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Journal of Clinical Oncology, Vol 26, No 3 (January 20), 2008: pp. 503-504 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.3784
Mucosa-Associated Lymphoid Tissue Lymphoma of the CervixDepartment of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA A 56-year-old woman presented to her gynecologist complaining of vaginal spotting, for which endometrial and cervical biopsies were performed and found to be negative for malignancy. Pelvic ultrasound showed a mass adjacent to the cervix with magnetic resonance imaging showing a 3.1 x 4.0 x 8.0 cm mass posterior to the cervix, which appeared to be originating from the cervix and had cystic spaces suggestive of a cervical fibroid with cystic degeneration (Fig 1). The patient underwent total abdominal hysterectomy with bilateral salpingo-oophrectomy. A large cervical mass with a smooth contour was found intraoperatively.
The histologic sections of the cervix and vaginal cuff demonstrated a variably dense, polymorphous lymphoid infiltrate that in some areas appeared somewhat spindled (Fig 2). There were some small cysts present. Most of the lymphoid cells were relatively small and some had angulated nuclei. There were irregular paler areas suggesting infiltration of germinal centers by the smaller lymphocytes (Fig 3). A large panel of immunohistochemical stains showed many admixed CD20+ B-cells (Fig 4) and CD3+ T-cells. The B-cells were CD5 and CD10 negative. The areas suggestive of germinal centers had bcl-6 positivity and showed less bcl-2 expression than the remainder of the infiltrate. Nuclear bcl-10 expression could not be documented. A stain for Helicobacter pylori was negative. Polymerase chain reaction studies performed on DNA from paraffin-embedded material showed clonal rearrangement of the immunoglobulin heavy chain gene (in a polyclonal background), but not of the T-cell receptor  chain gene. These findings led to the conclusion that this was a definite small B-cell lymphoma, most likely one of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.
Due to positive surgical margins, she was treated with 3D-conformal radiation therapy to the pelvic area using 18 MV photons to 30.6 Gy in 17 fractions. She also received four weekly infusions of rituximab (anti-CD20 monoclonal antibody). She tolerated treatment well and finished without complications. At 28 months follow-up, she was still asymptomatic and free of disease. Primary lymphoma of the cervix is a rare malignancy with follicular and diffuse large-cell lymphoma being the most common types.1 MALT lymphoma is a distinctive extranodal marginal zone B-cell lymphoma,2 which is most commonly seen in the GI tract (an estimated 60% to 70% of MALT lymphomas occur inside the GI tract), followed by the orbit, salivary glands, lung, and skin.3,4 Less commonly it is seen in the thyroid, breast, liver, bladder, and other tissues. MALT lymphomas typically occur in the setting of infection, such as with H pylori infection in the stomach, or in the setting of autoimmune disorders, such as with Sjogren's syndrome in the salivary glands.5 It has been speculated that the cervix, with its endocervical columnar epithelium and acidic mucous layer, might provide a suitable environment for H pylori, but studies have failed to detect its presence in the cervix of patients with cervicitis, and our stain for it was negative.6 Diagnosis can be difficult because of coexistence of an inflammatory lymphoid infiltrate as seen in this patient. MALT lymphoma is often highly responsive to radiotherapy, with doses of 25 Gy to 35 Gy leading to local control rates of up to 95%.7,8 Relapse may occur in up to 40% of patients, most often distant from the original site.4,9 While randomized trials of CD20 antibody therapy for nongastrointestinal MALT lymphomas have not been conducted, its use has been reported in numerous cases, especially for tumors refractory to other treatment.5,10 In a study of 35 patients, 20 of whom had nongastric MALT lymphoma, CD20 antibody therapy had a 73% response rate.11 There has been only one previous case reported of a typical low-grade MALT lymphoma of the cervix.12 Interestingly, the preoperative diagnosis in that case was also fibroid tumor with lymphoma being confirmed in the final surgical specimen. Clinicians should be aware that seemingly benign cervical masses have the potential to be MALT lymphomas that can be effectively treated with local surgery and/or radiation. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Clement PB: Miscellaneous primary tumors and metastatic tumors of the uterine cervix. Semin Diagn Pathol 7:228-248, 1990[Medline] 2. Tsang RW, Gospodarowicz MK: Low-grade non-hodgkin lymphomas. Semin Radiat Oncol 17:198-205, 2007[CrossRef][Medline] 3. Isaacson PG: Update on MALT lymphomas. Best Pract Res Clin Haematol 18:57-68, 2005[Medline] 4. Zinzani PL, Magagnoli M, Galieni P, et al: Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: Analysis of 75 patients. J Clin Oncol 17:1254, 1999 5. Ferreri AJ, Zucca E: Marginal-zone lymphoma. Crit Rev Oncol Hematol 63:245-256, 2007[CrossRef][Medline] 6. Yildirim B, Acikbas I, Sengul M, et al: Is Helicobacter pylori a pathogenic agent of the cervix uteri? Gynecol Obstet Invest 61:160-163, 2006[CrossRef][Medline] 7. Zucca E, Conconi A, Pedrinis E, et al: Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood 101:2489-2495, 2003 8. Hitchcock S, Ng AK, Fisher DC, et al: Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys 52:1058-1066, 2002[CrossRef][Medline] 9. Thieblemont C, Bastion Y, Berger F, et al: Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behavior: Analysis of 108 patients. J Clin Oncol 15:1624-1630, 1997[Abstract] 10. Raderer M, Wohrer S, Streubel B, et al: Activity of rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone in patients with relapsed MALT lymphoma. Oncology 70:411-417, 2006[CrossRef][Medline] 11. Conconi A, Martinelli G, Thieblemont C, et al: Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood 102:2741-2745, 2003 12. Pelstring RJ, Essell JH, Kurtin PJ, et al: Diversity of organ site involvement among malignant lymphomas of mucosa-associated tissues. Am J Clin Pathol 96:738-745, 1991[Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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