Plasmablastic Differentiation Research Articles

Plasmablastic lymphomas with light chain restriction – plasmablastic extramedullary plasmacytomas?

It is diagnostically difficult to differentiate plasmablastic lymphomas (PBLs) from plasma cell neoplasms with plasmablastic differentiation. Plasmablastic lymphomas are currently classified as 'PBL of the oral mucosa' and 'PBL with plasmacytic differentiation'. Forty-five cases of PBL were retrieved from the Departments of Oral Pathology of the Universities of Pretoria and Limpopo, South Africa. Clinical features and HIV status were recorded and each case was classified as 'PBL of the oral mucosa type' or as 'PBL with plasmacytic differentiation'. Immunohistochemistry included: CD45, CD3, CD20, CD79a, CD38, CD138, MUM1, Ki-67 and kappa and lambda light chains. Positivity was recorded based on the percentage of positive staining cells as focal (5-20%); intermediate (20-70%) or diffuse (>70%). In situ hybridization was performed for Epstein-Barr virus (EBV) and HHV-8. Results were recorded as positive or negative. All cases showed some degree of plasmacytic differentiation. All were negative for CD20 with reactive T cells detected with CD3. Diffuse and strong positive staining was found with Ki-67 and MUM1, but variable immunoreactivity was found with CD79a, CD45, CD38 and CD138. Twenty cases (47%) showed light chain restriction. Epstein-Barr virus was detected in 44/45 cases and HHV-8 in none. The morphological classification of PBLs is not valid as all cases showed some degree of plasmacytic differentiation. We propose that PBLs with light chain restriction be reclassified as 'plasmablastic extramedullary plasmacytomas' and managed accordingly. The rest represents true PBLs. The true nature of these neoplasms as an entity should be further investigated with molecular and genetic studies.

Lymphomas in the bone marrow

Lymphomatous infiltrates are most commonly encountered in a bone marrow biopsy (BMB) taken for lymphoma staging or for diagnosis of a suspected haematological abnormality. Crucial for staging, the BMB may show classic and variant patterns of lymphomatous infiltration and immunoprofile. Exceptions to the common profiles may be associated with variant cytogenetics and have prognostic implications. Diagnosis should be multifaceted and flow cytometry and molecular studies may be required to arrive at a final diagnosis. Assessment of haematopoiesis should be included in all reports. In follow-up biopsies, disease bulk may be markedly reduced and reactive lymphoid proliferation may complicate the morphological assessment. Transformation of the original lymphoma to a higher grade or the development of a new type of lymphoma may occur or the BMB may be discordant with the lymph node diagnosis. Plasma cell myeloma and related disorders must be considered in the differential diagnosis of lymphoid proliferations with plasmacytic and plasmablastic differentiation. Diffuse interstitial lymphocytosis, lymphoid aggregates, lymphoid follicles with germinal centres and reactive lymphohistiocytic infiltrates may mimic lymphomas.

A Case Report with Plasmablastic Lymphoma of the Jejunum

Plasmablastic lymphoma (PBL) is a recently identified entity that is considered to be a type of diffuse large B-cell lymphoma with a unique immunophenotype and a predilection for the oral cavity of patients with the human immunodeficiency virus (HIV). Although its clinical features may help in the differential diagnosis, an extraoral location in a patient without HIV makes it more difficult to suspect clinically. This case report is the first to describe a patient with PBL originating from the jejunum in a 60-yr-old, HIV-seronegative man. Computed tomography of the face, chest and abdomen showed about a 9.4×9.0 cm mass of the proximal jejunum, multiple masses in the musculoskeletal soft tissue, and multiple lymphadenopathies. The histological examinations demonstrated a large cell lymphoma with plasmablastic differentiation. The neoplastic cells were diffusely positive for MUM1, epithelial membrane antigen and lambda light chains, and focally positive for CD79a; but negative for CD3, CD20, CD30, CD34, CD45RO, CD56, CD99, and CD117. The proliferation index by Ki-67 immunohistochemistry was approximately 70%. These findings were compatible with the diagnosis of PBL. The findings in this case suggest that PBL should be included in the differential diagnosis of a small bowel mass even in a HIV-negative patient.

ALK-positive Diffuse Large B-cell Lymphoma With the t(2;17)(p23;q23)

Diffuse large B-cell lymphoma (DLBCL) with plasmablastic features associated with t(2;17)(p23;q23) and characteristic granular cytoplasmic anaplastic lymphoma kinase-1 (ALK1) protein expression is a rare lymphoma subtype. Nodal and extranodal involvement has been reported. Our case is a 32-year-old man with right cervical adenopathy. Lymph node biopsy showed large atypical cells with prominent plasmablastic differentiation, abundant amphophilic cytoplasm, and prominent central nucleoli. Paraffin immunohistochemistry showed finely granular cytoplasmic ALK1 expression, positive CD138, IgA, p63 (VS38), focal positive epithelial membrane antigen and CD4, and lambda light chain restriction whereas negative CD20 and CD30 staining. While reports show detection of the unique CLTC-ALK fusion by either reverse transcription-polymerase chain reaction or fluorescence in situ hybridization, our case represents the second case in the literature to detect the t(2;17)(p23;q23) translocation by multiplex karyotyping (multiplex fluorescence in situ hybridization) and the usefulness of this technique to detect hidden translocations not seen by G-banding. An add(2)(p23) was also seen not previously reported. Differential diagnoses of neoplasms with plasmablastic differentiation and a comprehensive molecular/cytogenetic literature review of ALK+DLBCL is discussed.

CD20-Negative CD138-Positive Leukemic Large Cell Lymphoma with Plasmablastic Differentiation with an IgH/MYC Translocation in an HIV-Positive Patient

A 49-year-old HIV-positive Japanese man was referred to our hospital for multiple skin nodules. Many plasmablastic atypical lymphocytes were observed in the peripheral blood. He was diagnosed with diffuse large B cell lymphoma (DLBCL) by a biopsy of the inguinal lymph node. IgH/MYC translocation was detected by in situ hybridization of the lymph node and chromosomal analysis of bone marrow cells showed 46, XY, t(8 ; 14)(q24 ; q32)add(14)(q32), der(21)t(1 ; 21)(q12 ; p11). He showed a transient response to multi-agent chemotherapy, and during the course of salvage chemotherapy, he died of urinary infection. This case has unique clinical features compared with previously reported DLBCLs with plasmablastic differentiation.

Carcinoma Versus Cytokeratin-Positive Lymphoma: A Case Report Emphasizing the Diagnostic Role of Electron Microscopy

Lymphoma diagnosis rarely needs electron microscopy (EM), but one area where it can be useful is in the distinction of cytokeratin-positive lymphoma from carcinoma. The authors describe such a case, where difficulties were encountered due to lack of antibody specificity, distinguishing reactive from tumoral cells, and suboptimal sampling for EM. The tumor was in a lymph node next to the right submandibular gland in a 69-year-old man. This was a malignant tumor, composed of sheets of monomorphic large round cells. Interpretation on the part of a team of pathologists who examined this tumor was divided. On histological sections, the differential diagnosis was between carcinoma and lymphoma, which was modified to cytokeratin-positive lymphoma versus carcinoma since tumor cells were found to be cytokeratin-positive. EM of tumor retrieved from formalin showed plasmablastic features, in keeping with lymphoma with plasmablastic differentiation, one of the light microscopy diagnoses. The moderately strong positivity of cytokeratin and the positivity for Ber-EP4, however, supported carcinoma, and further sampling for EM was carried out, specifically on a cytokeratin-positive area of the wax block. Tonofibrils were found, supporting carcinoma. The final diagnosis was undifferentiated carcinoma with unknown primary site. The study emphasizes the need to take into account the imperfect specificity of cytokeratin, which can be found in several hemolymphoid neoplasms, to distinguish reactive from neoplastic cells, and to secure appropriate sampling for EM. This is one of the occasions where dewaxing (of an immunohistochemically defined wax block) offers positive advantages, despite compromised structural preservation, in the search for diagnostically important organelles.

Minimum diagnostic criteria for plasmablastic lymphoma of oral/sinonasal region encountered in a tertiary cancer hospital of a developing country

Haematolymphoid tumours other than plasmablastic lymphoma (PBL) may reveal plasmablastic differentiation with overlapping immunoreactivity causing diagnostic dilemma. Elaborate ancillary diagnostic techniques can make the process expensive, tedious and out of reach for pathology laboratory in a developing country. Out of 98 total cases of primary non-Hodgkin's lymphoma and plasmacytoma of oral-sinonasal region recorded in our institute over 4 years, 39 cases showing varied plasmablastic differentiation were selected. Morphological and immunohistochemical criteria were applied to identify minimum diagnostic criteria for PBL. Human Immunodeficiency Virus (HIV) correlation and Epstein-Barr virus expressed RNA (EBER) in-situ hybridisation studies were also performed. Minimum morphological criteria required to diagnose PBL were: (1) predominant population of plasmablasts which are large monomorphic cells with high nuclear-cytoplasmic ratio, moderate amount of amphophilic cytoplasm and round nucleus with prominent central nucleolus, (2) high mitotic and/or apoptotic index and (3) absence of neoplastic plasma cells in the background. Essential diagnostic immunophenotype consisted of CD20 negativity, LCA +/-, CD138/VS38c diffuse positivity, light chain restriction and high MIB-1 index (>60 %). Twenty-five of the total 32 PBL cases thus identified, involved oral cavity. Of these, 84% affected gingivo-buccal complex. Twenty-eight cases were HIV positive. EBER positivity confirmed the diagnosis in all the HIV-negative cases. A triad of 'rapidly growing lesion with predilection for oral mucosa, classical plasmablastic morphology and limited immunohistochemical panel' can render a reliable diagnosis of PBL, irrespective of HIV and EBV status, especially in developing countries with limited resources.

Plasmablastic lymphoma: One or more entities?

American Journal of HematologyVolume 83, Issue 10 p. 763-764 CommentaryFree Access Plasmablastic lymphoma: One or more entities?† Antonino Carbone, Corresponding Author Antonino Carbone [email protected] Department of Pathology, National Cancer Institute of Milan, Milan, ItalyDepartment of Pathology, Fondazione IRCCS, Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milano, ItalySearch for more papers by this authorAnnunziata Gloghini, Annunziata Gloghini Department of Pathology, National Cancer Institute of Milan, Milan, ItalySearch for more papers by this author Antonino Carbone, Corresponding Author Antonino Carbone [email protected] Department of Pathology, National Cancer Institute of Milan, Milan, ItalyDepartment of Pathology, Fondazione IRCCS, Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milano, ItalySearch for more papers by this authorAnnunziata Gloghini, Annunziata Gloghini Department of Pathology, National Cancer Institute of Milan, Milan, ItalySearch for more papers by this author First published: 22 July 2008 https://doi.org/10.1002/ajh.21259Citations: 29 † Conflict of Interest: Nothing to report. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 ES Jaffe, NL Harris, H Stein, JW Vardiman, Editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001. 2 Delecluse HJ,Anagnostopoulos I,Dallenbach F, et al. Plasmablastic lymphomas of the oral cavity: A new entity associated with the human immunodeficiency virus infection. Blood 1997; 89: 1413– 1420. 3 Castillo J,Pantanowithz L,Dezube BJ. HIV-associated plasmablastic lymphoma: A literature review of 112 cases. Am J Hematol, in press. 4 Nador RG,Cesarman E,Chadburn A, et al. Primary effusion lymphoma: A distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 1996; 88: 645– 656. 5 Dupin N,Diss TL,Kellam P, et al. HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma. Blood 2000; 95: 1406– 1412. 6 Deloose ST,Smit LA,Pals FT, et al. High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma. Leukemia 2005; 19: 851– 855. 7 Carbone A,Gloghini A,Vaccher E, et al. KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects: Report of two cases with anaplastic large cell morphology and plasmablastic immunophenotypes. J Clin Pathol 2005; 58: 1039– 1045. 8 Klein U,Gloghini A. Gaidano G, et al. Gene expression profile analysis of AIDS related primary effusion lymphoma (PEL) suggest a plasmablastic derivation and identifies PEL-specific transcripts. Blood 2003; 101: 4115– 4121. 9 Carbone A,Gloghini A,Larocca LM, et al. Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells. Blood 1999; 93: 2319– 2326. 10 Klein U,Dalla-Favera R. Germinal centres: Role in B-cell physiology and malignancy. Nat Rev Immunol 2008; 8: 22– 33. 11 Vockerodt M,Morgan S,Kuo M, et al. The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype. J Pathol, [Epub ahead of print]. 12 Colomo L,Loong F,Rives S, et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol 2004; 28: 223– 228. 13 Petitjean B,Jardin F,Joly B, et al. Pyothorax-associated lymphoma: A peculiar clinicopathologic entity derived from B-cells at late stage of differentiation and with occasional aberrant dual B- and T-cell phenotype. Am J Surg Pathol 2002; 26: 724– 732. 14 Carbone A,Gloghini A.Vaccher E, et al. Kaposi's sarcoma-associated herpes virus/human herpes virus type 8-positive solid lymphoma. A tissue-based variant of primary effusion lymphoma. J Mol Diagn 2005; 7: 17– 27. Citing Literature Volume83, Issue10October 2008Pages 763-764 ReferencesRelatedInformation

Cytomorphology and Molecular Characterization of CLTC-ALK Rearrangement in 2 Cases of ALK-Positive Diffuse Large B-cell Lymphoma with Extensive Bone Marrow Involvement

Aanaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is an unusual disease entity first reported in 1997 as DLBCL with expression of full-length ALK protein. The World Health Organization classification enlists the disease as a rare variant of DLBCL. Herein we describe two cases of ALK-positive DLBCL with cytomorphologic and molecular characteristics for the first time in Korea. The patients were 35-yr-old and 24-yr-old male patients. Immunohistochemical studies on the lymph nodes revealed large sized neoplastic cells with plasmablastic differentiation, which were negative for CD30 and positive for ALK with the characteristic granular staining in the cytoplasmic region. Extensive involvement of bone marrow was observed in both cases showing large, extremely atypical cells. Fluorescence in situ hybridization and molecular studies on the bone marrow aspirate specimens led to the detection of a clathrin (CLTC)/ALK rearrangement. Despite aggressive chemotherapy, the patients died 15 and 17 months after the diagnosis, indicating poor prognosis of the disease entity. This is the first report demonstrating the cytomorphologic findings of ALK-positive DLBCL cells on bone marrow aspirates.

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma

The tissue inhibitor of metalloproteinase-1 (TIMP-1) is a stromal factor that promotes plasmablastic differentiation, and the survival of germinal center B-cells. The expression of TIMP-1 is known to be correlated with a subset of non-Hodgkin lymphoma at the mRNA level, and Epstein–Barr virus infection in vitro. To characterize TIMP-1(+) diffuse large B-cell lymphoma, TIMP-1 expression was investigated in tissue microarrays from 182 cases of de novo diffuse large B-cell lymphoma and compared with prognostic factors, immunophenotypes, and Epstein–Barr virus infection status. TIMP-1 was expressed not only in tumor cells themselves, in 14 of 182 cases (8%), designated as TIMP-1(+) diffuse large B-cell lymphoma, but also in stromal cells like fibroblasts and endothelial cells. In univariate analysis and hierarchical clustering, our findings suggest that TIMP-1 expression may represent a distinct subgroup. In multivariate analysis, TIMP-1(+) diffuse large B-cell lymphoma (n=14) was associated with unfavorable outcomes compared to TIMP-1(−) diffuse large B-cell lymphoma (n=168) (odds ratio=2.5, P=0.049). Together with TIMP-1 expression, age (greater than 60 years), the presence of B-symptoms, abnormal lactate dehydrogenase level, or more advanced stage (III/IV) was correlated with a poor overall survival. However, TIMP-1 expression in diffuse large B-cell lymphoma was not correlated with other prognostic factors including: clinical stage, international prognostic index score, and nongerminal center B-cell phenotype, as well as Epstein–Barr virus infection. Our results suggest that TIMP-1 expression may be an independent negative prognostic factor in patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphomas with plasmablastic differentiation

Recent evidence suggests that diffuse large B-cell lymphoma (DLBCL) with plasmablastic differentiation represents a clinically heterogeneous spectrum with different clinicopathologic characteristics representing distinct entities. Subtypes of DLBCL with plasmablastic features and terminal B-cell differentiation include plasmablastic lymphoma (PBL) of oral mucosa type; PBL with plasmacytic differentiation; primary effusion lymphoma (PEL); KSHV-positive solid lymphoma/extracavitary PEL/HHV-8 associated DLBCL; and DLBCL expressing ALK. In contrast, PBL associated with multicentric Castleman disease, DLBCL with secretory differentiation, pyothorax-associated lymphoma, and atypical Burkitt lymphoma with plasmacytoid differentiation have morphologic appearances of plasma cell differentiation but maintain a mature B-cell (CD20 positive) phenotype. These tumors as well as extramedullary plasmablastic tumors secondary to multiple myeloma or plasmacytomas are included in the differential diagnosis. In this review, we discuss recently described clinicopathologic insights, case observations, and recently reported molecules involved in terminal B-cell or plasma cell differentiation and their possible roles in disease pathogenesis.

Plasmablastic lymphoma of oral mucosa type: A case report

A case of the plasmablastic lymphoma of oral mucosa type is described. A 60-year-old white man presented an ulcerated and bleeding swelling in the upper lip. The right hard and soft palate showed a swelling covered by a yellowish membrane. Microscopical examination showed a monotonous diffuse lymphoid proliferation of large cells with plasmablastic differentiation. The cells were immunopositive for VS38c. A PCR demonstrated IgH with monoclonal pattern and EBV DNA. The lesions resolved after treatment with local radiotherapy and systemic chemotherapy. The patient remains free of the disease after twenty-three months of treatment.

Tissue inhibitor of metalloproteinase 1 (TIMP-1) promotes plasmablastic differentiation of a Burkitt lymphoma cell line: implications in the pathogenesis of plasmacytic/plasmablastic tumors

AbstractTissue inhibitor of metalloproteinase 1 (TIMP-1) is a stromal factor with multiple functions. Overexpression of TIMP-1 correlates with aggressive clinical behavior of a spectrum of tumors. Here, for the first time, we address the role of TIMP-1 in the pathogenesis of B-cell lymphomas. An Epstein-Barr virus (EBV)-negative Burkitt lymphoma cell line with ectopic TIMP-1 expression (TIMP-1JD38) was used to identify genes induced/repressed by TIMP-1. Differentially expressed genes were analyzed by cDNA microarray, and they were validated by immunohistochemistry, flow cytometry, and Western blotting. Analysis revealed changes of genes coding for B-cell growth/differentiation, transcription, and cell cycle regulators. TIMP-1 repressed expression of germinal center (GC) markers CD10, Bcl-6, PAX-5 and up-regulated plasma cell-associated antigens CD138, MUM-1/IRF-4, XBP-1, and CD44, suggesting a plasma cell differentiation. This is accompanied by activation of signal transducer and activator of transcription 3 (STAT-3) and switch to cyclin D2 expression. However, TIMP-1JD38 cells expressed an inactive form of XBP-1, lacking antibody production/secretion. This incomplete plasmacytic differentiation occurs without altering cell proliferation, and despite c-Myc deregulation, indicating an arrested plasmacytic/plasmablastic stage of differentiation. Further validation in human lymphoma cell lines and in primary B-cell tumors demonstrated a predominant TIMP-1 expression in tumors with plasmacytic/plasmablastic phenotypes, including multiple myelomas. These findings strongly support TIMP-1 as an important factor in the pathogenesis of plasmacytic/plasmablastic tumors. (Blood. 2005;105:1660-1668)

Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities.

Plasmablastic lymphoma was initially described as a variant of diffuse large B-cell lymphoma (DLBCL) involving the oral cavity of HIV+ patients and characterized by immunoblastic morphology and a plasma cell phenotype. However, other lymphomas may exhibit similar morphologic and immunophenotypic features. To determine the significance of plasmablastic differentiation in DLBCL and examine the heterogeneity of lymphomas with these characteristics, we examined 50 DLBCLs with low/absent CD20/CD79a and an immunophenotype indicative of terminal B-cell differentiation (MUM1/CD38/CD138/EMA-positive). We were able to define several distinct subgroups. Twenty-three tumors were classified as plasmablastic lymphoma of the oral mucosa type and showed a monomorphic population of immunoblasts with no or minimal plasmacytic differentiation. Most patients were HIV+ and EBV was positive in 74%. Eleven (48%) cases presented in the oral mucosa, but the remaining presented in other extranodal (39%) or nodal (13%) sites. Sixteen cases were classified as plasmablastic lymphoma with plasmacytic differentiation. These were composed predominantly of immunoblasts and plasmablasts, but in addition exhibited more differentiation to mature plasma cells. Only 33% were HIV+, EBV was detected in 62%, and 44% had nodal presentation. Nine cases, morphologically indistinguishable from the previous group, were secondary extramedullary plasmablastic tumors occurring in patients with prior or synchronous plasma cell neoplasms, classified as multiple myeloma in 7 of the 9. Two additional neoplasms were an HHV-8+ extracavitary variant of primary effusion lymphoma and an ALK+ DLBCL. HHV-8 was examined in 39 additional cases, and was negative in all. In conclusion, DLBCLs with plasmablastic differentiation are a heterogeneous group of neoplasms with different clinicopathological characteristics that may correspond to different entities.

Epstein–Barr virus-related plasmablastic lymphomas arising from long-standing sacrococcygeal cysts in immunosuppressed patients

Epstein–Barr virus-related plasmablastic lymphomas arising from long-standing sacrococcygeal cysts in immunosuppressed patients

AIDS-related Burkitt's lymphoma. Morphologic and immunophenotypic study of biopsy specimens.

In patients infected with HIV, high-grade B-cell non-Hodgkin's lymphomas (NHL), including the small noncleaved cell (SNCC) category, exhibit pleomorphic features, which makes precise definition difficult. Sixty-nine pathologic specimens with HIV-related systemic lymphomas, including 42 SNCC, 20 immunoblastic lymphomas (IBL), and 7 cases with features "intermediate" between SNCC and IBL were morphologically and immunophenotypically investigated. The host immune status was also analyzed in 57 of 69 patients. In 29 representative SNCC lymphomas, in 9 IBL cases, and an additional 3 intermediate lymphomas, both p53 protein overexpression and the association of Epstein-Barr virus (EBV) genetic information were assessed. Small noncleaved cell lymphomas included tumors exhibiting features of the 2 established subtypes (27 Burkitt's and 15 non-Burkitt's). In the seven intermediate cases, cells showed features intermediate between SNCC with plasmablastic differentiation and immunoblasts plasmacytoid. Immunoblast-like cells were also present. p53 protein overexpression and EBV association were found in a proportion of SNCC (14 of 29; 7 of 29) and intermediate (3 of 3; 2 of 3) lymphomas. Conversely, IBL cases were consistently p53 negative, but showed a high EBV association (7 of 9). All the evaluated patients with intermediate lymphomas had a considerably lower mean (76.6 per mm3 +/- 77.4 SD) and median (54 per mm3) number of CD4+ lymphocyte count than SNCC patients (mean 227.9 per mm3 +/- 186.9 SD, median 193 per mm3), thus mirroring IBL patients (mean 95.3 per mm3 +/- 82.8 SD, median 81 per mm3). All data provide evidence that lymphomas showing intermediate features constitute a distinct subgroup from either SNCC or IBL.

Monocytoid B cell lymphoma.

The clinical, light microscopic, ultrastructural, immunocytochemical and cytogenetic features of a case of monocytoid B cell lymphoma were investigated. The tumour initially affected the cervical and supraclavicular nodes, but 33 months later affected the left parotid salivary gland. The patient had subclinical Sjögren's syndrome. The neoplastic cells showed characteristic morphological features and had peri- and interfollicular distribution in the node. Immunocytochemically the tumour cells were L26, 4KB5, MB2, CD19, CD20, CD22 and IgM/kappa positive. Prominent plasmablastic plasmacytoid differentiation was present in the recurrent tumour, suggesting an origin from post-follicular B cells. The lymphoma cells showed unusual cytogenetic abnormalities.

Gastric Large Cell Lymphoma Expressing Cytokeratin but no Leukocyte Common Antigen: An Editorial Dilemma

A case of undifferentiated malignant tumor of the stomach is reported. The immunohistochemistry of biopsy specimens pointed to a diagnosis of carcinoma, the tumor cells being cytokeratin positive and leukocyte common antigen (LCA) negative. After resection, however, histopathologic results showed that the tumor was a large cell lymphoma with plasmablastic differentiation. A new immunohistologic study confirmed, on the one hand, the diagnosis of lymphoma with its monotypic character IgA kappa and, on the other, positivity with three different cytokeratins of the lymphoma cells and their negativity with LCA. The aberrant immunophenotyping of this lymphoma is exceptional and must not undermine the recognized usefulness of LCA and cytokeratin, which both are basic antibody markers of immunohistochemistry in undifferentiated malignant neoplasms.

Gastric Large Cell Lymphoma Expressing Cytokeratin but No Leukocyte Common Antigen: A Diagnostic Dilemma

A case of undifferentiated malignant tumor of the stomach is reported. The immunohistochemistry of biopsy specimens pointed to a diagnosis of carcinoma, the tumor cells being cytokeratin positive and leukocyte common antigen (LCA) negative. After resection, however, histopathologic results showed that the tumor was a large cell lymphoma with plasmablastic differentiation. A new immunohistologic study confirmed, on the one hand, the diagnosis of lymphoma with its monotypic character IgA kappa and, on the other, positivity with three different cytokeratins of the lymphoma cells and their negativity with LCA. The aberrant immunophenotyping of this lymphoma is exceptional and must not undermine the recognized usefulness of LCA and cytokeratin, which both are basic antibody markers of immunohistochemistry in undifferentiated malignant neoplasms.

High‐grade non‐Hodgkin's lymphoma of B‐cell type. I. Histopathology

One hundred and twenty-eight cases of high-grade malignant B-cell lymphoma were studied with a plastic re-embedding technique and classified according to the Kiel classification. The cytological details could be better recognized than in the original paraffin sections, thus permitting a more precise definition of the various lymphoma types. The entities centroblastic and immunoblastic lymphoma are more precisely defined and supplemented by the addition of several new variants. In contrast to the present Kiel classification we separate Burkitt's from lymphoblastic lymphoma. In all cases investigated, the B-cell nature of the tumour cells was proven by immunohistochemistry using monoclonal antibodies. The four entities of high-grade malignant B-cell lymphoma described in this paper are: (1) centroblastic lymphoma with four morphological variants (monomorphic, polymorphic, multilobated and centrocytoid); (2) immunoblastic lymphoma with three morphological variants (with or without plasmacytic differentiation, with many lymphocytes); (3) Burkitt's lymphoma and the closely related Burkitt's lymphoma-like lymphoma with plasmablastic differentiation; and (4) lymphoblastic lymphoma. Only the centroblastic lymphomas (in 17%) showed occasional follicular growth pattern, which further confirms the view that they are derived from germinal centre cells.