Breast carcinoma masquerading as primary ovarian neoplasm

Breast Carcinoma Masquerading as Primary 0varian Neoplasm ROBERT H. YOUNG, MB,* ROBERT W. CAREY, MD, AND STAN EY J. ROBBOY. MD

Metastases which present as palpable masses in the pelvis occasionally masquerade as primary neoplasms of the ovary. Although most such cancers originate in the stomach and large intestine, the histories of two patients are presented in whom the ovarian tumors were discovered prior to the detection of the breast primary. Three similar cases were found in the literature and are reviewed. Cancer 48:210-212, 1981.

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s t o m a c h and i n t e s t i n e s o m e t i m e p r e s e n t clinically as a pelvic mass t h a t m a s q u e r a d e s as a p r i m a r y t u m o r of t h e o v a r y . A l t h o u g h r e p o r t s indicate t h a t a p p r o x i m a t e l y 30% of b r e a s t c a n cers m e t a s t a s i z e t o t h e ovary,”’“ it is a l m o s t always in t h e form of microscopic d e p o s i t s t h a t are d e t e c t e d s u b s e q u e n t t o t h e discovery of t h e b r e a s t t u m o r . T h i s r e p o r t highlights the rare situation where palpable ovarian m e t a s t a s e s precede recognition of t h e p r i m a r y malignancy in t h e b r e a s t .

Case Reports Case I: A 42-year-old white woman complained of abdominal pain. At least five members of her close family had had cancer, including two aunts and a cousin with breast carcinoma. Physical examination disclosed a 10 x 1 1 cm mass in the left adnexa and a 6-cm mass in the right adnexa. A 2.5-cm mass from which no fluid could be aspirated was also palpable in the upper portion of the left breast. At laparotomy a ruptured left ovarian cyst with a 3-cm exophytic tumor on its surface was present. A rnultinodular tumor replaced the right ovary. On microscopic examination both tumor masses evidenced poorly differentiated adenocarcinoma. A breast biopsy was performed one week later which was followed by a radical mastectomy. The tumor in the breast was identical histologically with that present in the ovaries. All lymph nodes were free of tumor. The patient was treated with a total of six courses of melphalan, 40 mg, over five days each, spread over nine months, after

which the program was modified because of severe thrombocytopenia. A right-sided pelvic mass developed after 13 months. Laparotomy disclosed four masses in the pelvis, which were microscopically similar to the tumors previously examined. Subsequently, liver function tests became abnormal and liver metastases were found on scan. The patient is alive 2% years following the original diagnosis and is receiving combination chemotherapy. Case 2: A 54-year-old white woman complained of a large mass in the left lower quadrant of the abdomen. Laparotomy revealed ascites, a large mass in the left ovary, and metastases throughout the mesentery. Microscopically the neoplasm was a poorly differentiated adenocarcinoma (Fig. I , left). Immediately thereafter, a mass in the right breast was found that was located at the junction of the upper and lower inner quadrants. Biopsy disclosed tumor that on microscopic examination was similar to that in the ovary (Fig. I , right). Therapy with Adriamycin and Cytoxan was begun and the pelvic tumor shrank slowly in size. One year later, abdominal cramps became more severe and a palpable mass appeared in the right adnexa. A biopsy was not performed. The patient is alive and receiving chemotherapy.

Review of the Literature Cuse 3”: A 20-year-old woman was admitted to the hospital because of the development of ascites two days after she had given birth to a female infant with an enlarged clitoris. During the seventh month of pregnancy, the mother’s voice had deepened and subsequently she developed generalized hirsutism and acne of the chest and back. The urinary level of 17-ketosteroid was 122 mg/24 hours. Physical examination revealed a large pelvic mass and at laparotomy, 30 x 15 X 13 cm and 12 x 6 x 6 cm bilateral ovarian tumors were found. Microscopic examination disclosed metastatic signet-ring-cell adenocarcinoma and luteinization of the ovarian stromal cells. After the ovarian masses were excised, the symptoms of virilization regressed and the urinary levels of 17-ketosteroid returned to within normal limits.

From the Departments of Pathology and Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusett s. * Dr. Young is a recipient o f a Junior Faculty Clinical Fellowship from the American Cancer Society. Address for reprints: Dr. Robert H . Young, Department of Pathology, Massachusetts General Hospital, Boston, MA 021 14. The authors thank Dr. Maurice Webb who provided additional clinical information about Case #4. Accepted for publication June 1 I , 1980. 0008-543X/81!0701:0210

$0.70 0 American Cancer Society

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BREASTCA MASQUERADING AS OVARIAN NEOPLASM* Young et al.

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FIG. 1 . Adenocarcinorna of breast (left) metastatic to ovary (right) (H & E, x16O-x256).

cancer and to the reason for which the ovary was examined. When the therapy of breast cancer includes routine removal of the ovaries, about one-third of ovarian metastases are found within one year.I3 On the other hand, if laparotomy is postponed until the ovarian metastases become clinically apparent, then only 10% of the metastases are detected within a year'; 60% become symptomatic during the next eight years and 30% in the ninth year and thereafter.' In contrast to patients with breast primaries, primary neoplasms arising in the genital or gastrointestinal tracts are usually associated with earlier detection of the ovarian metastases because the ovaries are normally inspected or removed during laparotomy. In one series, 83% of ovarian metastases were identified at the time of lapaDiscussion rotomy for genital tract tumor and 60% at the time of Metastatic carcinoma to the ovary, which accounts laparotomy for gastrointestinal cancer^.'^ for 6% of ovarian cancers detected at ~ p e r a t i o n , ~ Ovarian metastases may also be detected before the primary tumor is discovered. Sometimes the ovarian originates in order of decreasing frequency in the breast, colon, rectum, and ~ t o m a c h . Frequently, '~ the metastases are discovered because they are functioning metastases are microscopic and not recognizable as with carcinoid tumors.6 Metastases, commonly of grossly, especially when the ovaries are removed as colonic origin'" and sometimes of gastric origin," may part of the therapeutic regimen of prophylactic castraelicit luteinization of the ovarian stroma, which in turn tion for breast cancer. Approximately 30% of such may result in clinical signs of masculinization. The patients have ovarian meta~tases,~," and in two-thirds metastases may also be detected because of the the involved ovary is grossly unremarkable.3 Ovarian presence of a large pelvic mass, and it is only after the specimen has been examined pathologically that the involvement with metastatic cancer is also frequent at autopsy where tumor has spread widely throughout the metastatic nature of the lesion is appreciated. Adenoabdominal cavity.2a6 carcinoma of the colon is, in our experience, the tumor The interval between detection of a primary cancer that most frequently gives rise to large ovarian and the subsequent ovarian metastases appears related metastases. Identification of the stomach as the source both to the location of the organ with the primary of the primary lesion may be the most difficult to prove. Three months later, both breasts were noted to be enlarged and when a biopsy was done they evidenced infiltrating ductal adenocarcinoma. The patient died shortly thereafter and at autopsy had widespread metastatic tumor. Case 413: A 29-year-old woman had complained of right lower quadrant pain for five years. At laparotomy both ovaries were slightly enlarged and were removed. Microscopic examination disclosed metastatic adenocarcinoma. A lump was palpated in the left breast several weeks later, which on microscopic examination was similar to the ovarian metastases. Case 5': A woman, who was over 40 years of age, presented with "clinical symptoms" of ovarian metastasis one month before the discovery of a primary tumor in the breast. She died five months later.

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In some cases, both ovaries may contain signet-ring cells indicative of a Krukenberg tumor, but the primary tumor cannot be detected with upper gastrointestinal roentgenographic studies, and may not be found until the stomach is examined at autopsy. The present cases indicate that cancer of the breast may also give rise to ovarian metastases that clinically precede detection of an asymptomatic primary neoplasm in the breast. This observation is important since the microscopic appearance of breast metastases can be confused with other primary and metastatic ovarian neoplasms, including poorly differentiated common epithelial tumors, carcinoid tumors, both primary in the ovarys and metastatic from the intestinal tract,6 granulosa cell tumors, lymphomas ,9 and signet-ringcell carcinomas of gastric origin.”.’.’ Whenever ovarian tumors are bilateral, metastases to the ovary should be considered and, where appropriate, search for a clinically silent primary site should be undertaken. REFERENCES 1. Johansson H. Clinical aspects of metastatic ovarian cancer of extragenital origin. Acra Gynecol 1960; 39:681-696. 2. Luisi A . Metastatic ovarian tumours. In: Gential F, Junqueira

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AC, eds. Ovarian Cancer (UICC monograph series), vol. 2. Berlin: Springer-Verlag, 1968; 87- 104. 3. Lum G, MacKenzie DH. The incidence of metastases in adrenal glands and ovaries removed for carcinoma of the breast. Cancer 1958; 12:521-526. 4. Puga FJ, Gibbs CP, Williams TJ. Castrating operations associated with metastatic lesions of the breast. Ohsrer Gynecol 1973 ; 4 l:7 15-7 19. 5. Robboy SJ, Norris HJ, Scully RE. Insular carcinoid primary in the ovary: A clinical pathologic analysis of 48 cases. Cancer 1975; 36:404-418. 6. Robboy SJ, Scully RE, Norris HJ. Carcinoid metastatic to the ovary, a clinico-pathologic analysis of 35 cases. Cancer 1974; 33:798-811. 7 . Santesson L, Kottmeier HL. In: Gential F, Junqueira AC, eds. Ovarian Cancer (UICC monograph series), vol. 2. Berlin: Springer-Verlag, 1968; 1-8. 8. Saphir 0. Signet ring cell carcinoma. Mil Surg 1951: 109: 360-369. 9. Scully RE. Recent progress in ovarian cancer. Hum Pathol 1970; 1:73-98. 10. Scully RE, Richardson GS. Luteinization of the stroma of metastatic cancer involving the ovary and its endocrine significance. Cancer 1961; 14:827-840. 1 1 . Spadoni LR, Lindberg MC, Mottet NK, et al. Virilization co-existing with Krukenberg tumor during pregnancy. Am J Obstet Gynecol 1965; 92:981-991. 12. Turksoy N . Ovarian metastasis of breast carcinoma. A surgical surprise. Ohsrer Gynecol 1960; 15:573-578. 13. Webb MJ, Decker DG, Mussey E. Cancer metastatic to the ovary. Factors influencing survival. Obsfef Gynecol 1975; 45: 39 1-396.