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Ovarian clear cell carcinoma with bilateral breast metastasis

1 Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi, India
2 Department of Radiation Oncology, Homi Bhabha Cancer Hospital, (Affiliated to HBNI, Mumbai), Sangrur, Punjab, India

Date of Submission30-Jun-2022
Date of Acceptance04-Aug-2022
Date of Web Publication01-Nov-2022

Correspondence Address:
Aashita ,
Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrcr.jrcr_38_22


Clear cell carcinoma of ovary (CCCO) is a rare subtype of epithelial ovarian tumors that is associated with poorer prognosis due to relative chemoresistance and higher chances of recurrence. Metastasis to the breast is extremely rare. Here, we report a case of ovarian cancer with metastasis to bilateral breasts. A 46-year-old female presented with pain abdomen and mild distension. Examination revealed pelvic mass and bilateral breast lumps. Staging laparotomy and fine-needle aspiration cytology from bilateral breast lumps were done. Histopathology revealed CCCO with metastasis to bilateral breasts. Due to the rarity of CCCO, there are no standard guidelines for management. The patient should be subjected to maximum cytoreduction and chemotherapy. Metastasis to the breast from ovary can occur either due to retrograde lymphatic or hematogenous spread that confers a worse prognosis. Hence, in a patient with breast mass especially with a history of malignancy, breast metastasis should be differentiated from primary breast cancer.

Keywords: Breast metastasis, metastasis, ovarian clear cell carcinoma

How to cite this URL:
Aashita, Sharma R, Yadav V, Thakur P. Ovarian clear cell carcinoma with bilateral breast metastasis. J Radiat Cancer Res [Epub ahead of print] [cited 2022 Dec 4]. Available from:

  Introduction Top

Clear cell carcinoma of ovary (CCCO) constitutes 3% of epithelial ovarian cancer that is distinctly different clinically, histopathologically, and genetically from other common subtypes.[1] More often than other subtypes, CCCO presents in early stage with a large abdominopelvic mass and has relatively good prognosis but it becomes extremely poor if the disease is in advanced stage. Ovarian cancers initially spread intra-abdominally followed by widespread metastasis.[2] Breast metastasis is extremely rare from primary ovarian malignancy. Only one case of CCCO with metastasis to bilateral breast has been reported before. In this article, we report the second case of ovarian clear cell carcinoma with bilateral breast metastasis who presented to our hospital.

  Case Report Top

A 46-year-old female with no known comorbidities and no family history of cancer presented with abdominal distension and epigastric discomfort for 3 months. On abdominal examination, there was a firm, nontender, cystic mass of size up to 14 weeks palpable more towards right side arising from pelvis whose lower border could not be reached. Cervix and vagina were healthy with a negative Pap smear. In addition, a lump of size 1.5 cm × 1.5 cm was palpable in the right breast and another lump of size 2 cm × 2 cm in the left breast with a firm and mobile left level I axillary node of 1 cm × 1 cm. Ultrasonography revealed 9 cm × 8.5 cm × 5 cm lesion anterosuperior to the uterine fundus with solid cystic component and internal and peripheral vascularity without internal calcification. The right ovary was normal while the left ovary was not separately visualized. The uterus was anteverted with an endometrial thickness of 6 mm–7 mm. CA-125 was elevated to 201.8 U/mL, CEA <0.5 ng/mL, alpha-fetoprotein (AFP) −2.47 ng/mL and β-HCG <2 mIU/mL.

Fine needle aspiration from both breast lumps and left supraclavicular lymph node showed metastatic clear cell carcinoma [Figure 1]. She underwent staging laparotomy followed by debulking surgery by total abdominal hysterectomy with pelvic and para-aortic lymphadenectomy and omentectomy. On pathological examination, it was a 12 cm × 9 cm × 2 cm tubo-ovarian mass suggestive of clear cell carcinoma with omental metastasis. It was positive for vimentin and CD10 but was negative for CK 7, 20, 30, Placental alkaline phosphatase, epithelial membrane antigen, AFP, and calretinin. Peritoneal fluid was negative for malignant cells. Postoperative CA-125 was 75U/mL.
Figure 1: Histopathological evaluation showing clear cell carcinoma of a section of an ovarian mass. (a) low power (×4). (b) high power (×10)

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Following the reports, metastatic workup was done with contrast-enhanced computed tomography that showed:

  1. Multiple lesions in bilateral breast parenchyma − 15 mm × 14 mm × 15 mm in upper and inner quadrant of the right breast and 21 mm × 17 mm × 19 mm in upper and inner quadrant of the left breast
  2. Multiple necrotic lymph nodes in the right axilla (largest 15 mm × 17 mm × 17 mm), mediastinal, and abdomen
  3. Multiple subcentimetric noncalcified left lung nodules
  4. Lytic lesion in D4 and L1 vertebrae left ilium and 5th rib.

The patient was started on palliative chemotherapy with paclitaxel and carboplatin. After three cycles, CA-125 increased to 470U/mL and there was no response radiologically, so, the regime was changed to cisplatin and irinotecan. The patient is currently on second-line chemotherapy.

  Discussion Top

Women with CCCO are relatively younger at diagnosis, of Asian descent, and present usually in earlier stages with a large pelvic mass compared to other subtypes of epithelial ovarian cancer.[3] Almost 60%–80% of patients present in early stage with 14% showing nodal involvement and less possibility of hematogenous spread. In advanced stage, metastasis occurs to the lung or liver that is found in 38% of patients.[1],[4] There are no standard guidelines of treatment. Staging laparotomy followed by total hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies followed by adjuvant chemotherapy is preferred for the early stage. Whereas in advanced stage, debulking surgery is done but patients have a poor prognosis with resistance to standard chemotherapy.[3]

The breast is a very unusual site of metastasis from extra-mammary malignancy. It constitutes only 1%–2% of all breast malignancies.[5] Metastasis to the breast can be a result of lymphatic or hematogenous spread but is rare because of its anatomical location, large areas of fibrous tissue, and poor blood supply.[6] Common tumors that metastasize to breast include lymphoma and malignant melanoma. Metastasis can occur to both breasts and bilateral axillary lymph nodes simultaneously but has been reported infrequently. A breast lump may be the first symptom with which patient reports to the hospital.[5] Hence, breast lump poses a diagnostic and treatment challenge and should be differentiated from primary breast cancer and metastatic deposit in breast. Diagnosis is difficult due to overlapping features and histopathology is confirmatory of metastasis. Metastasis to breast portends poor overall survival with a median duration of <1 year.[5]

Patients may also have synchronous or metachronous breast cancer with ovarian cancer. Metastasis of ovarian cancer to breast (MOCB) is seen in 0.3% of breast malignancy. Only 110 cases of MOCB have been reported in literature.[2] Metastasis from primary CCCO to breast is an extremely rare event and requires Histopathological evaluation (HPE) to differentiate from primary breast cancer because of similar morphology and clinical presentation. Only one case has been reported till now of a 61-year-old female with metastasis to both breasts.[1] Furthermore, bone metastasis is reported only in 2% of cases of ovarian cancers.[7] In our case, the presence of lump in both breast and pelvic mass with lytic lesions in multiple bone gives a clinical picture of bilateral breast cancer with extensive metastasis but surprisingly histopathology suggests ovarian clear cell carcinoma with metastasis to bilateral breasts and bone.

  Conclusion Top

CCCO has a poor prognosis compared to other subtypes due to chemoresistance and recurrence. Due to the rarity of CCCO, there are no standard guidelines for management. Complete cytoreduction is the treatment of choice followed by chemotherapy even in lower stages. A pattern of metastasis in CCCO is not yet fully understood. Although metastasis to the breast from solid tumors occurs rarely, it should be considered when a patient presents with a breast mass with symptoms of a synchronous malignancy or a history of malignancy.

Declaration of patient consent

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

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Conflicts of interest

There are no conflicts of interest.

  References Top

Galili Y, Lytle M, Bartolomei J, Amandeep K, Allen N, Carlan SJ, et al. Clear-cell carcinoma of the ovary with bilateral breast metastases. Case Rep Oncol Med 2019;2019:8013913.  Back to cited text no. 1
Tempfer CB, El Fizazi N, Ergonenc H, Solass W. Metastasis of ovarian cancer to the breast: A report of two cases and a review of the literature. Oncol Lett 2016;11:4008-12.  Back to cited text no. 2
Fujiwara K, Shintani D, Nishikawa T. Clear-cell carcinoma of the ovary. Ann Oncol 2016;27 Suppl 1:i50-2.  Back to cited text no. 3
del Carmen MG, Birrer M, Schorge JO. Clear cell carcinoma of the ovary: A review of the literature. Gynecol Oncol 2012;126:481-90.  Back to cited text no. 4
Sato T, Muto I, Fushiki M, Hasegawa M, Hasegawa M, Sakai T, et al. Metastatic breast cancer from gastric and ovarian cancer, mimicking inflammatory breast cancer: Report of two cases. Breast Cancer 2008;15:315-20.  Back to cited text no. 5
Shah P, Mustafa F, Aiman A, Shafi S, Charak A, Rafiq D, et al. Metastases to breast: Clinico-pathological and radiological correlation. Br Biomed Bull 2014;2:272-9.  Back to cited text no. 6
Kumar A, Gilks CB, Mar C, Santos J, Tinker AV. Patterns of spread of clear cell ovarian cancer: Case report and case series. Gynecol Oncol Case Rep 2013;6:25-7.  Back to cited text no. 7


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