Differences in clinical behaviour and immunophenotype between primary cutaneous and primary nodal anaplastic large cell lymphoma of T-cell or null cell phenotype

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.

Download Full-text

Anaplastic Large Cell Lymphoma Arising in Bone

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-1339-alclai ◽

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.

Download Full-text

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 ◽

10.1159/000164108 ◽

1997 ◽

Vol 65 (2) ◽

pp. 83-90 ◽

Cited By ~ 18

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

Download Full-text

Molecular Biology of Anaplastic Lymphoma Kinase–Positive Anaplastic Large-Cell Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2002.12.033 ◽

2002 ◽

Vol 20 (17) ◽

pp. 3691-3702 ◽

Cited By ~ 82

Author(s):

Jeffery L. Kutok ◽

Jon C. Aster

Keyword(s):

T Cell ◽

Anaplastic Large Cell Lymphoma ◽

Anaplastic Lymphoma Kinase ◽

Cell Lymphoma ◽

Cellular Transformation ◽

Large Cell ◽

Null Cell ◽

Anaplastic Lymphoma ◽

Downstream Effectors ◽

Large Cell Lymphoma

ABSTRACT: Anaplastic large-cell lymphoma (ALCL) provides an excellent example of how molecular insights into tumor pathogenesis are influencing and improving tumor classification. ALCL was described initially as a subtype of T-cell/null-cell lymphoma characterized by unusual tumor cell morphology and the expression of CD30. However, it was soon recognized that a subset of ALCLs contained chromosomal translocations involving anaplastic lymphoma kinase (ALK), a novel receptor tyrosine kinase gene. These rearrangements create chimeric genes encoding self-associating, constitutively active ALK fusion proteins that activate a number of downstream effectors, including phospholipase C-gamma, phosphoinositol 3'-kinase, RAS, and signal transducer and activator of transcription proteins, all of which seem potentially important in cellular transformation. Not all tumors classified as ALCLs have ALK rearrangements and, conversely, ALK rearrangements occur in lymphomas of widely varying morphology. Hence, only molecular markers can reliably identify ALK+ ALCL. The importance of doing so is reflected by clinical studies suggesting that ALK+ ALCLs have a significantly better prognosis than other aggressive peripheral T-cell or B-cell lymphomas, including ALK− ALCLs. The unique molecular pathogenesis of ALK+ ALCL is likely to lead to novel therapeutic approaches directed at specific inhibition of ALK or downstream effectors.

Download Full-text

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

Blood ◽

10.1182/blood.v93.11.3913.411k22_3913_3921 ◽

1999 ◽

Vol 93 (11) ◽

pp. 3913-3921 ◽

Cited By ~ 13

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.

Download Full-text

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

Blood ◽

10.1182/blood.v93.11.3913 ◽

1999 ◽

Vol 93 (11) ◽

pp. 3913-3921 ◽

Cited By ~ 352

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 < .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.

Download Full-text

Anaplastic Large Cell Lymphoma of T–Cell Phenotype in Acquired Immunodeficiency Syndrome

Southern Medical Journal ◽

10.1097/00007611-199705000-00023 ◽

1997 ◽

Vol 90 (5) ◽

pp. 559-567 ◽

Cited By ~ 8

Author(s):

PETER BOZNER ◽

MOHAMED Y. ELKHALIFA

Keyword(s):

T Cell ◽

Anaplastic Large Cell Lymphoma ◽

Acquired Immunodeficiency Syndrome ◽

Cell Lymphoma ◽

Large Cell ◽

Cell Phenotype ◽

Acquired Immunodeficiency ◽

Large Cell Lymphoma ◽

Immunodeficiency Syndrome

Download Full-text

ALK+ Anaplastic Large Cell Lymphoma of Null Cell Phenotype With Leukemic Transformation and Leukemoid Reaction

Turkish Journal of Hematology ◽

10.4274/tjh.galenos.2019.2019.0021 ◽

2019 ◽

Author(s):

Shih-Sung Chuang ◽

Yen-Chuan Hsieh ◽

Hung-Chang Wu

Keyword(s):

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

Cell Phenotype ◽

Leukemic Transformation ◽

Leukemoid Reaction ◽

Null Cell ◽

Large Cell Lymphoma

Download Full-text

51 Small cell/lymphohistiocytic morphology is associated with CD8 positivity, retained T cell markers, a trend of decreased PD-L1 expression, but not outcome in adults with ALK+ ALCL

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0051 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A54-A54

Author(s):

Mahsa Khanlari ◽

Shaoying Li ◽

Roberto N Miranda ◽

Swaminathan Iyer ◽

Cameron Yin ◽

...

Keyword(s):

T Cell ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

Small Cell ◽

Adult Patients ◽

World Health ◽

Proliferation Index ◽

Cell Markers ◽

Large Cell Lymphoma

BackgroundSeveral morphologic patterns of ALK+ anaplastic large cell lymphoma (ALCL) are recognized: common, small cell, lymphohistiocytic, Hodgkin-like, and composite patterns.1 Small cell (SC) and lymphohistiocytic (LH) patterns are thought to be closely associated with poorer outcome in children with ALK+ ALCL.2 However, the clinicopathologic and prognostic features of SC/LH patterns of ALK+ ALCL are not yet reported in adults. Recently, we found PD-L1 expression in a large subset of ALK+ ALCL cases, however, PD-L1 expression in SC/LH versus non-SC/LH ALCL has not been reported.MethodsAmong 102 adult patients with ALK+ ALCL seen at our institution from January 1, 2007 through August 30, 2018, 18 (18%) cases had a SC and/or LH pattern. The clinical, pathologic, and outcome data were compared between SC/LH and non-SC/LH ALK+ ALCL cases using Fisher’s exact test. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test.ResultsThere were no significant differences in clinical features including age, gender, nodal versus extranodal involvement, B symptoms, stage, leukocytosis/lymphocytosis, and serum LDH levels between patients with SC/LH versus non-SC/LH ALK+ ALCL. Compared to non-SC/LH cases, SC/LH ALCL was more often positive for CD2 (92% vs. 36%, p = 0.0007), CD3 (81% vs. 15%, p = 0.0001), CD7 (80% vs. 37%, p = 0.03), and CD8 (54% vs. 7%, p = 0.0006). SC/LH ALCL showed a trend of decreased PD-L1 expression than non-SC/LH cases (24% vs. 46%, p = 0.11). There were no significant differences in the expression of CD4, CD5, CD25, CD43, CD45, CD56, TCR A/B, TCR G/D, cytotoxic markers, EMA, Ki-67 proliferation index. The induction chemotherapy and response rate in patients with SC/LH ALK+ ALCL were similar to patients with non-SC/LH ALK+ ALCL. After a median follow-up of 30.5 months (range, 0.3–224 months), there was no significant difference in OS between patients with SC/LH versus non-SC/LH ALK+ ALCL (p = 0.88).ConclusionsIn adults with ALK+ALCL, the SC/LH morphologic pattern is associated with a CD8+ T cell immunophenotype and retention of expression of T cell markers (CD2, CD3, and CD7). The trend of decreased PD-L1 expression in SC/LH ALCL suggests that these patients may not be ideal candidates for PD-L1 immunotherapy. The SC/LH patterns of ALK+ ALCL have no impact on the prognosis of adult patients which is in contrast to the reported association of the SC/LH patterns with poorer outcome in children with ALK+ ALCL.Ethics ApprovalThe study was approved by the Institutional Review Board at MD Anderson Cancer Center, Approval number: PA16-0897ReferencesSwerdlow SH, Campo E, The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375–2390.Brugières L, Deley MC, CD30 (+) anaplastic large-cell lymphoma in children: Analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood 1998;92:3591–3598.

Download Full-text