Cytotoxic Cell Antigen Expression in Anaplastic Large Cell Lymphomas of T- and Null-Cell Type and Hodgkin's Disease: Evidence for Distinct Cellular Origin

Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 980-989 ◽  
Author(s):  
Laszlo Krenacs ◽  
Axel Wellmann ◽  
Lynn Sorbara ◽  
Andreas W. Himmelmann ◽  
Eniko Bagdi ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Expression ◽  
Large Cell ◽  
Cell Phenotype ◽  
Cytotoxic Lymphocytes ◽  
Cell Type ◽  
Null Cell ◽  
Cytotoxic Cell ◽  
Granule Protein ◽  
Cytotoxic Granule

Abstract Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre, cells of T- or null-cell phenotype that show a preferential sinusoidal growth pattern and consistent CD30 positivity. Whether these tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule component, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further investigate this possibility, we performed an immunohistochemical study of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/or CD30 positivity. We found that 76% of ALCLs, representing all subtypes except the PC forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1 and perforin were highly correlated (P < .001). On the basis of their immunophenotypic profiles, several subtypes of cytotoxic antigen positive and negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33) displayed an immunophenotypic profile consistent with cytotoxic T cells. Six cases expressed cytotoxic granular proteins in the absence of lineage specific markers, and one case expressed both T-cell – and natural killer cell–like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxic granule protein negative. All but one of these displayed a T-cell phenotype. Cytotoxic granule protein expression did not correlate with the presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found to be TIA-1+, and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic granule proteins in the majority of ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases originate from lymphocytes with cytotoxic potential. Furthermore, the demonstration of cytotoxic cell related proteins may be a useful addition to the current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL.

Anaplastic Large Cell Lymphoma Arising in Bone

2000 ◽  
Vol 124 (9) ◽  
pp. 1339-1343
Author(s):  
Mark A. Lones ◽  
Warren Sanger ◽  
Sherrie L. Perkins ◽  
L. Jeffrey Medeiros
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Correct Diagnosis ◽  
Cell Lineage ◽  
Antigen Expression ◽  
Large Cell ◽  
Null Cell ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

Abstract Anaplastic large cell lymphoma (ALCL) represents approximately 2% of all non-Hodgkin lymphomas according to the recent Non-Hodgkin Lymphoma Classification Project. As defined in the revised European-American classification of lymphoid neoplasms (REAL), ALCL is a neoplasm of T-cell or null-cell lineage; 20% to 60% of cases are associated with the t(2;5)(p23;q35) translocation. ALCL commonly involves nodal as well as a wide variety of extranodal sites, although primary or secondary involvement of bone is rare. We describe the case of a 71-year-old man with stage IE T-cell ALCL, monomorphic variant, arising in the left anterior fifth rib and involving adjacent soft tissue without other sites of disease. The monomorphic histologic features hindered the initial recognition of this neoplasm as ALCL. However, strong uniform CD30 antigen expression and subsequent demonstration of the t(2;5)(p23;q35) translocation and anaplastic lymphoma kinase (ALK) immunoreactivity led to the correct diagnosis. We identified only 5 reported cases of T-cell and null-cell ALCL arising in bone and only 2 of these cases involved a single bone site. All 5 previously reported cases were ALCL of the classic type. We report a case of ALCL that is unique to our knowledge. This case of monomorphic ALCL was localized to bone and tumor cells contained the t(2;5)(p23;q35) translocation.

Clinical features and treatment outcome for children with CD30+ large-cell non-Hodgkin's lymphoma.

1994 ◽  
Vol 12 (5) ◽  
pp. 895-898 ◽  
Author(s):  
J T Sandlund ◽  
C H Pui ◽  
V M Santana ◽  
H Mahmoud ◽  
W M Roberts ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
T Cell ◽  
Clinical Features ◽  
Large Cell ◽  
Cell Phenotype ◽  
Advanced Stage ◽  
Skin Involvement ◽  
Null Cell ◽  
Stage Disease ◽  
Working Formulation

PURPOSE To determine the frequency of CD30 expression and its relationship to clinical features, immunophenotype, histotype, and outcome in childhood large-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS We reviewed 45 cases of large-cell NHL in children treated at St Jude Children's Research Hospital from 1975 to 1990 for whom there was sufficient tissue to perform immunophenotypic studies. All 45 were screened with a panel of antibodies to detect the presence of CD30 and T-cell and B-cell antigens. Cases were classified according to the National Cancer Institute (NCI) Working Formulation and the Kiel classification system. Clinical features, immunophenotype, pathologic classification, and treatment outcome were compared for CD30+ and CD30- cases. RESULTS CD30 expression was documented in 18 cases (40%). These 13 boys and five girls had a median age of 13 years at diagnosis. Most (n = 14) had advanced-stage (III and IV) disease. Nodal disease was equally common in CD30+ and CD30- cases, whereas skin involvement was significantly more frequent in CD30+ cases (P = .007). There was no significant association of CD30 expression with histologic subtype according to the NCI Working Formulation, but CD30+ cases were more likely to be anaplastic by the Kiel classification (P < .001). All CD30+ cases had either T-cell or null-cell phenotype, while the majority of CD30- cases were B-cell phenotype (P < .001). Among patients with limited-stage disease, the mean +/- SE estimated 5-year event-free survival (EFS) was 75% +/- 22% for CD30+ cases and 92% +/- 9% for CD30- cases (P = .10); estimates for advanced-stage disease were 57% +/- 17% and 29% +/- 17%, respectively (P = .096). For patients with advanced-stage disease, CD30 expression was associated with a significantly better overall 5-year survival probability (84% +/- 12% v 27% +/- 16%, P = .0016). CONCLUSION CD30 is frequently expressed in pediatric large-cell NHL and is significantly associated with T-cell or null-cell phenotype, anaplastic morphology, skin involvement, and better overall survival among advanced-stage patients.

Primary Cutaneous CD30-Positive Anaplastic Large Cell Lymphoma in Childhood: Report of 4 Cases and Review of the Literature

2005 ◽  
Vol 8 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Shimareet Kumar ◽  
Stefania Pittaluga ◽  
Mark Raffeld ◽  
Michael Guerrera ◽  
Nita L. Seibel ◽  
...  
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Subcutaneous Tissue ◽  
Pediatric Population ◽  
Large Cell ◽  
Lymphoid Cells ◽  
Cell Phenotype ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

We present the clinicopathologic findings in 4 children with primary cutaneous anaplastic large cell lymphoma (C-ALCL). The patients ranged in age from 13 months to 8 years, with 3 females and 1 male. All presented with a rapidly enlarging mass involving the skin and subcutaneous tissue. Histologic evaluation showed sheets of large pleomorphic lymphoid cells that were diffusely and strongly CD30+. Tumor cells were CD45+ in 1 of 4 cases. Cells were of T-cell phenotype, with variable positivity for CD3 (3 of 4 cases) and CD5 (2 of 4 cases). All 4 cases were positive for CD4 and clusterin. Staining for anaplastic lymphoma kinase was negative in all cases. No evidence of systemic involvement was noted at initial presentation or over a follow-up of 5 to 78 months, although 3 patients had cutaneous recurrences. Primary C-ALCL has only rarely been described in the pediatric population. The high-grade histologic appearance of this lymphoma belies its generally favorable clinical course and prognosis. Recognition of this entity and its differentiation from other T-cell lymphomas that secondarily involve the skin is important to avoid unnecessarily aggressive therapy in these children.

Angiotropic (Intravascular) Large Cell Lymphoma of T-Cell Phenotype Presenting as Acute Appendicitis in a Patient With Acquired Immunodeficiency Syndrome

1999 ◽  
Vol 123 (4) ◽  
pp. 335-337 ◽  
Author(s):  
Denise M. Malicki ◽  
Yae K. Suh ◽  
Gregory N. Fuller ◽  
Sung S. Shin
Keyword(s):  
T Cell ◽  
Acute Appendicitis ◽  
Acquired Immunodeficiency Syndrome ◽  
Cell Lymphoma ◽  
Immunohistochemical Analysis ◽  
Large Cell ◽  
Cell Phenotype ◽  
Acquired Immunodeficiency ◽  
Large Cell Lymphoma ◽  
Immunodeficiency Syndrome

Abstract We describe a patient with acquired immunodeficiency syndrome who presented with acute appendicitis but was found to have angiotropic large cell lymphoma (ALCL) by pathologic examination of the appendectomy specimen, without acute inflammation. Very rare cases of angiotropic large cell lymphoma have been reported in patients with human immunodeficiency virus infection, and most cases of this rare lymphoma are of B-cell origin, but in this instance immunohistochemical analysis showed a T-cell phenotype.

scholarly journals Anaplastic large-cell lymphomas of T-cell and null-cell phenotype express cytotoxic molecules

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 4005-4011 ◽  
Author(s):  
HD Foss ◽  
I Anagnostopoulos ◽  
I Araujo ◽  
C Assaf ◽  
G Demel ◽  
...  
Keyword(s):  
T Cell ◽  
Granzyme B ◽  
Large Cell ◽  
Cell Receptor ◽  
Null Cell ◽  
Cellular Origin ◽  
T Cell Receptor Beta ◽  
Cytotoxic Molecules ◽  
Beta Chain Genes ◽  
Receptor Beta

To further specify the cellular origin and nature of anaplastic large- cell lymphoma (ALCL) and its relationship to other lymphoid neoplasms, particularly Hodgkin's disease (HD), we investigated the presence of cytotoxic molecules in a large well-characterized series of these tumors. For expression of the cytotoxic molecules perforin and granzyme B, in situ hybridization (ISH) and immunohistology were used, respectively. Overall, 23 of 25 ALCLs of T/null phenotype and five (three mixed cellularity and two nodular sclerosis) of 57 HD cases showed the presence of perforin transcripts and/or granzyme B molecules in neoplastic cells. Polymerase chain reaction (PCR) analysis of ALCLs showed that most (10 of 11) cases of null-cell ALCL (null-ALCL) contained a clonal rearrangement of T-cell receptor beta-chain genes, as did T-cell ALCL (T-ALCL; 9 of 10 cases). However, both cytotoxic molecules and clonally rearranged T-cell receptor beta-chain genes were absent in seven of seven and eight of nine cases of B-cell ALCL (B-ALCL), respectively. These data show that all or nearly all T-ALCLs, irrespective of the clinical subform or the lack of T-cell-associated molecules, are derived from activated cytotoxic T cells. The same appears to be true for the neoplastic cells of rare HD cases. These findings indicate that T-ALCLs are different from B-ALCLs and the majority of HD cases, and suggest that some HD cases, especially those with T-cell antigen-positive tumor cells, may be closely related to T- ALCL, at least in terms of cellular origin.

scholarly journals CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2905-2917 ◽  
Author(s):  
DA Filippa ◽  
M Ladanyi ◽  
N Wollner ◽  
DJ Straus ◽  
JP O'Brien ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Bone Marrow Involvement ◽  
Skin Lesions ◽  
Cell Phenotype ◽  
Cell Type ◽  
Null Cell

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage- specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty- two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT- PCR) in four of five cases studied. All nine cases were of T- or null- cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus- positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.

scholarly journals The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 848-858 ◽  
Author(s):  
H Stein ◽  
DY Mason ◽  
J Gerdes ◽  
N O'Connor ◽  
J Wainscoat ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
Cell Phenotype ◽  
Cell Type ◽  
Lymphomatoid Papulosis ◽  
T Cell Lymphomas ◽  
Immunoblastic Lymphadenopathy

Abstract Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an “activation state.” In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

scholarly journals The immunologic and clinicopathologic heterogeneity of cutaneous lymphomas other than mycosis fungoides

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 464-472 ◽  
Author(s):  
GS Wood ◽  
JS Burke ◽  
S Horning ◽  
RS Doggett ◽  
R Levy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Survival Data ◽  
Large Cell ◽  
Cell Phenotype ◽  
Time Interval ◽  
Histologic Subtype ◽  
Interval Therapy ◽  
Cutaneous Lymphomas

Abstract Twenty-one cases of non-Hodgkin's lymphoma with cutaneous involvement, other than mycosis fungoides, were evaluated immunologically, histologically, and clinically. Ten patients presented with skin disease alone, seven with concurrent cutaneous and extracutaneous disease, and four with extracutaneous disease only. Twenty of the 21 cases were nonepidermotropic tumors and were equally likely to express B or T phenotypes. None of the cases expressed a true histiocytic phenotype. Almost all cases expressed la and class 1 HLA determinants. Immunophenotypes were stable regardless of time interval, therapy, or body site sampled in seven of eight patients studied serially. In contrast to mycosis fungoides, the T lymphomas exhibited noncerebriform cytology, tumor la expression, lack of mature helper T-cell phenotype, nonepidermotropic histology, a tendency for marrow involvement, and presented as nodules rather than patches or plaques. Since each T lymphoma expressed an abnormal but uniform T-cell phenotype other than mature cytotoxic/suppressor or helper, the neoplastic population could be distinguished from reactive T cells. Reactive elements averaged one- third of the cellular infiltrates and were mainly T cells and macrophages. Langerhans cells were generally normal in number and distribution. Several histopathologic subtypes were identified with diffuse large cell lymphomas, including immunoblastic lymphomas, comprising 71% of cases (15/21). Prediction of the immunophenotype based on cytologic criteria was correct in 67% of cases (14/21). All errors occurred among the 13 high-grade lymphomas. Survival data were consistent with those of prior studies that have indicated that clinical course is dependent on stage and histologic subtype. Non- Hodgkin's cutaneous lymphomas constitute an immunologically, histologically, and clinically heterogeneous group of neoplasms.

scholarly journals BCL-6 Protein Expression in Human Peripheral T-Cell Neoplasms Is Restricted to CD30+ Anaplastic Large-Cell Lymphomas

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2445-2450 ◽  
Author(s):  
Antonino Carbone ◽  
Annunziata Gloghini ◽  
Gianluca Gaidano ◽  
Riccardo Dalla-Favera ◽  
Brunangelo Falini
Keyword(s):  
T Cell ◽  
Protein Expression ◽  
Lymph Nodes ◽  
Cell Lines ◽  
Biological Significance ◽  
Large Cell ◽  
Lymphoid Cells ◽  
Null Cell ◽  
The Relationship ◽  
Cell Proliferations

Abstract The expression pattern of the BCL-6 transcription factor has been assessed in normal and neoplastic B-cell populations and in Hodgkin's disease. However, little is known about BCL-6 expression and its biological significance in T-cell neoplasms. In this study, a series of 59 lymphoma samples, including 27 CD30+ anaplastic large-cell lymphomas (ALCLs), 24 other peripheral T-cell neoplasms, and 8 T-cell lymphoblastic lymphomas (T-LBLs), as well as a panel of t(2; 5)-positive lymphoma-derived human cell lines, were evaluated for BCL-6 protein expression by immunohistochemistry on frozen sections and cell smears. To define the relationship between BCL-6 protein and CD30 antigen in CD30+ ALCLs and in non-neoplastic lymph nodes, serial section immunohistochemistry and two-color staining were used in selected CD30+ ALCLs as well as in reactive lymph nodes with non-neoplastic T-cell proliferations. BCL-6 protein was expressed in 12 of 27 (45%) CD30+ ALCL cases, irrespective of their antigenic phenotypes (T-cell or null-cell type), and in the t(2; 5)-positive cell lines. In contrast, the remaining 24 peripheral T-cell neoplasms as well as the 8 T-LBLs were considered negative for BCL-6 expression. Coexpression of CD30 and BCL-6, as detected in CD30+ ALCLs, was also found in a subset of non-neoplastic lymphoid elements, namely the large lymphoid cells scattered in the interfollicular areas of reactive lymph nodes. These findings suggest that CD30+ ALCLs may represent the neoplastic transformation of extrafollicular CD30+ cells and that BCL-6 may provide an additional marker for characterizing CD30+ ALCLs.

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