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Abstract
Metastasis from non-mammary malignant neoplasms to the breast is rare and represents 0.2%-1.3% of all breast malignancies. Fine needle aspiration cytology (FNAC) is the first line of investigation for any breast lump and cyto-morphological appearance of primary breast malignancies is well documented. Occasionally metastasis to the breast may be the initial presentation and can masquerade clinically as primary breast malignancy. The present case describes the clinical and cytological challenges in an unusual case of ovarian carcinoma with initial presentation as breast mass, mimicking as inflammatory carcinoma. In cytology the breast lesion was initially misdiagnosed as primary breast carcinoma and subsequently diagnosed as metastatic ovarian carcinoma based on core needle biopsy findings, aberrant immuno-profile and clinical findings; thus making the complex case worthy of discussion.
Keywords: Breast carcinoma, FNAC, inflammatory carcinoma, metastasis, ovary
How to cite this article: Introduction 
Intramammary metastases from solid neoplasms account for about 0.2%-1.3% of all breast malignancies, and the frequent sites are from lymphomas, melanomas, sarcomas, lung cancer, ovarian tumors, and renal carcinomas.[1],[2] These tumors usually have a poor prognosis because most patients have concomitant disseminated disease at the time of presentation.[3] Ovarian cancer usually spreads intra-abdominally manifesting as peritoneal carcinomatosis. Supradiaphragmatic metastases are rare, and axillary lymph node metastases are still exceptional. Metastasis to the breast is diagnosed on an average of three years after the initial diagnosis of a primary ovarian malignancy.[4] Initial presentation as breast metastasis is an extremely rare event and is clinically mistaken as primary breast malignancy. The present case describes the clinical and cytological difficulties in an unusual case of ovarian carcinoma metastasizing to breast mimicking as inflammatory carcinoma. In cytology, the breast lesion was initially misdiagnosed as primary breast carcinoma, but the final diagnosis was clinched by judicious application of immunohistochemical stains on the cell block and tru-cut biopsy.
Case Report A 63-year-old post-menopausal female presented with a large left breast lump, extending to the left axilla with ipsilateral axillary and cervical lymphadenopathy. The breast swelling was ill-defined, measuring approximately 10 × 10 cm, noticed since 6 months. The overlying skin was also erythematous, swollen with peau d'orange appearance [Figure 1]a. With a clinical diagnosis of inflammatory carcinoma of the breast, Fine needle aspiration cytology (FNAC) was advised. On aspiration, the breast swelling yielded 20 ml of serosanguinous fluid. Cytocentrifuged deposit smears were sparsely cellular displaying moderately pleomorphic neoplastic epithelial cells arranged mostly in cohesive clusters and papillaroid fronds having moderate cytoplasm with cytoplasmic vacuolation, over a hemorrhagic background admixed with inflammatory cells and cyst macrophages [Figure 1]b. There was moderate anisokaryosis with irregular chromatin distribution and conspicuous nucleoli in some [Figure 1]c, [Figure 1]d. Aspirates from the left cervical and axillary lymph nodes were richly cellular, displaying papillaroid fragments of similar tumor cells [Figure 1]e, [Figure 1]f. A diagnosis of breast carcinoma with ipsilateral axillary and cervical node metastasis was suggested. From the remainder of the breast aspirate, cell block was done.
Figure 1: (a) Breast swelling with peaud'orange appearance along with axillary swelling (arrow). (b-d) Smears from breast lump aspirate showing malignant epithelial cells in papillaroid pattern over a haemorrhagic background (PAP, x 100), still higher magnification showing moderate nuclear atypia (PAP, x 400) and cytoplasmic vacuolation (Diff Quik, x400). (e and f) Smears from ipsilateral axillary lymph node aspirate showing metastatic deposit of similar type of cells. (H&E, x100 and x400)Meanwhile, she also complained of diffuse abdominal swelling and on examination, the abdomen was distended with moderate ascites. For evaluation of the abdominal distension, contrast-enhanced computed tomography (CECT) of the abdomen and pelvis was performed, which showed an ill-defined solid cystic right adnexal lesion of size 14.7 × 15.9 × 12 cm extending up to the umbilicus, which was seen displacing the uterus and bowel loop laterally [Figure 2]a. Multiple hepatic metastases, retroperitoneal lymphadenopathy, gross ascites was noted along with bilateral mild pleural effusion [Figure 2]b. with these findings, possibilities of either primary carcinoma of the ovary or metastatic deposit from carcinoma of the breast were suggested.
Figure 2: (a and b) CECT Abdomen showing predominantly cystic large adnexal mass and multiple heteroenhancing liver parenchymal lesions. (c) Chylous ascitic fluid. (d and e) Ascitic fluid cytology shows richly cellular smears comprising of slender branching papillary fragments. (H&E, x40) and (H&E, x400). (f and g) Lower and higher magnification of cell block sections of ascitic fluid. (H&E, x100) and (H&E, x100) respectivelyTherapeutic and diagnostic paracentesis was done and 3 liters of chylous fluid was tapped [Figure 2]c. Fluid cytology revealed richly cellular smears with morphologically similar tumor cells [Figure 2]d, [Figure 2]e. Cell blocks of the breast and the ascitic fluid sample showed slender branching papillary fragments of moderately pleomorphic cuboidal to low columnar cells [Figure 2]f, [Figure 2]g.
Later, tru-cut biopsy from the breast lump revealed slender papillae and nests of neoplastic cells of similar morphology as described above and multiple lymphatic emboli [Figure 3]a. Initially immunohistochemical (IHC) stain for Estrogen Receptor (ER), Progesterone Receptor (PR), Human epidermal growth factor receptor (HER2/neu) and mammaglobin were done. But, surprisingly only ER was positive, but rests of the markers were negative including mammaglobin [Figure 3]b, [Figure 3]c, [Figure 3]d, [Figure 3]e. To solve the diagnostic dilemma, a second IHC panel of stains with CA125, WT1, p53 and PAX8 were done. The tumor cells were positive for all the markers in the second panel [Figure 3]f, [Figure 3]g, [Figure 3]h, [Figure 3]i, thus confirming the final diagnosis of a metastatic papillary serous adenocarcinoma of the ovary with metastasis to the breast. Similarly, the cell block sections were also immunopositive CK7, PAX8, p53 and WT1, while negative for CK20, calretinin and GATA3. Her serum CA125 level was 8525 U/ml before chemotherapy.
Figure 3: (a) Trucut biopsy section of breast lump showing tumor cells arranged in slender papillae and presence of lymphatic emboli (arrow) (H&E, x100). (b-i) (IHC results): Tumor cells showing diffuse nuclear positivity for ER (b), negative for PR (c), HER2/neu negativity (d), negative for Mammaglobin (e), diffuse WT1 positivity (f), diffuse PAX8 positivity (g), diffuse p53 immunostaining (mutation type) (h) and diffuse cytoplasmic positivity for CA 125 (i) [diaminobenzidine, x100]She did not have a family history of breast or ovarian cancer.
The patient received palliative chemotherapy with paclitaxel and carboplatin every 3 weeks. Post 3 cycles she attained a partial response with decrease in serum CA125 and disease burden; but after cycle 6 chemotherapy, she was found to have intestinal obstruction with perforation, peritonitis and the patient succumbed to the illness.
Discussion/Conclusion Overall, the incidence of metastasis to the breast from primary gynecological malignancies is very infrequent and a study by Hadju and Urban involving 4,051 breast cancer patients found an overall incidence of primary gynecologic cancers metastatic to the breast of 0.17%, with only 0.07% of metastatic disease originating from a primary ovarian tumor.[5] Clinical features suggestive of metastasis to the breast are rapid growth, superficial location of the lump, either adherent to the skin or subcutaneous tissue without nipple discharge or retraction, lack of microcalcification in mammogram and on histopathological examination, lack of in-situ disease.[6] In our case, the presence of a large breast lesion that was difficult to localize and associated skin changes (peau d'orange) provoked a clinical diagnosis of primary breast malignancy. Breast metastasis presenting as inflammatory carcinoma is still rare, and till now a handful of cases have been reported in English literature.[7],[8],[9]
FNAC is the initial line of investigation in any breast lump and is particularly very informative with detailed clinical data. There are case reports and a few case series, describing the FNAC findings in metastasis from lymphoma, carcinoma, melanoma and sarcoma. Among carcinomas, large cell carcinoma of the lung, ovarian adenocarcinoma, squamous cell carcinoma of the cervix, endometrial adenocarcinoma, and gastric adenocarcinoma are more commonly encountered.[9] In our case, as the malignant epithelial cells were in papillary pattern and cohesive clusters, a possibility of invasive papillary carcinoma of the breast was thought. This dilemma was solved by biopsy and IHC, thus suggesting that in cytology we can only suggest presence of adenocarcinoma cells in the breast, but primary site of breast tumor can be determined with detailed clinical examination and breast biopsy.
Biopsy sections of the present case didn't have any in-situ component, rather showed many lymphatic emboli. Erythema and swelling of the breast were due to infiltration of the dermal lymphatics causing mechanical obstruction and clinically masquerading as inflammatory carcinoma. Consistent with our findings, it is observed that ovarian cancers and malignancies of the gastrointestinal tract are the most common tumors that follow a spread pattern of lymphatic metastases.[10] On IHC the hormone receptor study was variable for ER and PR, which can be explained in serous carcinoma of the ovary.[11],[12] PAX8 positivity (a marker of Müllerian differentiation) and CA125 positivity (membranous) are indicative of an ovarian primary; whereas WT1 positivity denotes a serous carcinoma.[11],[12]
A positive Breast Cancer (BRCA) gene mutation increases the risk of ovarian and breast carcinomas. Our patient did not have a germline BRCA mutation.
The reasons to consider non-primary breast cancer in our case were; the clinical presentation of abdominal swelling and clinical examination suggesting ascites, extensive cystic component with aspirate of 20 ml fluid in FNAC, which is highly unusual in primary breast cancer and the papillary fronds of the type typically seen in serous ovarian cancer, which is very rare in a primary breast cancer.
Though unusual, the practicing cytopathologists should be aware of metastasis to the breast as a possibility in cases of an unusual aspirate and cytomorphological pattern. A thorough evaluation with a detailed clinical history inclusive of serum tumor markers and ancillary studies like cell block/core needle biopsy with IHC clinches the diagnosis and helps the clinician in planning the appropriate treatment.
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References 
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CheckDOI: 10.4103/ijpm.ijpm_561_21
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