Morphological and Phenotypic Features in Pediatric Large Cell Lymphoma and Their Correlation with ALK Expression and the t(2;5)(p23;q35) Translocation

2001 ◽  
Vol 4 (2) ◽  
pp. 129-137 ◽  
Author(s):  
C.G. Sherman ◽  
M. Zielenska ◽  
A.N. Lorenzana ◽  
K.A.F. Pulford ◽  
D.Y. Mason ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Single Case ◽  
Pediatric Population ◽  
Age Groups ◽  
Large Cell ◽  
Cell Phenotype ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
The Difference

Anaplastic large cell lymphoma (ALCL) was proposed as a clinicopathologic entity over 14 years ago, but has been somewhat controversial due to the variability of its defining features and variable occurrence in different age-groups. To evaluate this entity in a pediatric population, 36 cases of childhood large cell lymphoma were evaluated for abnormalities of the anaplastic lymphoma kinase (ALK) gene that has been associated with ALCL morphology and immunophenotype. ALK abnormalities were evaluated by assay for the t(2;5)(p23;q35) translocation by RT-PCR and/or expression of NPM-ALK fusion protein by immunohistochemistry. Results showed 17 patients to have evidence of ALK gene expression. All of these children (mean age, 9.3 years) had tumors that were of T-cell phenotype (with the exception of a single case of null phenotype) and that expressed CD30. In contrast, 19 children with no evidence of ALK expression were older (mean, 12.7 years), and the majority (12/19) had tumors of B-cell phenotype. CD30 was also diffusely expressed in 8 of these 19 tumors. The difference in mean age between the two groups was statistically significant ( P = 0.015). In three cases tested for both ALK and the t(2;5), ALK protein was detected in the absence of the t(2;5) translocation but no cases showed the reverse pattern, consistent with ALK fusion to genes other than NPM or activation of the ALK gene by another mechanism. These findings provide further support that ALK-positive ALCL is a distinct pathologic entity among pediatric large cell lymphomas primarily characterized by expression of T-cell markers, CD30, and EMA, and by a younger mean age.

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.

Prognostic Significance of Anaplastic Lymphoma Kinase (ALK) Protein Expression in Adults With Anaplastic Large Cell Lymphoma

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3913-3921 ◽  
Author(s):  
Randy D. Gascoyne ◽  
Patricia Aoun ◽  
Daniel Wu ◽  
Mukesh Chhanabhai ◽  
Brian F. Skinnider ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Expression ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Normal Serum ◽  
Cell Phenotype ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Alk Protein

Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23;q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK+ and ALK− groups, except that the ALK+ patients were younger (median age, 30 v 61 years; P < .002). The ALK+ cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK+. The 5-year overall survival (OS) of the entire cohort was 65%. The 5-year OS of the ALK+ and ALK− cases was 79% and 46%, respectively (P < .0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK+ cases and only 37% for the ALK− cases (P < .00001). Univariate analysis of the clinical features showed that age ≤60 years (P < .007), a normal serum lactate dehydrogenase (LDH) (P < .00001), a good performance status (Eastern Cooperative Oncology Group [ECOG] <2) (P< .03), ≤1 extranodal site of disease (P < .012), and an IPI score ≤3 (P < .00001) were associated with improved OS. Although a younger age correlated with ALK positivity, multivariate analysis showed that only a normal serum LDH (P < .00001), an IPI score of ≤3 (P < .0005), and ALK protein expression (P < .005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein expression is an independent predictor of survival and serves as a useful biologic marker of a specific disease entity within the spectrum of ALCL.

Prognostic Significance of Anaplastic Lymphoma Kinase (ALK) Protein Expression in Adults With Anaplastic Large Cell Lymphoma

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3913-3921 ◽  
Author(s):  
Randy D. Gascoyne ◽  
Patricia Aoun ◽  
Daniel Wu ◽  
Mukesh Chhanabhai ◽  
Brian F. Skinnider ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Expression ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Normal Serum ◽  
Cell Phenotype ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Alk Protein

Abstract Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23;q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK+ and ALK− groups, except that the ALK+ patients were younger (median age, 30 v 61 years; P &lt; .002). The ALK+ cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK+. The 5-year overall survival (OS) of the entire cohort was 65%. The 5-year OS of the ALK+ and ALK− cases was 79% and 46%, respectively (P &lt; .0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK+ cases and only 37% for the ALK− cases (P &lt; .00001). Univariate analysis of the clinical features showed that age ≤60 years (P &lt; .007), a normal serum lactate dehydrogenase (LDH) (P &lt; .00001), a good performance status (Eastern Cooperative Oncology Group [ECOG] &lt;2) (P&lt; .03), ≤1 extranodal site of disease (P &lt; .012), and an IPI score ≤3 (P &lt; .00001) were associated with improved OS. Although a younger age correlated with ALK positivity, multivariate analysis showed that only a normal serum LDH (P &lt; .00001), an IPI score of ≤3 (P &lt; .0005), and ALK protein expression (P &lt; .005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein expression is an independent predictor of survival and serves as a useful biologic marker of a specific disease entity within the spectrum of ALCL.

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.

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.

HIV-associated anaplastic large cell lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19563-e19563
Author(s):  
J. Castillo ◽  
C. Milani ◽  
L. Pantanowitz
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Opportunistic Infections ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Cd4 Count ◽  
Term Survival ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

e19563 Background: Anaplastic large cell lymphoma (ALCL) is a CD30+ T-cell lymphoma that is generally unrelated to EBV in the non-HIV setting. Based upon anaplastic lymphoma kinase (ALK) expression, the new WHO classification provisionally distinguishes between ALK+ (favorable) and ALK- (unfavorable) ALCL. The characteristics of ALCL, such as ALK expression and EBV coinfection, in individuals with HIV infection have not been adequately evaluated. The aim of this study was to investigate these features in HIV-associated ALCL cases. Methods: A MEDLINE search for all cases of HIV-associated non-cutaneous ALCL was undertaken. Data regarding patient age, gender, HIV status (CD4 count, viral load, opportunistic infections), HAART, lymphoma features (B symptoms, stage, sites of involvement, immunophenotype, ALK expression, molecular studies), EBV coinfection, therapy and outcome (survival, cause of death) were extracted and analyzed. Results: A total of 23 cases were included. Patients were of median age 39 years with a male:female ratio of 7:1. Median CD4+ count was 76 cells/mm3 and HIV viral load 416,500 copies/ml. Most (67%) patients had an opportunistic infection, although only 3 (17%) were on HAART. ALCL was extranodal in 22 cases (96%) affecting most commonly lung, soft tissue and liver. Many (78%) patients had stage IV disease and B symptoms were reported in 9 cases (50%). T-cell receptor gene rearrangement was present in all cases, CD30 was positive in 22 (96%), and the vast majority (90%) were ALK-negative. EBV was identified in 8 (35%) cases. Therapy for ALCL was documented in 15 (67%) cases; 64% received CHOP. In 2 of the 3 patients who were on HAART, long-term survival was achieved. Many (68%) patients died, with a median survival of 9 months. Death was caused by either lymphoma progression (42%) or infection (58%). Conclusions: HIV-associated non-cutaneous ALCL appears to affect younger individuals and is associated with EBV infection in a subset of cases. Apart from marked immunosuppression, the poor prognosis of HIV-associated ALCL appears to be related to the absence of ALK expression, advanced stage at presentation with prominent extranodal disease, inadequate therapy including HAART, and poor response to CHOP. Further research is needed to better understand and treat this unique HIV-associated lymphoma. No significant financial relationships to disclose.

Uniform Expression of Cytotoxic Molecules in Anaplastic Large Cell Lymphoma of Null/T Cell Phenotype and in Cell Lines Derived from Anaplastic Large Cell Lymphoma

Pathobiology ◽  
1997 ◽  
Vol 65 (2) ◽  
pp. 83-90 ◽  
Author(s):  
Hans-Dieter Foss ◽  
Gudrun Demel ◽  
Ioannis Anagnostopoulos ◽  
Iguaracyra Araujo ◽  
Michael Hummel ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Cell Phenotype ◽  
Cytotoxic Molecules ◽  
Large Cell Lymphoma

scholarly journals The prognostic significance of the immunotype in diffuse large-cell lymphoma: a comparative study of the T-cell and B-cell phenotype

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 436-441 ◽  
Author(s):  
SM Lippman ◽  
TP Miller ◽  
CM Spier ◽  
DJ Slymen ◽  
TM Grogan
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Cell Group ◽  
Cell Phenotype ◽  
Diffuse Large Cell Lymphoma ◽  
Patient Groups ◽  
Large Cell Lymphoma ◽  
Disease Free

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas is controversial. Therefore, we conducted the present study of 103 consecutively accrued diffuse large-cell lymphoma (DLCL) patients to define, independently of histologic subtypes, the prognostic importance of phenotyping. We used an extensive panel of monoclonal antibodies to T- and B-cell antigens to assign all patients immunologically into the T-cell (20 patients) or B-cell group (83 patients). The only significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of bulky disease (greater than 10 cm) in B-cell patients (P = .008) and more frequent skin involvement in the T-cell group (P less than or equal to .001). Multiagent doxorubicin-containing chemotherapy regimens were employed as initial therapy in over 83% of the patients in each group. Our study revealed that disease-free survival (DFS) was significantly shorter in the T-cell patients than in the B-cell DLCL patients (median DFS, 10.8 months for T-cell and 42.7 months for B- cell; P = .01, log rank). No patient with T-cell DLCL remained disease free for longer than 2 years, whereas 55% of the B-cell group were disease free at 2 years. Univariate and multivariate analyses of all major prognostic factors of DFS suggest that the T-cell phenotype indicates an incurable subset of DLCL patients. Although the B-cell group had a twofold advantage in median survival (35 months v 18 months), actuarial overall survival was not significantly different between the two patient groups (P = .23). Our results indicate the need for new approaches in the search for a curative treatment for T-cell DLCL.

scholarly journals Hemophagocytic Lymphohistiocytosis in Association with Primary Cutaneous Anaplastic Large Cell Lymphoma

2014 ◽  
Vol 2014 ◽  
pp. 1-7
Author(s):  
Aneesh Basheer ◽  
Somanath Padhi ◽  
Ramesh Nagarajan ◽  
Vinoth Boopathy ◽  
Sudhagar Mookkappan ◽  
...  
Keyword(s):  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Lymphoproliferative Disorders ◽  
Elderly Male ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Large Cell Lymphoma

Hemophagocytic lymphohistiocytosis (HLH) has a well known association with lymphomas, especially of T cell origin. Prognosis of lymphoma associated HLH is very poor, especially in T cell lymphomas; and, therefore, early diagnosis might alter the outcome. Though association of HLH with systemic anaplastic large cell lymphoma (ALCL) is known, its occurrence in primary cutaneous ALCL (C-ALCL) is distinctly rare. We aim to describe a case of C-ALCL (anaplastic lymphoma kinase (ALK)−) in an elderly male who succumbed to the complication of associated HLH, which was possibly triggered by coexistent virus infection. We briefly present the literatures on lymphoma associated HLH and discuss the histopathological differentials of cutaneous CD30+ lymphoproliferative disorders. We do suggest that HLH may pose diagnostic challenges in the evaluation of an underlying lymphoma and hence warrants proper evaluation for the underlying etiologies and/or triggering factors.

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