Interfollicular small lymphocytic lymphoma: the diagnostic significance of pseudofollicles

The pathologic, immunologic, and clinical features of 25 cases of interfollicular (IF) small lymphocytic lymphoma (SLL) characterized by pseudofollicles (PFs) in the IF region of the lymph nodes and by multiple reactive follicles (RFs) were examined. IFSLL is characterized morphologically by variable numbers and sizes of prolymphocytes (nuclei showing one centrally located prominent nucleolus) in the PFs and by small round lymphocytes in the IF region. The lymph nodes in our cases had multiple RFs (100%) and patent or partially patent sinuses (72%), with moderate expansion of the IF region (48%) and typically absent or minimal perinodal infiltration (48%). In 48% of the cases, the PFs surrounded the RFs, producing a pseudo-mantle zone pattern. Immunologic study showed the medium and large prolymphocytes to be mildly LN 1- and LN 2-positive, whereas the small prolymphocytes and lymphocytes were LN 1-negative and moderately LN 2-positive. Few cells in the IF region stained with UCHL-1 antibody. These data indicate the marked preponderance of the non-follicular center cell type of B cells in the IF areas. In all 11 cases tested, a monoclonal B cell population was found. The mean age of the patients was 62 years, with a male to female ratio of 1:1.7. B symptoms were present in 20% of the patients. Nineteen percent of the patients had clinical stage I or II disease, whereas 81% had stage IV disease. The median absolute lymphocyte count was 3,239 X 10(6), with a range of 767 to 13,770 X 10(6) cells/L. In six cases, the lymphocyte count was above 4,000 X 10(6), and in no case was it more than 15,000 X 10(6). It was difficult to distinguish these cases of IFSLL from lymphadenitis and other non-Hodgkin's lymphomas because it was difficult to recognize the subtle PF pattern in the presence of a partially preserved lymph node architecture. Because of the partially retained lymph node architecture and the expansion of the IF region by PFs, this lymphoma is thought to originate from the IF small B lymphocytes, which displayed an in situ growth pattern. Moreover, because of the predominant disease in the lymph nodes and the similarity of features in PFs and follicles, we conclude that IFSLL is a disease that is primary to the lymph nodes. IFSLL should be distinguished from mantle zone lymphoma and chronic lymphocytic leukemia.