Lymphoma of the Ovary: A Case Report and a Review of the Literature HOWARD D. Fox, D.O.,’ E. N. CARTNICK, M.D., FACOG, PANTELEYMON SHOHOV, M.D.,FCAP, AND EDWARD C. ZAINO, M.D.,FACP Departments of Obstetrics and Gynecology of Mercy Hospital, Rockville Centre, New York, and Nassau County Medical Center, East Meadow, New York, and Department of Pathology, Mercy Hospital. Rockville Centre, New York Received
August 19, 1975
Malignant lymphoma involving the ovary in cases of generalized lymphomatous disease is not infrequent in autopsy findings. Actural clinical problems involving lymphoma of the ovary are much less common. In this report a case is discussed to show an actual clinical situation that covers pre- and postoperative care and therapy. A review of the literature concerning the incidence, arguments for primary or secondary involvement of the ovary, and a variation of treatment of lymphoma of the ovary is presented.
Malignant lymphoma designates “primary malignant tumors of reticular tissue that are composed of primitive reticular cells, their histocytic or lymphocytic derivatives or combinations of these cells” [ 11. From the existing literature, primary or secondary malignant lymphomatous involvement of the female genital tract is rarely encountered; when involvement is present, it is the ovary that is most frequently affected . At autopsy, lymphoma of the ovary is not an infrequent finding in generalized lymphomatous disease, but only a small fraction of women will have ovarian involvement as an initial manifestation of the disease I?, 3,41. A review of the literature shows surprisingly few case reports of clinically significant lymphomatous involvement of the ovary. In a report in 1963, among all the cases of sarcoma, lymphoma, and unclassified tumors recorded in the Ovarian Tumor Registry of the American Gynecological Society, there were 35 cases of lymphoma of the ovary [ 41. The occurrence of malignant lymphomas (generalized or localized) affecting females in relation to cases with ovarian involvement is seen in Table 1. CASE REPORT A 16yr-old white female, Gravida 0, Pat-a 0, whose last menstrual period occurred 3 weeks prior to admission was admitted to Mercy Hospital with a 3-week history of abdominal distention and discomfort. She described a loss of appetite and 5-lb weight loss over the past month. She also reported low grade fever for the 4 days prior to admission. 1 Send correspondence York 11501.
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FOX ET AL. TABLE
OCCURRENCE OF MALIGNANT LYMPHOMA (GENERALIZED OR LOCALIZED) AFFECTING FEMALES IN RELATION TO CASES WITH OVARIAN INVOLVEMENT
Author Sugarbaker [ 11J stout [ll] Lucia  Johnson [ 1I] Bruntsch [ 91 Hahn  Arneson [ 121 Nelson  Weingold [ 21 Woodruff  Lathrop [ lo] Freeman [ 141 Chorlton 
Number of lymphomas 196 218 11 43 36 8 6 5 44 105 689 9500
2 8 16 0 5 6 0 23 2 19
Her past history revealed no surgery or serious medical problems. Her menses started about 1 yr prior to admission and were described as regular, occurring every month, with no recent changes in pattern. Initial physical examination revealed a thin, pale, white female appearing chronically ill. The abdomen was markedly distended with ascites. A large, soft nodular, ballotable mass was palpated in the lower abdomen to the umbilicus. Rectopelvic examination revealed a large, tender mass filling the pelvis and separate from the previous mass. There was no axillary, cervical, or inguinal lymphadenopathy. The liver and spleen were not enlarged. Initial pertinent laboratory data included: white blood count, 12,500; Hemoglobin, 10.2 g; hematocrit, 29.3%, with normochromic, normocytic indices. Differential included three nonsegmented polymorphonuclear leukocytes, 65 polymorphonuclear leukocytes, 27 lymphocytes (one atypical), and 5 monocytes. The platelets were described as slightly increased. Blood urea nitrogen, 8 mg% ; total protein, 6 g%; serum albumin, 2.8 g%; alkaline phosphatase, 60 mu/ml; lactate dehydrogenase (LDH), 230 mu/ml. Intravenous pyelogram revealed a large homogeneous, soft tissue mass extending to the level of L2. There was slight dilatation of both calices, pelves, and ureters. The ureters were displaced laterally. Pressure was noted on the urinary bladder related to the pelvic mass. The chest X ray was negative. The impression of the examiner was that the patient had bilateral ovarian tumors with ascites, probably malignant. The patient was taken to the operating room and an exploratory laparotomy was performed. Bilateral solid ovarian tumors were found along with 2100 cc of clear ascitic fluid. The right ovary measured 20 cm in diameter and the left, 15 cm in diameter. The uterus was small. An 8.5-cm mass encompassing the appendix was noted. A 2.5-cm paraaortic node at the level of the bifurcation of the aorta was also noted. The liver was smooth with no nodularities or abnormalities. The spleen was not enlarged.
OF THE OVARY
FIG. 1. Cut surfaces of both ovaries.
No other retroperitoneal nodes were palpable. The omentum and bowel were free of any involvement. A total abdominal hysterectomy and bilateral salpingooophorectomy, omental biopsy, removal of the para-aortic node and periappendiceal mass, and an appendectomy were done. Gross Pathological Description The ovaries appeared as oval-shaped, smooth, grayish-pink masses. The right ovary weighed 1300 g and the left, 650 g. On sectioning, a homogeneous, glistening, rubbery, grayish-pink surface with focal cystic areas and hemorrhage was noted. The lymph node and periappendiceal mass were grossly similar, with cut surfaces suggestive of a “fish flesh” appearance (Fig. 1). Microscopic Description The ovarian tissue had been replaced totally by uniform sheets of cells. Areas of hemorrhage were encountered. The cells were arranged, at times, in clusters circumscribed by inconspicuous fibrous septa. The cells were large and had a polyhedral appearance. They had predominantly vesicular nuclei with thickened nuclear membranes. Mitoses were frequent. In addition there were larger pale cells, phagocytic histiocytes, with clear cytoplasm and abundant debris (Fig. 2). In the area where the histiocytes were prominent, the tissue had a “starry sky” appearance.
FIG. 2. Lymphoblasts with rather uniform large nuclei mixed with mature lymphocytes. Occasional histiocytes engulf debris (H and E x 400).
Histological Diagnosis Malignant lymphoma, poorly differentiated lymphocytic (lymphoblastic) type, replacing the right and left ovary with involvement of the appendix, periappendiceal mass, para-aortic lymph node, and the right fallopian tube. The ascitic fluid revealed atypical cytology, Pap Class II, but no evidence of malignancy. The omental biopsy specimen revealed mesothelial cell hyperplasia. The patient was studied further postoperatively after the diagnosis of lymphoma was made. A liver and spleen radioisotope scan showed no abnormalities. A liver biopsy specimen revealed normal liver tissue. A bone marrow aspiration revealed mild eosinophilic hyperplasia and mild hemosiderosis. The case was presented to the hospital Tumor Board. The recommendation of this board was that radiation therapy was not to be used initially as the patient was considered to have a Stage IV lymphoma and all grossly visible tumor had been removed at the time of laparotomy. The patient was started on chemotherapy consisting of nitrogen mustard, vincristine, procarbazine, and prednisone. After 8 weeks the patient then received total abdominal radiation, shielding the
FIG. 3. Electronmicrograph of lymphocytic cells displaying variation of size of the nuclei and prominent nucleoli (X 680).
kidneys. The chemotherapy was switched to prednisone, vincristine, and cytoxan. DISCUSSION
The argument concerning primary or secondary lymphomatous involvement of the ovary is seen throughout the literature. Zeigerman, Imbriglia, Makler, and Smith state that terms “primary” and “secondary,” for ovarian lymphoma, are misleading. They believe it best to consider lymphosarcoma occuring in multiple sites as having arisen from cells at those sites rather than having metastasized from another source [ 51. Nelson, Dockerty, Pratt, and ReMine believe that primary extranodal genesis of malignant lymphoma is rare and occurs in locations that normally exhibit aggregates of lymphocytes. These aggregates are never seen in the normal ovary. Secondary ovarian lymphomas may arise simultaneously from cells trapped in the ovary either through seeding, direct transperitoneal spread, or retrograde flow through the lymphatics from a primary source . Bare and McCloskey believe that malignant lymphomas, including Hodgkins disease, are generally considered to be unicentric in origin [ 71. Dufee considered the tumor in his report as primary in the ovary simply because it was the largest mass present. Walther, in reporting his primary cases,
stated that the retroperitoneal nodes were minimally enlarged . Zeigerman, Imbriglia, Makler, and Smith’s patient with primary lymphosarcoma died 9 months postoperatively with abdominal lymphosarcomatosis in spite of no apparent gross lesion other than those involving the ovaries at the time of laparotomy . Scamecchia and Mulla’s case is questionable because 5 yr prior to finding the primary ovarian lymphoma, the patient had a lymphoma removed from the abdominal wall [ 81. Chorlton, Norris, and King’s report sums up the question of primary or secondary ovarian lymphoma by stating that the problem cannot be answered at this time because of the doubt cast on the visual staging of the disease when detection may rest on microscopic examination. They believe that lymphoma can present as an initial manifestation in the ovary and have no extraovarian involvement detectable by current investigative techniques [ 31. The difficulty in diagnosing lymphosoma of the ovary has presented problems. The microscopic diagnosis is often difficult. In 54 of 65 diagnoses other than lymphoma, from the Ovarian Tumor Registry, the differential diagnosis on microscopic examination was either dysgerminoma, medullary carcinoma, or granulosa cell tumor . The therapy of ovarian lymphoma as with other malignancies is dependent on the clinical staging. Ovarian lymphoma should be staged as a lymphoma rather than by FIG0 staging of ovarian cancer. This’ is to make comparisons from one study to another and to access therapy and prognosis [ 31. Variation in the therapy of these lesions is probably related to their rarity and the lack of experience in their management . When the tumor is clearly limited to an accessible site, the therapy of choice is radical surgery followed by external radiation [ 2, 7, 9, lo]. If the pelvic disease is found to be part of a generalized process, conservative irradiation and chemotherapy are indicated [2, 41. Stage IIIb and IV lesions should be initially treated with chemotherapy. REFERENCES 1. Rappaport, H. Tumors of the hematopoietic system, in Atlas of tumor pathology, Armed Forces Institute of Pathology, Washington, D.C., Sect. 3, Fascicle 8, pp. 239-285 (1966). 2. Weingold, A. B., Stone, M. L., and Parente, J. T. Gynecologic aspects of malignant lymphoma, Obstet. Gynecol. 18, 461-467 (1961). 3. Chorlton, I., Norris, H. J., and King, F. M. Malignant reticula-endothelial disease involving the ovary as a primary manifestation: A series of I9 lymphomas and one granulocytic sarcinoma, Cancer 34, 397-407 (1974). 4. Woodruff, J. D., Noli Costillo, R. D., and Novak, E. R. Lymphoma of the ovary: A study of 35 cases from the Ovarian Tumor Registry of the American Gynecological Society, Amer. J. Obstet. Gynecol. 85, 9 12-9 18 (1963). 5. Zeigerman, J. H., Imbriglia, J., Makler, P., and Smith, J. J. Ovarian lymphosarcoma: Report of a case with a review of the literature, Amer. J. Obstet. Gynecol. 72, 1357-1360 (1956). 6. Nelson, G. A., Dockerty, M. B., Pratt, J. H., and ReMine, W. H. Malignant lymphoma involving the ovaries, Amer. J. Obstet. Gynecol. 76, 86 1-87 1 (1958). 7. Bare, W. B., and McCloskey, J. F. Primary Hodgkins Disease of the ovary: Report of a case, Obstet. Gynecol. 17, 477-480 (1961). 8. Scarnecchia, J. L., and Mulla, N. Lymphosarcoma of the ovary: Report of a case, Obstet. Gynecol. 15, 244-246 (1960). 9. Hahn, G. A. Gynecologic considerations in malignant lymphoma, Amer. J. Obstet. Gynecol. 75, 673-681 (1958).
10. Lathrop, J. C. Malignant pelvic lymphoma, Obsret. Gynecol. 30, 137-145 (1967). 11. Johnson, C. E., and Some, E. H. Malignant lymphoma as a gynecologic problem: Report of five cases including one primary lymphosarcoma of the cervix uteri, Obstet. Gynecol. 9, 149-157 (1957). 12. Arneson, A. N. Discussion following Hahn  Amer. J. Obstet. GynecoL 75, 681-682 (1958). 13. Collins, J., and Piper, P. Lymphosarcoma of the ovary: Report of a case with a review of the literature, Obstet Gynecol. 20, 686-689 (1962). 14. Freeman C., Berg, J. W., and Cutler, S. J. Occurrence and prognosis of extranodal lymphoma, Cancer 29, 252-260 (1972).