A morphologic and immunologic surface marker study of 299 cases of non-Hodgkin lymphomas and related leukemias.

This study relateds the cytologic types of the classification of malignant lymphoma of Lukes and Collins to the results of immunologic surface marker studies as part of a systematic multiparameter study of 299 cases of non-Hodgkin lymphomas. The results support the hypothesis that malignant lymphomas are neoplasms of the immune system and involve the B- and T-cell systems and, rarely, histiocytes. The morphologic features of the cytologic types of Lukes and Collins are predictive of the subtypes of lymphoma and considerably more effective than the immunologic surface marker techniques in identifying homogeneous groups. There are considerable methodologic and interpretive problems that are evaluated in detail. The verification of the B- and T-cell subtypes of the Lukes and Collins classification indicates that the time has come to change from the terminology and classification of lymphomas of the past to a modern immunologic approach.     

Primary pulmonary non-Hodgkin's lymphomas

We report a retrospective study of the pathological features in 69 primary pulmonary non-Hodgkin's lymphomas which have previously been clinically reviewed. The tumours consisted of 61 (88%) low-grade and eight (12%) high-grade malignant lymphomas. Fifty-four of the low-grade malignant lymphomas were MALT lymphomas. Lymphoepithelial lesions were observed in bronchial, bronchiolar and alveolar lining. All tumours were composed of nodules, forming a lymphangitic pattern at the periphery and a confluent central mass. Invasion of pleura and vessels was often seen but this without any consequence on survival. Granulomas were found in 20% of cases. Six of the eight high-grade tumours were centroblastic and another two were B-cell lymphomas of undetermined type. In four cases, associated areas of low-grade malignant lymphoma with lympho-epithelial lesions indicated a preexisting MALT lymphoma. Clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasms. However, non-invasive diagnostic methods need to be developed.     

Comparison of histologic and immunologic heterogeneity of non-Hodgkin's lymphomas.

The lymphocyte surface marker phenotype in 11 selected cases of non-Hodgkin's lymphomas was determined with anti-immunoglobulin and mouse monoclonal antibodies against human lymphocyte antigens. A complement-mediated cell cytotoxicity assay on suspensions of the tumor cells was compared with an indirect immunoperoxidase technique on frozen tissue sections. Both methods gave good results in tumors with a uniform cell population, but the frozen section technique was superior in heterogeneous tumors. The six B-cell neoplasms were heterogeneous with respect to expression of surface immunoglobulin and Ia antigens. The five T-cell tumors were morphologically heterogeneous and also highly variable in their expression of different T-cell specific antigens.     

22例骨原发恶性淋巴瘤分析

对２２例骨原发恶性淋巴瘤进行临床病理组织学和免疫组织化学的研究，结果：２０例为单骨病变，１例有引流区淋巴结累及；２例多骨病变。Ｘ光见溶骨型为９ｌ％。按照ＷＦ（Ｗｏｒｋｉｎｇｆｏｒｍｕｌａ－ｔｉｏｎｆｏｒｃｌｉｎｉｃａｌｕｓａｇｅ）的分类小淋巴细胞性２例，淋巴浆细胞性１例，小裂细胞性１例，大裂细胞性３例，混合细胞性６例，大无裂细胞性６例，透明细胞２例，曲核细胞１例。用７种单克隆抗体，对１５例存档蜡块的标记结果为Ｂ细胞阳性１０例，Ｔ细胞阳性３例，另２例无阳性表达。作者同时讨论了鉴别诊断问题，并指出影响标记结果的客观因素。     

Primary gastric non-Hodgkin's lymphomas in Japan

Summary A pathological study was carried out on 124 cases of primary gastric non-Hodgkin's lymphoma (NHL) in Japan. Macroscopically the cases were divided into three groups; flat, polypoid, and ulcerative types. Early lymphomas were distinguished from advanced by the depth of infiltration. Histologically the commonest type was ML, immunoblastic (ML, ibl.). Most were high grade malignancy, in terms of morphology. Lymph node involvement was found in 44 cases. Correlation between macroscopical appearance, histological diagnosis, stage and accompanying reactive lymphoid hyperplasia (RLH) was studied. Three main prototypes of gastric NHL were noted: The first was macroscopically ulcerative type, histologically high grade malignancy and lacked RLH; the second was mostly flat, ML, lymphoplasmacytic/ lymphoplasmacytoid (ML, l-p.) or ML, ibl., associated with RLH, and arose from neoplastic proliferation of the interfollicular lymphoid cell in RLH (termed gastric NHL of interfollicular type); the third was mostly flat, ML, centroblastic (ML, cbl.) or lymphoblastic (ML, lbl.), associated with RLH, and originated from neoplastic proliferation of the follicular center cell in RLH (gastric NHL of follicular type).This work was supported in part by a Grant-in-aid for Cancer Research from the Ministry of Education, Science and Culture     

Malignant lymphomas in Gabon (equatorial Africa): a morphologic study of 72 cases.

A retrospective morphologic analysis was conducted on 72 malignant lymphomas collected in Gabon, a country of the equatorial area in Africa. Non-Hodgkin's lymphomas (NHLs) were by far the most frequent type of lymphoma, representing 67 cases (93%); only five patients (7%) had Hodgkin's disease. Non-Hodgkin's lymphomas were classified according to two modern systems (Kiel and Working Formulation). The age distribution of NHL patients was bimodal, with the highest peak in the 0 to 14 years age group (these cases were almost exclusively associated with Burkitt's lymphomas), and with the second highest peak in the 55 to 64 years age group. The male to female ratio was 2.5:1, and the overall median age was 44 years. According to the Working Formulation, the NHL cases were composed of one follicular lymphoma (1.5%), 55 diffuse lymphomas (82%), and 11 miscellaneous lymphomas (16.5%). Burkitt's lymphoma was the most frequent NHL (17 cases; 25.4%), followed by diffuse large cell lymphoma (15 cases; 22.4%) and immunoblastic lymphoma (nine cases; 13.4%). Consequently, high-grade NHL formed the largest group (28 cases; 42%), intermediate-grade NHL formed the next largest group (21 cases; 31.3%), and low-grade NHL formed the smallest group (seven cases; 10.4%). These data are compared with series from developed and developing countries, and the observed differences in distribution of the histologic subtypes of malignant lymphoma are discussed.     

Primary mediastinal giant cell tumors: a clinicopathologic and immunohistochemical study of two cases

Two cases of posterior mediastinal giant cell tumors are presented. The patients are a woman and a man, 31 and 18 years old, respectively. One of the patients had symptoms of paresthesias while the other was completely asymptomatic. Complete physical examination did not disclose evidence of tumor elsewhere. Neither patient had a previous history of malignancy. Surgical resection was performed. Histologically, both tumors were composed of a proliferation of osteoclast-like giant cells associated with a mononuclear cell population composed of oval and spindle cells. Mitotic activity and mild cellular atypia were present in the mononuclear cell component. No evidence of necrosis or hemorrhage could be demonstrated in either case. Immunohistochemically, both tumors showed strong positive reaction in the mononuclear component for antibodies against vimentin and CD68, while keratin, epithelial membrane antigen, CD45, S-100 protein, and desmin were negative. On clinical follow-up, both patients are alive and well without evidence of recurrence or metastasis 6 and 108 months after surgery. The present cases highlight the ubiquitous distribution of soft tissue giant cell tumors and the importance of considering these tumors in the differential diagnosis of posterior mediastinal neoplasms.     

Primary non-Hodgkin's lymphomas of the central nervous system

Thirty-five primary non-Hodgkin's lymphomas (NHL) of the central nervous system (CNS) were examined in a retrospective study and classified according to the Kiel classification. Diagnosis was made on surgical biopsies in 28 cases and on autopsy specimens in seven cases. The tumors were predominantly located in the frontal lobe and were unifocal in all but two cases. Patients ranged in age from seven to 74 years, with a male-female ratio of 1.3:1. The lymphomas were probably all of B cell type. In contrast to NHLs of the lymph nodes, the NHLs of the CNS we encountered were more often high grade (immunoblastic, lymphoblastic) than low grade malignant. All but one low grade malignant NHL found in our study were lymphoplasmacytoid (LP) immunocytomas.     

Correlations of immunologic markers with histologic features of human non-Hodgkin's lymphomas.

Twenty-five lymph nodes from patients with non-Hodgkin's lymohomas were evaluated by immunologic technics applied to cell suspensions and tissue sections. Malignant lymphomas with cytologic characteristics similar to those of neoplastic cells were found to be immunologically heterogeneous. The distribution as well as the number of neoplastic cells with distinctive immunologic surface markers could not be related to the cytologic type of malignant lymphomas. The number of malignant cells simultaneously expressing the T- and B-cell markers was increased in malignant lymphoma nodes. Cells positive for the triple markers (Ig+, EAC+, T+, where Ig = immunoglobulin, EAC = erythrocytes sensitized with antibody and complement, and T = T marker) represented the predominant population in these nodes, and the distributions of these cells were useful in diagnosis. Monoclonal immunoglobulins were detected in all lymphoma cells but not in the patients' sera. The tissue distribution of EAC-positive cells may have a prognostic significance. The paucity of cells with the Fc receptors was a characteristic feature of all lymphoma cells studied. Evaluations of immunologic markers on lymphoma cells in conjunction with the histologic characteristics may provide a sounder basis for diagnosis.     

Interdigitating cell sarcoma: A morphologic and immunologic study of lymph node lesions in four cases

lnterdigitating cell sarcoma is an extremely rare tumor. Its presentation and histologic appearance has varied among the reported cases. In this study, the authors investigated four cases of the hematolymphoid malignancy arising within lymph nodes, which were considered to be of interdigitating cell origin. All patients presented in the 6th to 8th decade of life with peripheral lymphadenopathy, and had a relatively indolent clinical course, without bone marrow or skin involvement. Carcinomas were observed as a second neoplasm in two of four patients. Distinctive morphologic features are proliferation of histiocyte-like cells with nuclear pleomorphism and occasionally multinucleated, paracortical distribution sparing of B-cell regions, fibrosis, sinus infiltration, and a prominent eosinophi/plasma cell infiltrates. The combination of light microscopic, fine structural, and immu-nohistochemical features suggested that these tumors derive from interdigitating cells: these tumor cells expressed CD68 (KP1), S-100 protein and HLA-DR, but lack CD21 (1F8), desmosomes and Birbeck granules. The diagnosis of interdigitating cell sarcoma should be considered on any pleo-morphic tumor with the features described in this report.     

Macrophage infiltration in non-Hodgkin's lymphomas: a quantitative in situ study

The frequency and distribution pattern of macrophages within 93 non-Hodgkin's lymphomas (NHL) were evaluated in situ by immunomorphometry using stereological methods. For the identification of macrophages (M phi), several antibodies (Mono 1, Mono 2, OKM 1) reactive with surface antigens on cells of the monocyte-macrophage series and cytochemical staining for acid phosphatase were applied. The average number of macrophages within lymph node tissue of NHL was 6,299 +/- 760 cells/microliter (similar to reactive lymphatic tissue: 6,559 +/- 1,027). The highest number of infiltrating macrophages was detected in immunoblastic NHL (17,306 +/- 2,773), differing significantly from other histological subtypes and reactive lymphatic tissue (p less than 0.005). The possible impact of tumor-infiltrating macrophages on lymphoma cell proliferation and differentiation is discussed.     

Cytology and immunophenotyping of low- and intermediate-grade B-cell non-Hodgkin's lymphomas with a predominant small-cell component: a study of 56 cases

Diagnosis of non-Hodgkin's lymphomas based on cytologic evaluation of fine-needle aspirates and body cavity fluids has gained increasing acceptance. However, the accurate diagnosis and classification of low- and intermediate-grade B-cell lymphomas with a predominant small-cell population still present a diagnostic challenge. In this study, we reviewed the cytology and immunophenotype of 56 cases of low- and intermediate-grade non-Hodgkin's B-cell lymphomas composed of predominantly small cells, with histologic correlation in all cases. These cases consisted of 23 small lymphocytic lymphomas (SLL), 15 follicular center lymphomas (FCL), grade I (small cell predominant), 8 lymphoplasmacytoid lymphomas (LPL), 6 mantle-cell lymphomas (MCL), and 4 marginal zone lymphomas (MZL) including mucosa-associated lymphoid tissue (MALT) lymphoma. Histologic comparison was available in all cases. A cytologic diagnosis of malignant lymphoma was made in 46 (82%) cases. Based on cytomorphology and immunophenotyping of cytologic material, 39 (85%) cases were correctly classified using the Revised European and American Lymphoma classification. In 7 (11%) cases, which included 3 FCLs, 2 MALT lymphomas, and 2 SLLs, the findings were atypical but not diagnostic of lymphoma. There were 3 (5%) false-negative cases. They were 2 SLLs and a FCL. Immunophenotyping done in 4 "atypical" cases was noncontributory. No marker studies were done in the remaining "atypical" case and all false-negative cases. We conclude that cytology, when used in conjunction with immunophenotyping, can accurately diagnose and in most instances subclassify low- and intermediate-grade B-cell non-Hodgkin's lymphoma with a predominant small-cell population.     

Primary lymphomas of the small intestine in Iraq: a pathological study of 145 cases

The histopathology of 145 malignant lymphomas of the small intestine in Iraq have been studied and results compared with the clinical and immunological findings. The most common pathology was an intense mucosal lymphoplasmacytic proliferation effacing the villi and crypts partially or completely. This was either 'pure', usually of mature plasma cells limited to the lamina propria or associated with a fullblown lymphoplasmacytic lymphoma, almost always of the upper small intestine. The syndrome presented as abdominal pain, chronic diarrhoea, clubbing and, sometimes, the serological demonstration of alpha heavy chains. Other types of lymphomas were associated with 'non-specific' mucosal inflammation or follicular lymphoid hyperplasia. They were either lymphocytic, plasmacytic or lymphoblastic with 'starry sky' histiocytic reaction, representing distinct clinicopathological entities unrelated to 'alpha heavy chain disease'. Hodgkin's disease was extremely rare in this series.     

Sinonasal non-Hodgkin's lymphomas and Wegener's granulomatosis: A clinicopathological study

Summary Reports of sinonasal non-Hodgkin's lymphomas, analysed with monoclonal antibodies, are scarce, and differentiation of these lymphomas from Wegener's granulomatosis can be difficult. In this study, we investigated histopathologically and immunohistologically 20 cases of non-Hodgkin's lymphoma, primary in the sinonasal region, and sinonasal biopsies from 11 patients with Wegener's granulomatosis. All T-cell lymphomas (n=7) and plasmacytomas (n=4) were stage I at clinical presentation, while all B-cell lymphomas (n=9) presented at higher stages. T-cell lymphomas tended to be more frequent in the nasal cavity and paranasal sinuses; B-cell lymphomas more often presented in the nasopharynx. Remarkably, 1 B-cell lymphoma expressed MT1, and 1 T-cell lymphoma expressed L26 (CD 20). The follow-up of 2 patients with a clinical diagnosis of Wegener's granulomatosis was suggestive of non-Hodgkin's lymphoma. Retrospective immunohistochemical analysis revealed that the original histological diagnosis of non-specific inflammation had to be changed to T-cell lymphoma, pleomorphic small cell type. We conclude that a biopsy from the sinonasal region with a dense inflammatory infiltrate, consisting predominantly of Tlymphocytes, renders a diagnosis of Wegener's granulomatosis unlikely and is at least suspicious of T-cell lymphoma. Immunohistochemical analysis is warranted for this type of biopsy.     

Immunologic methods in cytology: definitive diagnosis of non-Hodgkin's lymphomas using immunologic markers for T- and B-cells

The cytologic diagnosis of malignant lymphoma can be extremely difficult because the cytologic features of the malignant cells in small cell and mixed small and large cell lymphomas may be indistinguishable from those of reactive lymphoid cells. In addition, large cell lymphoma can be difficult to distinguish from undifferentiated carcinoma in cytologic specimens. Using the avidin-biotin immunoperoxidase technic and antibodies to the B-cell markers alpha, gamma, and mu heavy chains and kappa and lambda light chains, to the T-cell markers Leu-1, Leu-2a, and Leu-3a, to the lymphoid marker T200, to TdT, and to Leu-M3, the authors studied 35 cytologic specimens including pleural, cerebrospinal, and ascites fluids and fine-needle aspirations. Immunologic staining allowed them to make a definitive diagnosis of lymphoma or reactive effusion in every case studied and resulted in a significant modification of the morphologic diagnosis in over 50% of cases. In 16 cases the lymphoid cells were monoclonal B-cells: ten expressing IgM kappa; four expressing IgM lambda; one expressing IgA kappa; and one expressing kappa without demonstrable heavy chain expression. Although there are no good markers of monoclonality for T-cells, the authors were able to make a positive diagnosis in two cases of T-cell lymphoid malignancies by the expression of an aberrant phenotype on the malignant cells. The expression of TdT confirmed the diagnosis in one case of common ALL and one lymphoblastic lymphoma. In a patient with a "null cell" large cell lymphoma, the expression of T200 on the malignant cells ruled out the possibility of carcinoma. In 15 cases the marker studies indicated a reactive lymphoid proliferation. The authors conclude that immunologic markers are very useful in the cytologic diagnosis of lymphoma.     

Primary thyroid lymphomas: clinicopathologic study of 30 cases and review of the literature

During a both retrospective and prospective study of thyroid cancers treated in the Basse Normandie between 1960 and 1999, we have identified 32 patients with thyroid lymphoma. The correct diagnosis was made initially in 69% of all cases. In the other cases, the diagnosis was secondarily corrected after review of the pathological material. According to the REAL classification, 7 (21%) corresponded to low grade MALT lymphomas, 2 to low grade lymphomas, 10 to high grade MALT Lymphomas and 10 (31%) to high grade lymphomas, one plasmocytoma and two unclassified lymphomas. According to the Ann Arbor classification, stage was IE for 56%, IIE for 19%, IIIE for 3% and 9% for IV. Median survival was 28 months with a mean at 61 months. 20 patients died (62%), 12 from the lymphoma and 8 from intercurrent causes. The overall survival at 5 years was 36% (9 5% CI 16 54%). A comparison of our results with those of the literature was performed.     

Primary mediastinal melanotic schwannian tumors: A clinicopathological and immunohistochemical study of 5 cases

Mediastinal neurogenic tumors are unusual and more so is the presence of melanotic neurogenic tumors. We present five cases of mediastinal melanotic neurogenic tumors. The patients are five men between the ages of 34 and 43 years (average: 38.5 years). All patients presented with non-specific symptoms that included back pain and cough. Diagnostic imaging revealed the presence of a posterior mediastinal mass without connection to the spinal canal, and surgical resection was accomplished in all of the patients. Histologically, the five tumors showed a spindle epithelioid cellular proliferation, nuclear atypia, mitotic activity, and melanin deposition. Histochemical stain for Fontana Masson clearly demonstrated the presence of melanin pigment in all the cases, while S-100 protein was only focally positive in tumor cells. Other immunohistochemical stains including SOX-10, MITF, HMB-45, and Melan A were negative. Clinical follow-up showed that two patients died 22 and 30 months after initial diagnosis; one remains alive, 6 months after initial diagnosis; two patients were lost to follow up. Melanotic neurogenic tumors represent a diagnostic challenge for pigmented thoracic tumors and careful analysis of the morphology and immunohistochemistry is required to lead to proper diagnosis.     

Primary malignant lymphomas of the central nervous system: a histological and immunohistological study of 12 cases

Paraffin sections of surgical and autopsy material from 12 cases of primary non-Hodgkin's lymphomas of the central nervous system were examined for histopathological diagnosis and for the demonstration of cytoplasmic immunoglobulins. According to the Kiel classification, there were five cases of lymphoplasmacytoid polymorphous lymphoma, five of immunoblastic lymphoma, one of lymphoblastic lymphoma of convoluted cell type. There was also one of the recently described multilobated lymphoma. An immunohistological study of light and heavy chains by peroxidase-antiperoxidase (PAP) technique and avidin-biotin complex (ABC)technique was performed. Intracellular immunoglobulins were demonstrated in seven cases: four cases were classified as immunoblastic lymphomas and three cases as lymphoplasmacytoid lymphomas. Negative immunoglobulin staining was observed in five cases: two lymphoplasmacytoid lymphomas, one immunoblastic, one lymphoblastic of convoluted cell type and one multilobated. A 'monoclonal' pattern of immunoglobulin staining was detected in six cases. One case, classified as immunoblastic lymphoma, showed 'bitypic' staining for kappa and lambda chains. It was concluded that primary CNS non-Hodgkin's lymphomas of the present series showed morphological and immunohistological features similar to those of malignant lymphomas arising in extraneural sites. In particular, the presence in our series of a multilobated lymphoma, as a primary CNS tumour, is emphasized.