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.

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.

Histologic Subtypes Do Not Confer Unique Outcomes in Early-Stage Lymphoma: Long-Term Follow-Up of SWOG 8736.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3263-3263 ◽  
Author(s):  
Catherine M. Spier ◽  
Michael LeBlanc ◽  
Ellen M. Chase ◽  
Richard I. Fisher ◽  
Thomas P. Miller
Keyword(s):  
T Cell ◽  
Early Stage ◽  
Large Cell ◽  
Advanced Stage ◽  
Histologic Type ◽  
Limited Disease ◽  
Histologic Subtype ◽  
Limited Stage ◽  
Stage Disease ◽  
Histologic Subtypes

Abstract Analysis of patients with advanced non-Hodgkin’s lymphoma (NHL) suggests unique clinical presentations and outcome according to histologic subtype. Little is known of outcome as it relates to histologic subytpe in patients with limited disease. In a previous report (NEJM1998;339:21–6), 401 patients with limited disease (Stage I or non-bulky II) intermediate or high grade NHL, enrolled in SWOG study 8736, were randomized to chemotherapy or chemotherapy plus radiotherapy. Results at 5 years showed superior survival and less toxicity for those treated with 3 cycles of CHOP chemotherapy plus radiotherapy. These 401 patients, with additional followup and reclassification of histology according to World Health Organization (WHO) criteria, form the basis of the current report. Of the 401 pts, 2 were excluded because of clinical findings and 34 patients were excluded for insufficient pathology material. 365 pts were evaluable. On the basis of hematoxylin-eosin and immunohistochemistry results, pt cases were classified as diffuse large B cell (174pts), follicular, Grade 3 (36), Burkitt-like (27), peripheral T cell, unspecified (9), anaplastic large T cell (4), morphologically consistent with mantle cell (4), morphologically consistent with MALToma (3), morphologically diffuse small cleaved cell (2), unclassifiable (1), suggesting anaplastic large cell CD30+ (1), diffuse large cell without immunohistochemical results (104). At 10 years, there was no significant difference in overall survival (OS) or failure free survival (FFS) between the 2 treatments (OS, p=0.48; FFS, p=0.77) (Blood2001;98:724a). When analyzed by histology, including T lineage, neither OS nor FFS were different for any histologic subytpe (OS, p=0.94; FFS, p=0.99). In addition, the estimated shapes of the survival curves were similar for all histologic subtypes among these 365 evaluable pts. On the basis of these findings it does not appear that either the WHO or the Working Formulation (WF) classification system is able to predict outcome for limited stage disease pts treated with CHOP +/− radiotherapy. Therefore, histologic type should not be a criterion for exclusion for limited stage studies of lymphoma. Further, it does not appear that any histologic subtype presenting as early stage disease needs CNS prophylaxis or a unique chemotherapy treatment strategy. There was only one central nervous system (CNS) relapse (in a patient with testis involvement), and none among the 27 Burkitt-like pts. The lack of an observed survival plateau in the first 10 years of followup for these pts is in contrast to advanced stage pts who achieve a plateau within 6 years. The biology of limited stage lymphoma may be fundamentally different from that of advanced stage disease and more significanct in determining outcome than histologic type.

Primary Ki-1 anaplastic large-cell lymphoma in adults: clinical characteristics and therapeutic outcome.

1993 ◽  
Vol 11 (5) ◽  
pp. 937-942 ◽  
Author(s):  
L N Shulman ◽  
B Frisard ◽  
J H Antin ◽  
C Wheeler ◽  
G Pinkus ◽  
...  
Keyword(s):  
B Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Cell Phenotype ◽  
Advanced Stage ◽  
Extranodal Involvement ◽  
Stage Disease ◽  
Large Cell Lymphoma ◽  
Disease Free

PURPOSE A study was undertaken to improve our understanding of the clinicopathologic features and therapeutic outcome for adults with primary Ki-1 anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS A retrospective review of records of 31 adult patients with primary Ki-1 ALCL was performed. The analysis included stage and distribution of disease, tumor-cell phenotype, response to initial and salvage therapy, and disease-free and overall survival. RESULTS The median age of patients was 44 years (range, 16 to 86). Forty-eight percent of patients tested had lymphomas of T-cell phenotype, 30% lymphomas of B-cell phenotype, and 22% of non-T-, non-B-cell phenotype. Twenty-nine percent of patients had stages I and II disease, 65% demonstrated extranodal involvement, and 32% had skin involvement at presentation. Most patients received intensive chemotherapy and 48% achieved a sustained complete remission (CR), with an additional 17% of patients treated successfully with salvage therapy. Stage was highly predictive of achieving a sustained CR, but bulk disease and B symptoms did not predict for relapse after initial therapy or survival. Of seven patients who underwent autologous bone marrow transplantation (ABMT), three remain disease-free 9 to 42 months after transplant. CONCLUSION Patients with Ki-1 ALCL have a high frequency of advanced-stage disease and extranodal involvement and are more likely to have tumors of T-cell phenotype than patients with large-cell lymphoma. However, response to standard lymphoma chemotherapy is similar to other patients with large-cell lymphoma, with a high remission rate in early-stage disease. Patients with advanced-stage disease have a poor remission duration and may require more intensive therapy, as may also be the case with large-cell lymphoma.

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.

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.

Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3082-3087 ◽  
Author(s):  
Suzanne O. Arulogun ◽  
H. Miles Prince ◽  
Jonathan Ng ◽  
Stephen Lade ◽  
Gail F. Ryan ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Transformation ◽  
Early Stage ◽  
Large Cell ◽  
Tumor Stage ◽  
Advanced Stage ◽  
Long Term Outcomes ◽  
Stage Disease ◽  
Large Cell Transformation

Abstract Although mycosis fungoides (MF) is typically an indolent disease, patients with advanced-stage disease (stages IIB-IVB), including Sézary syndrome (SS), often have a poor outcome. A 31-year, retrospective analysis of our cutaneous lymphoma database, of 297 patients with MF and SS, was undertaken to study long-term outcomes and identify clinical predictors of outcome in patients with advanced-stage disease (ASD, n = 92) and large cell transformation (LCT, n = 22). Two-thirds of patients with ASD presented with de novo ASD. The median overall survival (OS) for ASD was 5 years with a 10-year predicted OS of 32%. Age at initial diagnosis (P = .01), tumor stage (P = .01), and clinical stage (P = .001) were found to be significant predictors of outcome. Patients who presented with de novo ASD demonstrated better outcomes that were not statistically significant than those with a prior diagnosis of early-stage MF (P = .25). Transformation developed in 22 of the 297 MF/SS patients (7.4%), with a transformation rate of only 1.4% in patients with early-stage disease, compared with stage IIB (27%) and stage IV (56%-67%) disease. The median OS from diagnosis of LCT was 2 years. We confirm that the incidence of LCT is strongly dependent on tumor stage at diagnosis, and we demonstrate a much lower overall risk of LCT than previously reported.

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 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.

Sign in / Sign up

Export Citation Format

Share Document