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CASE REPORT Table of Contents  
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Invasive micropapillary carcinoma of the breast and bilateral ovarian mature cystic teratoma with benign Brenner tumor in a postmenopausal woman – An uncommon occurrence

1 Department of Pathology and Lab Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
2 Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India

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Date of Submission13-Dec-2021
Date of Decision18-Feb-2022
Date of Acceptance19-Feb-2022
Date of Web Publication27-Jan-2023


The synchronous occurrence of bilateral ovarian tumors and breast malignancy often raise the suspicion of a Krukenberg tumor or a hereditary breast and ovarian cancer syndrome, both of which are uncommon in clinical practice. A 58-years-old postmenopausal woman had a right breast lump and was diagnosed as infiltrating duct carcinoma, no special type, and incidentally detected bilateral adnexal mass with the clinical suspicion of Krukenberg tumor. However, following the radical surgical excision of the right breast and bilateral ovaries, the right breast showed invasive micropapillary carcinoma (IMPC) while the ovaries showed mature cystic teratoma (MCT) with benign Brenner tumor. IMPC of the breast along with bilateral ovarian MCT with benign Brenner tumor is an unusual clinical occurrence in a postmenopausal female and thus worthy of documentation. It should be categorized as a non-hereditary synchronous tumor. The histomorphology augmented by immunohistochemistry and appropriate clinical context is pivotal in rendering a correct diagnosis.

Keywords: Brenner tumor, GATA3, invasive micropapillary carcinoma, mature cystic teratoma, postmenopausal female

How to cite this URL:
Ayyanar P, Mitra S, Imaduddin M, Muduly DK. Invasive micropapillary carcinoma of the breast and bilateral ovarian mature cystic teratoma with benign Brenner tumor in a postmenopausal woman – An uncommon occurrence. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Jun 3]. Available from:

   Introduction Top

Invasive micropapillary carcinoma (IMPC) of the breast is an aggressive neoplasm, accounts for 0.9–2% of all invasive breast cancers.[1] Mature cystic teratoma (MCT) of the ovary accounts for approximately 20% of all ovarian neoplasms with a wide range of age distribution. Various benign tumors can be associated with MCT like struma ovarii and Brenner tumor.[2],[3],[4] The occurrence of Brenner tumor in MCT is an uncommon occurrence. The synchronous occurrence of MCT with benign Brenner tumor in bilateral ovaries and IMPC in the right breast is unheard of. Although probably a chance of occurrence, this case raises a possibility of a Krukenberg tumor (KT) and thus poses a diagnostic difficulty.

   Case Details Top

A 58-years-old postmenopausal female presented with a lump in the right breast for the past 6 months. She denied a history of breast malignancy. Local examination of the right breast revealed a 5 × 5 cm hard mobile lump in the upper outer quadrant. Skin, nipple, and areola were normal. The 1 × 1 cm mobile lymph nodes were palpable in the right axilla while the left breast and the axilla were normal. The mammogram showed a well-defined lobulated radio-opaque heterogeneous mass with significant internal vascularity in the upper and outer quadrant of the right breast (breast imaging-reporting and data system-V [BIRADS-V]); the left breast was unremarkable. Trucut biopsy from right breast lump showed very scanty tissue with features of infiltrating ductal carcinoma, no special type with high nuclear grade. A micropapillary pattern was also noted. Immunohistochemistry was performed. Immunostains for estrogen receptor (ER) and progesterone receptor (PR) were positive (Allred score 8/8), while Her-2/neu was negative (score 0). Contrast-enhanced computed tomography (CECT) thorax and abdomen revealed a fat density lesion in the left adnexa and left ovary measuring 6.9 × 5.5 cm; a well-defined cystic lesion measuring 7 × 5.4 cm noted in the right adnexa and right ovary; the spine, liver, and bilateral lungs were within normal limits.

The patient was planned for total abdominal hysterectomy with bilateral salpingo-oopherectomy (TAH with BSO), infracolic omentectomy, and right modified radical mastectomy (MRM). Intraoperative frozen section examination of TAH with BSO was performed. Grossly, both ovaries measured 7.5 x 6.5 x 5.5 cm with a smooth, intact capsule. Cut section of both the ovaries showed unicystic lesions, smooth inner surface. The right ovarian cyst contained yellowish thick fluidy material, while the left ovarian cyst contained pultaceous material and a few hairs. No solid area or papillary projections were noted. Microscopic features showed MCT. The uterus, cervix, and bilateral fallopian tubes wereunremarkable.

Post-operatively, the right MRM specimen revealed a grey-white tumor with infiltrative margin measuring 4.6x4.0x3.5 cm in the upper outer quadrant with normal overlying skin, nipple & areola, and the deep resection margin. Microscopic features showed an infiltrative tumor characterized by the presence of a micropapillary pattern in >90% of the tumor area [Figure 1]a; arranged as nests and acini of tumor cells usually lying within retraction spaces [Figure 1]b and [Figure 1]c. These tumor cells showed a reverse pattern of epithelial membrane antigen (EMA) positivity (EMA highlighting the abluminal side) [Figure 1]d. Three lymph nodes showed metastatic deposits without any extranodal extension (3/27).
Figure 1: (a) Microscopic examination of the breast mass showed an infiltrative tumor characterized by the presence of micropapillary pattern within retraction spaces (H&E, 20×); (b and c) these micropapillae were identified as nest (H&E, 100×) and acini (H&E, 400×); and (d) these tumor cells showed a reverse pattern (abluminal side) of EMA positivity (IHC, 400×)

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Gross examination of rest of frozen specimen of TAH with BSO revealed the same gross features; in addition showed a solitary homogenous gray-white firm nodule measuring 1 cm and 1.2 cm in diameters in the right and left ovary, respectively. No other solid area or papillary projections were noted. Multiple sections from both ovarian lesions showed cysts containing derivatives of all three germ cell layers in a haphazard distribution characterized by squamous epithelium, pilosebaceous units [Figure 2]a, pseudostratified ciliated columnar epithelium [Figure 2]b, gastric mucosa, adipose tissue, smooth muscle, nerve bundles and ganglion cells, hyaline cartilage, and seromucinous salivary acini [Figure 2]c . No immature neuroectodermal component was seen. The solid nodule in both ovaries showed an encapsulated mass with nests of cells separated by fibrous septa [Figure 2]d and [Figure 2]e. These cells had oval nuclei with nuclear grooving, evenly dispersed bland chromatin, inconspicuous nucleoli, and a moderate amount of pale eosinophilic cytoplasm. The nuclear pleomorphism, necrosis, and mitosis were absent [Figure 2]f. The solid nodule showed immunopositivity for GATA-3 [Figure 2]g while immunonegative for EMA, synaptophysin, inhibin-A, and calretinin. The uterus, cervix, and bilateral fallopian tubes were histologically unremarkable. IHC for MLH1, PMS2, MSH2, and MSH6 showed nuclear positivity (mismatch repair-proficient) in the breast and the ovarian tumors. A final diagnosis of IMPC of the right breast (pT2N1M0; stage IIB) and benign Brenner tumor in a MCT of bilateral ovaries was rendered. The patient is on a regular follow-up to date (1.5 years) without any features of recurrence.
Figure 2: (a) Sections from right ovarian lesion showed cysts lined by keratinized squamous epithelium, underlying pilosebaceous units, adipose tissue, smooth muscle bundles fibrocollagenous tissue, and nerve bundles (H&E, 20×); (b) pseudostratified ciliated columnar epithelium with underlying hyaline cartilage (H&E, 100×); (c) lobules of seromucinous salivary acini (H&E, 100×); (d) solid area from the tumor showed nests of tumor cells separated by fibrous septa (H&E, 200×); (e) section from solid nodule in the left ovarian lesion showed similar pattern of tumor (H&E, 100×); (f) these cells had oval nuclei with nuclear grooving, evenly dispersed bland chromatin, inconspicuous nucleoli, and moderate amount of pale eosinophilic cytoplasm. No nuclear pleomorphism or increased mitotic activity (H&E, 400×); and (g) these tumor cells showed immunopositivity for GATA-3 (IHC, 400×)

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   Discussion Top

Evaluation of an adnexal mass in a case of breast cancer is crucial for patient management. The differential diagnosis of this scenario includes tubo-ovarian abscess, endometriosis, fallopian tube, and ovarian malignancy, and metastatic malignancy from breast primary.[5] The metastatic malignancy from the breast, also known as KT in common parlance, is a major concern due to poor prognosis, difficult management, and diagnostic challenge.[6] Besides, KT is often bilateral and asymptomatic.

Breast is a common source of primary in KT.[7] Histomorphologically; the ovarian tumor looks similar to the primary tumor or its poorly differentiated component. Therefore, signet-ring cells, indicative of poorly-differentiated components of an adenocarcinoma, are often observed in KT. Although IMPC is not known to metastasize to the ovaries, a clinical possibility of an invasive breast malignancy to the ovary appears logical. An immunohistochemistry panel in case of suspected breast malignancy with ovarian metastasis must include GATA3, a sensitive marker of breast carcinoma. However, GATA3 also shows immunopositivity in the tumors of urothelial origin, Brenner tumor, and a subset of many other tumors lacking specificity. The GATA3 positivity in the index case can be interpreted as a metastatic deposit from the breast to the novice. Besides, the nesting pattern of the Brenner tumor and IMPC may mimic each other. However, the Brenner tumor shows grooved nuclei, bland chromatin, lack of pleomorphism, and mitosis, and is negative for EMA, settling the diagnostic dilemma.

The coexistence of primary ovarian carcinoma and primary breast carcinoma in the same patient should raise a high index of suspicion for an underlying hereditary breast and ovarian cancer syndrome. Approximately 50% of ovarian epithelial carcinomas are deficient in homologous recombination repair, and 15% of these are due to germ line mutations in the BRCA1 or BRCA2 genes.[8],[9],[10] The other syndromes include the involvement of TP53, PTEN, mismatch repair genes, and STK11 genes. The possibility of an underlying hereditary syndrome in the index case is remote considering the type of the ovarian tumor. Besides, the authors have excluded the possibility of a mismatch repair by immunohistochemistry.

   Conclusion Top

The index case highlights an uncommon occurrence of IMPC of the breast along with bilateral ovarian MCT with benign Brenner tumor in a postmenopausal female. The histomorphology, immunohistochemistry, and appropriate clinical context are pivotal in rendering a correct diagnosis in this case.

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

Yang YL, Liu BB, Zhang X, Fu L. Invasive micropapillary carcinoma of the breast: An update. Arch Pathol Lab Med 2016;140:799-805.  Back to cited text no. 1
Burg J, Kommoss F, Bittinger F, Moll R, Kirkpatrick CJ. Mature cystic teratoma of ovary with struma ovarii and benign Brenner tumor: A case report with immunohistochemical characterization. Int J Gynecol Pathol 2002;21:74-7.  Back to cited text no. 2
Tsujimoto T, Takaichi M, Endo H, Yasuda K, Kishimoto M, Noto H, et al. A patient with diabetes and breast cancer in whom virilization was caused by a testosterone-producing mature cystic teratoma containing a Brenner tumor. Am Med Sci 2011;341:74-7.  Back to cited text no. 3
Adhya AK, Mohanty R. Triple synchronous tumour of female genital tract: Cervical squamous cell carcinoma, right ovarian dermoid cyst and left ovarian benign Brenner tumour. BMJ Case Rep 2019;12:e230695. doi: 10.1136/bcr-2019-230695.  Back to cited text no. 4
Reinert T, Nogueira-Rodrigues A, Kestelman FP, Ashton-Prolla P, Graudenz MS, Bines J. The challenge of evaluating adnexal masses in patients with breast cancer. Clin Breast Cancer 2018;18:e587-94.  Back to cited text no. 5
Jha S, Mitra S, Patra S, et al. Krukenberg tumor of ovary during pregnancy: Learning from a mistake. Int J Gynecol Pathol 2021;40:617-20.  Back to cited text no. 6
Chiesa-Vottero A. CDX2, SATB2, GATA3, TTF1, and PAX8 immunohistochemistry in Krukenberg tumors. Int J Gynecol Pathol 2020;39:170-7.  Back to cited text no. 7
Fishman A, Dekel E, Chetrit A, Lerner-Geva L, Bar-Am A, Beck D, et al. Patients with double primary tumors in the breast and ovary- clinical characteristics and BRCA1-2 mutations status. Gynecol Oncol 2000;79:74-8.  Back to cited text no. 8
Ledermann JA, Drew Y, Kristeleit RS. Homologous recombination deficiency and ovarian cancer. Eur J Cancer 2016;60:49-58.  Back to cited text no. 9
Pan Z, Xie X. BRCA mutations in the manifestation and treatment of ovarian cancer. Oncotarget 2017;8:97657-70.  Back to cited text no. 10

Correspondence Address:
Pavithra Ayyanar,
Senior Resident, Dept. of Pathology and Lab Medicine, AIIMS, Bhubaneswar, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_1207_21


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