Department of Gynecologic, Obstetrics and Urologic Sciences - “Sapienza” University of Rome, Italy
Received February 11, 2016; Accepted April 13, 2016; Published April 18, 2016
Citation: Domenici L, Monti M, Tomao F, Giorgini M, Sabatucci I, et al. (2016) Unexpected Metastasis of High Grade Serous Ovarian Cancer to Breast: Case Report and Literature Review. J Clin Case Rep 6:764. doi:10.4172/2165-7920.1000764
Copyright: © 2016 Domenici L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Introduction: Metastasis of ovarian serous carcinoma to breast and/or axillary lymph nodes represents an unusual event. Nevertheless, their detection and distinction from mammary carcinoma are of huge clinical importance because the treatment and prognosis diverge significantly. Case presentation: We report a case of a 47 year-old Caucasian female patient with unforeseen metastasis to the breast and to axillary lymph nodes due to ovarian serous carcinoma. Conclusion: In patients with history of OSC who present with axillary or breast mass, an accurate histological diagnosis should be obtained since this has a great impact on treatment outcomes.
Metastasis to breast; Ovarian cancer
Ovarian serous carcinoma (OSC) usually compares at an advanced stage, but with disease limited to the peritoneal cavity in the majority of patients (roughly 85%) . However, metastasis of ovarian cancer to retroperitoneal organs such as kidney or distant organ metastases involving brain have also been previously stated but very few reports describe extra-abdominal lymph node involvement in this kind of tumour. In particular, metastases to breast from OSC are almost exceptional. Clinical studies have revealed that the incidence of metastases to breast arrays from 0.5-1.2% [2,3]. We present a case of metastatic carcinoma to breast in a patient with a known history of OSC and a new breast lump. Importantly, this case had histopathologic features that can be confused with ductal carcinoma in situ.
A 47-year-old Caucasian female patient with past medical history of stage IIA high grade serous OC 9 months after cytoreductive surgery and three lines of adjuvant chemotherapy (carboplatin AUC6 plus taxol 175 mg/mq every three weeks for 6 cycles) referred to the clinic for regular follow-up visit. CA-125 levels were normal and she had no evidence of disease. She had a very good primary response to OSC standard treatment. Her medical history was negative excluding OSC. On physical examination, a 2 cm diameter, non-tender, round, firm, and fixed breast mass was discovered in superior inner quadrant of the left breast of the patient. Patient was unaware of this mass. Left axilla examination was positive for two solid, fixed and nodes.
On mammography, a mass of 18 mm was detected (Figure 1a). Sonogram of bilateral breasts was performed which showed a 29 × 21 × 18 mm vascularized left breast mass (Figure 1b) and two suspicious left axillary lymph nodes of 12 and 15 mm respectively (Figure 1c). Whole body CT scan executed two months before was negative for other possible metatstatic sites. A surgical excision of the mass and an elective axillary clearance were made after accurate counselling and discussion of the treatment possibilities with the patient. No minor or major complications were collected. To a first microscopical examination, the breast mass was identified as a ductal carcinoma in situ. Thirteen lymph-nodes were gained from the axillary fat. Of the 13 axillary lymph nodes got, five showed metastatic deposits that were identical to the ovarian primary. Immunohistochemical studies revealed that the tumour cells expressed estrogen receptor (80%) and progesterone receptor (20%). There was no expression of HER-2/neu oncoprotein. Immunohistochemical staining performed on the nodes was positive for WT-1, p16, and CA-125 while cytokeratin 20 (CK20) and gross cystic disease fluid protein-15 (GCDFP-15) were negative. According to microscopic and immunocytochemical findings, the origin of axillary lymph node metastasis was ovarian cancer. An immunohystochemical review of the breast tumour and of the ovaries previously removed was executed. The analysis established a metastasis of papillary serous adenocarcinoma of the ovary on the breast tissue. The histomorphology of both tumors was similar regarding cytological atypia, which shown high nuclear pleomorphism and several mitoses. However, their growth patterns were dissimilar. The breast metastasis exhibited a predominantly solid-nodular growth pattern, whereas the primary ovarian tumor, underneath solid sheets with slit-like spaces, also contained small foci with a typical papillary growth pattern. The latter finally led to the diagnosis of a primary OSC. In all the slides assessed, the tumors displayed matching immunohistochemical profile: nearly all the tumor cells revealed positive reactions for cytokeratins 5 and 6, which in general is not the case in invasive breast cancer, but is in ovarian cancer. CA 125 and WT-1 were positive in both specimens. GCDFP-15 and cytokeratin 17 (CK17) showed negative immunoreactions. The summarized immunoprofile of both tumors strongly supported the histomorphological diagnosis of OSC. A PET/CT scan was repeated after surgery and it showed a progression of the disease with multiple enlarged celiac, para-aortic, aorto-caval and axillary lymph nodes (SUV max 7.4). CA125 level as 41.5 U/ml at that time. She received a combination therapy of cisplatin(75 mg/m2, d1 of a 21-day cycle) and gemcitabine (1000 mg/m2, on day 1 and 8 of a 21-day cycle). After three chemotherapy cycles, a PET/CT showed a good response to chemotherapy with a stable radiological and clinical response (SCR). No adverse event during chemotherapy have been registered.
Figure 1: A) Mediolateral oblique (MLO) view of a mammogram shows breast mass (red row). B) Breast mass with smooth margin and homogenous echotexture. Color Doppler reveals irregularly branching neovascularity. C) Round hypoechoic lymph node with a diffusely enlarged cortex is seen on US, and color Doppler US shows increased central flow.
Ovarian carcinoma is the second most common gynaecologic malignancy. OSC accounts for as many as 75% of them . Metastasis of ovarian serous carcinoma to the breast and axillary lymph nodes is uncommon [5,6], only few cases have been reported in the literature. Recine et al.  reported a series of 18 cases of stage III-IV OSC, which had metastases to breast four cases, in axillary lymph nodes in six cases or both in eight cases.
The breast and/or ipsilateral lymph node metastases were discovered at an average of 30 months after presentation as in our case (36 months).
When tumours in the breast or axillary lymph nodes are discovered before or simultaneously with an OSC, diagnostic difficulties may arise. The use of immunohistochemical markers such as WT-1 and GCDFP-15 may aid in defining the origin of the tumour if an ovarian primary should be contemplated carefully, because the treatments of these two entities are completely different.
Furthermore, metastatic cancer to the breast from an OSC is associated with a poor prognosis, infact the majority of patients dying in one year [6,7]. Kayikcioglu et al.  described the case of a patient that was initially stage IIC epithelial ovarian cancer. After two years, she presented with bilateral metastatic breast disease originated from the primary ovarian cancer. Although she was heavily treated, she died 18 months after diagnosis. Breast metastases from ovarian cancer were found an average of 2 years after initial diagnosis  and were usually a clue of advanced disease. It is interesting that in our patients there was no evidence of disseminated disease at the beginning.
Immunohistochemical markers may benefit in determining the origin of breast or axillary lymph node metastases. Yamamoto et al.  analysed WT-1 immunoreactivity in 119 patients with OSC and disclosed that WT-1 positivity is positively linked with high grade, advanced stage and higher Ki-67 index, higher bcl-2 expression and poorer outcome in a study. Although WT-1 positivity can be seen in many solid tumours, it has been recognized as a possible marker mostly for ovarian cancer.
We suggest that, in patients with history of OSC who present with axillary or breast mass, every effort should be made to obtain an accurate histological diagnosis since this has a great impact on treatment outcomes. It is critical to distinguish histologic pattern and recognize it from de novo ductal carcinoma in situ. Immunohistochemistry is crucial to confirm the diagnosis
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