- Email: [email protected]
Malignant Lymphoma of the Ovary: Report of a Case Successfully Managed with Surgery and Chemotherapy
GYNECOLOGIC ONCOLOGY ARTICLE NO.
70, 137–140 (1998)
GO985033
CASE REPORT Malignant Lymphoma of the Ovary: Report of a Case Successfully Managed with Surgery and Chemotherapy Anh H. Dao, M.D. Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 Received June 2, 1997
Incidental finding of a primary malignant lymphoma of the ovary in a 20-year-old patient is presented. Two and a half years following ablative surgery and adjuvant chemotherapy, the patient is alive and disease free. Ovarian lymphoma is a disease of reportedly poor prognosis. However, many previously reported cases of ovarian lymphoma actually represented ovarian involvement by a more diffuse lymphomatous process. If stringent criteria are used for case selection, true primary ovarian lymphoma usually carries a favorable prognosis. © 1998 Academic Press
Involvement of the ovary by malignant lymphoma can present either as a primary lesion or, more frequently, as a focus of involvement in cases of disseminated malignancy. Ovarian involvement as a manifestation of clinically occult or overt lymphomatous malignancy is well recognized with frequency as high as 26% in some autopsy series [1]. Primary malignant lymphoma of the ovary as an extranodal disease, on the other hand, is rare with only few cases reported [2– 6]. The exact number of cases is not known due to the fact that there are no clearly defined and accepted criteria for primary ovarian lymphoma (POL). We report a case of POL successfully managed with a combination of surgery and adjuvant chemotherapy. CASE REPORT A 20-year-old woman, 1421 weeks pregnant, was admitted because of a large pelvic mass discovered on routine ultrasound examination. The patient was asymptomatic and past medical history was noncontributory. Physical examination revealed a 14-week size uterus which was displaced anteriorly by a solid mass of the left adnexa. The mass measured 13 cm in diameter and appeared septated by ultrasonography. Laboratory work-up was within normal limit except for a high lactate dehydrogenase value of 1569 units/L (normal, 90 –156 units/L). The patient was explored and a 13-cm multinodular mass was found involving the left ovary. It was not adherent to adjacent organs and was removed with the left fallopian tube
without difficulties. The right fallopian tube and ovary, the uterus and kidneys were normal. The liver, diaphragm and omentum were not involved. No enlarged lymph nodes were identified in the abdomen. Peritoneal washing was performed, showing no abnormal cells. The patient had an uneventful postoperative period and a complete recovery. A bone marrow biopsy performed 1 week later showed no abnormalities. A diagnosis of malignant lymphoma, diffuse, large B-cell type of intermediate grade was made. The patient was treated with a combination of chemotherapeutic agents including vincristine, cytoxan, and prednisone with no major side effects. She had a spontaneous vaginal delivery at 34 weeks of a viable male fetus weighing 4 lb 10 oz. The patient continued to do well with no evidence of recurrent lymphoma. Twelve months after delivery of the first child, she was 1321 weeks pregnant with triplets and was admitted for cervical cerclage. Delivery of the triplets by C-section was carried out 4 months later. The patient was alive and well, free of disease 30 months postdiagnosis. On gross examination, the left ovarian mass measured 13.5 3 9.5 3 7.5 cm and weighed 537 g. The external surface was pink white, lobulated, and smooth. There was a 3-cm-long, normal looking fallopian tube attached. The cut surface of the mass was lobulated and tan colored, with multiple small foci of calcifications (Fig. 1). Microscopic examination revealed complete replacement of ovarian tissue by sheets of neoplastic cells which were divided into small round nests by thin fibrous septae (Fig. 2). Cytologically, the tumor cells were large with pleomorphic, often folded nuclei, finely dispersed chromatin, and multiple nucleoli. There was an abundant amount of pale but distinct cytoplasm (Fig. 3). Mitoses were frequent, averaging 15 per 10 high power fields. Focal infiltration of the stroma by small lymphocytes was noted throughout. Paraffin immunoperoxidase studies showed strong positive marking of the neoplastic cells for CD45 (LCA) and CD20 (L-26). Scattered large tumor cells were also CD75 (LN-1) positive. Tumor cells were negative for T-cell markers CD3 and CD45RO (UCHL-1). No monoclonal population was demonstrated with staining for immunoglobulin heavy and light
137
0090-8258/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.
FIG. 1.
The cut surface of the ovarian lesion is lobulated with irregular nodules of soft, white tan tissue separated by depressed, scar-like bands of fibrous tissue.
FIG. 2. Medium power view of the lesion shows an organoid pattern with small rounded nests of tumor cells surrounded by thin fibrous septae (hematoxylin and eosin, 3200). 138
CASE REPORT
FIG. 3.
139
On high power view, the tumor cells exhibit large, often folded nuclei and abundant pale cytoplasm (hematoxylin and eosin, 3400).
chains. No immunoreactivity was noted with staining for the following markers: CD15 (Leu M1), CD30 (Ki-1), CD68, epithelial membrane antigen, cytokeratin, vimentin, S-100, and placental alkaline phosphatase. These findings were in favor of an intermediate grade malignant lymphoma, diffuse large cell type of B-cell lineage. The CD75 positivity suggested a possible follicular center cell origin. DISCUSSION POL is a rare disease and its very existence as an entity is questioned by many authors. Since the normal ovary is devoid of any lymphoid tissue, other sources such as lymphoid aggregates in the ovarian hilum, or chronic inflammatory cells in the ovary in response to ovarian lesions such as pelvic inflammatory disease and endometriosis, were cited as possible origins for POL [7]. More recent studies have found benign lymphoid aggregates in approximately half of normal ovaries [6]. It is hypothetically possible that on rare occasions these lymphoid aggregates may undergo malignant transformation, giving rise to a POL. In the past, the diagnosis of POL required only substantiation by histologic examination of the ovarian lesion. Many cases of POL reported in larger series were actually cases of malignant lymphoma with ovarian enlargement as the present-
ing symptom [2– 4]. All types of lymphomas were represented, mostly non-Hodgkin’s lymphoma with rare cases of Hodgkin’s disease included [2, 3]. Prognosis was generally poor with survival rates ranging from 7 to 38% [2– 4]. In 1976, Fox and Langley [8] proposed the following criteria for the diagnosis of POL: (i) At the time of diagnosis the lymphoma is clinically confined to the ovary and full investigation fails to reveal evidence of lymphoma elsewhere. A lymphoma can still be considered as ovarian primary if spread has occurred to immediately adjacent lymph nodes or if there has been direct spread to infiltrate immediately adjacent structures. (ii) The peripheral blood and bone marrow should not contain any abnormal cells. (iii) If further lymphomatous lesions occur at sites remote from the ovary then at least several months should have elapsed between the appearance of the ovarian and extraovarian lesions. If these stringent criteria are applied, POL becomes vanishingly rare. Skodras et al. in 1994 reviewed the literature and found 15 cases of ovarian lymphoma meeting the above described criteria [9]. The patients’ ages ranged from 2 to 63 years (mean age, 37.7 years). Nine patients were found to have diffuse large cell or mixed large and small cell lymphoma. Following treatment which consisted of ablative surgery with
140
ANH H. DAO
or without adjuvant chemotherapy, all 15 patients were alive with no evidence of disease except 1 who developed multiple local recurrences. Our patient met the criteria for POL and had a favorable outcome similar to those reviewed in this series. Monterroso et al. in 1993 reported 39 patients with nonHodgkin’s lymphoma who initially presented with ovarian enlargement [6]. On the basis of staging studies and clinical followup, only 4 of the patients were felt to have POL. Mean age of these four patients was 41.8 years. Three patients were cured of the disease following surgical excision and chemotherapy. All three had diffuse large cell lymphoma of B-cell lineage. The fourth patient died of lymphoma 4 years 6 months after diagnosis. She had diffuse mixed small and large cell lymphoma. From the observation of the 19 above cited patients and our personal case, POL appeared as a disease of young to middle age patients. Diffuse large cell or diffuse mixed large and small cell lymphomas were the most often diagnosed histologic types. The majority of the patients were staged as stage I by the Ann Arbor system. A favorable outcome was seen in most patients following ablative surgery with or without adjuvant chemotherapy, with only one death noted. One exception to the rarity of POL is seen in countries where Burkitt’s lymphoma is endemic. In these areas, ovarian involvement by Burkitt’s lymphoma accounted for almost half of malignant ovarian tumors in children [10]. Enlargement of one or both ovaries is the second most common form of presentation of Burkitt’s lymphoma after involvement of the jaw [10].
REFERENCES 1. Rosenberg SA, Diamond HD, Jaslowitz B, Craver LF: Lymphosarcoma: A review of 1269 cases. Medicine 40:31– 84, 1961 2. Chorlton I, Norris HJ, King FM: Malignant reticuloendothelial disease involving the ovary as a primary manifestation: A series of 19 lymphomas and 1 granulocytic sarcoma. Cancer 34:397– 407, 1974 3. Rotmensch J, Woodruff JD: Lymphoma of the ovary: Report of twenty new cases and update of previous series. Am J Obstet Gynecol 143:870 – 875, 1982 4. Osborne BM, Robboy SJ: Lymphomas or leukemia presenting as ovarian tumors: An analysis of 42 cases. Cancer 52:1933–1943, 1983 5. Fox H, Langley FA, Govan ADT, Shirley Hill A, Bennett MH: Malignant lymphoma presenting as an ovarian tumor: A clinicopathological analysis of 34 cases. Br J Obstet Gynecol 95:386 –390, 1988 6. Monterroso V, Jaffe ES, Merino MJ, Medeiros LJ: Malignant lymphomas involving the ovary: A clinicopathologic analysis of 39 cases. Am J Surg Pathol 17:154 –170, 1993 7. Woodruff JD, Noli Castilla RD, Novak ER: Lymphoma of the ovary—A study of 35 cases from the Ovarian Tumor Registry of the American Gynecological Society. Am J Obstet Gynecol 185:912–918, 1963 8. Fox H, Langley FA: Tumours of the Ovary, London, Heinemann, 1976, p 293 9. Skodras G, Fields V, Kragel PJ: Ovarian lymphoma and serous carcinoma of low malignant potential arising in the same ovary: A case report with literature review of 14 primary ovarian lymphomas. Arch Pathol Lab Med 118:647– 650, 1994 10. Scully RE: Tumors of the ovary and maldeveloped gonads, in Atlas of Tumor Pathology, 2nd series, Fasc. 16, Washington, DC, AFIP, 1979, pp 346 –347
70, 137–140 (1998)
GO985033
CASE REPORT Malignant Lymphoma of the Ovary: Report of a Case Successfully Managed with Surgery and Chemotherapy Anh H. Dao, M.D. Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 Received June 2, 1997
Incidental finding of a primary malignant lymphoma of the ovary in a 20-year-old patient is presented. Two and a half years following ablative surgery and adjuvant chemotherapy, the patient is alive and disease free. Ovarian lymphoma is a disease of reportedly poor prognosis. However, many previously reported cases of ovarian lymphoma actually represented ovarian involvement by a more diffuse lymphomatous process. If stringent criteria are used for case selection, true primary ovarian lymphoma usually carries a favorable prognosis. © 1998 Academic Press
Involvement of the ovary by malignant lymphoma can present either as a primary lesion or, more frequently, as a focus of involvement in cases of disseminated malignancy. Ovarian involvement as a manifestation of clinically occult or overt lymphomatous malignancy is well recognized with frequency as high as 26% in some autopsy series [1]. Primary malignant lymphoma of the ovary as an extranodal disease, on the other hand, is rare with only few cases reported [2– 6]. The exact number of cases is not known due to the fact that there are no clearly defined and accepted criteria for primary ovarian lymphoma (POL). We report a case of POL successfully managed with a combination of surgery and adjuvant chemotherapy. CASE REPORT A 20-year-old woman, 1421 weeks pregnant, was admitted because of a large pelvic mass discovered on routine ultrasound examination. The patient was asymptomatic and past medical history was noncontributory. Physical examination revealed a 14-week size uterus which was displaced anteriorly by a solid mass of the left adnexa. The mass measured 13 cm in diameter and appeared septated by ultrasonography. Laboratory work-up was within normal limit except for a high lactate dehydrogenase value of 1569 units/L (normal, 90 –156 units/L). The patient was explored and a 13-cm multinodular mass was found involving the left ovary. It was not adherent to adjacent organs and was removed with the left fallopian tube
without difficulties. The right fallopian tube and ovary, the uterus and kidneys were normal. The liver, diaphragm and omentum were not involved. No enlarged lymph nodes were identified in the abdomen. Peritoneal washing was performed, showing no abnormal cells. The patient had an uneventful postoperative period and a complete recovery. A bone marrow biopsy performed 1 week later showed no abnormalities. A diagnosis of malignant lymphoma, diffuse, large B-cell type of intermediate grade was made. The patient was treated with a combination of chemotherapeutic agents including vincristine, cytoxan, and prednisone with no major side effects. She had a spontaneous vaginal delivery at 34 weeks of a viable male fetus weighing 4 lb 10 oz. The patient continued to do well with no evidence of recurrent lymphoma. Twelve months after delivery of the first child, she was 1321 weeks pregnant with triplets and was admitted for cervical cerclage. Delivery of the triplets by C-section was carried out 4 months later. The patient was alive and well, free of disease 30 months postdiagnosis. On gross examination, the left ovarian mass measured 13.5 3 9.5 3 7.5 cm and weighed 537 g. The external surface was pink white, lobulated, and smooth. There was a 3-cm-long, normal looking fallopian tube attached. The cut surface of the mass was lobulated and tan colored, with multiple small foci of calcifications (Fig. 1). Microscopic examination revealed complete replacement of ovarian tissue by sheets of neoplastic cells which were divided into small round nests by thin fibrous septae (Fig. 2). Cytologically, the tumor cells were large with pleomorphic, often folded nuclei, finely dispersed chromatin, and multiple nucleoli. There was an abundant amount of pale but distinct cytoplasm (Fig. 3). Mitoses were frequent, averaging 15 per 10 high power fields. Focal infiltration of the stroma by small lymphocytes was noted throughout. Paraffin immunoperoxidase studies showed strong positive marking of the neoplastic cells for CD45 (LCA) and CD20 (L-26). Scattered large tumor cells were also CD75 (LN-1) positive. Tumor cells were negative for T-cell markers CD3 and CD45RO (UCHL-1). No monoclonal population was demonstrated with staining for immunoglobulin heavy and light
137
0090-8258/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.
FIG. 1.
The cut surface of the ovarian lesion is lobulated with irregular nodules of soft, white tan tissue separated by depressed, scar-like bands of fibrous tissue.
FIG. 2. Medium power view of the lesion shows an organoid pattern with small rounded nests of tumor cells surrounded by thin fibrous septae (hematoxylin and eosin, 3200). 138
CASE REPORT
FIG. 3.
139
On high power view, the tumor cells exhibit large, often folded nuclei and abundant pale cytoplasm (hematoxylin and eosin, 3400).
chains. No immunoreactivity was noted with staining for the following markers: CD15 (Leu M1), CD30 (Ki-1), CD68, epithelial membrane antigen, cytokeratin, vimentin, S-100, and placental alkaline phosphatase. These findings were in favor of an intermediate grade malignant lymphoma, diffuse large cell type of B-cell lineage. The CD75 positivity suggested a possible follicular center cell origin. DISCUSSION POL is a rare disease and its very existence as an entity is questioned by many authors. Since the normal ovary is devoid of any lymphoid tissue, other sources such as lymphoid aggregates in the ovarian hilum, or chronic inflammatory cells in the ovary in response to ovarian lesions such as pelvic inflammatory disease and endometriosis, were cited as possible origins for POL [7]. More recent studies have found benign lymphoid aggregates in approximately half of normal ovaries [6]. It is hypothetically possible that on rare occasions these lymphoid aggregates may undergo malignant transformation, giving rise to a POL. In the past, the diagnosis of POL required only substantiation by histologic examination of the ovarian lesion. Many cases of POL reported in larger series were actually cases of malignant lymphoma with ovarian enlargement as the present-
ing symptom [2– 4]. All types of lymphomas were represented, mostly non-Hodgkin’s lymphoma with rare cases of Hodgkin’s disease included [2, 3]. Prognosis was generally poor with survival rates ranging from 7 to 38% [2– 4]. In 1976, Fox and Langley [8] proposed the following criteria for the diagnosis of POL: (i) At the time of diagnosis the lymphoma is clinically confined to the ovary and full investigation fails to reveal evidence of lymphoma elsewhere. A lymphoma can still be considered as ovarian primary if spread has occurred to immediately adjacent lymph nodes or if there has been direct spread to infiltrate immediately adjacent structures. (ii) The peripheral blood and bone marrow should not contain any abnormal cells. (iii) If further lymphomatous lesions occur at sites remote from the ovary then at least several months should have elapsed between the appearance of the ovarian and extraovarian lesions. If these stringent criteria are applied, POL becomes vanishingly rare. Skodras et al. in 1994 reviewed the literature and found 15 cases of ovarian lymphoma meeting the above described criteria [9]. The patients’ ages ranged from 2 to 63 years (mean age, 37.7 years). Nine patients were found to have diffuse large cell or mixed large and small cell lymphoma. Following treatment which consisted of ablative surgery with
140
ANH H. DAO
or without adjuvant chemotherapy, all 15 patients were alive with no evidence of disease except 1 who developed multiple local recurrences. Our patient met the criteria for POL and had a favorable outcome similar to those reviewed in this series. Monterroso et al. in 1993 reported 39 patients with nonHodgkin’s lymphoma who initially presented with ovarian enlargement [6]. On the basis of staging studies and clinical followup, only 4 of the patients were felt to have POL. Mean age of these four patients was 41.8 years. Three patients were cured of the disease following surgical excision and chemotherapy. All three had diffuse large cell lymphoma of B-cell lineage. The fourth patient died of lymphoma 4 years 6 months after diagnosis. She had diffuse mixed small and large cell lymphoma. From the observation of the 19 above cited patients and our personal case, POL appeared as a disease of young to middle age patients. Diffuse large cell or diffuse mixed large and small cell lymphomas were the most often diagnosed histologic types. The majority of the patients were staged as stage I by the Ann Arbor system. A favorable outcome was seen in most patients following ablative surgery with or without adjuvant chemotherapy, with only one death noted. One exception to the rarity of POL is seen in countries where Burkitt’s lymphoma is endemic. In these areas, ovarian involvement by Burkitt’s lymphoma accounted for almost half of malignant ovarian tumors in children [10]. Enlargement of one or both ovaries is the second most common form of presentation of Burkitt’s lymphoma after involvement of the jaw [10].
REFERENCES 1. Rosenberg SA, Diamond HD, Jaslowitz B, Craver LF: Lymphosarcoma: A review of 1269 cases. Medicine 40:31– 84, 1961 2. Chorlton I, Norris HJ, King FM: Malignant reticuloendothelial disease involving the ovary as a primary manifestation: A series of 19 lymphomas and 1 granulocytic sarcoma. Cancer 34:397– 407, 1974 3. Rotmensch J, Woodruff JD: Lymphoma of the ovary: Report of twenty new cases and update of previous series. Am J Obstet Gynecol 143:870 – 875, 1982 4. Osborne BM, Robboy SJ: Lymphomas or leukemia presenting as ovarian tumors: An analysis of 42 cases. Cancer 52:1933–1943, 1983 5. Fox H, Langley FA, Govan ADT, Shirley Hill A, Bennett MH: Malignant lymphoma presenting as an ovarian tumor: A clinicopathological analysis of 34 cases. Br J Obstet Gynecol 95:386 –390, 1988 6. Monterroso V, Jaffe ES, Merino MJ, Medeiros LJ: Malignant lymphomas involving the ovary: A clinicopathologic analysis of 39 cases. Am J Surg Pathol 17:154 –170, 1993 7. Woodruff JD, Noli Castilla RD, Novak ER: Lymphoma of the ovary—A study of 35 cases from the Ovarian Tumor Registry of the American Gynecological Society. Am J Obstet Gynecol 185:912–918, 1963 8. Fox H, Langley FA: Tumours of the Ovary, London, Heinemann, 1976, p 293 9. Skodras G, Fields V, Kragel PJ: Ovarian lymphoma and serous carcinoma of low malignant potential arising in the same ovary: A case report with literature review of 14 primary ovarian lymphomas. Arch Pathol Lab Med 118:647– 650, 1994 10. Scully RE: Tumors of the ovary and maldeveloped gonads, in Atlas of Tumor Pathology, 2nd series, Fasc. 16, Washington, DC, AFIP, 1979, pp 346 –347