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Ovarian cancer metastatic to the breast
GYNECOLOGIC
ONCOLOGY
24,
97-102 (1986)
Ovarian Cancer Metastatic to the Breast STEVEN LAIFER, Division
of Gynecologic
M.D., JOSEPH BLJSCEMA, M.D., TIM H. PARMLEY, M.D., AND NEIL B. ROSENSHEIN, M.D.’ Oncology,
The Johns Hopkins Hospital,
Baltimore,
Maryland
21205
Received October 16, 1984 The breast is an uncommon site for metastasis from epithelial ovarian cancer. Such lesions are purportedly secondary to blood-borne metastases. The accurate classification of ovarian epithelial neoplasms is the cornerstone of decisions regarding therapy and prognosis. Taylor, in 1929, reported a hyperplastic variety of papillary cystadenoma which, on occasion, produced multiple implants on the peritoneum but usually behaved in a benign fashion. The International Federation of Gynecologists and Obstetricians adopted a classification of benign cystadenomas, cystadenocarcinomas of low malignant potential (LMP), and cystadenocarcinomas. The serous tumors of LMP rarely metastasize outside of the abdominopelvic cavity. This case, of a serous tumor of LMP with breast metastasis, permits an analysis of metastatic breast lesions secondary to epithelial ovarian cancer. c&T1986 Academic
Press. Inc.
CASE REPORT
A.S. is a 39-year-old white female P2041 who presented with an &month history of abdominal pain, increasing abdominal girth, and menstrual irregularity. Her past medical history was remarkable for Dubin Johnson’s syndrome with occasional episodes of jaundice. She underwent a right partial salpingectomy and left salpingooophorectomy in association with two ectopic pregnancies. Upon admission, physical examination suggested ascites. Evaluation included a negative chest X ray, an abdominal CT scan consistent with ascites, and a small bowel series demonstrating extrinsic compression. Liver-spleen scan and intravenous urogram were negative. The patient underwent peritoneoscopy and biopsy of a peritoneal implant which revealed adenocarcinoma, consistent with metastasis from an ovarian primary. The patient was subsequently referred to the Division of Gynecologic Oncology of The Johns Hopkins Hospital. She underwent exploratory laparotomy disclosing a right ovarian mass adherent to the bladder and rectosigmoid, a left pelvic sidewall mass, and diffuse carcinomatosis involving the diaphragm, large and small bowel, and their mesentery, and a tumor mass was also noted extending
’ To whom reprint requests should be addressed. 97 0090-8258186$ I SO Copynght CC 1986 by Academic Press. Inc. All rightr of reproductmn in any form reserved.
98
LAIFER ET AL.
from the omentum into the left upper quadrant. Cytoreductive surgery was carried out comprising subtotal hysterectomy, right salpingo-oophorectomy, tumor debulking of the left pelvic sidewall, partial bladder resection, and omentectomy. Despite this aggressive effort, residual disease greater than 2 cm remained at the completion of surgery. Histopathology demonstrated papillary serous cystadenocarcinoma, characterized by numerous psammomabodies, absence of stromal invasion, complex branching papillary fronds, mild to moderate cellular atypia, nuclear enlargement with prominent nucleoli and very infrequent mitoses, all features compatible with a tumor of low malignant potential (LMP) (Fig. 1). The patient was classified as a Stage III ovarian cancer. In the ensuing year, the patient received 12 courses of hexamethylmelamine, cyclophosphamide, &-platinum, and Adriamycin. A partial response was achieved as adjudged by decrease in tumor size and disappearance of ascites. The patient underwent abdominal reexploration immediately following chemotherapy, which disclosed diffuse carcinomatosis of the peritoneum and a 3 x 3-cm tumor nodule involving the left pelvic sidewall. The nodule was resected and the histologic appearance was consistent with a tumor of LMP involving two lymph nodes and the soft tissue. She received an additional 6 courses of the aforementioned chemotherapy and continued to display excellent performance status. Pelvic examination, at the completion of therapy, revealed only thickening of the left side of the pelvis, and abdominopelvic CT scan displayed no masses,
FIG. 1. Serous cystadenocarcinoma of LMP. Note papillary nature of lesion with prominent calcification and/or psammoma bodies at center, and minimal nuclear and cytologic atypia. x 400.
CASE REPORTS
99
Follow-up, 1 year later, found the patient in generally excellent health. The pelvic examination was unremarkable; however, a mass in the upper outer quadrant of the right breast was detected. Xeroradiogram revealed scattered and focal microcalcifications in the upper outer quadrant of the right breast with an illdefined mass and skin retraction (Figure 2). Breast biopsy disclosed papillary adenocarcinoma consistent with her ovarian tumor. Laparoscopy was performed 1 month later to determine tumor status and demonstrated diffuse carcinomatosis with seeding of the bowel, peritoneum, and right and left pelvic masses. Biopsy revealed papillary adenocarcinoma consistent with her previous ovarian tumor and the breast biopsy. A right total mastectomy and axillary node sampling were performed in September 1983. The margin of resection was clear and the axillary nodes were negative. The histopathology was consistent with a metastatic papillary cystadenocarcinoma of LMP (Figs. 3A, B). She was subsequently started on megestrol acetate, continuing to have an excellent performance status with no tumor progression on physical examination until September 1984. A chest wall lesion was then discovered and when excised was compatible with previous histology.
FIG. 2. Mammogram of right breast. Note calcified lesion.
100
LAIFER ET AL.
F%G. 3. (A) Low power of lesion in right breast demonstrating papillary features of serous tumol Cal cification at lower left. x 275. (B) Higher power of breast lesion displaying minimal nuclear antd CYtologic atypia and focal calcification at center. x 400.
CASE
REPORTS
101
DISCUSSION The breast is an organ that complies with Virchow’s concept of malignancy; as a frequent site of primary neoplasms, it is an uncommon site of metastatic disease from extramammary malignancies [l]. Nevertheless, among lesions metastatic to the breast, the opposite breast, multicentric lymphoid malignancies, and disseminated melanoma constitute the most likely sources. When cancers arising in other discrete organs are considered, ovary, lung, and stomach predominate
M. The first example of ovarian cancer with breast metastasis was described by Sitzenfrey in 1907, who described a papillary serous cystadenocarcinoma of the ovary with metastases to one breast, the opposite ovary, the uterus, and intestines [3]. In 1928, Brown and O’Keefe described a bilateral ovarian lymphosarcoma that had metastasized to both breasts [4], and Charache, in 1953, reported two cases of ovarian carcinoma metastatic to the breast, one with metastases to the uterus and breast, the second with metastases to one breast, the ribs, and peritoneum [5]. In 1964, Ibach reported the first case of a metastatic inflammatory breast carcinoma secondary to an ovarian mutinous cystadenocarcinoma [2]. Subsequently, bilateral metastatic inflammatory breast carcinoma has been reported arising from a well-differentiated infiltrating papillary adenocarcinoma [6]. One case in which radiologically identified calcification occurred in a breast cancer metastatic from a papillary serous cystadenocarcinoma was reported in 1974 171. The most recent case of metastatic breast carcinoma from a poorly differentiated papillary serous cystadenocarcinoma of the ovary was described in 1983 by Hughes et al. [8]. In a review of 51 cases of cancers metastatic to the breast, 3 cases secondary to papillary serous cystadenocarcinomas of the ovary were reported [9]. Paulus and Libshitz reported a series of five women with primary ovarian carcinoma with breast metastases [IO]. In a study of 1000 consecutive autopsies of patients with malignant epithelial neoplasms, there were 64 cases of primary ovarian carcinoma, of which 2 had metastases to the breast [I I]. Ovarian carcinoma metastatic to the breast is purportedly an example of hematogenous dissemination. A review of metastatic disease to the breast disclosed that metastases appeared approximately 2 years after discovery of the primary lesion, most commonly as solitary discrete lesions, with multiple well-defined lesions or diffuse involvement being less common. The lesions tended to be superficially located in the upper outer quadrant of the breast, and axillary node involvement was frequently encountered [12]. Nearly half of the cases in one review of breast metastases were adherent to the skin and superficially located in the subcutaneous and immediate adjacent breast tissues [9]. The most common radiographic appearance of blood-borne metastases to the breast are round, discrete nodules [lo]. Bohman et al. emphasize the close correlation between size of the palpable lesions and mammographic appearance of metastatic breast nodules, in distinction to breast primary lesions which are palpably larger than their mammographic counterpart [2]. Calcification in metastatic lesions is very uncommon; Paulus and Libshitz maintain that the presence of tumor calcification virtually excludes metastatic disease to the breast [IO]. Ex-
102
LAIFER
ET
AL.
ceptions to this are three reports of calcifications in metastases from a primary ovarian carcinoma [7,10,14]. The currently reported case is added to the group of radiologically calcified lesions. SUMMARY This case represents an ovarian carcinoma of LMP metastatic to the breast. It is consistent with previously described metastatic lesions in that it occurred more than 2 years following initial treatment for the ovarian cancer, appeared as a solitary lesion, was superficial and adherent to the skin, and occurred in the upper outer quadrant of the breast. The ovarian tumor in this case was one of low malignant potential which, typically, does not leave the confines of the abdominopelvic cavity. This case represents the first tumor of this type which has metastasized to the breast. A possible explanation for this occurrence could be attributed to the two aggressive surgical cytoreductive efforts which may have been permissive for hematogenous dissemination of the breast. The nature of the breast lesion, the histopathologic correlations between primary and metastatic lesions, and the fact that the patient is 3i years following diagnosis and is doing well with an excellent performance status despite the presence of tumor support the clinical impression of a metastatic tumor of low malignant potential arising from the ovary. REFERENCES 1. Virchow, R. Die Krankhaften Geschwulste, Vol. 1, Hirschwald, Berlin, p. 69 (1863). 2. Ibach, J. R., Jr. Carcinoma of the ovary metastatic to the breast, Arch. Surg. 88, 410 (1964). 3. Sitzenfrey, A. Mamma karzinom zwei jahre nach abdominaler radikaloperation wegen doppelseitigen carcinoma ovarii. Prag. Med. Wschr. 32, 221 (1907). 4. Brown, J. B., and O’Keefe, C. D. Sarcoma of the ovary with unusual oral metastases. Ann. Surg. 84, 467 (1928). 5. Charache, H. Metastatic tumors in the breast with a report of ten cases, Surgery, 33, 385 (1953). 6. Krishnan, E. U., Phillips, A. K., Randell, A., Taylor, B., and Garg, S. K. Bilateral metastatic inflammatory carcinoma in the breast from primary ovarian cancer, Obstet. Gynecol. Suppl. 55, 3 (1980). 7. Royen, P. M., and Ziter, F. M. H. Ovarian carcinoma to the breasts, hit. J. Radio/. 47, 356 (1974). 8. Hughes, J. D., Hynes, H. E., and Lin, J. J. Ovarian carcinoma metastatic to breast, South. Med. J. 76(S), 667 (1983). 9. Hajdu, S. I., and Urban, J. A. Cancers metastatic to the breast, Cancer 29, 1691 (1972). 10. Paulus, D. D., and Libshitz, H. I. Metastasis to the breast, Radio/. C/in. North Amer. 20(3), 561 (1982). 11. Abrams, H. L., Spiro, R., and Goldstein, N. Metastases in carcinoma: Analysis of 1000 autopsied cases, Cancer 3, 74 (1950). 12. Toombs, B. D., and Kalisher, L. Metastatic disease to the breast: Clinical, pathologic and radiographic features, Amer. J. Roefgenol. 129, 673-676 (1977). 13. Bohman, L. G., Bassett, L. W., Gold, R. H., and Voet, R. Breast metastases from extramammary malignancies, Radiology 144, 309-312 (1982). 14. Moncada, R., Cooper, R. A., Garces, M., ef al. Calcified metastases from malignant ovarian neoplasm. Radiology 113, 31 (1974).
ONCOLOGY
24,
97-102 (1986)
Ovarian Cancer Metastatic to the Breast STEVEN LAIFER, Division
of Gynecologic
M.D., JOSEPH BLJSCEMA, M.D., TIM H. PARMLEY, M.D., AND NEIL B. ROSENSHEIN, M.D.’ Oncology,
The Johns Hopkins Hospital,
Baltimore,
Maryland
21205
Received October 16, 1984 The breast is an uncommon site for metastasis from epithelial ovarian cancer. Such lesions are purportedly secondary to blood-borne metastases. The accurate classification of ovarian epithelial neoplasms is the cornerstone of decisions regarding therapy and prognosis. Taylor, in 1929, reported a hyperplastic variety of papillary cystadenoma which, on occasion, produced multiple implants on the peritoneum but usually behaved in a benign fashion. The International Federation of Gynecologists and Obstetricians adopted a classification of benign cystadenomas, cystadenocarcinomas of low malignant potential (LMP), and cystadenocarcinomas. The serous tumors of LMP rarely metastasize outside of the abdominopelvic cavity. This case, of a serous tumor of LMP with breast metastasis, permits an analysis of metastatic breast lesions secondary to epithelial ovarian cancer. c&T1986 Academic
Press. Inc.
CASE REPORT
A.S. is a 39-year-old white female P2041 who presented with an &month history of abdominal pain, increasing abdominal girth, and menstrual irregularity. Her past medical history was remarkable for Dubin Johnson’s syndrome with occasional episodes of jaundice. She underwent a right partial salpingectomy and left salpingooophorectomy in association with two ectopic pregnancies. Upon admission, physical examination suggested ascites. Evaluation included a negative chest X ray, an abdominal CT scan consistent with ascites, and a small bowel series demonstrating extrinsic compression. Liver-spleen scan and intravenous urogram were negative. The patient underwent peritoneoscopy and biopsy of a peritoneal implant which revealed adenocarcinoma, consistent with metastasis from an ovarian primary. The patient was subsequently referred to the Division of Gynecologic Oncology of The Johns Hopkins Hospital. She underwent exploratory laparotomy disclosing a right ovarian mass adherent to the bladder and rectosigmoid, a left pelvic sidewall mass, and diffuse carcinomatosis involving the diaphragm, large and small bowel, and their mesentery, and a tumor mass was also noted extending
’ To whom reprint requests should be addressed. 97 0090-8258186$ I SO Copynght CC 1986 by Academic Press. Inc. All rightr of reproductmn in any form reserved.
98
LAIFER ET AL.
from the omentum into the left upper quadrant. Cytoreductive surgery was carried out comprising subtotal hysterectomy, right salpingo-oophorectomy, tumor debulking of the left pelvic sidewall, partial bladder resection, and omentectomy. Despite this aggressive effort, residual disease greater than 2 cm remained at the completion of surgery. Histopathology demonstrated papillary serous cystadenocarcinoma, characterized by numerous psammomabodies, absence of stromal invasion, complex branching papillary fronds, mild to moderate cellular atypia, nuclear enlargement with prominent nucleoli and very infrequent mitoses, all features compatible with a tumor of low malignant potential (LMP) (Fig. 1). The patient was classified as a Stage III ovarian cancer. In the ensuing year, the patient received 12 courses of hexamethylmelamine, cyclophosphamide, &-platinum, and Adriamycin. A partial response was achieved as adjudged by decrease in tumor size and disappearance of ascites. The patient underwent abdominal reexploration immediately following chemotherapy, which disclosed diffuse carcinomatosis of the peritoneum and a 3 x 3-cm tumor nodule involving the left pelvic sidewall. The nodule was resected and the histologic appearance was consistent with a tumor of LMP involving two lymph nodes and the soft tissue. She received an additional 6 courses of the aforementioned chemotherapy and continued to display excellent performance status. Pelvic examination, at the completion of therapy, revealed only thickening of the left side of the pelvis, and abdominopelvic CT scan displayed no masses,
FIG. 1. Serous cystadenocarcinoma of LMP. Note papillary nature of lesion with prominent calcification and/or psammoma bodies at center, and minimal nuclear and cytologic atypia. x 400.
CASE REPORTS
99
Follow-up, 1 year later, found the patient in generally excellent health. The pelvic examination was unremarkable; however, a mass in the upper outer quadrant of the right breast was detected. Xeroradiogram revealed scattered and focal microcalcifications in the upper outer quadrant of the right breast with an illdefined mass and skin retraction (Figure 2). Breast biopsy disclosed papillary adenocarcinoma consistent with her ovarian tumor. Laparoscopy was performed 1 month later to determine tumor status and demonstrated diffuse carcinomatosis with seeding of the bowel, peritoneum, and right and left pelvic masses. Biopsy revealed papillary adenocarcinoma consistent with her previous ovarian tumor and the breast biopsy. A right total mastectomy and axillary node sampling were performed in September 1983. The margin of resection was clear and the axillary nodes were negative. The histopathology was consistent with a metastatic papillary cystadenocarcinoma of LMP (Figs. 3A, B). She was subsequently started on megestrol acetate, continuing to have an excellent performance status with no tumor progression on physical examination until September 1984. A chest wall lesion was then discovered and when excised was compatible with previous histology.
FIG. 2. Mammogram of right breast. Note calcified lesion.
100
LAIFER ET AL.
F%G. 3. (A) Low power of lesion in right breast demonstrating papillary features of serous tumol Cal cification at lower left. x 275. (B) Higher power of breast lesion displaying minimal nuclear antd CYtologic atypia and focal calcification at center. x 400.
CASE
REPORTS
101
DISCUSSION The breast is an organ that complies with Virchow’s concept of malignancy; as a frequent site of primary neoplasms, it is an uncommon site of metastatic disease from extramammary malignancies [l]. Nevertheless, among lesions metastatic to the breast, the opposite breast, multicentric lymphoid malignancies, and disseminated melanoma constitute the most likely sources. When cancers arising in other discrete organs are considered, ovary, lung, and stomach predominate
M. The first example of ovarian cancer with breast metastasis was described by Sitzenfrey in 1907, who described a papillary serous cystadenocarcinoma of the ovary with metastases to one breast, the opposite ovary, the uterus, and intestines [3]. In 1928, Brown and O’Keefe described a bilateral ovarian lymphosarcoma that had metastasized to both breasts [4], and Charache, in 1953, reported two cases of ovarian carcinoma metastatic to the breast, one with metastases to the uterus and breast, the second with metastases to one breast, the ribs, and peritoneum [5]. In 1964, Ibach reported the first case of a metastatic inflammatory breast carcinoma secondary to an ovarian mutinous cystadenocarcinoma [2]. Subsequently, bilateral metastatic inflammatory breast carcinoma has been reported arising from a well-differentiated infiltrating papillary adenocarcinoma [6]. One case in which radiologically identified calcification occurred in a breast cancer metastatic from a papillary serous cystadenocarcinoma was reported in 1974 171. The most recent case of metastatic breast carcinoma from a poorly differentiated papillary serous cystadenocarcinoma of the ovary was described in 1983 by Hughes et al. [8]. In a review of 51 cases of cancers metastatic to the breast, 3 cases secondary to papillary serous cystadenocarcinomas of the ovary were reported [9]. Paulus and Libshitz reported a series of five women with primary ovarian carcinoma with breast metastases [IO]. In a study of 1000 consecutive autopsies of patients with malignant epithelial neoplasms, there were 64 cases of primary ovarian carcinoma, of which 2 had metastases to the breast [I I]. Ovarian carcinoma metastatic to the breast is purportedly an example of hematogenous dissemination. A review of metastatic disease to the breast disclosed that metastases appeared approximately 2 years after discovery of the primary lesion, most commonly as solitary discrete lesions, with multiple well-defined lesions or diffuse involvement being less common. The lesions tended to be superficially located in the upper outer quadrant of the breast, and axillary node involvement was frequently encountered [12]. Nearly half of the cases in one review of breast metastases were adherent to the skin and superficially located in the subcutaneous and immediate adjacent breast tissues [9]. The most common radiographic appearance of blood-borne metastases to the breast are round, discrete nodules [lo]. Bohman et al. emphasize the close correlation between size of the palpable lesions and mammographic appearance of metastatic breast nodules, in distinction to breast primary lesions which are palpably larger than their mammographic counterpart [2]. Calcification in metastatic lesions is very uncommon; Paulus and Libshitz maintain that the presence of tumor calcification virtually excludes metastatic disease to the breast [IO]. Ex-
102
LAIFER
ET
AL.
ceptions to this are three reports of calcifications in metastases from a primary ovarian carcinoma [7,10,14]. The currently reported case is added to the group of radiologically calcified lesions. SUMMARY This case represents an ovarian carcinoma of LMP metastatic to the breast. It is consistent with previously described metastatic lesions in that it occurred more than 2 years following initial treatment for the ovarian cancer, appeared as a solitary lesion, was superficial and adherent to the skin, and occurred in the upper outer quadrant of the breast. The ovarian tumor in this case was one of low malignant potential which, typically, does not leave the confines of the abdominopelvic cavity. This case represents the first tumor of this type which has metastasized to the breast. A possible explanation for this occurrence could be attributed to the two aggressive surgical cytoreductive efforts which may have been permissive for hematogenous dissemination of the breast. The nature of the breast lesion, the histopathologic correlations between primary and metastatic lesions, and the fact that the patient is 3i years following diagnosis and is doing well with an excellent performance status despite the presence of tumor support the clinical impression of a metastatic tumor of low malignant potential arising from the ovary. REFERENCES 1. Virchow, R. Die Krankhaften Geschwulste, Vol. 1, Hirschwald, Berlin, p. 69 (1863). 2. Ibach, J. R., Jr. Carcinoma of the ovary metastatic to the breast, Arch. Surg. 88, 410 (1964). 3. Sitzenfrey, A. Mamma karzinom zwei jahre nach abdominaler radikaloperation wegen doppelseitigen carcinoma ovarii. Prag. Med. Wschr. 32, 221 (1907). 4. Brown, J. B., and O’Keefe, C. D. Sarcoma of the ovary with unusual oral metastases. Ann. Surg. 84, 467 (1928). 5. Charache, H. Metastatic tumors in the breast with a report of ten cases, Surgery, 33, 385 (1953). 6. Krishnan, E. U., Phillips, A. K., Randell, A., Taylor, B., and Garg, S. K. Bilateral metastatic inflammatory carcinoma in the breast from primary ovarian cancer, Obstet. Gynecol. Suppl. 55, 3 (1980). 7. Royen, P. M., and Ziter, F. M. H. Ovarian carcinoma to the breasts, hit. J. Radio/. 47, 356 (1974). 8. Hughes, J. D., Hynes, H. E., and Lin, J. J. Ovarian carcinoma metastatic to breast, South. Med. J. 76(S), 667 (1983). 9. Hajdu, S. I., and Urban, J. A. Cancers metastatic to the breast, Cancer 29, 1691 (1972). 10. Paulus, D. D., and Libshitz, H. I. Metastasis to the breast, Radio/. C/in. North Amer. 20(3), 561 (1982). 11. Abrams, H. L., Spiro, R., and Goldstein, N. Metastases in carcinoma: Analysis of 1000 autopsied cases, Cancer 3, 74 (1950). 12. Toombs, B. D., and Kalisher, L. Metastatic disease to the breast: Clinical, pathologic and radiographic features, Amer. J. Roefgenol. 129, 673-676 (1977). 13. Bohman, L. G., Bassett, L. W., Gold, R. H., and Voet, R. Breast metastases from extramammary malignancies, Radiology 144, 309-312 (1982). 14. Moncada, R., Cooper, R. A., Garces, M., ef al. Calcified metastases from malignant ovarian neoplasm. Radiology 113, 31 (1974).