Characterization of Non-Hodgkin''s Lymphomas Using Multiple Cell Markers: Immunologic, Morphologic, and Cytochemical Studies of 72 Cases

Tissues from 72 cases (87 specimens) of various non-Hodgkin's lymphomas were analyzed for cell markers using multiple techniques. Cell suspensions were evaluated for E, EAC, and IgGEA rosette forming cells; Fc receptor cells; and surface immunoglobulin bearing cells. Cryostat section studies topographically defined EAC binding cells. Cytochemical determinations and immunoperoxidase methods for detection of intracellular immunoglobulin and lysozyme complemented other techniques in evaluating infiltrates containing large neoplastic cells. B-cell malignancies comprised 58 cases (80%) of this series and included well and moderately well differentiated lymphocytic lymphomas (10/10); nodular (23/23) and diffuse (10/18) poorly differentiated lymphocytic lymphomas; and lymphomas of mixed lymphocytic-“histiocytic” (3/3), “undifferentiated” (3/3), and “histiocytic” (9/13) types. Nodular lymphomas were characterized as B-cell neoplasms but also revealed a prominent population of T lymphocytes (39 ± 12%). Alkaline phosphatase activity, a cytochemical marker for lymphoid cells of follicular cuffs, was most consistently observed in B-cell lymphomas of moderately well differentiated lymphocytic type (4/6 cases). In some diffuse lymphomas, cryostat section studies (EAC rosettes) suggested a pre-existing nodular proliferation. One unusual B-cell lymphoma of large cell type exhibited IgGEA rosette formation and a strong receptor for the Fc portion of IgG. Ten lymphomas (14%) were of T-cell type and were represented by cases of diffuse poorly differentiated lymphocytic lymphoma (5/18, including 3 lymphoblastic lymphomas), Sézary syndrome (1), mycosis fungoides (1), and a cytologically distinctive large cell (“histiocytic”) lymphoma (3/13). Acid phosphatase activity was a consistent marker for the T-cell malignancies, some of which also revealed α-naphthyl butyrate esterase activity. No true histiocytic lymphomas were detected. Three cases of diffuse poorly differentiated lymphocytic lymphoma and one “histiocytic” lymphoma were null.     

Non-hodgkin lymphomas of the thyroid

Summary Twenty-nine cases of non-Hodgkin lymphomas presenting in the thyroid were classified according to Rappaport and Lukes and Collins. In the Rappaport classification there were 19 histiocytic, three mixed, five nodular PDL and two undifferentiated lymphomas. According to Lukes and Collins, 21 cases were follicular center cell lymphomas, eight were immunoblastic sarcomas. Cases classified as histiocytic according to Rappaport fell into the immunoblastic sarcoma and large cleaved or non-cleaved follicular center cell lymphoma groups. Immunoperoxidase studies confirmed the B cell nature of some of these cases.Survival was dependent on clinical stage, but this appeared to reflect the predominant cell type. Thus, follicular center cell lymphomas of the large non-cleaved type presented predominantly in stage I, while immunoblastic sarcoma was mostly stage IV and tumors of the small cleaved follicular center cell (FCC) type had excellent survival despite a usual presentation in stage IV. It is concluded that probably only lymphomas of the large non-cleaved FCC type and immunoblastic sarcoma (IBS) occur as true primary thyroid tumors, while small cleaved FCC lymphomas most likely represent systemic disease when first presenting in the gland. The median survival for large non-cleaved lymphomas in stages I and II was 31.5 months compared to 5.5 months for stage IV IBS. Although strongly suggestive these correlations were not statistically significant.An association with severe chronic lymphocytic thyroiditis was observed in 22 cases, including all cases of immunoblastic sarcoma as well as nine of ten large non-cleaved follicular center cell tumors.The prognostic significance of the Lukes-Collins classification is discussed in relation to these examples of thyroid lymphoma.Supported in part by grant CA 19449 National Institutes of Health.Dr. Maurer was supported by a scholarship of the Swiss and Zurich Cancer League.     

Non-Hodgkin's lymphoma, multilobated B-cell type: report of nine cases with immunohistochemical and immunoultrastructural evidence for a follicular center cell derivation

The clinical, pathologic, and immunologic features in nine cases of non-Hodgkin's lymphoma of the multilobated B-cell type are described. Clinical and phenotypic heterogeneity was observed in these B-cell neoplasms. A probable follicular center cell derivation for these cytologically unusual B-cell lymphomas is supported by antecedent histories of follicular center cell neoplasms in three cases; a focal nodular pattern in one case; the demonstration of peanut lectin (PNA) receptors, a marker for follicular center cells, on neoplastic multilobated B cells; and immunoultrastructural studies of nonneoplastic tonsillar cells that identified and characterized rare multilobated cells, immunoreactive for B1, B2, and Ia membrane antigens, a phenotype consistent with follicular center-type cells. Comparison of B- and T-cell multilobated lymphomas revealed that only immunologic studies accurately discriminated between these neoplasms.     

Polymerase chain reaction for bcl-2 in diagnostic lymph node biopsies

bcl-2 is a marker for the translocation t(14;18)(q32;q21) indicative of follicular B-cell lymphoma. We studied 115 cases of lymphoproliferative disease with the polymerase chain reaction for bcl-2 oncogene using biotin and radiolabeled probes to the major breakpoint and minor cluster regions. Twenty-three percent of B-cell lymphomas were positive for bcl-2. These included 12 of 20 cases of nodular follicular center cell lymphoma (nine small cleaved cell, one mixed small and large cell, and two large cell types). bcl-2 translocation was detected in only three of 45 cases of diffuse B-cell lymphoma, and cases of AIDS-related malignant lymphoma, monocytoid B-cell lymphoma, and mantle zone lymphoma were all negative. Nonneoplastic lymphoid proliferations were negative for bcl-2 including nine cases of abnormal follicular hyperplasia from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Cases of T-cell lymphoma and five cases of Hodgkin's disease were also negative. The polymerase chain reaction for bcl-2 is a rapid, sensitive technique in the evaluation of follicular B-cell proliferations, and the use of biotinylated probes and the alkaline phosphatase reaction eliminates the requirement for radioactive reagents.     

Primary lymphoma of the thyroid: a clinical, histological and immunohistochemical study of 20 cases

Twenty cases of malignant lymphoma arising in the thyroid gland were studied clinically, histologically and immunohistochemically. Nineteen cases were non-Hodgkin's lymphoma (15 diffuse and four follicular lymphoma) and one was a plasmacytoma. Immunohistochemical analysis of the lymphomas using paraffin-embedded sections disclosed that 17 lymphomas were B-cell type and two were T-cell type. The plasmacytoma was of IgG kappa type. The large majority of the lymphomas were associated with an underlying chronic thyroiditis. The 5-year survival rate of the patients was 70%. An unfavourable diagnosis was more likely when the tumour was diffuse rather than follicular, when it was of diffuse large cell type or of immunoblastic type and when there was cervical lymph node involvement.     

Study of vimentin expression in non-Hodgkin's lymphoma using paraffin sections.

Human non-Hodgkin's lymphomas were studied by means of an avidin-biotin complex immunoperoxidase method using several monoclonal antibodies against the intermediate filament protein, vimentin. The study cases were 61 B-cell lymphomas (including 2 plasmacytomas) and 30 T-cell lymphomas (including 8 cases of mycosis fungoides). Twelve of the 61 B-cell lymphomas were positive for vimentin, and were composed of extrafollicular-center cells such as immunoblastic and plasmacytoid cells. On the other hand, lymphomas of follicular center cell origin were negative for vimentin. All cases of T-cell lymphoma except for 14 (all of 9 AILD-type lymphomas, all of 4 lymphoblastic lymphomas and one diffuse mixed small/large lymphoma) were positive for vimentin. Although vimentin expression appeared to be influenced by various conditions such as the proportion of T- and B-cell subsets, or B-cell proliferation rate, follicular center cells were constantly negative for vimentin.     

Nasopharyngeal and nasal malignant lymphoma: a clinicopathological study of 54 cases

Forty-one cases of nasopharyngeal and 13 cases of nasal malignant lymphoma have been examined histologically and immunohistochemically. All of the cases were non-Hodgkin's lymphoma; one case was of follicular type and the remaining 53 were of diffuse type. Large cell lymphoma comprised 48% of cases and most of the immunoblastic lymphomas showing pleomorphism occurred in the nose. Twenty-seven cases were of T-cell and 21 of B-cell phenotype. The predominance of T-cell lymphoma was due to an increased incidence of these in the nose, the T:B ratio of 3.33:1 contrasting with a 1:1.05 ratio in the nasopharynx. Nasopharyngeal lymphomas seem to show an intermediate incidence between the T-cell predominance in the nose and a B-cell predominance in the oropharynx. Since the large cell type of lymphoma was predominant, the differential diagnosis from undifferentiated carcinoma is important and is facilitated by the use of immunostaining methods.     

Clinicopathological and cell immunophenotypic analysis of 54 cases of malignant nasopharyngeal/nasal lymphoma]

54 cases of nasopharyngeal/nasal non-Hodgkin's malignant lymphoma (NP/N-ML), including 41 cases of NP-ML and 13 cases of N-ML, were analyzed histologically and immunohistochemically and all of these materials were prepared in paraffin sections. They were all of diffuse type but one, of follicular type. Large cell type lymphomas were more commonly seen in this series (53.1%), and immunoblastic type with cell pleomorphism was more common in N-ML. A panel of monoclonal antibodies composed of LCA, L26, LN2, UCHL1, Leu22, Mac387 and Leu7 was used in this study. There were 27 cases exhibiting T-cell phenotype and 21 cases showing B-cell phenotype. No histiocytic type was found. The ratio of T, B cell lymphomas was different in NP-ML(T: B = 17: 18) and N-ML (T: B = 10: 3) groups, and the predominance of T-cell N-ML was obvious. Immunostaining with cytokeratin, LCA, L26, UCHL1 is of great help in differential diagnosis and immunophenotyping.     

ENZYME HISTOCHEMICAL CHARACTERISTICS OF NON-HODGKIN'S LYMPHOMAS

Fourteen cases of non-Hodgkin's lymphoma were investigated by both light and electron microscopic enzyme histochemical methods. These cases included 3 mycosis fungoides (MF), 1 chronic lymphocytic leukemia (CLL), 1 hairy cell leukemia (HCL), 5 diffuse histiocytic (DH), 1 nodular histiocytic (NH) and 3 diffuse lymphocytic, poorly differentiated (DLPD) lymphomas. All of these cases except 2 MF and 1 DH were further characterized by an identification of surface markers. Enzymes studied were alkaline phosphatase (AlPase), acid phosphatase (AcPase), β-glucuroddase (β-Gase), adenosine triphosphatase (ATPase), 5'-nucleotidase (YNase), α-naphthyl acetate esterase (α-N. acet eat), naphthol AS-D chloroacetate esterase (N. AS-D chlor eat), naphthol AS acetate esterase (N. AS acet eat) and α-naphthyl butyrate esterase (α-N. but eat). Strong ATPase activity was observed in 4 DH bearing B-cell markers. Four lymphomas (lMF, 2DPLD and 1DH) having T-cell markers never revealed such an ATPase activity. However, lymphomas with T-cell character showed stronger eccentrically localized activity of β-Gase and/or AcPase in the majority of neoplastic cells. One DLPD with B-cell markers showed AlPase activity. Localized α-N. acet eat activity was demonstrated in 2MF, 1DH and 1DLPD. No activity of S'Nase, N. AS-D chlor eat, N. AS acet eat and α-N. but eat was found in the neoplastic cells of all cases. It is suggested that ATPase, β-Gase and AcPase are considered to be an easy method for differentiating either T- or B-cell nature and useful in the classification of non-Hodgkin's lymphomas.     

Clinicopathological analysis of 501 non-Hodgkin's lymphomas in Korea according to the revised European-American classification of lymphoid neoplasms

AIMS: The clinical relevance of the Revised European-American Classification of Lymphoid Neoplasms (REAL) is still debated. To test the clinical validity of the REAL classification in Korea, where the incidence of T-cell lymphoma is higher, we investigated the clinicopathological features of non-Hodgkin's lymphoma (NHL) from Korea Cancer Center Hospital. METHODS AND RESULTS: Five hundred and one patients with NHL were reclassified according to the REAL classification and clinicopathologically analysed. Immunophenotypically, B-cell lymphoma accounted for 67.9% and T- and NK-cell type for 30.5%. Approximately 48.5% of cases were forms of diffuse large B-cell lymphoma (DLBCL), while only 5.4% were follicular lymphoma. Peripheral T-cell lymphoma unspecified (PTCL-U; 10.8%) and angiocentric lymphomas (11.8%) comprised the majority of T-cell lymphomas. Most of the angiocentric lymphomas presented with localized nasal/nasopharyngeal or tonsillar primaries. All peripheral T-cell lymphomas (PTCL) showed a significantly low overall survival compared to DLBCL (P = 0.02, log rank). Overall survival rates for DLBCL and PTCL-U were also significantly different (P = 0.0043, log rank), though for DLBCL and angiocentric lymphoma there was no significant difference (P = 0.2142, log rank). Angiocentric lymphoma, however, was characterized by a shorter median survival time than DLBCL (54 months vs. 96 months). Among DLBCL patients according to the REAL classification, overall survival was significantly better in nonimmunoblastic type (intermediate-grade, WF-F,G) as compared to large cell immunoblastic type (high-grade, WF-H) (log rank, P < 0.001). The morphological distinction of the immunoblastic and nonimmunoblastic among DLBCL of the REAL classification bears significant prognostic relevance worthy of further consideration. CONCLUSION: We conclude that lineage assignment (T vs. B) in the REAL classification is a clinically important distinction, but that it is necessary to subdivide the broad category of DLBCL.     

Diffuse large B-cell lymphoma and its variants

According to the World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues, diffuse large B-cell lymphoma comprises about 40% of adult cases of non-Hodgkin s lymphoma. It consists of the following morphological variants: 1) centroblastic (with or without multilobulated nuclei); 2) immunoblastic (>90% of immunoblasts); 3) T cell/histiocytes rich; and 4) anaplastic. Rare morphological variants plasmablastic type, mediastinal (thymic) diffuse large B-cell lymphoma, intravascular, and primary effusion B-cell lymphoma are considered distinct variants of diffuse large B-cell lymphoma due to their unique topographic presentation and clinical behavior, as well as immunophenotypic and genetic characteristics. T-cell/histiocyte-rich B-cell lymphoma is morphologically characterized by up to 25% of large neoplastic B cells and 75-90% of reactive, non-neoplastic T cells. Mediastinal (thymic) diffuse large B-cell lymphoma is considered a subtype of diffuse large B-cell lymphoma arising in the mediastinum, with distinctive morphological, immunohistochemical, genotypic, and clinical features. Mediastinal diffuse large B-cell lymphoma is an aggressive disease with poor outcome, which probably originates from thymic B cells at the terminal stage of differentiation. During the 1997-2001 period, 720 patients were diagnosed with non-Hodgkin s lymphoma in our institution. Out of 101 (14%) patients with diffuse large B-cell lymphoma, 17 had T-cell-rich B-cell lymphoma and their median survival was less than 20 months, with no difference regarding sex, bone marrow involvement, CD30 positivity, or histiocytic component of the tumor. Twenty out of 101 patients had mediastinal B-cell lymphoma and their median survival was 21 months, with sex or degree of necrosis of the involved lymph node having no impact on survival. We studied the frequency of bcl-2 gene rearrangement in fusion with immunoglobulin receptor gene of t(14;18) and found no such event among 20 of our patients with mediastinal diffuse large B-cell lymphoma. Despite extensive efforts and constant progress in our understanding of non-Hodgkin s lymphoma pathogenesis, the diffuse large B-cell lymphoma group remains heterogeneous entity awaiting further pathological and clinical stratification.     

Expression of a T-cell antigen (Leu-1) by B-cell lymphomas.

The Leu-1 antigen has been defined by monoclonal antibodies (L17F12, T101, and OKT-1) as a pan-T-cell antigen present on all human peripheral blood T cells and thymocytes. Although originally thought to be confined to T-cell lineage, some cases of B-cell chronic lymphocytic leukemia have been found to react with these antibodies. Using a frozen section immunoperoxidase staining technique, 125 lymphomas with B-cell differentiation were examined for the presence of Leu-1 antigen. Leu-1 antigen was detected in 4 of 11 cases of diffuse small lymphocytic lymphoma (Rappaport''s DWDL) and 3 of 4 cases of diffuse intermediate lymphocytic lymphoma. Follicular lymphomas less often expressed this antigen--2 of 29 cases of the small cleaved cell type (Rappaport''s NPDL), none of 13 cases of mixed small cleaved and large cell type (Rappaport''s NM), and 1 of 6 cases of large cell type (Rappaport''s NH). Diffuse lymphomas of presumed follicular center cell origin expressed this antigen infrequently as well--1 of 3 cases of the small cleaved cell type (Rappaport''s DPDL), neither of 2 cases of mixed small cleaved and large cell type (Rappaport''s DM), and 3 of 43 of large cell type (cleaved/noncleaved) (Rappaport''s DH). Diffuse large cell, immunoblastic lymphoma of B-cell type expressed Leu-1 in 1 of 6 cases. None of the 3 cases of Burkitt''s lymphoma or of the three small noncleaved non-Burkitt''s lymphoma (Rappaport''s undifferentiated) expressed detectable Leu-1. B-lymphoblastic lymphoma (1 case) and B-cell unclassified lymphoma (1 case) both failed to express detectable Leu-1. It appears that this pan-T-cell antigen is mainly found on those B-cell lymphomas composed predominantly of small lymphocytes. This finding may be of use in distinguishing extranodal neoplastic collections of small lymphocytes from lymphocytic hyperplasias.     

Clinical significance of histology and immunophenotype in childhood diffuse large cell lymphoma

To correlate the histologic subtype of diffuse large cell (DLC) lymphoma with immunophenotype, clinical features, and treatment outcome, 88 consecutively diagnosed children with this disease were studied. Of these cases, 42 (48%) were immunoblastic (IB), polymorphous subtype; 17 (19%) IB, plasmacytoid; 8 (9%) IB, clear cell; 6 (7%) IB, not otherwise specified; and 15 (17%) DLC-follicular center cell (DLC-FCC) type. Of 34 cases successfully phenotyped from paraffin sections, 13 were T cell and 9 were B cell; of the remaining cases, 8 were suggestive of T-cell lineage, 3 of B-cell lineage, and 1 of histiocytic differentiation. Although histologic subtype did not correlate with clinical features or outcome, it did correlate with immunophenotype among those cases for which lineage could be unequivocally assigned (5 of 18 IB vs. 4 of 4 DLC cases were B cell; P = 0.02) Immunophenotype was also correlated with stage of disease (11 of 13 T-cell vs. 3 of 9 B-cell cases had stage III-IV disease; P = 0.03). (Stage III includes all primary thoracic tumors; stage IV includes all with central nervous system and/or bone marrow involvement.) Significant prognostic features were clinical stage and era (thus type) of therapy (P less than 0.001). The authors conclude that most cases of large cell non-Hodgkin's lymphoma in children are of IB morphologic type, most frequently of T-cell lineage, and those with T-cell phenotype appeared to have more advanced disease.     

Non-Hodgkin's lymphoma in the first two decades

Summary The histopathologic and anatomoclinical features of 211 cases of non-Hodgkin's lymphoma (NHL) were reviewed and each case reclassified according to Lukes-Collins, Kiel and Rappaport criteria. Immunologic determination of cell phenotype in 63 cases as well as assessments of immunoglobulin and lysozyme by immunoperoxidase in 48 cases, permitted a precise definition of cell lineage on a functional basis and showed a high degree of predictability of immunologic phenotype of lymphoma cells by conventional morphology. The results of immunologic cell typing and immunoperoxidase studies were consistent with functional schema of Lukes-Collins and Kiel. True histiocytic proliferations, (9 cases) showed biologically different behavior from malignant lymphoma (ML), by a high incidence of extralymphatic (skin and soft tissue) presentation, rapid course, and frequent conversion to histiocytic leukemia. Fifty-two percent of studied ML cases were categorized morphologically as B-cell line proliferations, 36.7% as T-cell line and 6.9% as undefined group (ML U type). The ratio of T-cell to B-cell malignancies was 11.4. The convoluted type lymphoma was characterized by a high incidence (70%) of anterior mediastinal presentation, high incidence (over 60%) of hematologic and CNS involvement, and a high probability of testicular relapse, especially late. In contrast to malignancies of the T-cell line, B-cell proliferations tended to be localized below the diaphragm, and the most common anatomic location of lymphoma growth appeared to be the gastrointestinal tract, where small and large noncleaved follicular center cell types predominated. The nodular lymphoid hyperplasia in the vicinity of intestinal lymphoma and lack of secretory component within enterocytes were other substantial findings in abdominal B-cell malignancies. Among immunoblastic proliferations, the B-cell type was found to predominate over T-cell and was characterized as highly aggressive disease with a relatively common marrow infiltration. A low anatomic stage of disease and a favorable outcome were closely related to small cleaved type of follicular center cell lymphoma, which comprised only 1.5% of the patients studied. The less defined and morphologically heterogeneous group formed ML U, which in over 95% of patients converted to acute lymphocytic leukemia. This joint analysis of primary leukemic and non-leukemic NHL patients disclosed striking differences in anatomic presentation and natural history of disease between T, B and null cell proliferations versus related cytologic types.Supported by Cancer Center Support (CORE) Grant CA 21765 from the National Cancer Institute, Grant IN 99-E from the American Cancer Society and by ALSAC     

Primary gastric lymphomas: Morphologic, immunohistochemical and immunogenetic analyses

Morphologic, lmmunohistochemical and lmmunogenetic studies were performed on 28 cases of primary gastric lymphoma from fresh frozen tissue. Eight cases were diagnosed as diffuse large B-cell lymphoma, four as follicular center lymphoma (follicular), five as mucosa-associated lymphoid tissue (MALT) lymphoma, three as plasmacytoma, and three as T-cell lymphoma, two as mantle cell lymphoma, one as follicular center lymphoma (diffuse, predominantly small cell), and one as lymphoplasmacytoid lymphoma, and one as Hodgkin's disease.
From lmmunohistochemical studies, four types of morphologically similar low-grade lymphomas can be differentiated by a combination of various monoclonal antibodies. Cases of diffuse large B-cell lymphoma may have a germinal center origin. We observed lympho-epithelial lesions in cases of non-MALT lymphomas. We therefore consider that the current diagnostic criterion for MALT lymphoma may not always be valid.
Except for cases of T-cell lymphoma and Hodgkin's disease, 17 out of 22 cases revealed clonal rearrangement bands of the JH gene. In situ hybridization (ISH) and polymerase chain reaction (PCR) studies revealed the presence of Epstein-Barr (EB) virus genomes in two and three cases, respectively. Epstein-Barr virus may play a role in lympho-magenesis, although on relatively rare occasions.     

Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphomas

CD43 expression on B cells is an immunophenotypic feature suggestive of malignancy. In the light of its diagnostic importance, we performed a comprehensive survey of CD43 expression in various types of non-Hodgkin lymphoma (NHL) and determined the frequency of its expression in routinely fixed paraffin-embedded tissues. Tissue sections in 742 cases of NHL, pretreated by the heat-induced epitope retrieval technique, were immunostained using an anti-CD43 antibody. Three categories of CD43 positivity were found: (1) more than 90% of T-cell lymphoma, mantle cell lymphoma, B-cell small lymphocytic lymphoma, and Burkitt lymphoma cases were positive; (2) 20% to 40% of nodal and extranodal marginal zone lymphoma (MZL), diffuse large B-cell lymphoma, Burkitt-like B-cell lymphoma, and lymphoplasmacytoid lymphoma cases were positive; and (3) 0% to 6% of primary splenic MZL and various types of follicular lymphoma cases were positive. Most CD43+ follicular lymphomas were predominantly large cell type with focally diffuse areas; their follicular center cell origin in 4 of 8 cases was supported by the presence of CD10 immunoreactivity and/or t(14;18) fusion gene product. CD43 is frequently detectable in a subset of B-NHL, and, thus, it seems to be a highly sensitive marker for these tumors. CD43 also may be a useful marker for classifying B-cell NHLs by virtue of its differential expression in these tumors.     

Ultrastructural characteristics of malignant non-Hodgkin's lymphoma in baboons

The ultrastructure of 29 malignant non-Hodgkin's lymphomas of baboons including prolymphocytic lymphoplasmacytic, lymphoblastic, and immunoblastic malignant lymphomas is described. The ultrastructure of the cells of B-cell malignant lymphomas is characterized by a more developed strands system of rough endoplasmic reticulum in the tumor cell cytoplasm and the presence of structural abnormalities in the protein synthesis in some B-cell malignant lymphoma cells in the form of Russell's and Dutcher bodies. Analogous baboon and human tumors were shown to have a high degree of cell ultrastructure similarity. Rare forms of baboon malignant non-Hodgkin's lymphomas including a large-cell variant of T-cell lymphoblastic lymphoma with large multilobated nuclei and a variety of B-cell lymphoma with an intermediate degree of cell differentiation have been found. Malignant lymphoma of large multilobated T-cell type and lymphoma of the intermediate lymphocytic type occur rarely in human pathology too.     

The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796 cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T-cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T-cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T- and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV-1.     

Clusterin expression in malignant lymphomas: a survey of 266 cases.

Clusterin expression has been reported to be characteristic of systemic anaplastic large cell lymphoma and usually negative in cutaneous anaplastic large cell lymphoma as well as other lymphoma types. We surveyed clusterin expression using immunohistochemical methods in 266 cases of non-Hodgkin's lymphoma and Hodgkin's disease to further assess the diagnostic utility of this marker. Clusterin immunostaining was observed in 40 of 49 (82%) systemic anaplastic large cell lymphomas and 12 of 29 (41%) cutaneous anaplastic large cell lymphomas. Clusterin also was expressed in 5 of 43 (12%) diffuse large B-cell lymphomas (4 of 5 CD30+), 1 of 14 (7%) peripheral T-cell lymphomas, 1 of 32 (3%) cases of nodular sclerosis Hodgkin's disease, and 1 case of mycosis fungoides in large cell transformation. Clusterin was negative in all other neoplasms assessed including follicular lymphoma of all grades (n = 24), mantle cell lymphoma (n = 13), marginal zone B-cell lymphoma (n = 12), precursor T-cell or B-cell lymphoblastic leukemia/lymphoma (n = 10), mixed cellularity Hodgkin's disease (n = 8), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7), Burkitt lymphoma (n = 7), mycosis fungoides (n = 4), nodular lymphocyte predominant Hodgkin's disease (n = 3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (n = 2), and plasmacytoma (n = 2). We conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin's disease is useful. However, clusterin is also positive in a substantial subset of cutaneous anaplastic large cell lymphomas, a smaller subset of diffuse large B-cell lymphomas, and rarely in cases of peripheral T-cell lymphoma and nodular sclerosis Hodgkin's disease.     

Primary mediastinal non-Hodgkin's lymphomas: a morphologic and immunologic study of 19 cases

Nineteen, primary, non-lymphoblastic, non-Hodgkin's lymphomas were investigated by conventional morphologic studies as well as immunologic studies using the application of a battery of monoclonal antibodies to frozen tissue sections. Seventeen of the lymphomas were diffuse large cell; one was large cell immunoblastic and one was a follicular and diffuse lymphoma of intermediate differentiation. Thirty-seven percent of the lymphomas showed prominent sclerosis, sometimes associated with the superior vena cava syndrome. Six of the cases showed evidence of immunoglobulin production with light chain restriction. Twelve additional cases were shown to be of B-cell lineage by B1/T015 expression but did not show evidence of immunoglobulin production. One case was a T-cell lymphoma of helper phenotype. Ia expression was found in 14 of 18 cases studied.