Conservative Management in Primary Vaginal Lymphoma: Role of Chemotherapy

Introduction

Lymphomas account for 3.5% of all malignant neoplasms in females. Non-Hodgkin's lymphomas (NHLs) represent 70%–80% of all lymphomas. Usually these cancers occur in the lymph nodes whereas extranodal NHLs account for 20%–40% of all NHLs. Primary genital tract lymphomas are very rare neoplasms accounting for < 0.5% of all genital cancers. The most common genital localizations are the cervix, uterine corpus, and ovary, whereas primary lymphoma of the vagina is unusual. A case of primary NHL of the vagina treated successfully with chemotherapy alone, is described. The associated literature is also discussed.

Case

A 34-year-old nulligravida woman presented with a 3-month history of irregular vaginal bleeding and pelvic pain. The physical examination did not reveal lymphadenopathy or splenomegaly. A vaginal examination revealed a 30-mm hemorrhagic mass confined to the vagina. Pelvic MRI showed this mass, which extended up to the bladder wall. The biopsy of the lesion demonstrated a diffuse lymphoma, and immunohistochemical staining demonstrated that the tumor was a large B-cell type NHL with cluster differentiation (CD) 20+. A complete staging workup did not demonstrate any additional sites of disease; especially, bone marrow biopsies were negative for lymphoma. In conformity with the Ann Arbor staging system for extranodal lymphomas, the tumor was considered a stage IE. The patient was treated with 06 cycles of systemic chemotherapy including rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP). This chemotherapy was well tolerated and completed without adverse effects.

Results

A complete clinical and histological response were obtained and after 2 years of follow-up, the patient is well without any evidence of disease.

Discussion

Primitive lymphomas are unexpected disease in the female genital tract. They are most commonly localized in the ovaries (49%), uterus (29%) and Fallopian tubes (11%). ¹ Primary vaginal lymphomas are very rare (Chorlton et al. reported an incidence of 1 in 2,375 cases ² ). The age distribution shows a median < 50 years. Clinical symptoms usually include vaginal bleeding (70%), perineal discomfort (40%), and persistent vaginal discharge (20%), ³ and dyspareunia or urinary frequency may be present. Fever, night sweats, and weight loss are unusual symptoms.

Multiple and deep biopsies are necessary for the diagnosis because the lack of cervical ulceration causes the usual negativity of cervical cytology and colposcopic biopsy. ⁴ Immunohistochemical analyses and electron microscopy are valuable techniques for confirming the histological diagnosis. ⁵ The most common histological subtype is diffuse large B-cell lymphoma.

Differential diagnosis for vaginal NHL is basically the same for all gynecologic sites and includes other hematopoietic lesions (granulocytic sarcoma, Langerhan's cell histiocytosis), carcinoma, malignant mixed Mullerian tumor, epithelioid leiomyosarcoma, endometrial stromal tumors including endometrial stromal sarcoma, melanoma, and extra-osseus Ewing's sarcoma/primitive neuroectodermal tumor. ⁶ Also, chronic inflammation may lead to the misdiagnosis of NHL in a limited specimen.

Abdomino-pelvic computer tomography (CT) or magnetic resonance imaging (MRI) are useful for tumor staging.

The mainstay of the treatment for primary genital lymphomas is radiotherapy alone, or in combination with surgery and/or chemotherapy. ⁷ Radiotherapy is recommended as the first line treatment for localized disease because of the high response rates and low morbidity. ⁵

Chemotherapy as a first line treatment is controversial. Few cases of complete remission were reported in the literature after chemotherapy alone (CHOP, MACOP-B or CEOP).^8–10 The role of chemotherapy could be to: 1) reduce the neoplastic mass; 2) save the use of radiotherapy for local relapse; 3) reduce the radiotherapy-related local toxicity, especially in young women; and 4) preserve the endocrine potential. The significant disadvantage of radiotherapy is the infertility in young women caused by destruction of reproductive organs; therefore, cytotoxic chemotherapy may represent an alternative for these patients for whom preservation of fertility is relevant, and salvage radiotherapy has been shown to be successful if the tumor does not respond to the cytotoxic chemotherapy. ¹¹ Vaginal lymphoma's prognosis appears to be worse than the prognosis for nodal NHL because of the delayed diagnosis, ⁴ but it is relatively good when compared to the prognosis for ovarian lymphoma, with a 5-year survival rate ranging from 80 to 90%. ⁶

Conclusions

Because of the low incidence of primary NHL of the vagina, the optimal therapy is still to define. At least for young patients with primary large B-cell NHL of the lower female genital tract who desire fertility preservation, chemotherapy alone may be the treatment of choice with a possible complete remission, and radiotherapy could be restricted to the role of second line treatment. However this suggestion needs to be validated by prospective studies.