Case Report

A case of malignant lymphoma of the ovary manifestinglike an advanced ovarian cancer

Takashi Yamada,a,* Noriaki Iwao,b Hajime Kasamatsu,c and Hiroshi Moria

a Department of Pathology, Osaka Medical College, Osaka, Japanb 1st Department of Internal Medicine, Osaka Medical College, Osaka, Japan

c Department of Obstetrics and Gynecology, Hirakata City Hospital, Osaka, Japan

Received 23 September 2002

Abstract

Background. In recent years, true primary ovarian lymphoma has been considered to carry a favorable prognosis, although most studiesof supposedly primary ovarian lymphoma have reported a poor outcome.

Case. A 47-year-old woman presented with signs and symptoms suggestive of an advanced ovarian cancer. Ultrasonography and magneticresonance imaging revealed bilateral abdominal tumors, each measuring 10 cm in diameter, thickened omentum, and a large amount of ascitic fluid,but no enlarged lymph nodes. The diagnosis of malignant lymphoma was established from the biopsy specimen after exploratory laparotomy. Sixyears following chemotherapy, the patient is alive and disease free without additional surgery.

Conclusion. The prognosis of ovarian lymphoma was evaluated according to clinical stage, modality of onset, histologic type, andphenotype. It remains controversial whether this case can be considered truly primary ovarian lymphoma and not merely a localized initialmanifestation of a generalized disease. But if this case of advanced ovarian lymphoma were not primary, it could still be managedsuccessfully with chemotherapy appropriate for the specific histology.© 2003 Elsevier Science (USA). All rights reserved.

Keywords: Malignant lymphoma; Ovary

Introduction

Involvement of the ovary by malignant lymphoma is wellknown as a late manifestation of disseminated nodal disease.But primary ovarian lymphoma and secondary ovarian in-volvement as initial manifestation of lymphoma are unusual[1–10]. We present here a case of ovarian lymphoma, mani-festing like an advanced ovarian cancer, successfully managedby chemotherapy without resection surgery.

Case report

A 47-year-old woman, gravida 3, para 2, visited ourhospital with complaints of abdominal distension for a

month. Her height was 155 cm and her weight was 45 kg,but had increased by 2 kg in 5 months. A physical exami-nation revealed that the abdominal wall was elevated bytumor and ascitic fluid. Ultrasonography and magnetic res-onance imaging (MRI) revealed bilateral abdominal tumors,each measuring 10 cm in diameter, uterine myoma measur-ing 5 cm in diameter, thickened omentum, and a largeamount of ascitic fluid, but no enlarged lymph nodes (Fig.1). A metastatic ovarian tumor was suspected because of thebilateral solid tumors and positive cytology of the asciticfluid, but no primary lesion was found by any other exam-ination. The serum tumor markers were positive for CA125, 2,448 U/ml (normal range, �35 U/ml); lactic dehydro-genase (LDH), 1,323 IU/L (180–460 IU/L); and negativefor CA 19-9, 26.1 U/ml (�37 U/ml); carcinoembryonicantigen, 1.0 ng/ml (�5 ng/ml); and �-feto-protein, 2.6ng/ml (�20 ng/ml).

As the discomfort was getting worse, the patient wasexplored with an abdominal vertical midline incision. The

* Corresponding author. Department of Pathology, Osaka Medical Col-lege, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan. Fax: �81-726-84-6514.

E-mail address: yamatakashi@mub.biglobe.ne.jp (T. Yamada).

R

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peritoneum contained 2,500 ml of serous ascitic fluid, two10-cm multinodular masses with elongated Fallopian tubes,and diffuse nodular lesions on the surface of the peritoneum.The omentum was diffusely involved by the tumor, withchanges showing tumor caking (Fig. 2). Tumors were ad-herent to adjacent organs and could not to be removed. Thebiopsy specimen was taken from the peritoneum lesionabove the bladder. The liver and diaphragm were not in-volved macroscopically.

The histology of the frozen section was suspicious forundifferentiated carcinoma. The peritoneal cavity waswashed thoroughly with physiological saline solution.Drainage tubes (5 mm in diameter) for the intraperitonealadministration of anticancer drugs were fixed in the perito-neal cavity through the abdominal wall.

A mixture of 100 mg of cisplatin, 400 mg of etoposide,and 1,000 ml of physiological saline solution was adminis-tered into the peritoneal cavity during 15 min, 2 h aftersurgery for the prevention of reaccumulation of the asciticfluid. The intraperitoneal administration was repeated 2

weeks later, and drainage tubes were then extracted. Ultra-sonography revealed that the tumor size was clearly re-duced, and the ascitic fluid had disappeared. The size of theuterine myoma was not changed.

The definite pathologic diagnosis after immunostaining wasdiffuse, large-cell malignant lymphoma of B-cell lineage.Workup for the lymphoma after surgery included repeatedabdominal and thoracic computed tomographic scans, bonescintigraphy, systemic gallium scintigraphy and bone marrowbiopsies, and aspirations. The findings from all these studiesshowed no other site involved. The clinical stage was IVaccording to the Ann Arbor system and IIIc according to theInternational Federation of Gynecology and Obstetrics.

The patient later received an additional CHOP regimen(cyclophosphamide, 750 mg/m2 day 1; doxorubicin, 50mg/m2 day 1; vincristine, 1.4 mg/m2 day 1; prednisone, 50mg/m2 days 1–5) 8 times, intravenously. The accumulationof ascitic fluid stopped and the serum CA 125 level gradu-ally decreased to normal. At the end of the chemotherapy,MRI showed that the ovarian tumors and omental tumor had

Fig. 1. A pelvic magnetic resonance imaging shows bilateral abdominal tumors and thickened omentum (arrow).

216 T. Yamada et al. / Gynecologic Oncology 90 (2003) 215–219

disappeared and the uterine myoma was reduced to 2 cm indiameter. The patient is alive without disease 72 monthsafter the first chemotherapy without additional surgery.

In the cytology of the ascitic fluid, the tumor cells werelarge noncleaved with pleomorphic nuclei, finely dispersednuclear chromatin, and multiple nucleoli (Fig. 3).

Microscopic examination revealed the diffuse growthpattern of tumor cells with large vesicular nuclei and prom-inent nucleoli (Fig. 4).

Paraffin immunostaining studies showed strong positiv-ity of the neoplastic cells for CD20 (L-26) and CD45RA(MB-1). Tumor cells were negative for the T-cell markersCD43 (MT-1) and CD45RO (UCHL-1). No immunoreac-tivity was noted with staining for the following markers:synaptophysin, glial fibrillary acidic protein, epithelialmembrane antigen, cytokeratin, and vimentin. These find-ings were in favor of diffuse large-cell malignant lymphomaof B-cell lineage.

Discussion

Malignant lymphomas frequently involve the ovaries atnecropsy or autopsy with a frequency at 7–26% [1], but less

than 1% of patients with malignant lymphoma initiallypresent with ovarian enlargement [2]. Single cases or shortseries of malignant lymphoma affecting the ovary have beenreported [1–10]. The majority of those cases were of B-cellphenotype or were not examined immunophenotypically.

Primary ovarian lymphoma is extremely rare, accountingfor 0.5% of all non-Hodgkin’s lymphoma and 1.5% of allovarian neoplasms [7]. The occurrence of lymphomas pri-marily in the ovary has been debated. Earlier studies havesuggested that there is no proof that lymphomas originate inthe ovary since no lymphoid tissue is normally found in theovaries. Monterroso et al. [2] reported that they identifiedsmall numbers of lymphocytes in the ovaries, surroundingblood vessels in the hilus, and within or surrounding corporalutea in 54% of lymphoma patients with ovarian involve-ment. Their findings provided support for the hypothesisthat malignant lymphomas may arise in the ovary. Further-more, the scarcity of lymphoid tissue in “normal” ovariesalso may explain the rarity of this occurrence.

Fox et al. [4] proposed the following criteria for thediagnosis of a primary ovarian lymphoma:

1. At the time of the diagnosis the lymphoma is clini-cally confined to the ovary and a full investigation

Fig. 2. Bilateral multinodular masses and a part of tumor-caking omentum (arrow) were seen in the lower abdominal cavity.

217T. Yamada et al. / Gynecologic Oncology 90 (2003) 215–219

fails to reveal evidence of lymphoma elsewhere. Alymphoma can still, however, be considered as pri-mary if spread has occurred to immediately adjacentlymph nodes or if there has been direct spread toinfiltrate immediately adjacent structures.

2. The peripheral blood and bone marrow should notcontain any abnormal cells.

3. If further lymphomatous lesions occur at sites remotefrom the ovary then at least several months shouldhave elapsed between the appearance of the ovarianand extra-ovarian lesions.

If these stringent criteria are applied, primary ovarian lym-phoma becomes vanishingly rare and only 17 cases havebeen reported in the literature [5,8,10]. True primary ovar-ian lymphoma is considered to carry a favorable prognosis[5,8], although most studies have reported a poor outcome[2]. The reason may be that the majority of the primaryovarian lymphoma was staged as stage I by the Ann Arborsystem.

The question of whether some ovarian lymphomas canbe considered truly primary in the ovary and not merely alocalized initial manifestation of a generalized disease can-not be answered yet.

The bilateral ovarian involvement, peritoneal implant,

and omental involvement at the time of surgery may be usedas an argument against a primary ovarian disease in ourpatient. Nevertheless, although ovaries, omentum, and peri-toneum were markedly involved with malignant lymphoma,no other extra-abdominal lesions could be detected at thetime of surgery and after surgery by various investigativetechniques. Exploratory surgery followed by systemic che-motherapy cured the patient, and no recurrence could bedetected during a long follow-up of more than 6 years.Thus, the question of whether our patient represents a caseof a very rare primary ovarian malignant lymphoma ormerely represents a case of bilateral ovarian initial mani-festation of an occult generalized disease that had beencured by systemic chemotherapy cannot be answered.

Most of the reported cases underwent surgery, but de-bulking of the tumor was not considered to be related togood prognosis. The prognosis of ovarian lymphoma wasevaluated according to clinical stage, modality of onset (anacute onset having a negative prognostic value), and histo-logic type and phenotype, with B-cell tumors being associ-ated with longer survivals [3]. Nakamura et al. [9] reportedtwo cases of peripheral T/natural killer-cell lymphoma in-volving the ovary with poor prognosis. As a result ofprogress in defining techniques and in the availability of

Fig. 3. Cytology of the ascitic fluid. The tumor cells exhibit the cellular pleomorphism with finely dispersed nuclear chromatin and multiple nucleoli(Papanicolaou stain, original magnification �800).

218 T. Yamada et al. / Gynecologic Oncology 90 (2003) 215–219

monoclonal antibodies to cytotoxic molecules on paraffinsections, various kinds of lymphomas have been increas-ingly recognized. The histologic type is probably the mostimportant prognostic factor [6].

We concluded, with reference to a previous report, thatpatients with some type of ovarian lymphoma appear to be ableto expect a good prognosis. We therefore recommend that theyshould be treated with curative intent with combination che-motherapy regimens appropriate for their specific histology,even in the case of advanced ovarian lymphoma.

References

[1] Chorlton I, Norris HJ, King FM. Malignant reticuloendothelial dis-ease involving the ovary as a primary manifestation: a series of 19lymphomas and 1 granulocytic sarcoma. Cancer 1974;34:397–407.

[2] Monterroso V, Jaffe ES, Merino MJ, Medeiros LJ. Malignant lym-phomas involving the ovary: a clinicopathologic analysis of 39 cases.Am J Surg Pathol 1993;17:154–70.

[3] Linden MD, Tubbs RR, Fishleder AJ, Hart WR. Immunotypic andgenotypic characterization of non-Hodgkin’s lymphomas of theovary. Am J Clin Pathol 1988;90:156–62.

[4] Fox H, Langley FA, Govan ADT, Hill AS, Bennett MH. Malignantlymphoma presenting as an ovarian tumor: a clinicopathologicalanalysis of 34 cases. Br J Obstet Gynaecol 1988;95:386–90.

[5] Skodras G, Fields V, Kragel PJ. Ovarian lymphoma and serouscarcinoma of low malignant potential arising in the same ovary: acase report with literature review of 14 primary ovarian lymphomas.Arch Pathol Lab Med 1994;118:647–50.

[6] Breda E, Pauselli F, Temperilli L. Primary ovarian lymphoma withliver metastases: report of one case. Eur J Gynaecol Oncol 1996;17:53–4.

[7] Dimopoulos MA, Daliani D, Pugh W, Gershenson D, Cabanillas F,Sarris AH. Primary ovarian non-Hodgkin’s lymphoma: outcome aftertreatment with combination chemotherapy. Gynecol Oncol 1997;64:446–50.

[8] Dao AH. Malignant lymphoma of the ovary: report of a case suc-cessfully managed with surgery and chemotherapy. Gynecol Oncol1998;70:137–40.

[9] Nakamura S, Kato M, Ichimura K, Yatabe Y, Kagami Y, Suzuki R,et al. Peripheral T/natural killer-cell lymphoma involving the femalegenital tract: a clinicopathologic study of 5 cases. Int J Hematol2001;73:108–14.

[10] Mansouri H, Sifat H, Gaye M, Hassouni K, Mansouri A, El GueddariB. Primary malignant lymphoma of the ovary: an unusual presenta-tion of a rare disease. Eur J Gynaecol Oncol 2000;21:616–8.

Fig. 4. Medium-power view of the lesion shows the diffuse growth pattern of tumor cells with large vesicular nuclei and prominent nucleoli (hematoxylinand eosin stain, original magnification �200).

219T. Yamada et al. / Gynecologic Oncology 90 (2003) 215–219