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Immunophenotyping of lymphomas using paraffin-embedded lymphoid tissue, not previously distorted by frozen section, is useful in identifying the large neoplastic B cells that may be in the minority in T-cell rich B-cell lymphoma (TCRBCL). Even in cases in which frozen tissue sections are available, the improved morphology in unfrozen sections allows the proper classification of these lymphomas as large cell and identifies their B-cell lineage, which is important for clinical therapeutic studies. Seven cases initially believed to be diffuse mixed cell lymphoma of possible peripheral T-cell lineage showed the large cells to be immunoreactive with L-26 (pan B-cell marker) with the majority of smaller lymphocytes immunoreactive for UCHL-1 and Leu-22 (pan T-cell markers). K/lambda immunostaining on frozen sections was equivocal. In these cases, the diagnosis of large-cell lymphoma of B-cell lineage was confirmed by detection of immunoglobulin heavy- (all seven cases) and light- (six of seven cases) chain gene rearrangements, with germ-line configuration of the T-cell receptor beta-chain gene (all cases). Some cases of TCRBCL may not show detectable rearrangement of the immunoglobulin genes because of the low concentration of neoplastic cells in the samples submitted. The presence of rearrangements in these seven cases, however, supports the diagnosis of TCRBCL based on paraffin immunophenotyping when frozen tissue is not available or when molecular studies are not feasible. Although these seven cases are classified as large-cell lymphoma, an intermediate-grade lymphoma, the influence of the reactive T-cell population on the clinical behavior will require follow-up studies.

We report 16 cases of a distinctive, biologically aggressive variant of small lymphocytic lymphoma/leukemia (SLL/L) that is characterized by the diffuse proliferation of cells normally comprising the pseudoproliferation centers (so-called paraimmunoblasts). Demographically, the patients differed in no significant regard from patients with SLL/L of usual type. Rapidly progressive, generalized lymphadenopathy was the dominant clinical finding in 15 of the 16 patients; one patient presented with symptoms related to lymphomatous involvement of the stomach and regional lymph nodes. Splenomegaly was observed in five patients. Seven patients, two of whom had a history of indolent-phase chronic lymphocytic leukemia, had an absolute lymphocytosis at diagnosis. In most patients, bone marrow involvement was noted at diagnosis. It consisted predominantly of small lymphocytic infiltrates indistinguishable from those observed in SLL/L of usual type; significant paraimmunoblastic infiltration was infrequent and generally occurred late in the disease course. Immunohistochemical and cytogenetic study further substantiated the hypothesized relationship of these cases to SLL/L. Findings included (a) coexpression of sIg and Leu-1 antigen in the majority of cases and (b) the presence of a t(11;14) (q13;q32) chromosome translocation in two of three cases with analyzable metaphases. Although treatment protocols were not uniform, follow-up data indicated an accelerated clinical course. Eleven patients have died of their disease between 3 and 39 months after diagnosis; the median survival was 28 months.

Fifty patients whose lymph node biopsies showed reactive follicular hyperplasia with the presence of progressive transformation of germinal centers were evaluated for current status of health, prior or subsequent development of Hodgkin's disease, and etiology of the lymph node hyperplasia. Histologically, on a background of reactive follicular hyperplasia, the nodes contained one or more germinal centers showing progressive transformation. These were three to four times the diameter of the other germinal centers and composed predominantly of small, round lymphocytes admixed with scattered immunoblasts and occasional benign histiocytes. Clinically, the majority of these patients were young males presenting with an asymptomatic solitary enlarged lymph node. fifteen had prior Hodgkin's disease. Five had concurrent progressive transformation of germinal centers and lymphocytic predominance Hodgkin's disease (two of these also had a subsequent biopsy showing only progressive transformation of germinal centers). All are currently free of Hodgkin's disease at 1-21 years. The largest group of 31 patients had no prior or subsequent Hodgkin's disease. One of the 50 developed multiple myeloma. Recognition of this phenomenon is important so that it will not be misconstrued as recurrent Hodgkin's disease, as de novo Hodgkin's disease, or as follicular lymphoma, which occurred in 12 (24%) of the cases.

Three cases of a morphologically distinctive "sclerosis" of lymph nodes are presented. Two patients experienced recurring lymph node enlargement with associated mild malaise over an extended period. The first patient had unilateral axillary lymph node enlargement, but was asymptomatic and died of chronic obstructive pulmonary disease 17 years later with no evidence of lymph node enlargement at autopsy. Each patient had at least transient hypergammaglobulinemia, one with elevated IgM and IgA, one with elevated IgM, and one (from 1958) not further analyzed. Lymph node biopsies revealed extensive deposition of eosinophilic material in all three patients. Identical changes in lymph nodes have been described in chronic diseases. The eosinophilic material may be related to amyloid, but differs from it histochemically and ultrastructurally. The relationship of this lesion to the few cases reported as amyloidosis presenting as lymph node enlargement is discussed. Malignant lymphoma with sclerosis is the most important consideration in the differential diagnosis.

Primary lymphoma of the kidney is extremely rare; most lymphomatous renal masses represent extension from adjacent sites of disease or involvement by generalized disease (4,9,12). Three men and one woman, 45 to 71 years of age, presented with solitary renal masses clinically thought to be renal cell carcinoma. Each experienced abdominal pain, one with hematuria and one with "B" symptoms. Physical examination revealed no peripheral lymphadenopathy or hepatosplenomegaly. Lactic dehydrogenase (LDH) was elevated in three cases, and blood urea nitrogen (BUN) and creatinine were slightly increased in two. Two cases were diagnosed correctly from needle biopsy, with ultrastructural confirmation in one case and marker studies, DNA flow cytometry, and cytogenetics in the other. Because of a presumptive diagnosis of renal cell carcinoma, two patients underwent nephrectomy. Three cases were large-cell lymphoma, and one, small noncleaved cell lymphoma.

Because of the new drug combinations being used to treat follicular lymphomas, the small cleaved cell lymphomatous foci in bone marrow biopsies appear to be altered. They become progressively hypocellular and contain a few and sometimes no small cleaved cells within oligocellular paratrabecular fibrous foci. These hypocellular paratrabecular foci (HPF) (a) are a clue that deeper sectioning is necessary to determine whether there are diagnostic foci of residual involvement by small cleaved cell lymphoma, (b) may indicate that other portions of the patient's bone marrow still contain viable foci of small cleaved cell lymphoma, and further, (c) should alert the clinician to the possibility of recurrence of small cleaved cell lymphoma in subsequent bone marrow biopsies. A comparison of patients who developed HPF in one or more of their bone marrow biopsy specimens with those who did not indicates that the changes are related to combinations of chemotherapy other than CHOP-Bleo (cyclophosphamide, adriamycin, vincristine, prednisone, bleomycin). Eighty-one percent of patients who developed HPF had received additional chemotherapeutic regimens, whereas 75% of patients whose bone marrows did not contain HPF had received only CHOP-B. The older age of the HPF-negative patients (median age 64 versus median age 43 for HPF-positive cases) may reflect more aggressive chemotherapy in the younger age group. While HPF appear to reflect some increased chemotherapeutic cytotoxicity affecting the lymphomatous foci in bone marrow, they do not appear to predict for a longer survival or cure.