland, its dense consistence, nodular character, presence of autoimmune diseases in family history, high antibody capacity to thyroglobulins and microsomal fraction, development of hypothyroidism, positive response as reducing of goiter at prednisolone assay (20 mg of prednisolone during 7-10 days) all these distinguish autoimmune thyroiditis from endemic and sporadic goiter, Riedel's thyroiditis. It is usually impossible to differentiate autoimmune thyroiditis from thyroid cancer on the base of clinical, instrumental and laboratory findings. In this case exclusive value has the morphological investigation biopsy of thyroid gland or express histological investigation during operation. Macroscopically the gland is of pale-pink- greyish color with yellowish tone (instead of red-brown in norm), with atrophic sheath and thin-walled veins.

The manifestation of initial, vague and slightly expressed forms of thyrotoxicosis can resemble neuroses, rheumatic disease, tuberculosis, chroniosepsis, postcastrate syndrome, diencephalic lesions, and also malignant tumours. It particularly concerns those cases, when the enlargement of thyroid gland is slight or it is failed to detect.

All the mentioned diseases are characterized by palpitation, heart pain excessive sweating, subfebrile fever and loss of weight.

The acute development of thyrotoxicosis sometimes makes the necessity to rule out such acute infectious diseases, as dysentery, influenza or camp-fever.

The thyrotoxicosis with exophthalmos is necessary to differentiate with encephalitis, ophthalmopathy. Encephalitic exophthalmos is characterized by combination of looking upward paresis with diplopia, corneal ulceration, conjunctivitis, progressing, so-called malignant exophthalmos, which rather frequently can result in loss of eye. By the way, this type of exophthalmos is commonly unilateral.

Laboratory tests are important for differential diagnostics of thyrotoxicosis: detecting of thyroid hormones, serum protein-bounded iodine, thyroid-iodine uptake, biochemical, immunological investigations, sonography and scanning with the radioiodine or technetium.

In particularly severe cases it is advisable to apply trial antithyroid therapy.

 

 

Tactics and choice of treatment

 

There is no specific therapy of autoimmune thyroiditis for today. The phenomena of hypothyroidism require nominating of replaceable therapy by thyroid hormones (thyroidine, thyroxine). Glycocorticoids and antihistamine agents are used in subacute form of autoimmune thyroiditis.

Surgery is applied in case of compression of the neck organs and suspicion on malignant tumour of the thyroid. The volume of operation has been still controversial. Preserving operation (isthmusectomy in combination with wedge-like resection of lateral lobes, resection of thyroid gland) expedient only on initial stages of the disease with maintained thyroid activity. Taking into account a reality of malignancy, often relapses of goiter after small resections, the role of thyroid remnants as the foci of autoimmune aggression, the thyroidectomy is performed. After such operation the patients till the end of life should take substitution therapy by thyroid hormones. Is has been noticed, that after thyroidectomy, in comparison with thyroid resection, the patients considerably better response to substitution therapy by thyroid hormones.

 

 

 

Riedel's Thyroiditis

 

Invasive fibrous Riedel's thyroiditis (synonyms Riedel's goiter, "woody" goiter) is the extremely rare pathology, which consist of 0,005 % of persons undergone the surgery for different thyroid lesions. The disease described by Riedel in 1894 and 1897, occurs mainly in males.

 

Etiology and pathogenesis

 

The etiology of the disease is still unknown. There is the hypothesis that the Riedel's thyroiditis is the similar to such diseases, as idiopathic fibrous mediastinitis, sclerosing cholangitis and retrobulbar fibrosis. It gives the suggestion that the fibrous lesions of different organs can be the manifestation of one disease. Some authors suggest its infectious origin, though there are no reliable findings.

 

Pathology

 

This disease is represented by the development of connective tissue in thyroid gland with further transformation into a thick-fibber fibrous tissue. Between its layers there are small foci of adenomatous parenchyma, mainly of a microfollicular structure. The fibrous connective tissue spreads outside the thyroid, penetrates into muscles of the neck, untimely adherents to esophagus and trachea, causing their constriction and deformity.

 

Symptomatology and clinical course

 

The patients complain of goiter, dysphagia, difficult respiration and changes of a vote quality (chestvoice) down to aphonia. The gland becomes of woody or iron consistence, with change of configuration. Frequently observed the signs of tracheal and esophageal compression.

The disease is characterized by severe "malignant" course with aggressive growth of a fibrous tissue, which can go on even after thyroid resection and after repeated operations for goiter relapse.

The function of the gland commonly preserved, though occasionally the course of disease complicated with hypothyroidism.

The most common complication of the disease is compression of organs and tissues of the neck, which results in dysphagia, dyspnea, and vocal changes.

 

The diagnostic program

 

1. Clinical examination of the patient (palpation of thyroid gland).

2. Sonography of thyroid gland.

3. Scanning of thyroid gland.

4. Puncture biopsy of thyroid gland.

5. Morphological investigation of thyroid tissue during surgical management.

 

Differential diagnostics

 

Riedel's thyroiditis is necessary to differentiate with thyroid cancer. Such sings as nodular character, metastases in lymph nodes of neck and paralysis of recurrent nerves, are characteristic for cancer. Owing to high density of Riedel's thyroiditis a puncture biopsy of the thyroid is usually hardly performed. Thus, it is necessary to carry out intraoperative histological investigation.

Macroscopically the adhesion of neck muscles with thyroid capsule is observed. The tissue of the gland is grey, with pink foci, according to consistence resemble cartilage and homogeneous on incision.

The manifestation of initial, vague and slightly expressed forms of thyrotoxicosis can resemble neuroses, rheumatic disease, tuberculosis, chroniosepsis, postcastrate syndrome, diencephalic lesions, and also malignant tumours. It particularly concerns those cases, when the enlargement of thyroid gland is slight or it is failed to detect.

All the mentioned diseases are characterized by palpitation, heart pain excessive sweating, subfebrile fever and loss of weight.

The acute development of thyrotoxicosis sometimes makes the necessity to rule out such acute infectious diseases, as dysentery, influenza or camp-fever.

The thyrotoxicosis with exophthalmos is necessary to differentiate with encephalitis, ophthalmopathy. Encephalitic exophthalmos is characterized by combination of looking upward paresis with diplopia, corneal ulceration, conjunctivitis, progressing, so-called malignant exophthalmos, which rather frequently can result in loss of eye. By the way, this type of exophthalmos is commonly unilateral.

Laboratory tests are important for differential diagnostics of thyrotoxicosis: detecting of thyroid hormones, serum protein-bounded iodine, thyroid-iodine uptake, biochemical, immunological investigations, sonography and scanning with the radioiodine or technetium.

In particularly severe cases it is advisable to apply trial antithyroid therapy.

 

Tactics and choice of treatment

 

The treatment of invasive fibrous Riedel's thyroiditis only surgical and consists of complete removal of affected thyroid tissue. The advantage should be given to thyroidectomy.

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DISEASES OF MAMMARY GLAND

ANATOMY

Knowledge of the anatomy and embryology of the breast and the chest structures under it is required not only for the performance of surgical procedures but also in planning therapeutic radiation, predicting sites of locally recurrent disease, and assessing the adequacy of surgical procedures used in an increasing number of therapeutic trials. Embryologically, the human breast develops in the thickened portion of ectodermal tissue known as the milk streak coursing from the pubis to the axilla in early fetal life. Late in the first trimester, the milk streak atrophies, leaving only its pectoral portion, which continues to thicken and to form the nipple bud. The entire gland then forms as a dermally derived organ lying within the subcutaneous tissue in a manner similar to that of sweat gland development. The ductal system develops from the nipple bud by invasion and downgrowth of primitive ectodermal cells from the nipple surface. The mature breast parenchyma lies cushioned in fat between the layers of superficial pectoral fascia. Between the deep layer of the superficial fascia and the fascial investment of the pectoralis major muscle, the breast rests on a thin layer of loose areolar tissue, the retromammary space, containing lymphatics and small vessels. When a total mastectomy is performed, the correct plane is found under the pectoral fascia and includes the retromammary space as emphasized by earlier surgeons and anatomists.

Deep to the pectoralis major muscle, the pectoralis minor muscle is enclosed in the clavipectoral fascia that envelopes it and extends laterally to fuse with the axillary fascia. In a standard modified radical mastectomy, dissection along the lateral border of the pectoralis minor muscle divides the axillary fascia and exposes the contents of the axilla. The number of lymph nodes found in the axillary space of patients undergoing mastectomy varies depending on the extent of dissection and the diligence of methods used to identify these nodes. An upper limit is established by the work of Durkin and Haagensen using ethanol clearing. These investigators found an average of 50 nodes in 100 specimens obtained in the course of a Halsted-type radical mastectomy. The current approach to less radical procedures has reduced the number of nodes retrieved.

To standardize the extent of axillary dissection, the axillary space is arbitrarily divided into three levels. Level I nodes are those in the external mammary, scapular, axillary vein, and central axillary groups, which lie lateral to the lateral border of the pectoralis minor muscle. Level II nodes are those in the central axillary group, which lie under the pectoralis minor muscle. The level III nodes are difficult to visualize and remove unless the pectoralis minor muscle is sacrificed or divided and include those subclavicular nodes medial to the minor muscle. The apex of the axilla is defined by the costoclavicular ligament (Halsted's ligament), at which point the axillary vein passes into the thorax and becomes the subclavian vein. Lymph nodes in the space between the pectoralis major and minor muscles are known as the interpectoral group, or Rotter's nodes, described by Grossman and Rotter. Unless this group is specifically exposed, they are not encompassed in surgical procedures that preserve the pectoral muscles.

The lymphatic drainage of the breast is rich, and appreciation of the major pathways allows one to predict the sites most commonly containing lymph-borne metastases. Lymphatic channels within the breast follow centrifugal pathways from the subareolar plexus along major lactiferous ducts and then along efferent veins to draining nodal beds. The major site of drainage is to central axillary nodes. The internal mammary and interpectoral nodes, although primary routes of lymph flow, are rarely the sites of nodal metastasis from breast cancer in the absence of simultaneous axillary disease. Secondarily, the lymphatic spread of cancer is into the high axillary nodes in the subclavicular chain and henceforth into the supraclavicular fossa.

As the surgeon endeavors to remove the lymph nodes of the axilla, a keen knowledge of the nerve structures in the axilla is required to avoid their sacrifice. Coursing close to the chest wall on the medial side of the axilla is the long thoracic nerve, or the external respiratory nerve of Bell, which innervates the serratus anterior muscle. This muscle is important in fixation of the scapula to the chest wall during adduction of the shoulder and extension of the arm, and its denervation results in the winged scapula deformity. For this reason, the long thoracic nerve is carefully preserved during standard axillary dissection. The second major nerve trunk encountered during axillary dissection is the thoracodorsal nerve to the latissimus dorsi muscle at the lateral border of the axilla. This nerve arises from the posterior cord of the brachial plexus and enters the axillary space under the axillary vein, close to the entrance of the long thoracic nerve, and then crosses the axilla to the medial surface of the latissimus dorsi muscle. The thoracodorsal nerve is usually preserved during dissection of axillary nodes, unless its sacrifice is required for complete removal of tumor-containing nodes.

Innervation of the pectoralis major muscle has gained the attention of some who emphasize the advantage of protecting these nerves during modified radical mastectomy. Loss of innervation results in a flaccid and atrophic muscle and a diminished tissue covering over the chest wall after amputation of the breast. These investigators have named the pectoral nerves according to their actual position as encountered during axillary dissection. The lateral pectoral nerve has a variable course. In the majority of patients, the lateral pectoral nerve travels around the lateral margin of the pectoralis minor muscle and is in a vulnerable position during the division of the clavipectoral fascia and exposure of the axillary space. If possible, this branch can be saved without compromising the dissection.

The final nerves of interest to the surgeon are the large sensory intercostal brachial or brachial cutaneous nerves that span the axillary space and supply sensation to the undersurface of the upper arm and skin of the chest wall along the posterior margin of the axilla. Cutting these nerves, which is routinely done in removing the lymph node-containing tissues, causes cutaneous anesthesia in these areas. It is helpful to emphasize this to the patients before operation. Denervation of the areas supplied by these sensory nerves can cause chronic and uncomfortable pain syndromes in a small percentage of patients. Contemporary surgeons have advocated preservation of the most superior brachial cutaneous nerve, which crosses the central axilla to supply cutaneous sensation to the posterior upper arm. This nerve can be preserved without compromising the axillary dissection in many patients.

Microscopic Anatomy of the Breast

The mature breast is composed of three principal tissue types: epithelium, fibrous stroma and supporting structures, and fat. The relative amounts tend to vary with age, but there is even greater variability among individual women. In youth, the predominant tissues are epithelium and stroma, replaced by fat in the breast of older women. For this reason, mammography in women younger than 30 years of age, whose breast tissue is dense with stroma and epithelium, produces images without much definition that are rarely useful clinically. In contrast, fat absorbs relatively little radiation and provides a contrasting background that favors detection of small density lesions in the older patient. Throughout the fat of the breast, coursing from the overlying skin to the underlying deep fascia, strands of dense connective tissue provide shape and hold the breast upward. These strands, devoid of epithelial elements, are called Cooper's ligaments. Because they are anchored into the skin, tethering of these ligaments by a small scirrhous carcinoma commonly produces a dimple or subtle deformity on the otherwise smooth surface of the breast.

The glandular apparatus of the breast is composed of a branching system of ducts, roughly organized in a radial pattern, which spread outward and downward from the nipple-areolar complex. These lactiferous ducts are so named because they carry the milk produced in the more distal lobular groupings. At the summit of the arborizing ductal system, the subareolar ducts widen to form the lactiferous sinuses, which then exit through 15 to 20 orifices on the nipple. These large ducts close to the nipple are lined with a low columnar or cuboidal epithelium that abruptly meets the squamous epithelium of the nipple surface, which invades the duct for a short distance. Awareness of this junction helps understand Paget's disease of the nipple, described later.

At the opposite end of the ductal system and after progressive generations of branching, the ducts end blindly in clusters of spaces that are called terminal ductules or acini. These are the milk-forming glands of the lactating breast and together with their small efferent ducts or ductules are known as the lobular units or lobules. The terminal ductules are invested in a specialized loose connective tissue that contains capillaries, lymphocytes, and other migratory mononuclear cells. This intralobular stroma is clearly distinguished from the denser and less cellular interlobular stroma and from the fat within the breast.

Under the luminal epithelium, the entire ductal system is surrounded by a specialized myoepithelial cell of ductal epithelial origin that has contractile properties and serves to propel secretion of milk toward the nipple. Outside the epithelial and myoepithelial layers, the ducts of the breast are surrounded by a continuous basement membrane containing laminin, type IV collagen, and proteoglycans. The basement membrane layer is extremely important in differentiating in situ from invasive breast cancer. Continuity of this layer around proliferations of ductal cells guarantees that progression to an invasive cancer has not yet occurred.

BREAST DEVELOPMENT AND PHYSIOLOGY

In many mammalian species, full breast development requires the stimulation of copulation or pregnancy. Humans do not require either of these two events to initiate and complete breast maturation. Appreciation of the stages of breast development is necessary to understand many benign and even malignant states that come to clinical attention. During adolescence, the breast is composed primarily of dense fibrous stroma and scattered ducts lined with epithelium. In the United States, puberty begins at about 12 years of age, during which time there is hormone-dependent maturation of the genital organs. In the breast, this process entails increased deposition of fat, formation of new ducts by branching and elongation, and the first appearance of lobular units. This process of growth entails cell division and is under the control of estrogen, progesterone, adrenal hormones, pituitary hormones, and trophic effects of insulin and thyroid hormone. There is evidence that local growth factor networks are also important, including epidermal growth factor, which can replace estrogen as a developmental mammogen. The exact timing of these events and the coordinated development of both breast buds may vary from the average in individual patients. The term prepubertal gynecomastia refers to the symmetrical enlargement and projection of the breast bud in a young girl before the average age of 12, unaccompanied by the other changes of puberty. This process, which may be unilateral, should not be confused with neoplastic growth and should not be subjected to biopsy.

The mature or resting breast contains fat, stroma, lactiferous ducts, and lobular units. During phases of the menstrual cycle or in response to exogenous hormones, the breast epithelium and lobular stroma undergo cyclic stimulation. It appears that the dominant process is hypertrophy and alteration of morphology rather than hyperplasia. In the late luteal (premenstrual) phase, there is accumulation of fluid and intralobular edema that appears to correspond to the clinical complaint of breast engorgement, which may be painful.

On physical examination, and even by mammography, this may lead to increased nodularity and even be mistaken for development of a dominant tumor. Accordingly, ill-defined masses in premenopausal women are correctly observed through the course of one or two menstrual cycles. Finally, any alteration in the periodicity of the menstrual cycle, such as anovulatory cycles, can cause accentuation of engorgement, pain, and nodularity.

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With pregnancy, there is diminution of the fibrous stroma to accommodate the hyperplasia of the lobular units. This formation of many new acini or lobules is termed the adenosis of pregnancy and is influenced by high circulating levels of estrogen and progesterone and by levels of prolactin that steadily rise during gestation. After birth, there is sudden loss of the placental hormones and the continued high level of prolactin. This may be the principal trigger for lactation. The actual expulsion of milk is under hormonal control and is caused by the contraction of the myoepithelial cells that surround breast ducts and terminal ductules. There is no evidence for innervation of the myoepithelial cells; their contraction appears to be in response to the pituitary-derived peptide oxytocin. Stimulation of the nipple appears to be the physiologic signal for continued pituitary secretion of prolactin and for the acute release of oxytocin.

When breast feeding ceases there is a fall in prolactin and no stimulus for release of oxytocin. The breast then returns to a resting state and to the cyclic changes induced when menstruation begins again. With the approach of menopause, phases of the menstrual cycle may not be as symmetrical and regular. This irregularity can induce functional nodularity and breast pain where there had been none in earlier years. Menopause is defined by a cessation in menstrual flow for a significant period of time (i.e., 6 months or more) and the variable appearance of constitutional systems such as diaphoresis, minor psychological disturbances, or even clinical depression. For the breast, menopause results in involution and a general decrease in the epithelial elements of the resting breast. These changes include increased fat deposition, diminished connective tissue, and the virtual disappearance of the lobular units. The persistence of lobules, hyperplasia of the ductal epithelium, and even cyst formation can all occur under the influence of exogenous ovarian hormones. Most commonly, hormones are administered to relieve the symptoms of menopause, to prevent demineralization of bone, or to slow the appearance of atherosclerosis. The surgeon evaluating patients at any age for breast disease should inquire about the menstrual history, establish the cessation of menses in postmenopausal women, and record the use of any exogenous hormones. It is important that the pathologist who is examining biopsy material also have this information.

Abnormal Physiology and Development

Gynecomastia. Hypertrophy of breast tissue in men is a common clinical entity for which there is frequently no identifiable cause. Haagensen distinguishes pubertal hypertrophy, occurring in young boys between the ages of 13 and 17 years, from senescent hypertrophy, which occurs in men older than 50. The enlargement in teenage boys is very common and is frequently bilateral but may be unilateral. Unless it is unilateral or painful, it passes unnoticed and regresses with adulthood. Pubertal hypertrophy is generally treated by reassurance and without operation. Surgical excision should be discussed only if the enlargement fails to regress and the breast is cosmetically unacceptable.

Hypertrophy in older men is also common and may regress spontaneously. It is frequently unilateral, although the contralateral breast may enlarge with passage of time. The discoid mass is smooth, firm, and symmetrically distributed beneath the areola. It may be tender, and patients occasionally complain of breast discomfort. A number of commonly used medications, such as digoxin, thiazides, estrogens, phenothiazines, and theophylline, may exacerbate senescent gynecomastia. In addition, gynecomastia may be a systemic manifestation of hepatic cirrhosis, renal failure, and malnutrition. There should be little confusion with carcinoma occurring in the male breast. Carcinoma is usually not tender, it is asymmetrically located either beneath or beside the areola, and may be fixed to the overlying dermis or to the deep fascia. As with pubertal hypertrophy, gynecomastia in older men is usually left untreated. A dominant mass suspected of carcinoma should be sampled or carefully observed.

Nipple Discharge. The appearance of a discharge from the nipple of a nonlactating woman is frequently frightening to the patient and misunderstood by the physician. Nipple discharge is very common and rarely associated with an underlying carcinoma. It is important to establish whether the discharge comes from one breast or from both breasts, whether it comes from multiple duct orifices or from just one, and whether the discharge is grossly bloody or contains blood. A milky discharge from both breasts is termed galactorrhea. In the absence of lactation or history of recent lactation, galactorrhea may be associated with increased production of prolactin. Radioimmunoassay for serum prolactin is diagnostic. However, true galactorrhea is very rare and is diagnosed only when the discharge is milky (contains lactose, fat, and milk-specific proteins).

Unilateral non-milky discharge coming from one duct orifice is surgically significant and warrants special attention. However, the underlying cause is rarely a breast malignancy. In one review of 270 subareolar biopsy results of discharges coming from one identifiable duct, and without an associated breast mass, carcinoma was found in only 16 patients (5.9%). In each of these cases, the fluid was either grossly bloody or tested strongly positive for occult hemoglobin. In another series of 249 patients, including both multiple-duct and single-duct discharges, breast carcinoma was found in 10 (4%). In 8 of these patients, a mass lesion coexisted with the discharge. Among 67 patients with breast cancer presenting with nipple discharge and studied by Leis and colleagues, only 8 (12%) had no palpable mass and 7 (10%) had a negative mammogram. To conclude, nipple discharge that comes from a single duct and contains blood must be investigated further. However, in the absence of a palpable mass or a suspicious mammogram, this symptom is usually not associated with cancer.

The most common cause of spontaneous nipple discharge from a single duct is a solitary intraductal papilloma in one of the large subareolar ducts directly under the nipple. Fibrocystic change, or cystic mastopathy, typically produces multiple-duct discharge and is another commonly associated finding. Subareolar duct ectasia, producing inflammation and dilatation of large collecting ducts under the nipple, is a common finding in the aging breast and usually produces multiple-duct discharge. In summary, nipple discharge that is bilateral and comes from multiple ducts is usually not a surgical problem. Discharge from single ducts is not commonly associated with carcinoma in the absence of detectable blood or a palpable mass. Bloody discharge from a single duct requires surgical biopsy to establish diagnosis. Intraductal papilloma is found in the majority of cases. If an occult cancer is found, it invariably is an early intraductal lesion.

Breast Pain. Painful breast tissue is an exceedingly common symptom but is usually of functional origin and very rarely a symptom of breast cancer. Haagensen 24 carefully recorded the symptoms of women presenting with breast carcinoma and found pain as an unprompted symptom in only 5.4% of patients. Although not a symptom of cancer, breast pain is a common reason for patients to seek medical attention. Breast pain appears to be aggravated by abnormal menstrual cycles and may be seen in young women with menstrual irregularity, as a premenstrual symptom, or when exogenous ovarian hormones are administered during and after the menopause. In addition, fibrocystic change, in its severest forms, may cause disabling breast pain. Although many observers find painful cystic mastopathy is aggravated by excessive intake of caffeine, nicotine, or commonly used antihistamines, other investigators disagree.

Fibrocystic Change (Cystic Mastopathy, Cystic Mastitis). Fibrocystic change, popularly referred to as fibrocystic disease, represents a spectrum of clinical and histologic findings and describes a loose association of cyst formation, breast nodularity, stromal proliferation, and epithelial hyperplasia. Fibrocystic change appears to represent an exaggerated response of breast stroma and epithelium to a variety of circulating and locally produced hormones and growth factors. Clinically, patients with fibrocystic change have dense, firm breast tissue with palpable lumps and frequently gross cysts. This condition is commonly painful and tender to touch. Histologically, the lesion recognized as fibrocystic complex contains macrocysts, microcysts, stromal fibrosis, adenosis, and a variable amount of epithelial metaplasia and hyperplasia. All these changes can occur alone or in combination and to a variable degree in the normal female breast. Autopsy studies have questioned whether any of these changes, except perhaps macrocysts, are abnormal. In fact, all of these lesions occur commonly in the breasts of elderly patients and appear to have no particular pathologic potential. It appears preferable to describe each of the lesions separately and comment about the extent and severity of the process. The term fibrocystic disease should be abandoned in the absence of any well-defined clinical and pathologic syndrome.

As discussed later, there is no consistent association between fibrocystic complex and breast cancer. It is well established that women who have undergone breast biopsy for any reason, regardless of the underlying pathology, have a slightly higher risk of developing subsequent breast cancer. Moreover, the incidence of finding fibrocystic disease in autopsied breasts from women dying of causes other than breast cancer exceeds the incidence of these same changes in cancer-containing breasts. For those patients with fibrocystic changes, higher risk appears to concentrate in those whose biopsy specimens show abnormal ductal and lobular hyperplasia and, to a lesser extent, cyst formation. Therefore, the fibrocystic complex appears to be an exaggerated or abnormal response to otherwise physiologic stimuli in most patients and represents a health risk only in certain subsets.

Galactocele. A galactocele is a milk-filled cyst that is round, well circumscribed, and easily movable within the breast. It usually occurs after the cessation of lactation or when feeding frequency has been curtailed significantly. Haagensen states that it may occur up to 6 to 10 months after breast feeding has stopped. The pathogenesis of galactocele is not known for certain, but it is thought that inspissated milk within a large lactiferous duct is responsible. The tumor is usually located in the central portion of the breast or under the nipple. Needle aspiration produces thick, creamy material that may be tinged dark-green or brown. Although it appears purulent, the fluid is sterile. The treatment is needle aspiration. Withdrawal of thick milky secretion confirms the diagnosis, operation is reserved for those cysts that cannot be aspirated or that become superinfected.

Absent or Accessory Breast Tissue. Absence of breast tissue (amastia) or absence of the nipple (athelia) are very rare anomalies. Unilateral rudimentary breast development is much more common, as is adolescent hypertrophy of one breast with more normal development of the other. In contrast, accessory breast tissue (polymastia) and accessory nipples (supernumerary nipples) are both common. Supernumerary nipples are usually rudimentary and occur along the milk line from the axilla to the pubis in both males and females. They may be mistaken by the patient for a small mole. However, accessory nipples are removed only for cosmetic reason. True polythelia refers to more than one nipple serving a single breast and is very rare.

Accessory breast tissue is commonly located above the breast in the axilla. Rudimentary nipple development may be present, and lactation is possible with more complete development. Accessory breast tissue, which may present as an enlarging mass in the axilla during pregnancy, is treated by surgical removal if it is large, cosmetically deforming, or to prevent enlargement during future pregnancy.

Breast Imaging

The goal of any technique that seeks to image the breast is to extend the capability of physical examination to either detect smaller abnormalities or to provide more information about palpable abnormalities. Mammography is clearly the most sensitive and specific test that can be used to complement the physical examination of the breast. It is used either as a diagnostic modality that seeks to answer specific questions about the health of the breast or as a screening test that seeks to find any abnormality within the breast. A variety of other methods have been used to generate useful images of the breast. Of these, ultrasonography is the only one in common use today. Thermography, which images heat generated by the breast, was added to the Breast Cancer Detection Demonstration Project (BCDDP) to evaluate its usefulness as a screening tool. However, because of a low overall yield, thermography was dropped from the project. Computed tomography (CT) has been used by some investigators with success but can require contrast medium enhancement, has limited ability to resolve small abnormalities, and requires a larger exposure of radiation. CT appears to be the best way to image internal mammary nodes and to evaluate the chest and axilla after mastectomy. Magnetic resonance imaging (MRI) is a technique that requires expensive equipment. The long times required to construct a suitable image are acceptable for diagnostic applications but prohibit MRI as a screening tool. MRI may have a role in evaluating breasts that are difficult to image or after prosthetic implantation. Digital imaging is an evolving hybrid technology that has found application in chest radiography and may be used to store radiographic information in a digital format or to directly produce images. This technology is improving and may have application in mammography.

Diagnostic Mammography. Film-screen mammography has replaced xeromammography as the standard breast imaging technology. Xeromammography was developed by the Xerox corporation and produced a blue image viewed in ambient reflected light. Modern film-screen mammography uses a combination of an enhancing screen and a molybdenum anode tube that produces low kilovolt electron photons. The enhancing screen converts and amplifies a low-energy radiation beam into high-energy photons that, in turn, expose a standard x-ray film. This technique uses compression of the breast between plexiglass plates to lessen the thickness of the tissue through which the radiation must pass and to separate adjacent structures and improve resolution. The image, like standard x-rays, is viewed using transmitted light and is a negative image. Film-screen mammography delivers an average glandular dose of radiation that is less than 100 mrad. (0.1 cGy. or 0.1 rad.). In comparison, the average dose to the center of the breast in patients undergoing barium swallow is more than 10-fold the dose of two-view mammography.

The mammographic features of malignancy can be broadly divided into density abnormalities (including masses, asymmetries, and architectural distortions) and microcalcifications. Each mammogram should also be assessed for the presence of abnormalities in the axillary nodes and for the presence of skin or nipple changes, such as thickening or retraction. These mammographic features can coexist in any one particular abnormality and may exist in the presence or absence of physical findings. In fact, integration of each of the radiographic features and the physical findings leads to a prediction of malignancy.

Nonpalpable Mammographic Abnormalities. Mammographic abnormalities that cannot be detected by physical examination are classified in three broad categories: (1) lesions consisting of microcalcifications only, (2) density lesions (masses, architectural distortions, and asymmetries), and (3) those with both calcifications and density abnormalities. The incidence of malignancy after biopsy depends on the characteristics of the radiographic finding. Lesions with both microcalcifications and a mass effect, spiculated masses, and linear branching calcifications carry the highest probability of being malignant. However, even well-defined densities can be malignant. To be certain, not every abnormality should undergo biopsy, and recommendations must be made by the surgeon in consultation with an experienced radiologist. For those patients not undergoing biopsy, interval mammograms must be done to ensure stability of the abnormality.

If a biopsy is performed, it is usually done after mammographic placement of a needle or hook wire. A newer alternative is automated stereotactic core-needle biopsy. This procedure requires a large and dedicated unit, which is expensive. The patient generally lies prone with the breast hanging through the table. A robotic arm and biopsy gun is positioned by computerized analysis of triangulated mammographic images. A small amount of local anesthesia is used at the point of core-needle entry into the breast. Firing the machine obtains a core biopsy through the abnormality. Many series containing hundreds of patients have shown good correlation between stereotactic biopsy and subsequent needle-placement open biopsy. For lesions with calcification, a specimen radiograph must be done to confirm the presence of the abnormality in the specimen. This is true for both stereotactic and open biopsy procedures. Cooperation is required between the radiologist, surgeon, and pathologist for the correct interpretation of biopsy material obtained by either technique. If stereotactic biopsy is available to the surgeon, judgment must be used to determine the optimal biopsy strategy. Because stereotactic biopsy does not remove the abnormality, a subsequent localization and open procedure will be required if a cancer is found and the patient wishes to attempt breast conservation. If the abnormality proves benign after stereotactic biopsy, follow-up mammography needs to be done if the lesion is indeterminate. The false-negative rate of stereotactic biopsy is low but finite.

Screening Mammography. The goals of screening mammography differ from those of diagnostic mammography. Screening studies seek to identify any abnormality, maximizing sensitivity and cost effectiveness. During the past three decades, there have been eight major randomized controlled trials that compared a screened population to women given usual care. Although screening intervals and mammographic techniques differed, each of these studies included mammography with or without clinical breast examination in the screened arms. In the United States, a single uncontrolled study was done to demonstrate the feasibility of a population-based screening program. The BCDDP screened 280,000 women annually in 29 centers throughout the United States. Each center offered free mammograms and a breast examination and taught breast self-examination. Participants in the BCDDP have been followed for 14 years, and survival data were published. Because this was not a controlled trial, comparison has been made to national statistics compiled by the Surveillance, Epidemiology, and End Results (SEER) program within the National Cancer Institute (NCI). Comparison of survival data 8 years after diagnosis of cancer in the BCDDP to corresponding data from the SEER program demonstrates improved survival in the screened population, which seems to be explained by a shift to earlier stage disease in the BCDDP.

BENIGN BREAST TUMORS AND RELATED DISEASES

Breast Cysts. Cysts within the breast are fluid-filled, epithelial-lined cavities that may vary in size from microscopic to large, palpable masses containing as much as 20 to 30 ml. of fluid. As discussed, cysts are generally discovered by physical examination and confirmed by ultrasound or needle aspiration. At least one woman in every 14 will develop a palpable cyst, and 50% of cysts are multiple or recurrent. Cysts occur as solitary abnormalities, called macrocysts or gross breast cysts, or as part of a generalized process of microscopic cyst formation. This latter disease process is frequently bilateral and the cystic transformation can be extensive. The pathogenesis of cystic formation is not well understood; however, cysts appear to arise from destruction and dilation of lobules and terminal ductules. Three-dimensional microscopic studies and extensive sectioning have shown that stricture and fibrosis at or near terminal branching of small ductules, combined with continued secretion by the distal lobule, result in expansion of a cavity containing fluid and lined by ductal epithelium.

Cysts are unquestionably influenced by ovarian hormones, a fact that explains their sudden appearance during the menstrual cycle, their rapid growth, and their spontaneous regression with completion of the menses. Most women with new cyst formation present after the age of 35 and rarely before the age of 25 years. The incidence of cyst development steadily increases until the age of menopause and sharply declines after menopause. Autopsy studies of women dying with clinically normal breasts generally confirm the age relationship of gross cyst development but do find that the breasts of older women can contain gross and microscopic cysts. New cyst formation detected clinically in older women commonly is explained by the use of exogenous hormone replacement.

When encountered during operation, cysts are frequently dark. These are often referred to as blue dome cysts, and they reflect the dark cyst fluid contained within. Grossly, they are usually unilocular and lined by a smooth and glistening surface, although larger cystic structures may be trabeculated and multiloculated. Histologically, cysts are frequently lined by a flattened epithelium. However, the epithelial layer may display apocrine metaplasia or may have papillary features. Intracystic carcinoma is exceedingly rare. Rosemond was able to report only three examples in over 3000 cyst aspirations (0.1%), and other investigators confirm this exceedingly low incidence. Regarding the risk of developing cancer for women with cystic disease, no studies demonstrate an increased risk in women with small or microscopic cysts. For patients with large cysts, called gross cystic disease by Haagensen, there remains some controversy. Patey and Nurick found no increase in cancers subsequent to cyst aspiration. Of 810 cancers treated by Patey, only 10 had a previous history of gross cysts. Other recent reviews have emphasized that women with gross cysts have a risk of twofold to fourfold that of age-matched women without cysts. The studies of Page and associates and of Dupont and Page do not show a significant increase in cancers after long-term follow-up of over 2000 women who underwent biopsy of palpable cysts when compared with the slight increase borne by women who have had breast biopsy alone.

Fibroadenoma and Related Tumors. Fibroadenoma (adenofibroma) is a benign tumor composed of both stromal and epithelial elements in the breast. After carcinoma, fibroadenoma is the second most common solid tumor in the breast and is the most common tumor in women younger than age 30 years. The benign nature of this lesion was recognized in 1840 by Cooper, who referred to the lesions as chronic mammary tumors. Clinically, they present as firm, solitary tumors that may increase in size over several months of observation. They may be lobulated but will slip easily under the examining fingers. At operation, fibroadenomas appear to be well-encapsulated masses that may easily detach from the surrounding breast tissue. By history, fibroadenoma is favored over cyst in the adolescent or young adult; and on examination, these tumors are distinguished from cysts by the needle aspiration that yields no fluid. Mammography is of little help in distinguishing between cysts and fibroadenomas; however, ultrasound usually clearly shows the cavity of a cyst. The gross appearance and histopathology are distinctive of fibroadenoma. Grossly, the tumor appears well encapsulated, with smooth borders that may be lobulated. Histologically, a variable proportion of epithelial and stromal proliferation is present, and the stroma may be quite cellular or replaced by acellular swirls of collagen. In older patients, the lesions may contain deposits of calcium within dense fibrosis. The epithelium can display the entire spectrum of proliferative changes seen elsewhere in the breast. Although fibroadenomas are not considered to have a malignant potential, the epithelial elements appear to be at risk for neoplasia just as epithelium elsewhere in the breast. More than 100 invasive and noninvasive carcinomas have been reported in preexisting fibroadenomas since 1985. Most of these (50%) have been lobular carcinoma in situ, 35% were infiltrating carcinomas, and 15% were intraductal carcinoma. The risk of cancer in a newly discovered fibroadenoma found in the breast of a young woman is obviously exceedingly rare and is not an issue that influences treatment. A modest risk of subsequent carcinoma in women who have previously been treated for fibroadenoma has been reported, but the magnitude is about two times the general population. This is only slightly higher than the reported excess risk for all women who have had a breast biopsy.

The treatment of fibroadenoma follows that for any unexplained solid mass within the breast. The great majority of patients in the United States are treated by excisional biopsy to remove the tumor and establish the diagnosis. It is worth recognizing that a different approach is taken by physicians in other countries. A typical fibroadenoma is frequently left untreated by European physicians when the tumor is encountered in the breast of a young women. If excision is recommended, the approach to a young women with a typical fibroadenoma on examination should be very different than the approach in older women with indeterminate masses. Cosmetic incisions around the areola with a modest amount of tunneling to remove the lesion are commonly used techniques and are proper for the treatment of fibroadenoma. Emphasis should be placed on removing a minimum amount of breast tissue adjacent to a typical fibroadenoma. If the gross appearance is that of a fibroadenoma, frozen section is superfluous, the patient can be immediately reassured, and final diagnosis can be established by inspecting permanent sections.

 

Juvenile Fibroadenoma, Giant Fibroadenoma. Clinicians treating breast masses should be aware of these two terms, which are sometimes confusing. Giant fibroadenoma is a descriptive term that applies to a fibroadenoma that attains an unusually large size, typically greater than 5 cm. Haagensen calls these lesions massive adenofibromas in youth to denote their common occurrence in adolescent women. Juvenile fibroadenoma refers to the occasional large fibroadenoma that occurs in adolescents and young adults and histologically is more cellular than the usual fibroadenoma. Both these lesions overlap, and both may display remarkably rapid growth within the breast. Although alarming to the patient and physician, prompt surgical removal is always curative. The term benign cystosarcoma phyllodes refers to a tumor that may be difficult to distinguish clearly from juvenile fibroadenoma. If the tumor has been completely removed, the diagnosis of benign cystosarcoma should reassure the surgeon and the patient that the risk of recurrence is low, particularly if the patient is an adolescent or a young adult. Malignant cystosarcoma phyllodes is a distinctive and aggressive tumor discussed later.

Hamartoma and Adenoma. Although probably not of the same histogenesis as fibroadenoma, these tumors are benign proliferations of variable amounts of epithelium and stromal supporting tissue. The hamartoma is a discrete nodule that contains closely packed lobules and prominent, ectatic extralobular ducts. By physical examination, mammography, and gross inspection, the hamartoma is indistinguishable from fibroadenoma. The nodule is entirely benign, and removal is curative. The mammary adenoma or tubular adenoma has been a more elusive entity to define. Page and Anderson describe this tumor as a cellular neoplasm of ductules packed closely together and forming a sheet of tiny glands without supporting stroma. During pregnancy and lactation, these tumors may increase in size and histologic examination shows secretory differentiation. Malignancy is not a feature of tubular adenoma or lactating adenoma, but biopsy is required to establish the diagnosis.

Breast Abscess and Infections. Breast abscess commonly occurs in the subareolar breast tissue and may be recurrent and difficult to treat. Although the exact cause is not known, subareolar duct ectasia and obstruction of major ducts may lead to proliferation of bacteria and subsequent abscess. Further destruction of the normal ductal openings leads to fistula formation and chronic recurrent abscess. Mammary duct ectasia, first named by Haagensen, is an inflammatory condition that causes distortion and dilation of the lactiferous sinuses under the nipple. It is a common entity and is frequently responsible for nipple inversion in older women. In understanding subareolar abscess and probably mastitis in general, it is useful to remember that the nipple and areolar complex contains secretory ducts that are exposed to the environment. Chronic inflammation, duct dilation, and obstruction may combine at the nipple to produce circumstances that favor bacterial invasion.

The treatment of acute abscess of periareolar tissue should be conservative if possible. Antibiotics with broad-spectrum coverage should be used initially. More severe infections may require hospitalization and intravenous antibiotics. A small incision with drainage is preferred if the process cannot be controlled by antibiotics alone. Needle aspiration may be attempted, but the abscess cavity is usually multiloculated. Recurrent infection is best treated by excision of the diseased subareolar ducts as described by Haagensen and others. However, recurrence is common and leads to chronic and recurring infection.

Mastitis describes a more generalized cellulitis of breast tissue that may involve a large area of the breast but may not form a true abscess. The etiology appears to be an ascending infection beginning in subareolar ducts and extending outward from the nipple. Occasionally, mastitis involves areas of cystic disease and may be sterile. Mastitis presents with erythema of the overlying skin, pain, and tenderness to palpation. There is induration of the skin and underlying breast parenchyma. Especially in young women, an apparent mastitis may develop that is dramatic in its presentation and responds poorly to antibiotics but resolves spontaneously. The etiology is unknown but may be related to menstrual cycle irregularity. More commonly, mastitis complicates lactation, possibly due to inspissation of milk, obstruction, and secondary infection. Local measures such as application of heat, ice packs, or use of a mechanical breast pump on the affected side have all been recommended. If conservative measures are not effective, administration of broad-spectrum antibiotics is usually indicated. In many situations, the differential diagnosis of acute mastitis includes inflammatory carcinoma. It is important to follow patients with mastitis and confirm that there has been a complete resolution of symptoms and signs. The erythema produced by an inflammatory carcinoma will not resolve with conservative measures and generally will worsen in a short period of follow-up.

Papilloma and Related Ductal Tumors. Solitary intraductal papillomas are true polyps of epithelial-lined breast ducts. Solitary papillomas are located under the areola in the majority of cases. In contrast, certain patients have multiple intraductal papillomas that Haagensen believes are more likely to be peripherally located and associated with an increased risk of cancer. Solitary papillomas may be located in peripheral ducts and can grow to large size, presenting as a breast mass. When papillomas attain a large size, they may appear to arise within a cystic structure, probably representing a greatly expanded duct. In general, these lesions are less than 1 cm. but can grow to as large as 4 or 5 cm.

Tumors under the nipple and areolar complex often present with a bloody nipple discharge. Less frequently, they are discovered as a palpable mass under the areola or as a density lesion on the mammogram. Treatment is total excision through a circumareolar incision. The surgeon must keep in mind that one of the most difficult areas in differential diagnosis is between a papilloma and invasive papillary carcinoma. Because these lesions can infarct, scar, and even develop squamous metaplasia, they can appear bizarre and disordered. Most pathologists urge evaluation on permanent sections for the majority of papillary lesions before more extensive surgery is undertaken.

It is also important not to confuse the commonly used term papillomatosis with either solitary or multiple papillomas. Papillomatosis refers to epithelial hyperplasia that commonly occurs in younger women or is associated with fibrocystic change. This lesion is not composed of true papillomas. Hyperplastic epithelium in papillomatosis may fill individual ducts like a true polyp but has no stalk of fibrovascular tissue nor the frondlike growth. Solitary papillomas are entirely benign and do not predispose to development of cancer in the patients who have them. Page and Anderson state that the degree of subsequent risk for breast cancer in patients with either papillomatosis or with true papillomas, either solitary or multiple, relates to the degree of atypical epithelial proliferation associated with them.

MALIGNANT TUMORS OF THE BREAST

Epidemiology

The likelihood of developing breast cancer is highly dependent on both age and the interval over which an individual is at risk. Although the lifetime risk of developing breast cancer is estimated at 10%, more than one half of patients with breast cancer are older than 65. Furthermore, the 10% figure is based on a hypothetical interval that extends from birth to age 110. A more realistic view considers risk starting at a particular age and extends over a finite period of time. For instance, the chance that a woman age 35 will develop breast cancer during the next two decades of her life, until age 55, is only 2.5%. A woman who is 50 has close to a 5% chance of developing cancer before she turns 75 and a 65-year-old woman has a 5.5% chance of getting breast cancer before she turns 85 years of age. These figures apply to white women in the United States; the same idealized African-American woman has a lifetime risk of breast cancer that is 7% or 8%.

The odds of dying of breast cancer over the ideal lifetime of birth to 110 are about 3.6%. Although carcinoma of the lung has overtaken breast cancer as the leading cause of cancer-related death in American women, breast cancer remains far more common. Of 595,000 new cases of cancer among women in 1996, 186,000 occurred in the breast while 78,000 arose in the lung.

Several studies based on cancer registries in the SEER program of the NCI have reported an increasing attack rate for breast cancer in the United States. In Washington State there has been an annual estimated increase of 2.5%. A greater increase was apparent among black and low-income women. In the Connecticut Tumor Registry the overall annual incidence rose from 53 cases per 100,000 women during the years 1935 to 1939 to an average annual rate of 86.4 per 100,000 for the years 1975 to 1979. The annual rate of increase during 1980 to 1985 averaged 3%; during the past 5 years, this rate of increase has declined to about 1% per year. Data from other studies and from other western countries confirm the increase in the incidence of breast cancer. Despite this increased incidence, the age-adjusted death rate from carcinoma of the breast was stable until 1979 and may have decreased in the 5-year period between 1979 and 1984. Although it is tempting to speculate that this is a real improvement attributable to early diagnosis or improved therapy, no direct proof can be cited.

Pathology of Breast Cancer

Modern classification of breast cancer attempts to recognize morphologic patterns that reflect both the histogenesis of the malignancy and its biologic behavior, or prognosis. As such, these classifications impose artificial divisions on diseases that are fundamentally poorly understood. As advances are made in our understanding of breast malignancies, the classifications presented today will be improved on by future generations of surgeons and pathologists. Malignancies of the breast are broadly divided into epithelial tumors of cells lining ducts and lobules and nonepithelial malignancies of the supporting stroma. A second important division of the epithelial tumors that recognizes their evolution is between noninvasive and invasive cancers. The noninvasive malignancies are proliferations of either ductal or lobular cells confined to the basement membrane. These are true carcinoma in situ. As in other organs, carcinoma in situ commonly coexists with invasive cancer. In the breast, this association is very frequent and argues for the progression of cancer through stages of noninvasive proliferation, disruption of the basement membrane, and invasion of the supporting stroma.

Most pathologists utilize the classification scheme proposed by the World Health Organization (WHO) and outlined in the fascicles of the Armed Forces Institute of Pathology. Historically, Foote and Stewart presented most of this material in 1945, including a recognition of noninvasive carcinoma and the differentiation between tumors originating in the breast lobule from those arising in the lactiferous ducts.

Ductal Carcinoma in Situ (DCIS), Intraductal Carcinoma. The concept of a purely noninvasive form of breast cancer and recognition of various subtypes have evolved slowly since the beginning of this century. DCIS was probably recognized first by surgeons who appreciated its favorable prognosis. Bloodgood, at the Johns Hopkins Hospital, impressed by the tumor of an early patient of Halsted, recognized a disease he termed pure comedo tumor that had an extremely favorable prognosis. Pathologically, breast ducts become swollen with proliferating malignant epithelium. In the solid or comedo type, the ducts can expand to visible proportions 1 or 2 mm. in diameter. The term pure intraductal carcinoma refers to the absence of detectable invasion of the basement membrane. Devoid of blood supply, the center of the lesion undergoes necrosis and the intraductal spaces fill with necrotic cellular debris. The central detritus can undergo dystrophic calcification that is fine, focally clustered, and even linear and branching when seen on high-quality mammography. This process can locally produce a palpable mass if multiple ducts are involved.

Subtypes of DCIS are now well recognized and frequently reported pathologically. The solid or comedo type is most common and probably more virulent. Papillary or cribriform DCIS are characterized by papillary projections of tumor cells into the ductal lumen or by the presence of a branching, cribriform pattern filling ducts. These types are less likely to form palpable masses and uncommonly calcify to produce a mammographic abnormality. However, it is important to emphasize that these subtypes can coexist and that DCIS is best described by the pathologist in terms of its extent, multicentricity, and involvement of the surgical margin. Confusion arises in a number of ways. First, the uninitiated may confuse the term infiltrating ductal carcinoma with the term intraductal carcinoma; the former is invasive disease and the latter is noninvasive disease. Second, these two stages of tumorigenesis usually coexist, particularly when they are carefully searched for in pathologic specimens. Finally, as discussed later, the treatment and outcome for patients with intraductal disease may depend on variables such as multifocality, multicentricity, and extent of disease in a way more demanding for the pathologists and surgeons than in the past.

Lobular Carcinoma in Situ (LCIS) or Lobular Neoplasia. This disease of the breast lobules or acini was first clearly delineated by Foote and Stewart in 1941, who gave it the name lobular carcinoma in situ. Haagensen first used the term lobular neoplasia to emphasize its more benign course. Pathologically, it is a proliferation of small round epithelial cells within lumens of multiple breast acini. The resulting picture is multiple clusters of epithelial cells forming islands of neoplastic cells but maintaining a lobular architecture. Although the ducts expand with proliferating cells, they usually do not reach the large size seen with DCIS.

Unlike DCIS, LCIS never forms a palpable mass by itself and is therefore not recognized on physical examination. In addition, there are no mammographic findings in LCIS. It does not form a density and rarely calcifies, both of which are typical for DCIS. Therefore, this is a disease that is recognized incidentally after biopsy for another abnormality that is producing a clinical or mammographic finding. The treatment of this incidental pathologic entity remains controversial and is reviewed later.

Infiltrating Ductal Carcinoma. This is the most common malignant tumor in the breast recognized after biopsy. The term ductal carcinoma refers to its origin from ductal epithelium; infiltrating describes its growth pattern and distinguishes this lesion from noninvasive carcinoma. Some add the terms not otherwise specified (NOS) and no special type (NST) to emphasize that this disease is diagnosed after the other, more distinctive histologies have been eliminated. The tumor infiltrates into a variable amount of stroma as cords or islands of malignant epithelium. It may form primitive glandular forms, but not to the extent of a pure tubular carcinoma. As discussed, and as reflected in the WHO classification, many infiltrating carcinomas display an in situ component. This fact reflects its ductal origin and may be used to prove a mammary origin of the tumor. The stromal reaction may be intense and has led to the older term scirrhous carcinoma of the breast.

Clinically, most infiltrating ductal carcinomas present as a mass found on physical examination or as a density lesion on the mammogram. Microcalcifications seen mammographically are commonly found in the necrotic centers of the intraductal component but may be seen in the infiltrating component as well. The treatment of infiltrating carcinoma is discussed later, and the approach taken is generally the same regardless of the morphologic appearance. However, there is great biologic diversity among breast cancers; and after identification of an infiltrating ductal carcinoma, pathologists attempt to describe features that reflect the likely behavior of the tumor.

The evaluation of breast cancers should always specify the tumor size, the status of the surgical margin, and the content of estrogen and progesterone receptors. In addition, the nuclear and histologic grade is frequently reported and modern evaluation may include measurement of DNA content and estimation of the proliferating fraction, or S-phase. Vascular invasion, tumor necrosis, and the extent of the intraductal component are all used to make decisions about the primary or adjuvant treatment of patients with operable breast cancer. The dedicated breast surgeon must be acquainted with all of these parameters and their interpretation.

Invasive Lobular Carcinoma. This disease probably originates in the breast lobule. Invasive lobular carcinoma constitutes between 3% and 15% of all invasive breast cancers, depending on the series consulted. Histologically, the tumor is composed of small round cells that infiltrate surrounding stromal tissue in a peculiar Indian file fashion. Lobular carcinoma presents in an identical fashion as ordinary infiltrating ductal carcinoma and produces no distinguishing mammographic features. The treatment of lobular carcinoma is the same as for the more common ductal carcinomas and may carry a better prognosis. There may be a somewhat higher incidence of bilateral cancer or of second primary tumors in the contralateral breast. However, this is rarely used to justify prophylactic procedures in the contralateral breast in the absence of synchronous disease.

Less Common Forms of Ductal Carcinoma. These tumors, although heterogeneous, are all morphologic variants of common ductal carcinoma. In general, these less common variants have improved prognosis, reflecting their more differentiated phenotype. One exception to this rule is medullary carcinoma of the breast, which is pathologically characterized by bizarre and anaplastic tumor cells surrounded by a prominent lymphocytic infiltrate with a scant fibrous stroma. Although the epithelial component is undifferentiated, this phenotype appears to enjoy a small but significant survival advantage when compared with infiltrating ductal carcinoma NOS. Mucinous carcinoma, also called colloid carcinoma, is characterized by well-differentiated epithelial cells surrounded by a large accumulation of extracellular and extraluminal mucin that is secreted by the carcinoma cells. This histologic type enjoys a favorable prognosis in several published series. Although there are no definite clinical or mammographic signs of mucinous and medullary carcinoma, these tumor types are suggested by a well-circumscribed density with smooth borders that tend to be softer on physical examination. The final major histologic type that is distinctive and well differentiated is tubular carcinoma. This tumor is characterized by infiltrating tubular structures, lined by one cell layer, and with an open central space. The tumor is characteristically small, is scirrhous, and has an excellent prognosis after treatment. The descriptions of these histologic variants refer to their predominant features. However, each may coexist with more undifferentiated infiltrating carcinoma of the usual type. In general, if the tumor is composed of definite infiltrating ductal carcinoma of poor differentiation, the final diagnosis reflects the poorest histologic pattern. Because tubular and mucinous variants are less likely to metastasize, some modern breast surgeons tailor their primary approach to these lesions by, for instance, omitting axillary node dissections for small and well-differentiated lesions.

Modern Surgical Procedures for Invasive Breast Cancer

The surgical treatment of breast cancer, for the most part, concerns the treatment of potentially curable cancer that is confined to the breast and regional lymph nodes. For early stages of breast cancer, surgical removal provides a reasonable chance for cure. Although the approach to operable breast cancer has changed dramatically over the past century, so, too, has the clinical presentation of breast tumors changed. In 1894, Halsted presented his first 50 patients treated by the complete operation, which became the radical mastectomy. Over the next 75 years, radical mastectomy was used to treat virtually every breast malignancy operated on for cure in the United States. Examination of Halsted's first cases found at least two thirds with locally advanced disease and 60% with clinically evident axillary nodal metastases. By comparison, a 1980 survey by the American College of Surgeons found that 85% of patients presented with Stage I or Stage II disease. The frequency of cases with positive axillary lymph nodes was 40%, and the average tumor presenting to physicians in the 1970s measured 2 cm. or less. In addition to these fundamental changes, realization that 90% of treatment failures will be systemic or visceral recurrences has led surgical oncologists to explore alternatives to radical mastectomy as an initial approach to operable breast cancer.

Surgical Procedures Past and Present

In 1982, the American College of Surgeons investigated surgical practice in cases of operable breast cancer and compared results with practice in earlier years. Clearly, a change in surgical practice occurred in the mid 1970s with an abrupt shift from radical mastectomy to modified radical mastectomy. Procedures that preserved the breast, as described later, were performed in only 7.2% of cases in this survey. Current estimates of conservative breast procedures range between 20% and 40%, and this procedure probably continues to increase in popularity. The following paragraphs describe procedures in widespread use now and in the past.

Radical and Extended Radical Mastectomy. In the radical mastectomy, the breast and underlying pectoralis muscles are sacrificed leaving a bare chest wall. Regional lymph nodes along the axillary vein up to the costoclavicular ligament (Halsted's ligament) are removed with the breast specimen. This procedure frequently requires a skin graft and uses incisions placed either vertically or obliquely. Prosthetic reconstruction is impossible unless muscle flaps are mobilized to cover the anterior chest defect. Cure of breast cancer can certainly be achieved by the application of this procedure alone. Other studies document both the strengths and weaknesses of maximal local therapy represented by this procedure. The personal series of Haagensen reports results from treatment of 1036 patients; 727 patients with clinically negative nodes (Stage A, Columbia clinical staging) had a survival of 72.4% at 10 years. In contrast, only 42.3% of clinically node-positive patients (Stage B) survived at 10 years. These figures were confirmed by the National Surgical Adjuvant Breast and Bowel Project (NSABP) early trial of adjuvant thiotepa. By 10 years, 76% of patients with histologically positive nodes suffered recurrence of breast cancer and one fourth of patients with negative nodes failed surgical treatment. In contrast, local failure rates have been extremely low since introduction of the Halsted radical mastectomy. Published figures are generally between 5% and 7% and provide the standard against which newer procedures are judged.

The extended radical mastectomy is a standard radical mastectomy to which en bloc removal of internal mammary nodes is added. This procedure was popularized in the United States by Urban, who reported a 35.5% 10-year survival in patients undergoing extended radical mastectomy. Other studies have resulted in abandonment of the extended procedure. A large prospective trial and several uncontrolled series have failed to provide evidence of improved clinical outcome after extended radical mastectomy.

Modified Radical Mastectomy. Modified radical mastectomy refers to a procedure combining total mastectomy with removal of axillary lymph nodes in continuity with the mastectomy specimen. This is the most widely used procedure to treat operable breast cancer and is the alternative to breast-sparing procedures described later. Modified radical mastectomy leaves the pectoralis major muscle intact, providing a soft tissue covering over the chest wall and a normal-appearing junction of the shoulder with the anterior chest wall and avoiding the hollow defect inferior to the clavicle that accompanies the removal of the pectoralis muscle. The patient is left with intact musculature around the shoulder and a situation that is well suited to prosthetic reconstruction. Two forms of the procedure are in use by surgeons: the Patey procedure and modifications described by Scanlon and the procedure described by Auchincloss.

Patey, at the Middlesex Hospital in London, developed a procedure that preserves the pectoralis major muscle and sacrifices the underlying pectoralis minor muscle to remove levels I, II, and III lymph nodes in the axilla. A large number of Patey procedures performed by Handley, who wrote extensively about this procedure, were reviewed independently and reported by Donegan and associates. The survival of patients with negative axillary nodes was 82% at 10 years with a local recurrence rate of 5%. For patients with positive nodes, the survival was 48%, very similar to results with radical mastectomy. Thus, preservation of the pectoralis major muscle did not appear to produce inferior results. Scanlon modified the Patey procedure by dividing but not removing the pectoralis minor muscle, allowing removal of apical (level III) nodes and preservation of the lateral pectoral nerves to the major muscle.

The procedure described by Auchincloss differs from the Patey procedure by not removing or dividing the pectoralis minor muscle. This modification limits the complete removal of high axillary nodes but is justified by Auchincloss, who calculated that only 2% of patients will potentially benefit by removal of the highest level nodes. It is probable that the Auchincloss mastectomy was the most popular procedure for breast cancer in the United States during the past decade.

Wide Local Excision and Primary Radiation Therapy. Excision of the primary tumor with preservation of the breast has been referred to by many names, including partial mastectomy, segmentectomy, tylectomy, or lumpectomy. Wide local excision seems to be the most descriptive term for the procedure, which removes the malignancy with a surrounding rim of grossly normal breast parenchyma. An even more aggressive local procedure designed to remove 1 to 2 cm. of adjacent breast and overlying skin is called quadrantectomy. In modern practice, these more limited surgical procedures are applied as part of a multidisciplinary approach to breast cancer and always include postoperative radiation therapy, giving at least 4500 cGy. to the whole breast and usually including a boost of radiation to the tumor bed. Axillary dissection is done through a separate incision in the majority of patients. Therefore, conservative breast surgery or breast preservation usually refers to wide local excision of the primary tumor, whole breast radiation, and a separate axillary dissection.

The Management of Noninvasive (in Situ) Carcinoma

Special attention to the problem of in situ carcinoma is justified by the increasing frequency of its recognition and the controversy surrounding the proper treatment of noninvasive cancer of the breast. Treatment decisions require appreciation of the various types and stages of in situ disease and demand that the surgical oncologist understand this sometimes complicated disease process. Moreover, its relationship to invasive cancer is a fascinating biologic question. Understanding these early proliferative states should give investigators a clue to the underlying cause of breast cancer. Finally, finding early malignancy is the goal of population screening. It is hoped that the high cure rate after treatment of noninvasive breast carcinoma will someday contribute to a decline in mortality from this malignancy.

Ductal Carcinoma in Situ (DCIS) or Intraductal Carcinoma

Before modern mammography, intraductal lesions presented as palpable tumors in 50% or more of patients. In the 1980s, more were recognized by the calcifications they produce, observable on mammograms, than by physical detection. The comedo or solid form fills small mammary ducts and is likely to undergo central necrosis. The central detritus within ducts undergoes dystrophic calcification, producing fine punctate and even linear calcification, which is seen first on mammography long before invasive disease develops into a palpable mass. Clearly, these are early lesions that can be approached in a different manner from that for usual invasive disease. Treatment recommendations for patients with intraductal carcinoma are based on consideration of several issues, including (1) occult invasive cancer coexisting with the in situ lesion, (2) multicentricity of intraductal carcinoma, (3) the occurrence of disease in the contralateral breast, and (4) the natural history after diagnosis by biopsy.

Axillary metastases are very rare in lesions that appear to be pure intraductal cancers. In the three studies just listed, a total of 316 intraductal carcinomas were studied. Axillary metastases were present in only 5 of these; in one case a second primary invasive cancer in the ipsilateral breast was present. Although not all patients underwent axillary dissection, there were no nodal recurrences during the follow-up of these patients. Significantly, all patients with positive nodes had large tumors, palpable tumors, or microscopic invasion

Many authors who have written about intraductal carcinoma are influenced by the high incidence of multicentric, multifocal, and even bilateral disease. Multifocal is a term referring to disease within the vicinity or same quadrant as the dominant lesion. Multicentric refers to disease in distant sites or quadrants within the same breast. Bilateral implies the concurrent finding of disease in both breasts. The existence of multicentric disease has led many to favor mastectomy for the treatment of DCIS, and concerns about bilaterality have prompted the use of prophylactic procedures on the contralateral breast. The most widely reported figure for the incidence of multicentric disease within the ipsilateral breast is 33%, or one third of cases in which a biopsy discloses intraductal cancer as the predominant lesion. However, estimates vary depending on how extensively other quadrants of the breast are examined. For example, although a large review of NSABP material failed to find multicentric disease, only a single random section from remote quadrants was examined. In contrast, Schwartz reported an incidence of approximately 37% after examining four random sections from each remote quadrant and from under the areola. Other estimates range between the results of these two studies. The risk of multicentric disease appears to depend both on the histologic type of the intraductal tumor and on the size or extent of the primary cancer. In the study of Lagios and associates, 2 of 24 small tumors less than 2 cm. (8%) were associated with disease in other quadrants of the breast. In moderate size tumors, between 2 and 5 cm., 2 breasts of 16 examined (12.5%) had multicentric disease. In large tumors whose extent was greater than 5 cm., all 13 cases examined had disease in remote quadrants of the ipsilateral breast. The study of Patchefsky and colleagues examined multicentricity as a function of the histology of the primary tumor. In agreement with other authors, this series found that micropapillary pathology was associated with a high (80%) incidence of multicentric disease. An intermediate percentage (40%) of papillary and comedocarcinomas were associated with remote disease, and solid and cribriform types were lowest. Size was not noted in this study. Pathologic review of DCIS should include an estimate of size, a comment about pathologic margins, and assessment of multifocal disease within the surgical specimen. Histologic type should be noted and a statement made about the presence or absence of microscopic invasion.

Lobular Carcinoma in Situ

Lobular carcinoma in situ is a relatively uncommon disease that occurs predominantly in younger, premenopausal women. As noted earlier, this disease is rarely diagnosed before biopsy, does not form a palpable mass, and rarely calcifies. Haagensen has collected the largest series of patients, all of whom were identified by review of biopsy material. In this review, LCIS was found in 3.6% of more than 5000 biopsies done for benign disease. Haagensen prefers the term lobular neoplasia to emphasize that this pathologic entity predisposes to subsequent carcinoma after a long latency period. However, in a review of 297 patients with LCIS (lobular neoplasia) treated by biopsy and careful observation, Haagensen determined the actuarial probability of developing carcinoma at the end of 35 years was 21.4%. Compared with the Connecticut Tumor Registry data, a risk ratio (observed to expected cases) of 7:1 was calculated. Significantly, 40% of the carcinomas that subsequently developed were purely in situ lesions and one half of all subsequent carcinomas occurred in the contralateral breast. Haagensen preferred a practice of close observation after a biopsy diagnosis of LCIS. Similar data have led others to express doubts about the need for mastectomy. These authors have recommended a conservative policy of close observation after a biopsy diagnosis of LCIS or lobular neoplasia.