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Year : 2020  |  Volume : 63  |  Issue : 5  |  Page : 143-145
Secretory carcinoma of breast: A diagnostic dilemma

1 Department of Lab Medicine, Sahara Hospital, Lucknow, Uttar Pradesh, India
2 Department of Breast and Endocrine Surgery, Sahara Hospital, Lucknow, Uttar Pradesh, India
3 Department of Radiology, Sahara Hospital, Lucknow, Uttar Pradesh, India

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Date of Web Publication26-Feb-2020

How to cite this article:
Shukla A, Arshad F, Naseem I. Secretory carcinoma of breast: A diagnostic dilemma. Indian J Pathol Microbiol 2020;63, Suppl S1:143-5

How to cite this URL:
Shukla A, Arshad F, Naseem I. Secretory carcinoma of breast: A diagnostic dilemma. Indian J Pathol Microbiol [serial online] 2020 [cited 2023 Jun 7];63, Suppl S1:143-5. Available from:


Secretory carcinoma of the breast is a rare form of breast carcinoma seen primarily in children,[1] but it can also occur in adults and account for <0.15% of all breast cancers.[2] These lesions appear to have an excellent prognosis in women under the age of 20 years. The behavior in older women is less favorable with late recurrence. The World Health Organization fascicle on Breast (2012) classifies it as an exceptionally rare type and variant of breast cancer.[3] Its cytological features overlap with many benign as well as malignant lesions of breast and histology mimics with other primary breast tumors and even metastatic tumors of the breast. Recognition of the entity is important because it has a low-grade clinical course and is associated with a favorable prognosis.[4]

Herein, we present a case of secretory carcinoma in postmenopausal female and highlight the diagnostic challenges on cytodiagnosis in which there is florid proliferation of monomorphous epithelial cells and also pitfalls in interpreting hematoxylin and eosin (H and E) stained sections.

A 60-year-old female presented with subcutaneous left breast nodule that she had noted 2 months previously. It was gradually increasing in size. Physical examination revealed a 2.5-cm painless mobile nodule just below the areola of the left breast and no axillary nodes were palpable. Mammography showed well-defined, capsulated, lobulated lesion of size 28 × 25 × 28 mm (volume approximately 10.0 cc) at 12 o'clock position, which belongs to BI-RADS category IV lesion [Figure 1]a. Fine needle aspiration (FNA) of the nodule performed with a 22-gauge needle attached to a 20-cc plastic syringe mounted on a handle yielded mucoid material. Multiple smears stained with May-Grunwald-Giemsa, H and E, and Papanicolaou stain were studied. FNA smears were highly cellular and consisted of numerous papillaroid fragments, cell balls, and clusters of epithelial cells [Figure 1]b. The cells are having hyperchromatic nuclei, inconspicuous nucleoli, and abundant granular and vacuolated cytoplasm [Figure 1]c. Some mucinous material was seen in the background [Figure 1]d and no mitotic activity was identified in the tumor cells. Possibility of epithelial proliferative lesion was considered, and in view of high cellularity of FNA cytological material and absence of bipolar nuclei, a malignant pathology was suggested. Chest X-ray, abdominal ultrasound, and a bone scan did not show any evidence of metastatic disease. The patient underwent modified radical mastectomy and the specimen showed a subcutaneous lesion in the upper outer quadrant of the breast [Figure 2]a. Cut section of the specimen revealed well circumscribed, soft to firm, gray–tan lesion with pushing margins along with the area of hemorrhage measuring 2.5 cm in diameter [Figure 2]b. On microscopic examination, the sections revealed tumor cells arranged in tubuloalveolar, papillary, and microcystic pattern [Figure 2]c and [Figure 2]d. The cystic spaces showed eosinophilic secretions. The tumor cells were round to polygonal exhibiting mild atypia and intracytoplasmic vacuolation. Mitotic activity is infrequent. The secretion in the lumen of microcysts was Periodic acid- Schiff (PAS) stain positive. On immunohistochemistry the tumor cells were positive for Pan CK, CK7, CK5/6, S-100 protein [Figure 2]e, and Vimentin [Figure 2]f. Carcinoembryonic antigen (CEA) was patchy positive, while CK20, GCDFP, estrogen receptor (ER), progesterone receptor (PR), Her2, and P63 were negative. Based on morphology and immunohistochemistry, a diagnosis of secretory carcinoma was confirmed. Polymerase chain reaction (PCR)-based translocation assay for ETV6–NTR3 translocation was performed and a positive result was obtained for the same.
Figure 1: (a) Sonomammography suggesting BI-RADS category IV lesion. (b) Smear shows cellular papillaroid fragments, May-Grunwald-Giemsa ×10. (c) Cells with abundant vacuolated cytoplasm, May-Grunwald-Giemsa ×20. (d) Mucinous material on Papanicolaou staining, ×40

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Figure 2: (a) Gross examination illustrates subcutaneous lesion. (b) Cut surface of specimen shows a well-circumscribed, yellow-brown, solid lesion with central hemorrhage. (c and d) Tumor cells with tubuloalveolar, microcystic, and papillary pattern, hematoxylin and eosin ×20. (e) Tumor cells immunoreactive for S-100 and (f) Vimentin ×20

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Secretory carcinoma of the breast was initially termed as “Juvenile breast cancer” by McDivitt and Stewart,[1] based on the fact that the average age of the seven patients described in their series was 9 years (range 3–15). Subsequently, a number of cases were reported in adults, even in postmenopausal females and male patients.

The patients generally presented with painless and firm mass and most tumors are located in the outer upper quadrant of the breast. FNA diagnosis of this rare type of carcinoma with relatively bland cytology may be extremely difficult, especially in a younger woman in whom benign proliferative and secretory lesions far outnumber carcinoma. Cytology of lactational changes or lactating adenoma may mimic with secretory carcinoma in young patients, but in the latter case the cytoplasm will be abundant and fragile, and round central nuclei have distinct small nucleoli. Important diagnostic clues suggesting malignancy are high cellularity of the FNA cytologic material and absence of bipolar naked nuclei.[5] Other possibilities on cytology are primary papillary carcinoma, apocrine carcinoma, clear cell carcinoma (glycogen rich), lipid-rich carcinoma, and mucinous carcinoma. All these have to be excluded. In papillary carcinoma, columnar cells are seen in row, palisade, and single cell with variable nuclear enlargement and necrosis. Apocrine carcinoma is having highly atypical nuclear morphology, in clear cell carcinoma (glycogen rich) cell population is dispersed in the tigroid background, and in lipid-rich carcinoma microvacuolated cytoplasm with pleomorphic nuclei is seen. Small clumps of mucin-like material are seen in our case but absence of abundant mucin in the background and cells in small aggregate are not in favor of mucinous carcinoma. Adenoid cystic carcinoma, benign epithelial hyperplasia including collagenous spherulosis must also be differentiated from secretory carcinoma.[6]

Tumor in our case was seen in the subcutaneous region; therefore we also thought of salivary gland or skin adnexal tumors which although rare, occur in adult or elderly women and present as circumscribed tumor in subareolar area without connection to the overlying skin.

On gross examination, the tumor is well circumscribed and usually small. Microscopically margins are of pushing type and prominent hyalinization is often present in the central portion. Tubuloalveolar and focally papillary formations lined by cells with a vacuolated cytoplasm are seen forming lumina filled by eosinophilic PAS positive secretions. These histological features have to be differentiated from acinic cell carcinoma (ACCA), cystic hypersecretory carcinoma, invasive ductal carcinoma, as well as metastatic carcinoma from thyroid by immunohistochemistry.[7] Tumor cells of secretory carcinoma show strong reactivity for α-lactalbumin and S-100 protein, while ER, PR, HER2, and p63 are negative.[8]

Ultrastructurally, the tumor cells contain numerous membrane-bound intracytoplasmic secretory vacuoles.[9] Genetic abnormality found in secretory carcinoma is balanced translocation t(12;15), which leads to the formation of ETV6–NTRK3 gene.[9]

Demonstration of ETV6–NTRK3 is important not only for confirmation of diagnosis but also to exclude ACCA, which lacks hypernephroid features and proteins of salivary gland counterpart and ACCA does not show t(12;15) ETV6–NTRK3.[10]

Secretory carcinoma is a rare variant of breast carcinoma that must be considered in the differential diagnosis of a circumscribed lesion of the breast both in young as well as elderly patient. It is not only important that the pathologist is aware of the cytological features, but also that he/she carefully interprets cytological features, morphological features, and immunohistochemistry to ensure that the correct diagnosis is made.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

McDivitt RW, Stewart FW. Breast carcinoma in children. JAMA 1966;195:388-90.  Back to cited text no. 1
Botta G, Fessia L, Ghiringhello B. Juvenile milk protein secreting carcinoma. Virchows Arch A Pathol Anat Histol 1982;395:145-52.  Back to cited text no. 2
Eusebi V, Ichihara S, Vincent-Salomon A, Sneige N, Sapino A. Exceptionally rare types and variants. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, Vijver JV, editors. WHO Classification of Tumours of the Breast. 4th ed. Lyon: IARC Press; 2012. p. 71-6.  Back to cited text no. 3
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004;10:5367-74.  Back to cited text no. 4
Sukpan K, Chanmuenwai W, Khunamornpong S. Secretory carcinoma of the breast: A case report with cytologic and histologic findings. Chiang Mai Med Bull 2005;44:161-6.  Back to cited text no. 5
Shanthi V, Rama Krishna BA, Rao NM, Sujatha C. Cytodiagnosis of secretory carcinoma of the breast. J Cytol 2012;29:63-5.  Back to cited text no. 6
[PUBMED]  [Full text]  
Osako T, Takeuchi K, Horii R, Iwase T, Akiyama F. Secretory carcinoma of the breast and its histopathological mimics: Value of markers for differential diagnosis. Histopathology 2013;63:509-19.  Back to cited text no. 7
Li D, Xiao X, Yang W, Shui R, Tu X, Lu H, et al. Secretory breast carcinoma: A clinicopathological and immunophenotypic study of 15 cases with a review of the literature. Mod Pathol 2012;25:567-75.  Back to cited text no. 8
Tognon C, Knezevich SR, Huntsman D, Roskelley CD, Melnyk N, Mathers JA, et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2002;2:367-76.  Back to cited text no. 9
Reis-Filho JS, Natrajan R, Vatcheva R, Lambros MB, Marchió C, Mahler-Araújo B, et al. Is acinic cell carcinoma a variant of secretory carcinoma? A FISH study using ETV6'split apart' probes. Histopathology 2008;52:840-6.  Back to cited text no. 10

Correspondence Address:
Anju Shukla
Department of Lab Medicine, Sahara Hospital, Viraj Khand, Gomti Nagar, Lucknow - 226 010, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_367_18

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