|Year : 2020 | Volume
| Issue : 1 | Page : 104-106
Carcinoma of breast with apocrine differentiation: A distinct entity with typical histomorphology and molecular signature
Pranita Mohanty, Debasmita Das, Anima Hota, Tulasi Govardhan
Department of Pathology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
|Date of Submission||22-Apr-2020|
|Date of Decision||16-May-2020|
|Date of Acceptance||18-May-2020|
|Date of Web Publication||20-Jun-2020|
Dr. Pranita Mohanty
Department of Pathology, IMS and SUM Hospital, Bhubaneswar - 751 003, Odisha
Source of Support: None, Conflict of Interest: None
Apocrine Carcinoma (APC) is a rare and distinct entity among all the histological variants of invasive ductal carcinoma(IDC) of breast. It is common to encounter focal apocrine differentiation, but only 4% of IDCs show extensive apocrine differentiation. In the 2012 WHO classification of tumors of breast, it is placed under specialized subtypes of IDC and named “carcinomas with apocrine differentiation.” Apocrine differentiation is seen with IDC-no specific type (IDC-NST) as well as in special type carcinomas such as tubular, lobular, micropapillary, and medullary and that's why it does not represent as a separate entity. Although clinical, radiological, and gross appearance is indistinguishable from IDC-NST (the most common form), APC has a typical histomorphological picture with distinct molecular apocrine signature and immunohistochemistry. It is characterized by increased androgen expression overlapping with HER2/neu expression and estrogen receptor (ER) as well as progesterone receptor (PR) negativity. It is thought to have worse prognosis; hence, diagnosing this entity at the earliest is very important for implementation of new treatment modalities. Here, we report two such cases of carcinomas with apocrine features – 47-year-old and 52-year-old patients showing features of apocrine carcinoma and positivity for androgen receptor with negativity for ER and PR.
Keywords: Androgen receptor, apocrine carcinoma, invasive ductal carcinomas
|How to cite this article:|
Mohanty P, Das D, Hota A, Govardhan T. Carcinoma of breast with apocrine differentiation: A distinct entity with typical histomorphology and molecular signature. Arch Med Health Sci 2020;8:104-6
|How to cite this URL:|
Mohanty P, Das D, Hota A, Govardhan T. Carcinoma of breast with apocrine differentiation: A distinct entity with typical histomorphology and molecular signature. Arch Med Health Sci [serial online] 2020 [cited 2020 Oct 27];8:104-6. Available from: https://www.amhsjournal.org/text.asp?2020/8/1/104/287368
| Introduction|| |
Apocrine carcinoma of breast is a very rare form of malignancy accounting for <1% of invasive carcinomas. Strictly, APC is only defined when the typical histomorphology along with its classical immunohistochemistry is satisfied, and it is designated as “pure apocrine carcinoma” when the apocrine cells comprised >90% of tumor cells. APC demonstrates the same architectural growth pattern as invasive ductal carcinoma-no specific type (IDC-NST) microscopically but differs only in their cytological appearance. The cells have typical apocrine features of abundant eosinophilic granular cytoplasm with distinct cell border, vesicular nuclei, and prominent or multiple nucleoli. On immunohistochemical studies, apocrine carcinoma characteristically shows estrogen and progesterone receptor negativity and androgen receptor positivity (ER−/PR−/AR+)., Typically BCL-2 negative and GCDFP-15 positive are also evident. Earlier, it was considered to have the same clinical outcome when compared to IDC (NST), but after the molecular definition, it is seen to have worse prognosis.
| Case Reports|| |
A 47-year-old female patient presented with a history of fixed lump in the lower inner quadrant of her left breast for which modified radical mastectomy (MRM) was done in our hospital. We had received left MRM specimen together measuring 18 cm × 15 cm × 5 cm with overlying skin and nipple-areolar complex appearing normal. No scar mark was seen. The base was seen infiltrated by the tumor. The sections were taken from representative sites, processed, and stained with hematoxylin and eosin (H and E) stain. On light microscopy, the sections showed round-to-oval neoplastic cells arranged in sheets, glands exhibiting marked pleomorphism with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Microcalcification was seen along with an evidence of lymphovascular invasion with brisk mitosis (7/10 high-power field [HPF]). Bloom–Richardson score was 2 + 3 + 2 = 7 (Grade II). All lymph nodes, surgical margins, skin, nipple, and areola were free from tumor. Immunohistochemistry was done which showed ER, PR – negative; AR, Her2/neu -positive and Ki67 - 50% [Figure 1].
|Figure 1: (Case 1) (a and b) Gross morphology. (c and d) Photomicrograph shows cells arranged in sheets and glands. Exhibiting abundant granular cytoplasm with enlarged nuclei (H and E, ×40/×400). (e) Androgen receptor positivity (×400)|
Click here to view
A 52-year-old female patient presented with a history of firm lump over the upper quadrant of the right breast for which MRM was done in our hospital. We had received right MRM specimen together measuring 21 cm × 10 cm × 6 cm with overlying skin and nipple-areolar complex appearing normal. No scar mark was seen. The sections were taken and processed for H and E sections. On light microscopy, the sections revealed oval neoplastic cells arranged in sheets exhibiting marked pleomorphism with abundant eosinophilic granular cytoplasm, vesicular to hyperchromatic nuclei, and prominent nucleoli along with ductal carcinoma in situ component. Also seen was evidence of microcalcification and lymphovascular invasion with brisk mitosis (6/10 HPF). Bloom–Richardson score was 2 + 3 + 2 = 7 (Grade II). All lymph nodes, surgical margins, skin, nipple, and areola were free from tumor. On immunohistochemistry with ER, PR, Her2/neu, and AR, ER and PR came out to be negative with AR and Her2/neu positivity [Figure 2].
|Figure 2: (Case 2) (a) Gross morphology. (b) Photomicrograph shows cells exhibiting abundant granular cytoplasm with enlarged nuclei (H and E, ×400). (c) Androgen receptor positivity (×400)|
Click here to view
| Discussion|| |
The division of breast carcinoma into various histological types has been of interest to pathologists for many years. Malignant transformation of apocrine epithelium was first described by Krompecher in 1916. The incidence of infiltrating apocrine carcinoma is unclear. Gayatri et al. included this entity under the group of “relatively rare carcinomas.” Azzopardi reported an incidence of apocrine carcinoma between 0.3% and 0.4% of all breast carcinomas, Frable and Kay reported 1%, Bonser et al. reported 14.5%, and Haagensen reported 62%., Japaze et al., 2005, proposed that criteria are as follows: (1) apocrine features consisting of 75% of cells, (2) large cells with eosinophilic granular cytoplasm, (3) nucleus-to-cytoplasmic ratio of 1:2 or more, (4) nucleus large, round, and vesicular may be pleomorphic, and (5) sharply defined borders. Our cases have fulfilled all the five criteria. There is description of two types of apocrine cells – Type A and Type B. Type A cells are characterized by abundant, granular, intensely eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. Type B cells show abundant and foamy cytoplasm. Apocrine carcinoma always shows moderate-to-marked nuclear pleomorphism, and tubule formation is rarely >75%. Mitotic count is variable (1–3). Therefore, most apocrine carcinomas are modified Scarff–Bloom–Richardson Grade 2 or 3. Hormonal status of apocrine carcinomas is usually of Her2/neu-enriched breast cancer with androgen receptor positivity. The present cases were consistent with it being ER−/PR−/AR+/Her2+. Her2/neu positivity is seen in 30% of apocrine carcinomas of breast. Recent molecular analysis shows full-length ER-36alpha loss, frequent deregulation of the PIK3CA/phosphatase and tensin homolog pathway and HER2 activation, and lack of programmed death-ligand 1 expression. Her2/neu and epidermal growth factor receptor are mutually exclusive in these cases.
| Conclusion|| |
Apocrine carcinoma is a rare but distinct entity with morphological type of invasive breast cancer. Although previously considered to be prognostically the same as IDC-NST, the molecular definition has changed the game. It should be diagnosed as a different entity because of different hormonal profile and clinical behavior and worse prognosis with a unique response to androgens.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gayatri G, Mondita B, Asha B, Vishal A. Study on apocrine carcinoma of breast: Histomorphologic features and immunohistochemical behavior. Int J Basic Applied Med Sci 2012;2:190-3.
Yerushalmi R, Hayes MM, Gelmon KA. Breast carcinoma – Rare types: Review of the literature. Ann Oncol 2009;20:1763-70.
Durham JR, Fechner RE. The histologic spectrum of apocrine lesions of the breast. Am J Clin Pathol 2000;113:S3-18.
Tsutsumi Y. Apocrine carcinoma as triple-negative breast cancer: Novel definition of apocrine-type carcinoma as estrogen/progesterone receptor-negative and androgen receptor-positive invasive ductal carcinoma. Jpn J Clin Oncol 2012;42:375-86.
Frable WJ, Kay S. Carcinoma of the breast. Histologic and clinical features of apocrine tumors. Cancer 1968;21:756-63.
O'Malley F, Eusebi V, Lakhani SR. Carcinomas with apocrine differentiation. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, Van de Vijver MJ, editors. WHO Classification of Breast. 4th
ed. Lyon (France): IARC Press; 2012. p. 53-4.
Vranic S, Feldman R, Gatalica Z. Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers. Bosn J Basic Med Sci 2017;17:9-11.
[Figure 1], [Figure 2]