Primary Bilateral Ovarian Cancer Presenting with BilateralBreast Metastasis: Cytology, Immunohistochemistry,and Radiologic Findings

Yahya Daneshbod1, Khosrow Daneshbod1, Mahsa Khanlari1, Yousef Yousefi2, Ahmad Mosalaie3, Shahrzad Negahban1, Azita Aledavood1, Hossein Soleimanpoor1,Neda Bagheri1 and Ronil U Ayson4

Affiliations: 1Department of Pathology, Dr Daneshbod Pathology Lab, Shiraz, Iran; 2Department of General Surgery, Dena Hospital, Shiraz, Iran; 3Department ofRadiation Oncology, Namazee Hospital, Shiraz, Iran and 4Head of Publications and Editorial Director, San Lucas Medical Limited, London, UK

(Submission Date: 19 April 2011; Acceptance Date: 24 April 2012; Publication Date: 9 August 2012)

A B S T R A C T

BACKGROUND

Breast mass as the primary manifestation of ovarian cancer is rare. A 62-year-old patient presented with a right side breast tumor, whichturned out to be a metastasis of a primary ovarian cancer.

CASE REPORT

A 62-year-old lady with a right side breast tumor on both physical examination and imaging underwent fine needle aspiration. With thediagnosis of poorly differentiated carcinoma, the patient underwent lumpectomy. Pathology and immunohistochemical study was in favor ofovarian primary cancer. Further investigation and total abdominal hysterectomy and bilateral salpingo-oophorectomy confirmed a stage IIICepithelial ovarian cancer. Less than 2 years later, the patient presented with a mass on the other breast. Cytology and immunohistochemicalstudy for WT-1, gross cystic disease fluid protein-15 (BRST-2), and estrogen receptor confirmed metastasis of primary ovarianorigin. Morphologic and immunohistochemical examination of the specimen helped to clarify the correct diagnosis of primary ovariancarcinoma.

CONCLUSION

Ovarian carcinoma usually presents with signs and symptoms related to the tumor burden within the abdominal cavity. Isolated, breastinvolvement without intraabdominal disease is extremely rare. Determining the origin of the primary tumor is important in directing theactual therapy.

Keywords: ovarian cancer, epithelial ovarian cancer, breast metastatic mass, immunohistochemistry, cytology, fine needle aspiration

Correspondence: Mahsa Khanlari, Institute of Hematopathology, Dr Daneshbod Laboratory, Ordibehesht Street, 71347 Shiraz, Iran.Tel: 00987112337967; Fax: 00987112346325; e-mail: Khanlari_mahsa@yahoo.com

INTRODUCTION

The breast is an uncommon site for metastasis fromepithelial ovarian cancer. So, there may be greater difficultyin determining the differential diagnosis.1,2 Such lesions arereportedly secondary to blood-borne metastases. The accurateclassification of ovarian epithelial neoplasms is the corner-stone of decisions regarding therapy and prognosis.3

Invasive micropapillary carcinoma of the breast (IMPC) is aunique histologic subtype characterized by micropapillaryepithelial architecture surrounded by lymphatic duct-likeempty space.4

The histologic characteristics of IMPC are quite similar tothose of serous papillary adenocarcinoma (SA) of the femalegenital organs or peritoneum.5 If ovarian SA precedes breastcancer and if the breast cancer is IMPC, metastatic SA couldbe considered during the differential diagnosis. Although thepresence of ductal carcinoma in situ (DCIS) usually confirms

the breast origin, the DCIS component may be missed insmall-needle biopsy specimens or fine needle aspirations.

We describe a 62-year-old patient with ovarian carcinoma,who developed a right-sided breast mass enlargement in thefirst presentation. Final pathology for both the primary andmetastatic disease was consistent with papillary ovariancarcinoma, confirmed with immunohistochemistry studies.Patient was treated for stage IIIC epithelial ovarian cancer.Less than 2 years later, she presented with metastasis to theother breast consistent with her ovarian primary cancer.

CASE REPORTA 62-year-old postmenopausal gravid 3 para 3, Iranian

patient presented with painless right breast masses.

Clinically, multiple, nontender right breast masses werepalpable. A total of four hyperechoic oval masses with well-circumscribed margins (2 cm in greatest diameter) were

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identified by mammography. There was no evidence oflymphadenopathy, ascites, or abdominal masses.

Fine needle aspiration of one of the right breast masses inthe inner upper quadrant revealed aggregates and isolatedtumor cells with large, round nuclei, and prominent nucleoli,consistent with poorly differentiated carcinoma.

The patient underwent right breast lumpectomy. Grosspathologic examination showed a multiloculated cystic masswith papillary projections. Histopathologic analysis of thespecimen indicated that the neoplasm was composed of cysticspaces and solid areas comprising cells arranged in acomplex papillary branching pattern characterized by numer-ous psammoma bodies, absence of stromal invasion, colum-nar cells with a moderate amount of clear/eosinophiliccytoplasm, and pleomorphic nuclei with prominent nucleoli(Figure 1A). Adjacent breast tissue had adenosis.

Immunohistochemical stainings were negative for proges-terone receptor (PgR), human epidermal growth factorreceptor 2 protein (Her2/neu), cytokeratin (CK) 20, grosscystic disease fluid protein (GCDFP) 15, and positive for CK7,OC125, WT-1, and estrogen receptors (ERs) (Figure 1B).Based on these findings, metastasis to the right breast fromovarian cancer was suspected.

Pelvic and rectal examination did not reveal any abnorm-ality. Chest X-ray did not show any lung lesions. Ultrasoundshowed shadow of a left-sided ovarian neoplastic lesion withsigns of cystic degeneration. Computed tomography (CT)scans of the abdomen and pelvis revealed a complexleft ovarian mass of 6.5�6.0 cm, and right enlarged ovary,5.5�5.0 cm, and mild ascites without evidence of intraab-dominal lymphadenopathy or metastatic involvement.

An exploratory laparoscopy was performed. Findings werethat of a 7-cm left ovarian mass with severe adhesion andperitoneal seeding. The liver, diaphragmatic and subdiaph-ragmatic surfaces, stomach, small and large bowels were allnormal on inspection.

Needle biopsy of the left ovary and peritoneum showedpapillary cystadenocarcinoma, with multiple psammomabodies similar to the findings from the earlier right breastexcisional biopsy. Chemotherapy was initiated, with intra-venous cisplatin and cyclophosphamide every 3 weeks.

Suboptimal debulking with total abdominal hysterectomy,bilateral salpingo-oophorectomy, and omental biopsy wereperformed 9 months later. Histopathologic analysis revealedmoderately differentiated papillary serous adenocarcinomawith papillary and glandular structures in both ovaries. Theovarian capsule was breached by tumor in the left side.Carcinomatosis was present in the serosal surfaces of leftfallopian tube and omentum. The cervix and uterus werenegative for malignancy. Peritoneal washings were alsopositive for tumor cells. The diagnosis of serous papillarycystadenocarcinoma, grade II, and stage IIIC based on theInternational Federation of Gynecology and Obstetrics classi-fication system was established.

Postoperative recovery was uneventful, and the patient wascommenced on adjuvant chemotherapy with paclitaxel andcarboplatin.

Follow-up abdominal and pelvic CT at the end of che-motherapy showed no evidence of recurrent or residuallesions in the pelvis. In addition, no free fluid or adenopathywas demonstrated in the pelvis. The CA-125 level recorded atfollow-up was B5.0 U/mL.

Mammography showed one spiculated mass with asso-ciated microcalcifications in the upper outer quadrant of theleft breast 15 months after the last chemotherapy (Figure 2).Ultrasound revealed cystic lesion measuring 2.5�2 cm in the1 o’clock position with solid echogenic components.

Fine needle aspiration and cell block of the left breast massrevealed numerous papillary structures and psammomabodies, consistent with previous tumor of papillary cystade-nocarcinoma of ovaries (Figure 3A and B).

DISCUSSIONGenerally, metastatic tumors in the breast are unilateral,

solitary, superficial, oval, well-circumscribed, firm nodules,and are unlikely to be fixed to the surrounding structures.6

There is usually no skin retraction or peau d’orange. Somecases have been multiple or bilateral7; others have been

Figure 1. Right breast mass excisional biopsy (H&E): papillary carcinomawith psammoma bodies (�40) (A); immunohistochemical staining forWT-1 (B).

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associated with skin retraction and fixation to surroundingstructures,8 and with an inflammatory pattern.9,10 Radio-graphically, metastatic tumors are more likely to be dense,

well-circumscribed lesions compared with the irregular out-lines seen in primary tumors. Calcifications are usuallyabsent.11 However, upon careful review of published casesof metastatic ovarian carcinoma, it appears that there areexceptions to these generalizations. Calcifications have alsobeen reported, corresponding to the psammoma bodiespresent in serous tumors, as our case in the secondmammography of left breast.1

Metastatic involvement is more common in the left breast,especially the upper outer quadrant. Breast involvement maybe an isolated phenomenon or secondary to widespreaddissemination of the tumor.12

The common mode of metastasis in ovarian tumors is bydissemination of tumor cells transperitoneally to the perito-neum, omentum, and bowel surface. Distant metastases tothe lung, liver, and breast presumably follow the hemato-genous route.13,14 Distant metastases develop in 38% ofovarian cancers during the course of their disease.15 The liver,lung, and pleura are the most commonly involved organs.16�18

The breast as a site of metastasis from ovarian/peritonealprimary carcinomas is uncommon. In one study, 3% ofovarian cancer cases were found to have breast metastasis onautopsy,19 representing only 0.03%�0.6% of all breastmalignancies.19,20

The most common type of ovarian malignancy to metasta-size to the breast is serous carcinoma, which has been thehistologic type reported in 72% of the cases. The first casewas reported by Sitzenfrey in 1907.21

A characteristic feature is the presence of papillary architec-ture in the metastases. The absence of an intraductal compo-nent is helpful for distinguishing metastatic from primarytumors. The features of metastatic serous carcinoma on fineneedle aspiration cytology are hypercellularity and abundantpapillary fragments. The tumor cells have high nuclear-to-cytoplasmic ratios, anisocytosis, and marked nuclear atypia.Psammoma bodies may be present. The histopathology of

Figure 2. Left breast mass mammography showed one spiculated mass with associated microcalcifications.

Figure 3. Left breast mass fine needle aspiration revealed numerouspapillary structures (�40) (A); immunohistochemical staining for WT-1on cell block (B).

Primary bilateral ovarian cancer with bilateral breast metastasis

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breast and ovarian carcinomas can be very similar andconstitutes a potential pitfall in diagnosis.

First time breast fine needle aspiration in our case wasreported as poorly differentiated carcinoma with a solidgrowth pattern, and no evidence of ductal or papillarydifferentiation. Papillary clusters admixed with more solidareas having slit-like spaces were seen in the lumpectomyspecimen. Lack of pathologic changes in the surroundingbreast tissue and immunohistochemical markers were neededto arrive at the correct diagnosis.

The skin overlying the tumor is likely to be of normalconsistency with no signs of nipple discharge or retrac-tion;11,14,17 so, clinical examination of the breast should beundertaken on all follow-up visits for patients with ovarianmalignancy.

Disclosure: The authors declare no conflict of interest.

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