Clinicopathological and immunohistochemical study of male breast carcinoma: Experience from a tertiary care teaching hospital of South India

Panduranga Chikkannaiah; Srinivasamurthy Venkataramanappa; Vinutha Lakshman; Nidhi Nair

doi:10.4103/jms.jms_75_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 34 | Issue : 1 | Page : 41-46

Clinicopathological and immunohistochemical study of male breast carcinoma: Experience from a tertiary care teaching hospital of South India

Panduranga Chikkannaiah, Srinivasamurthy Venkataramanappa, Vinutha Lakshman, Nidhi Nair
Department of Pathology, Employees' State Insurance Corporation Medical College and PGIMSR, Bengaluru, Karnataka, India

Date of Submission	24-Aug-2020
Date of Acceptance	27-Sep-2020
Date of Web Publication	16-Nov-2020

Correspondence Address:
Panduranga Chikkannaiah
Department of Pathology, Employees' State Insurance Corporation Medical College and PGIMSR, Bengaluru - 560 010, Karnataka
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jms.jms_75_20

Abstract

Introduction: Male breast carcinoma (MBC) accounts for 1% of all breast carcinomas. Compare to female counter part, they present with advance stage and high lymph node positivity and carries a poor prognosis. Invasive ductal carcinoma (IDC) no special type was the most common histopathological type. They express high hormonal receptor positivity. Few epidemiological studies of MBC are available in the northern part of India, but studies in the Southern India are spares. Hence, this study was undertaken to document the clinicopathological parameters and IHC profile associated with MBC in this region of India.
Materials and Methods: This is a retrospective study for a period of 10 years. Each case was assessed for clinical presentation, laterality, quadrant of the breast involved, fine-needle aspiration cytology diagnosis, mammography, type of surgery, size of tumor, histopathological diagnosis, lymph node status, metastasis, SBR grading, and TNM staging. Immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (Her 2) Neu, and Ki 67 was graded as per the standard protocol.
Results: During the study period, 16 MBC were observed, constituting 1.5%. The median age is 59 years; painless lump is the most common presentation. IDC no special type is the most common variant. The left breast was commonly affected (81.25%). None of them had a family history of breast carcinoma; central subareola region is the most common anatomical site involved. 62.5% were in Grade 2 and 28.5% showed ipsilateral axillary lymph node involvement. High hormonal receptor positivity was noted in 100% cases, whereas 12.5% showed Her 2 amplifications.
Conclusion: Our study also conclude that the pathology of MBC is as most of the cases are presenting with Stage 2 and less lymph node involvement which may carry a better prognosis; however, more studies on the large sample are required to document the same.

Keywords: Clinicopathological characteristics, invasive ductal carcinoma, male breast carcinoma, staging

How to cite this article:
Chikkannaiah P, Venkataramanappa S, Lakshman V, Nair N. Clinicopathological and immunohistochemical study of male breast carcinoma: Experience from a tertiary care teaching hospital of South India. J Med Soc 2020;34:41-6

How to cite this URL:
Chikkannaiah P, Venkataramanappa S, Lakshman V, Nair N. Clinicopathological and immunohistochemical study of male breast carcinoma: Experience from a tertiary care teaching hospital of South India. J Med Soc [serial online] 2020 [cited 2023 Jun 5];34:41-6. Available from: https://www.jmedsoc.org/text.asp?2020/34/1/41/300553

Introduction

Male breast carcinoma (MBC) is an uncommon malignancy, with an incidence of 1% of all breast carcinomas. It accounts for 1% of all the malignancy diagnosed in men, and the incidence is increasing globally.^{[1],[2],[3],[4],[5],[6]} The reason for the low incidence of MBC is relatively less breast tissue and difference in the hormonal response. Even though breast tissue is less in males compare to females, carcinogenic agents are same.^[7] In comparison to female breast carcinoma (FBC), MBC occurs a decade later; hence, few authors consider that MBC imitates that of postmenopausal FBC.^{[1],[2],[3],[4],[5],[6],[7]} They present with advance stage and high lymph node positivity due to their central and superficial location and high access to dermal lymphatic's, pectoral fascia, and subareola lymphatic channels and carries a poor prognosis. In contrast, they express high hormone receptors. Like its female counter part, invasive ductal carcinoma (IDC) no special type is the most common histopathological type.^{[1],[2],[3],[4],[5],[6],[7]}

Due to the rarity of the disease, literature pertaining to this is also minimal. On review the literature, most of the studies are single case report and case series. Few authors have documented epidemiological and pathological parameters of MBC in the northern part of India, but studies in the Southern India are spares.^{[1],[2],[3],[4],[5],[6],[8],[9],[10],[11],[12],[13],[14],[15],[16]} Hence, this study was conducted to document the clinicopathological and immunohistochemical parameters associated with MBC in this region of India.

Materials and Methods

This is a retrospective study for a period of 10 years from January 2010 to December 2019, conducted in the department of pathology at a medical college and tertiary care teaching hospital of South India. All the cases which have been diagnosed as MBC upon fine-needle aspiration or histopathology were included. Demographic details were retrieved from the request form and case files from the medical record section. Cytology slides (when available) histopathology and immunohistochemistry slides were retrieved and re-assessed. If histopathology slides were not available, paraffin blocks were retrieved and 3–5 mm thin sections were cut and stained with hematoxylin and eosin and assessed. Each case was assessed for clinical presentation, laterality of the breast, quadrant of the breast involved, fine-needle aspiration cytology (FNAC) diagnosis, mammography, type of surgery, size of tumor, histopathological diagnosis, lymph node status, metastasis, SBR grading, and TNM staging. Immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (Her 2) Neu, and Ki 67 were graded as per the standard protocol, and the results were tabulated.

Results

During the study period of 10 years, a total of 1034 cases of breast carcinoma were observed, out of which 16 were of MBC, constituting 1.5% of all breast carcinoma. 2025 malignancy were documented among men, and MBC constitute 0.8%. The age of the patient ranged from 43 to 71 years with a median of 59 years. All the patients were presented with the lump in the breast, and one case had nipple discharge. FNAC was done in 11 cases, out of which 8 (72.5%) cases were IDC, 2 (18.25%) cases were reported as gynecomastia, and one case (9.25%) was reported as atypical ductal hyperplasia. The left breast was commonly affected than right (4.31). None of them had a family history of breast carcinoma. Mammography was available in four cases, 3 were in BIRADS 5, and one case in BIRADS 4. Fourteen patients were treated with modified radical mastectomy (MRM), one case each underwent simple mastectomy and true cut biopsy. In the entire 16 cases, tumor was located in the central subareola region [Figure 1]a-1e].

Figure 1: (a) Clinical photograph showing the lump in the left breast (red arrow). (b) Gross photograph showing gray white tumor in the subareolar region (black arrow). (c) Gross photograph of intracystic papillary carcinoma note the papillary extrestence (Yellow arrow). Mammography showing BIRADS 5 lesion, note subareolar locations of the tumor. (d) cytology smears showing single and clusters of malignant ductal cells arranged in clusters and singles (H and E, ×40). (e) Microphotograph showing infiltrating ductal carcinoma not special type, the tumor cells are arranged in clusters separated by desmoplastic stroma (H and E, ×40). (f) Microphotograph showing ILC note the Indian file arrangement of tumor cells (black arrow head) (H and E, ×40). (g) Microphotograph showing papillary carcinoma with well-formed fibro vascular core (H and E, ×40). (i) Microphotograph showing nuclear positivity of tumor cells for antiER antibody (black arrow head) (IHC Anti ER, ×40). (j) Microphotograph showing nuclear positivity of tumor cells for anti-PR antibody (black arrow head) (IHC Anti PR, ×40). (k) Microphotograph showing grade 3 membrane positivity of Her 2 new (black arrow head) (IHC Anti Her 2, ×40). (l) Microphotography showing nuclear positivity of score <14% for Ki 67 (black arrow head) (IHC Ki 67, ×40)

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At histopathology IDC, no special type was most common (12 cases, 75%) followed by intracystic papillary carcinoma (2 case, 12.5%), one case each of lobular (6.25%) and invasive papillary carcinoma (6.5%). Out of 16 cases, 10 were in Grade 2 (62.5%), 4 were in Grade 1 (25%), [Figure 1]f-1h] and two cases showed Grade 3 (12.5%). Out of 14 cases, 4 showed ipsilateral axillary lymph node involvement (28.5%) and two cases showed distant metastasis to the liver and lung. Out of 16 cases, 10 cases were confined to Stage 2 (62.5%), while 5 cases were in Stage 4 (31.25%) and one case was in Stage 3 (6.25%).

Immunohistochemistry findings were available in only 14 cases; all 14 cases expressed nuclear positivity for ER and PR. Only two cases showed Her 2 Neu positivity. Five cases showed high proliferative activity (ki-67 >14%) [Table 1] [Figure 1]i-1l].

Table 1: Clinicopathological parameters of male breast carcinoma

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Discussion

The incidence of MBC varies from the region to region. Moreover, in India, it varies from 0.5% to 4.1%, and our finding of 2.1% correlates with the literature.^{[1],[2],[3],[4],[5],[6]} MBC constitutes around 1% of all cancer recorded in the men, and our findings of 0.8% are in accordance with the literature.^[16] Review of surveillance, epidemiology, and end result (SEER) data indicate that MBC are increasing from 1/1 lakh male to 1.2/1 lakh male from 1970s to 2004. The mean age of occurrence of MBC in the present study is 59 years and is in consistent with the literature. Even though MBC are morphologically and prognostically similar to female counter part, biologically they are quite different. MBC are observed decade later and presents with advanced stage, lymph node positivity, and carries a high mortality.^{[1],[2],[3],[4],[5],[6]}

The risk factor MBC is increased estrogens/androgen ratio, obesity, liver disorders, exogenous estrogen, orchitis, epididymitis, radiation to chest following Hodgkin's lymphoma, gynecomastia, and Klinefelter's syndrome. Ten percent of men with MBC will have family history. Men with a family history of breast cancer in a female relative have 2–5 times increased risk of malignancy. BRCA 1 and 2 are responsible genes, and BRAC2 is more associated with MBC than BRCA 1.^{[1],[2],[3],[16]}

In the present study, the left breast was commonly involved than the right, and our findings are in consistent with Shukla et al.,^[8] Gogia et al.,^[12] Andleeb et al.,^[13] Sharma et al.,^[14] Pasricha et al.,^[2] and Das et al.^[16] Few authors also reported right dominance.^[1],[4],[6] Laterality of the tumor does not carry any prognostic significance.

Painless lump is the most common clinical manifestation associated with MBC. Others being nipple discharge and pain.^{[1],[2],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16]} Few authors observed that nipple involvement is the early clinical manifestation of the MBC.^[1] In the present study, painless lump is the most common clinical presentation.

Male breast is a rudimentary organ, and only little breast tissue is located in the central areola region (CRA), hence, most of the MBC occurs in CRA region followed by upper outer quadrant and rarely in other anatomical region.^[1],[3] In our study, all 16 cases had tumor in the CRA region, and the findings are in consistent with the literature.^{[1],[3],[6],[11],[13],[14],[16]}

Histopathologically, IDC no special type is the most common variant. SEER cancer registry showed that 93.7% of MBC are dutal, whereas 1.5% is lobular. In the present study, 75% were IDCs no special type. Other variants such as mucinous carcinoma, apocrine carcinoma, invasive lobular carcinoma (ILC), intracystic papillary carcinoma, invasive papillary carcinoma, adenoid cystic carcinoma, and others are also being reported.^{[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16]} Papillary carcinomas are comparatively more common in males than females.^[2] In the present study, we have observed two case of intracystic papillary carcinoma and 1 case of invasive papillary carcinoma. Due to the absence of lobules in the male breast, it was earlier thought that ILC is rare, but it is now known that true acini and lobules can develop in the male breast in the increased conditions of estrogens.^[1] We have observed only one case of ILC in the present study.

The diagnostic evaluation and staging system used for MBC are same as female breast cancer.^[1] Staging and lymph node status are the established prognostic factors for MBC. On reviewing the literature, older studies have documented that MBC at the time of diagnosis will be in the advanced stage and high proportion of lymph node positivity and hence carries a poor prognosis.^{[1],[3],[5],[8],[9],[10],[11],[12],[13],[14]} However, studies carried out by Chhabra et al.^[15] and. Pasricha et al.^[2] in 2019, Shah et al.^[4] in 2020, and the present study, MBC were in stage 2 at the time diagnosis, and also, proportion of the lymph node involvement is also less compared to previous studies. This may be due to increase awareness about disease and widely availability of reliable diagnostic modalities such as FNAC and mammography.^[4]

MBC shows the high expression of hormonal receptors (ER and PR) compared to female counter part. Result from the National Cancer Institute Surveillance shows more than 90% of MBC is ER positive.^[2] In the present study, IHC was available in 14 cases; all the cases showed high expression of ER and PR, and our observation are in accordance with the literature.^{[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15]} Her 2 neu over expression/amplification is a well-known prognostic factor in FBC. In comparison to FBC, Her 2 over expression/amplification is less in MBC. In the present study, two cases (14.2%) showed Her 2 overexpression and our findings in agreement with the literature.^[2]

MRM is the well-established treatment modality for MBC, and radical mastectomy is reserved for those cases having extensive chest wall involvement. Radiotherapy is indicated if breast conservative surgeries are done or if there is skin and nipple involvement. Adjuvant chemotherapy has increased the survival rate by 5–10 years. As most of the MBC is hormone receptor-positive tamoxifen or another hormone therapy for 5 years is recommended to those with HR receptor positive.^[7] Comparison of clinicopathological parameters with the published in the Indian literature is shown in [Table 2].

Table 2: The comparison of clinicopathological and immunohistochemical parameters with the published literature

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The limitations of the study are it is a single-institution study carried over a small sample size. As the disease is very rare, multi-institutional studies on large sample size are required to document the exact pathophysiology of MBC.

Conclusion

From the observation of the study and on review of the literature, we conclude that MBC is rare disease, and they tend to occur a decade later to FBC. IDC no special type is the most common histopathology. They express high hormonal receptors. Our study also conclude that the pathology of MBC is as most of the cases are presenting with stage 2 and less lymph node involvement which may carry a better prognosis; however, more studies on the large sample are required to document the same.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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