Case Presentation - Spring, 2005

NOTE: The diagnosis and analysis for this case study were provided by an independent physician. All conclusions and opinions are those of the physician and not Hologic, Inc.

History: 70 year old, female, post menopausal, cervical lesion, pelvic mass, history of lymphoma.

Specimen Type: Cervical ThinPrep® Pap Test

Case provided by: Bruce Dziura, MD of New England Pathology Associates Cytopathology Service, Springfield, MA.

Cytologic diagnosis: Non-Hodgkin's Lymphoma

Histologic diagnosis: Lymphoma, Diffuse Large cell type.

Diagnosing lymphoma of the female genital tract by cytology is very challenging, both because of its rarity, and since the disease is most likely submucosal in the cervix or vagina. Unless ulceration of the epithelium occurs, lymphoma cells are unlikely to be present in cervical smears. Due to the fact that ulceration of the mucosal surface is rare, the sampling of tumor cells even in accessible areas like the cervix and the vagina is limited.

Similar to other non-Hodgkin's lymphomas, diffuse large cell lymphoma displays a monotonous tumor cell population. Tumor cells have moderate pale cytoplasm. The nuclei are oval or cleaved with vesicular chromatin, 1 to 3 small peripheral nucleoli, and thin nuclear membranes. The nuclei are larger than the nuclei of reactive macrophages. Necrosis and evidence of increased mitotic activity are often present. In immunoblastic diffuse large cell lymphoma the nuclei of the large cells may be round with thick nuclear membranes, and single large centrally located nucleoli, resembling immunoblasts.

The occurrence of non-Hodgkin's lymphoma is increasing in the United States. More than 35,000 per year are now diagnosed. Lymphoma of the female genital tract may present itself either as a primary tumor or more commonly as systemic disease. Malignant lymphoma involving the uterus typically occurs between 20 to 80 years old, with a mean age of 40. The most common symptom is vaginal bleeding. Other symptoms that may occur are vaginal discharge, dyspareunia and pelvic pain. Lymphomas of the cervix usually present with diffuse enlargement of the cervix, resulting in a "barrel-shaped cervix".

More specifically, diffuse large cell lymphoma makes up 30 to 40% of all adult non-Hodgkin's lymphomas. This type of lymphoma can affect any age group but occurs more in older people. The median age is the mid-60s. Patients with diffuse large cell lymphoma present with single or multiple, rapidly growing masses in nodal or extranodal sites; up to 40% of these masses are extranodal.

The differential diagnosis includes benign lymphoid proliferations, e.g. follicular cervicitis, and poorly differentiated malignancies, such as malignant melanoma, undifferentiated carcinoma and certain adenocarcinomas such as renal, gastric or lobular breast.

Treatment and Prognosis
Treatment of lymphoma depends on the type of lymphoma and on the extent of the disease in the body. With diffuse large cell lymphoma the most common course of treatment is combination chemotherapy. The regimen usually consists of 4 drugs referred to as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone).

The prognosis of patients with diffuse large cell lymphoma depends on age and stage of disease. Effective combination chemotherapy treatments can prolong the survival rate from 30% to 60% even in those individuals with advanced disease. Those patients who are less advanced in the progression of their disease have an 80% chance of long-term survival. Unfortunately, even after a complete remission with an aggressive combination chemotherapy regime, 30% to 50% of patients relapse. Relapse usually occurs 2 years after completion of treatment. If after 2 years there is no relapse, the patient has a 70% to 90% probability of being cured.

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