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Obstetrics & Gynecology 2001;97:717-720
© 2001 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Primary Pelvic Non-Hodgkin’s Lymphoma

THERESE R. TRENHAILE, MD and MAUREEN A. KILLACKEY, MD

From the Department of Obstetrics and Gynecology and Division of Gynecologic Oncology, St. Luke’s-Roosevelt Hospital, New York, New York.

Address reprint requests to: Therese R. Trenhaile, MD Department of Obstetrics and Gynecology St. Luke’s-Roosevelt Hospital 1000 Tenth Avenue New York, NY 10019


   Abstract
Top
Abstract
Materials and Methods
 Results
 Discussion
 References
 
Objective: To describe five cases of primary pelvic non-Hodgkin’s lymphoma, a rare gynecologic malignancy.

Methods: The charts of five women with primary pelvic non-Hodgkin’s lymphoma were reviewed. Histologic classification was based on the Working Formulation, and staging was based on the Ann Arbor system. Disease status was monitored with physical examination and imaging studies.

Results: During a 10-month period, five women were diagnosed with primary pelvic non-Hodgkin’s lymphoma, including one parasacral, one uterine, one vaginal, and two ovarian tumors. Presentations included abdominal and pelvic pain, abdominal and pelvic mass, and abnormal vaginal bleeding. Treatment included combination chemotherapy, with or without radiation. Four patients were alive and disease free 20–33 months after therapy.

Conclusion: Primary pelvic non-Hodgkin’s lymphoma may present like other more common gynecologic cancers. It should be considered in the differential diagnosis of gynecologic malignancy.

Although advanced non-Hodgkin’s lymphoma frequently involves the female genital tract, primary pelvic non-Hodgkin’s lymphoma is rare. In the National Cancer Database for 1985–1988 and 1990–1993, only 1.5% of extranodal non-Hodgkin’s lymphoma originated in the female genital tract.1 The incidence of non-Hodgkin’s lymphoma has increased recently, however, with the rate of extranodal tumors increasing more than nodal tumors. In recent decades, primary pelvic non-Hodgkin’s lymphoma has been reported in the retroperitoneum, ovary, uterine corpus, uterine cervix, vagina, and vulva.2–10


   Materials and Methods
Top
Abstract
 Materials and Methods
Results
 Discussion
 References
 
During a 10-month period, five women were diagnosed with primary pelvic non-Hodgkin’s lymphoma. Chart reviews were conducted, and the cases are described. In all cases, biopsy or surgical excision made the diagnosis. Histologic classification was based upon the Working Formulation, and immunophenotyping was performed on all tumors. Staging was based on the Ann Arbor system. Treatment for all patients included combination chemotherapy with or without radiation. After treatment, disease status was assessed by physical examination and imaging studies.


   Results
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Abstract
 Materials and Methods
 Results
Discussion
 References
 
The first patient was a 66-year-old white woman who presented with increasing abdominal girth and post-menopausal bleeding. Pelvic examination revealed nodularity of the lateral vaginal wall and the posterior cervix with tumor prolapsing through the cervical os. She was referred for presumed cervical cancer. Biopsies of the vagina and cervix and curettings of the endocervix and endometrium showed high-grade diffuse large B cell non-Hodgkin’s lymphoma. After computed tomography (CT), stage IIE non-Hodgkin’s lymphoma of the uterus was diagnosed. The patient received chemotherapy and pelvic radiation, and remained disease free 25 months after therapy.

The second patient was a 54-year-old white woman who presented with pelvic pain and a nodular vaginal tumor. An ultrasound identified a posterior vaginal mass measuring 7.8 cm x 4.5 cm x 5.9 cm. She was referred for suspected vaginal cancer. A true cut biopsy of the rectovaginal septum revealed high-grade cleaved large B cell non-Hodgkin’s lymphoma of the vagina. Endocervical and endometrial curretings were normal. Stage IV disease was diagnosed after CT identified extensive pelvic lymphadenopathy. The patient received combination chemotherapy and pelvic radiation, and remained disease free 20 months after therapy.

The third patient was a 42-year-old white woman who presented with increasing abdominal girth and vague lower abdominal pain. On examination, the patient’s abdomen was distended, bulky, and bilateral adnexal masses were present. A CA-125 was 37 U/mL. The patient was referred for treatment of presumed ovarian cancer. An exploratory laparotomy was performed, revealing ascites, solid bilateral adnexal masses, and para-aortic lymphadenopathy. Surgical staging included a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathology showed high-grade diffuse large B cell non-Hodgkin’s lymphoma involving the ovaries, the parametria, the uterine serosa, and outer myometrium. Stage IV ovarian non-Hodgkin’s lymphoma was diagnosed, and combination chemotherapy was administered. The patient was disease free 20 months after therapy.

The fourth patient was a 68-year-old white woman who presented with abdominal pain, nausea, and vomiting. On examination, her abdomen was distended and diffusely tender. Computed tomography showed solid, bilateral adnexal masses measuring 5 and 4 cm, omental implants, ascites, and pelvic lymphadenopathy. She was referred for treatment of presumed ovarian cancer. An exploratory laparotomy was performed, revealing ascites, enlarged ovaries, and tumor nodules on the omentum, liver, small bowel, and diaphragm. A bilateral oophorectomy was performed, and multiple biopsies were taken. The pathology showed diffuse large B cell non-Hodgkin’s lymphoma involving the ovaries, peritoneum, omentum, and ascites. Stage IVB ovarian non-Hodgkin’s lymphoma was diagnosed. The patient had received four cycles of chemotherapy when she developed lymphomatous meningitis, a rare complication of this disease. Despite two courses of intrathecal chemotherapy, the patient died of cerebral infarction.

The last patient was a 25-year-old black woman who was 32 weeks pregnant when she developed cauda equina syndrome. Magnetic resonance imaging (MRI) revealed a 7.5-cm x 12.5-cm x 9.5-cm pelvic mass contiguous with the spinal cord and invading the iliac bones. The appearance of the tumor was consistent with a cordoma. A percutaneous, CT-guided biopsy, however, showed high-grade diffuse lymphoplasmacytoid non-Hodgkin’s lymphoma. Bilateral iliac bone marrow biopsies were positive. Because of the lack of any surrounding lymphadenopathy, the tumor was considered extranodal. The patient was diagnosed with stage IVB disease, and received combination chemotherapy and pelvic radiation. She remained disease free 33 months after therapy.

Overall, during a 10-month period, five women ranging in age from 25 to 68 years were diagnosed with primary pelvic non-Hodgkin’s lymphoma. Four, with presumed gynecologic cancer, were referred to a gynecologic oncologist. Two, who presented with findings suggestive of cervical and vaginal cancer, were found after biopsies to have uterine and vaginal lymphoma. Two other women underwent surgery for presumed ovarian cancer and were found to have ovarian lymphoma. Finally, one woman developed a pelvic lymphoma during pregnancy. All patients received combination chemotherapy. Specific regimens are provided in Table 1Go. Two patients also received radiation, and two patients underwent surgical cytoreduction. One patient died during treatment, and four patients were alive and disease free 20–33 months after treatment.


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  		Table 1. Characteristics, Treatment, and Response of Primary Pelvic Non-Hodgkin’s Lymphoma
 

   Discussion
Top
Abstract
 Materials and Methods
 Results
 Discussion
References
 
Primary pelvic non-Hodgkin’s lymphoma is a rare malignancy that has been reported in the retroperitoneum, ovary, uterine corpus, uterine cervix, vagina, and vulva.2–10 Freeman et al2 reviewed 1467 cases of extranodal non-Hodgkin’s lymphoma from the National Cancer Institute for 1950–1964. Only 16 cases of extranodal non-Hodgkin’s lymphoma originated in the female genital tract, including eight uterine tumors and two ovarian tumors. Crisp et al3 reviewed cases from three hospitals for 1969–1979 and identified only six cases of primary pelvic non-Hodgkin’s lymphoma, including one ovarian, one uterine, one cervical, and three retroperitoneal tumors.

The incidence of non-Hodgkin’s lymphoma, especially extranodal lymphoma, has increased in recent decades. The etiology of the increase has been hypothesized to include infectious agents such as the human immunodeficiency virus (HIV) immunosuppressive therapies, environmental exposures to pesticides and pollutants, and improved diagnostic techniques. Moreover, extranodal non-Hodgkin’s lymphoma is characteristic of AIDS-related lymphoma. None of our five patients, however, was HIV positive.

The presentation of primary pelvic lymphoma may include findings suggestive of gynecologic malignancy. Three series of vaginal, cervical, and uterine non-Hodgkin’s lymphoma are presented in Table 2Go.4–6 The most common presentations in these series were abnormal vaginal bleeding, pelvic pain, and pelvic mass. Similarly, ovarian lymphoma may mimic epithelial ovarian cancer, with common presentations including abdominal pain, abdominal distention, nausea, vomiting, and abdominal or pelvic mass.7–10


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  		Table 2. Outcome of Primary Pelvic Non-Hodgkin’s Lymphoma in Seven Case Series
 
In 1974, Chorlton et al7 reviewed the files at the Armed Forces Institute of Pathology and identified 19 primary ovarian lymphomas. Regardless of stage, 80% of patients presented with a pelvic mass. In 1983, Osborne and Robboy8 found that 65% of primary ovarian lymphoma presented with pelvic pain or mass. In the four series of ovarian lymphoma in Table 2Go, treatment almost always included surgery.7–10 However, no series directly addressed the frequency with which ovarian lymphoma was suspected preoperatively. One potentially useful and distinctive characteristic of ovarian lymphoma is its propensity to be bilateral. In the series in Table 2Go, ovarian lymphoma was bilateral in 41–71% of patients.

In general, the prognosis for extranodal lymphoma is worse than for nodal lymphoma. In part, this may be related to substandard treatment. The treatment of non-Hodgkin’s lymphoma usually involves various combinations of chemotherapy with or without radiation. According to the National Cancer Database, however, only 46% of extranodal lymphoma were treated with any chemotherapy, compared to 70% of nodal lymphoma. In addition, the diagnosis of extranodal lymphoma may be inaccurate or delayed. This may be especially true for pelvic lymphoma because it often presents with findings suggestive of more common gynecologic cancers. Frequent misdiagnoses in cervical, vaginal, and uterine lymphoma include sarcoma, poorly differentiated carcinoma, and chronic inflammation.7 Frequent misdiagnoses in ovarian lymphoma include granulosa cell tumors, dysgerminoma, and metastatic cancer.5

Although primary pelvic lymphoma is rare, the disease may be encountered more frequently as the incidence of extranodal non-Hodgkin’s disease increases. Moreover, pelvic lymphoma may present with findings suggestive of more common gynecologic cancers. Therefore, it is important for gynecologists to be aware of this disease, and to include pelvic lymphoma in the differential diagnosis of gynecologic cancer.


   Footnotes
 
Presented in the poster session at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in Philadelphia, Pennsylvania, May 15–19, 1999.

PII S0029-7844(00)01225-4

Received August 28, 2000. Received in revised form November 28, 2000. Accepted December 15, 2000.


   References
Top
Abstract
 Materials and Methods
 Results
 Discussion
 References
 
1. Glass AG, Karnell LH, Menck HR. The national cancer database report on non-Hodgkin’s lymphoma. Cancer 1997;80:2311–20.[Medline]

2. Freeman C, Berg JW, Cutler S. Occurrence and prognosis of extranodal lymphomas. Cancer 1972;29:252–60.[Medline]

3. Crisp WE, Surwit EA, Grogan TM, Freedman MF. Malignant pelvic lymphoma. Am J Obstet Gynecol 1982;143:69–73.[Medline]

4. Harris NL, Scully RE. Malignant lymphoma and granulocytic sarcoma of the uterus and vagina. Cancer 1984;53:2530–45.[Medline]

5. Stroh EL, Pelayo CB, Cox JD, Fuller LM, Cabanillas FF. Treatment of patients with lymphomas of the uterus or cervix with combination chemotherapy and radiation. Cancer 1995;75:2392–9.[Medline]

6. Perren T, Farrant M, McCarthy K, Harper P, Wiltshaw E. Lymphomas of the cervix and upper vagina: A report of five cases and a review of the literature. Gyn Oncol 1992;44:87–95.[Medline]

7. Chorlton I, Norris J, King FM. Malignant reticuloendothelial disease involving the ovary as a primary manifestation. Cancer 1974;34:397–407.[Medline]

8. Osborne BM, Robboy ST. Lymphomas or leukemia presenting as ovarian tumors. Cancer 1983;52:1933–43.[Medline]

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

10. Fox H, Langley FA, Govan ADT, Hill AS, Bennett MH. Malignant lymphoma presenting as an ovarian tumor: A clinicopathological analysis of 34 cases. Br J Obstet Gynecol 1988;95:386–90.[Medline]





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