Acta path. microbiol. immunol. scand. Sect. A. 90: 191-197. 1982.

MALE BREAST AT AUTOPSY

JOHAN A. ANDERSEN and JBRGEN B. GRAM

Institute of Pathology, Centralsygehuset. Esbjerg, Denmark

Andersen, J. A. & Gram, J. B. Male breast at autopsy. Acta path. microbiol. immunol. scand. Sect. A,

In a consecutive and unselected series of 100 male autopsies, the breasts were totally extirpated and histologically investigated. Gynecomasty was found in 5 5 cases. of which 48 were in healed and seven in still active, intermediate phase. All but two cases were bilateral. No clinical evidence of gynecomasty was established in any case. Thus. gynecomasty seems to be very common in men. In seven cases. severe intraductal epithelial hyperplasia was found, three of pagetoid and four of cribriform type. They belonged to the atypical hyperplastic - early intraductal carcinoma type. All cases were incidentally found and without known clinical relevance.

Key words: Gynecomasty: breast carcinoma.

Johan A. Andersen, Institute of Pathology, Centralsygehuset, DK-6700 Esbjerg, Denmark.

90: 191-197. 1982.

Accepted as submitted 13.xi.81 Gynecomasty and cancer are the main problems

in the male breast. Reports on the incidence and bilaterality of gynecomasty and co-existing carci- noma in situ vary in the individual studies, apparently conditioned by the clinical or patho- anatomic aspect. In the latter cases it also seems crucial whether the material is based on surgical or autopsy cases (Andersen & Gram 1982, Bannayan & Hajdu 1972, Gram & Andersen 1981, Karsner 1946, Menville 1933, Nicolis ef al. I97 1, Nydick et al. I96 I , Sandison 1962, Sirtori & Veronesi 1957, Treves 1958). It has therefore been our intention to evaluate the actual incidence of gynecomasty.

MATERIALS AND METHODS

The material consists of 100 unselected, consecutive autopsies from a regional hospital with a rather stable catchment area of approx. 50,000 male inhabitants. The autopsy frequency is more than 90 per cent of the ))hos- pital deadcc patients and corresponds at the same time to approx. 50 per cent of the ))regional deadcc persons (Juul & Andersen 1977).

Both breasts were totally extirpated. After fixation, the tissue was cut into 3 mm frontal slides. Specimen

radiography concerning microcalcifications was made before sectioning in the first 30 cases.

All tissue was paraffin embedded in a total of 752 blocks varying from 5 to 17 per case. The slides were routinely stained with hematoxylin-eosin. In case of severe epithelial hyperplasia and suspected intraductal carcinoma, the PAS/Alcian blue and argyrophilic staining methods (Bodian and Grimelius) were also used.

Detailed histological definitions have been reported in a previous paper (Andersen & Grum 1982). Gynecomasty is divided into three phases: I ) the active phase with both diffuse epithelial hyperplasia and periductal stromal hyperplasia with involvement of fatty tissue, 2) inactive phase with interductal hyaline fibrosis with replacement of fatty tissue and most often a clear demarcation of the glandular stroma against the surrounding, more fibril- lary and cellular stroma (Fig. I) . Fibroblasts and blood vessels are reduced in number but appear distinct because of the hyaline background. The duct epithelium is more or less atrophic but often with remnants of papillomato- sis and a general tendency to pseudo-acinar formation. 3) intermediate gynecomasty with both active and inactive areas.

The following histological parameters were evaluated as well: Ectasia of ducts, lobular formation, apocrine metaplasia, fatty tissue reaction, and severe epithelial hyperplasia.

Ectasia of ducts means a diameter of the individual ducts twice the size that of the surrounding ducts at the

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Fig. 1 . Inactive healed gynecomasty with hyaline fibrosis and rather small ducts. Note the replacement of fatty tissue and the rather clearcut demarcation against the reactive fatty tissue and fibrillary fibrotic stroma. H-E x 46.

same level. At the same time the epithelium is atrophic and there may be a slight periductal fibrotic and inflammatory reaction. Ectatic ducts in the areolar and papillary region are not included since ectatic apocrine and eccrine sweat glands are often seen intermingling with the original lactiferous ducts. Thus, it may be difficult to separate the types of duct. Ectatic lactiferous ducts filled with keratotic material are often seen in this region as well. Surrounding the mammary gland, progressing towards the areolar and papillary region, is a

rim of eccrine and apocrine sweat glands. A considerable intermingling of sweat glands and breast tissue is often seen. which hampers the evaluation of any lobular formation and Occurrence of apocrine metaplasia in the breast tissue itself. Only the cases with evident changes in the breast tissue have been included. Epidermoid rnetaplasia was evaluated only in the peripheral parts of the gland as there is a general tendency to epidermoid metaplasia in the infundibular area and the neighbouring part of the lactiferous ducts. As regards epithelial

TABLE I . Histological Findings in the Male Breast in 100 Autopsy Cases

Suspicion of Intermediate Inactive Inactive Normal Gynecomasty Gynecomasty Gynecomasty Breast

7 Cases 48 Cases 10 Cases 35 cases Total

Ectasia of ducts 2 17 2 9 30 Acinar formation 0 0 0 0 0 Apocrine metaplasia 0 3 0 I 4 Epidermoid metaplasia 1 0 0 0 I

hyperplasia 0 4 I 2 7 Severe intraductal

Fatty tissue reaction I 17 4 I 23

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f i g . 2 . Normal breast tissue with intermingling of fibrotic and fatty tissue and a few ducts. The fatty tissue is without inflammatory reaction. H-E x 46.

Fig. 3. Duct with cribriform growth pattern of uniform cells with rounded I@@ and abnormal polarisation. Authors' interpretation is early in situ carcinoma. H-E x 4601

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Fig. 4. In situ carcinoma of pagetoid type. Note the remnants of original ductal cells as flattened luminal cover. H- E X 184.

Fig. 5 . In situ carcinoma of pagetoid type with many typical ringlike intracytoplasmic lumina (arrows). PAS/Alcian blue x 460.

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hyperplasia: atypical ductal hyperplasia and intraductal carcinoma, the definitions stated in ))Problems in Breast Pathologycc by Azzopardi (1979) were applied.

The presumed relevant clinical and patho-anatomic data were retrospectively obtained from both the clinical and autopsy records.

RESULTS

Table I shows the Occurrence of the various histological parameters. Apart from the fatty tissue reaction it can be Seen that the histological parameters appear in both gynecomasty cases and cases with normal breast tissue without evident differences.

Forty-eight cases showed healed gynecomasty which was always bilateral apart from two cases. Seven cases showed intermediate, bilateral gyneco- masty, and in 10 cases there was considerable suspicion of healed, bilateral gynecomasty. In the last cases, however, the glandular tissue was often sparse and the evaluation therefore less certain. Thus, gynecomasty in still active and/or healed phase was demonstrated in 5 5 per cent while evident normal virile breast tissue (Fig. 2) was seen in 35 per cent.

Ectasia of ducts was seen in 30 cases and in seven cases the ectasy appeared diffusely in the mammary glands. Although lumina often contained an eosi- nophilic secretion. there were no cases of actual formation of comedones. Likewise, there was only a slight infiltration of lymphocytes and no granuloma formation. Furthermore, no fibro-elastotic nodules as a sign of healing duct ectasia were observed.

Only one case of epidermoid metaplasia in the peripheral ductal system was found. This case was combined with pronounced benign epithelial hy- perplasia in intermediate gynecomasty.

Two hemangiomas with a diameter of 2 and 3 mm respectively were demonstrated. One was related to a duct and the cther one in the stroma.

Reactive changes in the adjacent fatty tissue were seen in 23 cases. The changes consisted of inflammation with lymphocytes, plasma cells, and lipophages as well as blood-vessel proliferation. At the Same time the fat cells were often diminished but the nuclei still peripherally arranged. In I8 cases hereof, there was gynecomasty. in four cases doubtful, healed gynecomasty while the glandular tissue was sparse in one case which made the evaluation of gynecomasty or not uncertain.

Unilateral. severe epithelial hyperplasia of the atypical - early in situ carcinoma type was demonstrated in seven cases. In four of these cases, the epithelial hyperplasia was cribriform. Regular glandular lumina with bridging were seen, often

Number of Patients (+ Gymomsty)

4

Number of Patients (-Gyn.comasty)

20 5 n Fig. 6 . Age Distribution in the + Gynecomasty/- Gyne- comasty Groups.

with abnormal nuclear polarization (Fig. 3). Nuclei were generally rounded but not very hyperchro- matic, and only a few mitoses were demonstrated. However, in three cases the changes were pagetoid with many intracytoplasmic mucous lumina (Figs. 4 and 5 ) . The question of lobular or ductal pagetoid growth pattern could not be settled with certainty from determination of cell type. In one case only did the epithelial hyperplasia appear in a larger part of the mammary gland. In the remaining cases the changes were focal but most often present in several foci. Thus, no tumours were recognized either clinically or macroscopically. No argyrophilic gra- nules were demonstrated in the proliferating epithe- lium.

Metastasis to one breast from a pulmonary carcinoma was seen in one case. The metastasiza- tion was lymphogenic and many small formations were spread all over the mammary gland Wielsen et al. 1981).

Specimen radiography revealed no microcalcifi- cations or other changes.

Fig. 6 shows the age distribution in the gynecomasty and normal breast groups with the peak incidences occurring between 60 and 69 years and 70 and 19 years respectively. The mean values

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observed in the two groups are 65 .3 and 7 1.2 years respectively.

The patients' main diseases judged by the terminal clinico-pathological picture are summar- ized in Table 2. There were no clinical prostatic cancer cases in the cancer groups. The recorded drugs which might be of potential etiological interest appear in Table 3.

TABLE 2 . Main Diseases in 100 Autopsy Patients

+ Gynecomasty - Gynecornasty 55 Cases 45 Cases

Cancer Cardiovascular Chronic pulmonary Endocrine Chronic renal CNS Gastro-intestinal Blood Motor apparatus

14 13 29 16 12 I 4 I 2 I

I I 10 4 4 2 0 2 0

TABLE 3. Drugs of Potentially Etiological Signijkance Administered by 100 Patients in the Terminal Phase of the

Disease

+ Gyne- - Gyne- cornasty comasty

55 Patients 45 Patients

Digitalis glycosides

Diuretics<others

@-blocking agents Antipsycotic drugs Tricyclic antidepressants Benzodiazepine drugs Adrenal steroids Cherpotherapeutin of neoplastic diseases

Spironolacton 16 3

30 4 6 I

13 1

I

7 1

15 3 5 0

10 2

0

DISCUSSION

Our finding of intermediate and inactive gyneco- masty of 7 and 48 per cent respectively is thought- provokingly marked and greater than that found by Williams ( 1 963). In an autopsy study she found intermediate and inactive gynecomasty in 8 and 32 per cent respectively. These disparities in the Occurrence of gynecomasty might naturally be

partly caused by geographic conditions. Differences in the histological evaluation might also come into play. Although the criteria of healed gynecomasty in the vast majority of cases easily discriminates the condition against normal breast tissue, there is a middle group where the classification is uncertain. This uncertainty, however, only concerns healed gynecomasty where the question of fatty tissue replacement and stromal fibrosis is the decisive factor. The evaluation of these histological para- meters might naturally form the background of a certain subjective estimate. However, the question whether healed gynecomasty will always result in total replacement of fatty tissue and cognizable hyalinized fibrosis is also left open.

The very marked Occurrence of gynecomasty invalidates, in our opinion, gynecomasty as a premalignant condition. Our strikingly marked discovery of atypical hyperplasia - early intraductal carcinoma and their apparent even distribution over cases of gynecomasty and of normal breast tissue does not support the perception of gynecomasty as a premalignant lesion either.

In complete agreement with Nuttall ( 1979) and Nydick et al. (1 96 1) we find that gynecomasty is nearly always bilateral although clinically it often seems to appear like a unilateral lesion c4 ndersen & Gram 1982).

Ectasia of ducts is frequent in both normal breast tissue and gynecomasty cases. However, the lesion does not have quite the same character and is not as pronounced as that seen in the female breast and no clinical symptoms could be related to the lesion. The histological condition descriptively characterized by us as ectasia of ducts therefore hardly has the same etiology as duct ectasia in the female breast.

The demonstration of seven per cent having epithelial hyperplasia of the atypical - early intraductal carcinoma type is striking and much more than the four cases demonstrated by Bannayan & Hajdu ( 1 972) in a surgical material of 35 I cases of gynecomasty. It corresponds to our own demonstration in a surgical material of gyneco- masty, however Undersen & Gram 1982). All our cases of atypical hyperplasia - early intraductal carcinoma were unilateral and without known clinical relevance. They were demonstrated only because of careful histological investigation. We are, therefore, of the opinion that similar changes in surgical cases of gynecomasty must not be overesti- mated. This perception is in accordance with the conclusion reached by Kramer & Rush (1973) on the basis of a similar investigation in the female breast. The question whether the three cases of pagetoid carcinoma in situ were of ductal or lobular type is difficult to settle on general histological

I96

criteria. However, the marked Occurrence of mu- cous, intracytoplasmic lumina speaks for the lobular type (Andersen & Vendelboe I 98 1 ). It should be stressed, however, that the occurrence of intracytoplasmic lumina in male breast glandular tissue is not known.

As expected, the clinical and patho-anatomic records did not throw any light on etiological and potentially etiological factors in gynecomasty. How- ever, we found it remarkable that in no cases had present or previous gynecomasties been reported. This, in relation to the fact that more than half of the patients in an autopsy study have or have had gynecomasty, highly supports a recent investigation by Nuttall (1979): The finding (of gynecomasty) may be more common in otherwise normal men than generally realized.

REFERENCES

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8. Kramer, W. M. & Rush, B. F. Jr.: Mammary duct proliferation in the elderly: a histopathologic study. Cancer (Philad.) 31: 130-1 37, 1973.

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