Henry Rappaport

Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases.

A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castlemans disease) and is associated with significant morbidity and mortality.

Malignant lymphoma arising in angio-immunoblastic lymphadenopathy

This study is based upon 48 patients with angio‐immunoblastic lymphadenopathy and 36 patients whose lymph nodes revealed, in addition to angio‐immunoblastic lymphadenopathy (AILD), histologic features interpreted as malignant lymphoma of the immunoblastic type in the diagnostic biopsy. Progression into immunoblastic lymphoma (IL) was observed in 35%, or eight, of the 23 patients with AILD in whom follow‐up biopsies or autopsy were performed. Multiple clusters or islands of compactly arranged large lymphoid cells constituted the initial histologic evidence of IL. Subsequent tissue examination revealed progression of the disease in the form of diffuse replacement of lymph nodes by the neoplastic cellular proliferation. No significant differences in the past history, clinical or laboratory findings were observed between the patients with AILD and those whose lymph node biopsies were interpreted as AILD + IL. These two groups differed greatly, however, with respect to rate of complete remission following either prednisone or chemotherapy, or both (63% for AILD vs. 26% for AILD + IL; p = 0.01); median survival (35 months for AILD vs. six months for AILD + IL; p = 0.0004); incidence of malignant lymphoma at autopsy (20% for AILD vs. 82% for AILD + IL; p < 0.005); and the finding of extranodal malignant lymphoma at autopsy (10% in AILD vs. 64% in AILD + IL; p < 0.025). In the AILD group, median survival of patients who had complete remission after prednisone was significantly longer than that of patients who had partial or no remissions (p = 0.02) and the same was true for patients who were given chemotherapy (p < 0.003). In the AILD + IL group, a similar difference in the median survival was observed in patients treated with chemotherapy (p < 0.007), but not in those treated with prednisone (p = 0.31).

Further Evidence That Malignant Angioendotheliomatosis Is an Angiotropic Large-Cell Lymphoma

Malignant angioendotheliomatosis is a rare, generally fatal disease characterized by a multifocal proliferation of neoplastic mononuclear cells within the lumens of small blood vessels. Although the disease primarily involves the vasculature of the skin and central nervous system, vascular involvement of other organs may occur and may produce a variety of clinical findings. Some early investigators concluded that malignant angioendotheliomatosis was a neoplasm of endothelial cells, but recently others have suggested that it is of hematopoietic origin. We have studied three patients with the disease and have characterized the immunophenotype of the neoplasm on cryostat-cut fresh-frozen tissues. A detailed antigenic phenotyping of neoplastic lymphoid cells showed that one patient had the immunophenotype T11+, Leu-1+, Leu-3+, Leu-2+, B1-, B2-, SIg-, LN1-, LN2-, the predominant phenotype for peripheral T-cell lymphoma; the others had T11-, Leu-1-, Leu-3-, Leu-2-, B1+, B2+, SIg+, LN1+, LN2+, consistent with a B-cell-derived lymphoma. On the basis of our results, we suggest that angiotropic (intravascular) large-cell lymphoma would be more appropriate than malignant angioendotheliomatosis as a name for this disease.

Correlation of histopathology with other prognostic indicators in Hodgkin's disease.

The Rye Conference histologic classification of Hodgkins disease has been applied retrospectively to a series of 176 previously untreated cases of Hodgkins disease. Three different pathologists independently and unanimously agreed in two‐thirds of the cases on assignment of cases to one of the four categories: lymphocyte predominance, nodular sclerosis, mixed cellularity, and lymphocyte depletion. The classification was found to be effective in predicting prognosis even within clinical staging groups. Nodular sclerosis emerges as the largest histologic group and has a favorable prognosis. The usual manner of spread in Hodgkins disease was to adjacent lymph node groups. Noncontiguous dissemination, when it occurred, was more than twice as frequent in the mixed cellularity and lymphocyte depletion types, compared to nodular sclerosis. Nodular sclerosis involving lung has shown a favorable prognosis, unlike mixed cellularity. Survival appears to be increased in all histologic categories after intensive wide‐field megavoltage radiotherapy.

Hairy cell leukemia (leukemic reticuloendotheliosis). I. A clinical pathologic study of 21 patients

The clinical and pathologic findings in 21 patients with hairy cell leukemia (leukemic reticuloendotheliosis) are reviewed. The disease predominantly involved males, and was characterized by a chronic course with an insidious onset and marked splenomegaly. A hypersplenic syndrome with pancytopenia, “hairy cells” in the peripheral blood, and frequent “dry taps” on bone marrow aspiration were common features. Only one patient in this series was leukemic at the onset of disease. Pathologically, the changes in the spleen were distinct from those in other leukemias and malignant lymphomas, and consisted of a diffuse heavy infiltration of the red pulp cords and engorgement of the sinuses by a uniform population of mononuclear cells without mitoses. These cells were not identifiable as either monocytes or lymphocytes, although the pattern of infiltration was more consistent with histiocytic or monocytic than with lymphocytic proliferation. Infiltrates of similar cells were found in the bone marrow, lymph nodes, and livers of many patients early in the course of the disease. Despite this diffuse organ involvement, only 4 patients in this series died, and long survival was common. Splenectomy appeared to be the treatment of choice, whereas vigorous chemotherapy was contraindicated. Accurate diagnosis by recognition of the histologic criteria is therefore essential.

Leu-M1 antigen in human neoplasms. An immunohistologic study of 400 cases.

Several studies have shown that the Leu-Ml antigen, a monocyte/granulocyte-related marker, is consistently expressed by the neoplastic cells of patients with Hodgkins disease (HD). It has been suggested that reactivity of Reed-Sternberg cells with Leu-Ml can be used in support of a morphologic interpretation of HD, and that it is helpful in the differential diagnosis of HD from morphologically similar lesions. To evaluate the significance of the Leu-Ml positivity of Reed-Sternberg cells in the diagnosis of HD, we investigated the distribution of Leu-Ml antigen in a series of patients with HD, non- Hodgkins lymphomas, and nonhematopoietic neoplasms. We were able to demonstrate the presence of Leu-Ml antigen not only in the majority of patients with HD, but also in 12 of 18 (67%) peripheral T-cell lymphomas, as well as in a variety of nonhematopoietic neoplasms, which included 113 of 199 carcinomas, most of them (58%) adenocarcinomas. Only one of 34 sarcomas showed a focal positive reaction. Leu-Ml-related antigen was not detected in any of 18 mesotheliomas, 15 germ cell tumors, 13 melanomas, three schwannomas, or three astrocytomas. Our study indicates that Leu-Ml positivity has no value in supporting the diagnosis of HD in situations where the histologic diagnosis of HD is doubtful. However, since anti-Leu-Ml reacted positively in the majority of adenocarcinomas but was absent in mesotheliomas, melanomas, and most sarcomas, this antigen could serve as a new marker that may be helpful in situations in which carcinoma is a part of the differential diagnosis.

Observation of cells resembling Sternberg-Reed cells in conditions other than Hodgkin's disease.

The diagnosis of Hodgkins disease is based upon the finding of characteristic Sternberg‐Reed cells in appropriate cellular and architectural environments. The demonstration of cells with the nuclear and cytoplasmic features of Sternberg‐Reed cells is necessary, but not sufficient for the diagnosis of this disease. Many investigators, however, have erroneously regarded these cells as pathognomonic. This report emphasizes that cells indistinguishable from, or closely resembling, Sternberg‐Reed cells may be found in conditions other than Hodgkins disease. Their presence, therefore, should not be considered a diagnostic mandate. Thirteen cases are presented in which biopsy sections of both benign and malignant lesions revealed cells closely resembling or indistinguishable from Sternberg‐Reed cells.

Signet ring cell lymphoma. A rare morphologic and functional expression of nodular (follicular) lymphoma.

Nodular lymphomas and diffuse lymphomas of corresponding cellular composition have been shown to arise from follicular center cells. This paper describes a rare functional and morphological expression of malignant lymphomas arising from follicular center cells, namely, immunoglobulin production, an observation for which no detailed description or analysis is available in the literature. Furthermore, the unusual signet ring-like appearance of the lymphoma cells, which is due to retention of immunoglobulins within the cytoplasm, may result in an erroneous interpretation of metastatic adenocarcinoma or liposarcoma. Therefore, we are presenting a detailed analysis of light microscopic, histochemical, immunocytochemical, and ultrastructural observations. The lymphomas of all seven patients in our series showed nodular growth patterns; in all but one, diffuse areas were also observed. Five of the lymphomas were classified as poorly differentiated lymphocytic type and two as mixed cell type, according to Rappaports classification. In four of the seven patients, the majority of the neoplastic cells had a clear vacuolated cytoplasm, and in three of these cases, a few of the neoplastic cells showed immunoper-oxidase positivity for monoclonal IgG. This group in particular closely simulated metastatic carcinoma composed of so-called signet ring cells. In the remaining three cases, most of the neoplastic cells contained PAS-positive, Russell body-like monoclonal IgM. Ultrastructurally, the monoclonal IgG appeared as even-sized electron-dense spherules or irregular electron-dense clumps, while the monoclonal IgM appeared as membrane bound, homogeneous, electron-dense material. The implications of these findings and the morphologic features which are helpful in the identification of these lymphomas are discussed.

The pathology of so-called mediterranean abdominal lymphoma with malabsorption

Surgical specimens, postmortem material, or both from 22 patients with the syndrome designated as “Mediterranean abdominal lymphoma with malabsorption” were studied in detail. All patients exhibited a malabsorption syndrome. In most of those carefully followed from the onset of the disease, the syndrome seemed to have preceded the development of palpable abdominal masses. In 20 of the 22 patients, intestinal tissues were available for histologic study. In all specimens, diffuse severe plasma cell infiltrations were evident in the intestinal mucosa and submucosa. Malignant lymphomas in the form of single or multiple circumscribed intestinal tumors occurred in 14 of these 20 patients and malignant lymphomas of the mesenteric lymph nodes in two. In four patients, no malignant lymphomas were evident. These observations suggest that the diffuse plasma cell infiltrations, rather than the malignant lymphomas, were responsible for the malabsorption syndrome. There was no morphological evidence that the malignant lymphomas observed in 75% (16 of 20) of the patients were histogenetically related to the diffuse plasma cell infiltration. The possibility is suggested that this abnormal, though not provably neoplastic, proliferation of plasma cells is a morphological manifestation of an immune deficiency state which predisposes the patients to the development of malignant lymphoreticular neoplasms.

Monocytoid B-cell lymphoma in patients with Sjögren's syndrome: A clinicopathologic study of 13 patients

A recent clinicopathologic study of a series of patients with monocytoid B-cell lymphoma (MBCL) indicated that there is a frequent association between MBCL and Sjögrens syndrome (SS) and raised the possibility of a relationship between these two disease entities. To further investigate the possible relationship of MBCL and SS, we studied pathologic and clinical characteristics of 13 patients with MBCL who had clinically documented SS. In all patients, the lymphoma had the characteristic morphologic features of MBCL, and immunologic and molecular hybridization studies confirmed the B-cell nature of the lymphoma. Twelve of the 13 patients were female, with a median age of 66 years at diagnosis. Eleven had localized disease and presented with either salivary gland or cervical lymph node enlargement; one patient presented with a breast mass, and another with generalized lymphadenopathy and hepatosplenomegaly. In five of 13 patients, the MBCL was associated with or progressed to large cell lymphoma. In two patients, there was bilateral involvement of the parotid gland; one had a synchronous high-grade lymphoma in both parotid glands. In two patients, bone marrow biopsies showed involvement by MBCL. Eleven patients are alive 2 to 55 months after the diagnosis of MBCL. One patient died with the disease 8 months after the initial diagnosis. Another patient died of an unrelated cause without evidence of disease 16 months after the diagnosis of MBCL. We conclude that there is a more than fortuitous association between MBCL and SS. This concept is consistent with previously reported observations of reactive monocytoid B cells in patients with benign lymphoepithelial lesions of salivary glands, which may result from selective homing of reactive monocytoid B lymphocytes to the benign lymphoepithelial lesions and their subsequent neoplastic transformation.