Simultaneous cytomorphological and multiparameter flow cytometric analysis of ALK-positive anaplastic large cell lymphoma in children

Shen,Hongqiang; Tang,Yongmin; Xu,Xiaojun; Tang,Hongfeng; Gu,Weizhong

doi:10.3892/ol.2012.1034

Simultaneous cytomorphological and multiparameter flow cytometric analysis of ALK-positive anaplastic large cell lymphoma in children

Authors:
- Hongqiang Shen
- Yongmin Tang
- Xiaojun Xu
- Hongfeng Tang
- Weizhong Gu
View Affiliations

Affiliations: Division of Hematology-Oncology, Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Children's Hospital of Zhejiang University School of Medicine, Hangzhou 310003, P.R. China, Division of Pathology, Children's Hospital of Zhejiang University School of Medicine, Hangzhou 310003, P.R. China
Published online on: November 19, 2012 https://doi.org/10.3892/ol.2012.1034
Pages: 515-520

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of this study was to investigate the pathological features of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) in children and to establish the effectiveness of screening and diagnosing ALCL with multiparameter flow cytometry immunophenotyping (FCI) of lymphoid tissue samples. A total of 121 lymph node tissue specimens obtained from 121 patients with a suspected diagnosis of lymphoma were analyzed with cytomorphological and FCI analysis. Fifteen cases were diagnosed as ALK-positive ALCL based on the pathological features and immunohistochemical results. Of these, there were 3 different types, common type (10 cases), lymphohistiocytic type (4 cases) and neutrophil-rich type (1 case). Thirteen cases (10 common, 2 lymphohistiocytic and 1 neutrophil-rich type) were diagnosed as ALCL using FCI. These cases were CD30‑positive and aberrantly expressed at least two T-cell antigens, including CD4 (84.6%), CD2 (76.9%), CD7 (61.5%), CD3 (53.8%) and CD5 (38.4%). Neoplastic cells accounted for only a small proportion of the total cells in FCI, with a median of 19.3% (range, 7.9-31.8%), which was significantly higher than those in the control groups (all <1.0%). The sensitivity of FCI for diagnosing ALCL in lymph node samples was 86.7% with a specificity of 100%. The majority of neoplastic cells demonstrated high light forward and high light side scatter, similar to monocytes or granulocytes in dot plots. FCI may be used as an adjunct to histopathological examination for rapid and reliable diagnosis of pediatric ALCL. Flexible gating strategies and careful analysis are required to identify neoplastic cells with FCI.

View Figures

View References

1.	Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H and Jaffe ES: The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 117:5019–5032. 2011. View Article : Google Scholar : PubMed/NCBI
2.	Stein H, Mason DY, Gerdes J, et al: 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. 66:848–858. 1985.
3.	Falini B: Anaplastic large cell lymphoma: pathological, molecular and clinical features. Br J Haematol. 114:741–760. 2001. View Article : Google Scholar : PubMed/NCBI
4.	Medeiros LJ and Elenitoba-Johnson KS: Anaplastic large cell lymphoma. Am J Clin Pathol. 127:707–722. 2007. View Article : Google Scholar : PubMed/NCBI
5.	ten Berge RL, Oudejans JJ, Ossenkoppele GJ and Meijer CJ: ALK-negative systemic anaplastic large cell lymphoma: differential diagnostic and prognostic aspects - a review. J Pathol. 200:4–15. 2003.PubMed/NCBI
6.	Savage KJ, Harris NL, Vose JM, et al: ALK-anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. 111:5496–5504. 2008.PubMed/NCBI
7.	Sethuraman C, Simmerson M, Vora AJ and Cohen MC: Flowcytometric immunophenotyping in the diagnosis of pediatric lymphoma: how reliable is it and how can we optimize its use? J Pediatr Hematol Oncol. 32:298–303. 2010. View Article : Google Scholar : PubMed/NCBI
8.	Barrena S, Almeida J, Del Carmen Garcia-Macias M, et al: Flow cytometry immunophenotyping of fine-needle aspiration specimens: utility in the diagnosis and classification of non-Hodgkin lymphomas. Histopathology. 58:906–918. 2011. View Article : Google Scholar : PubMed/NCBI
9.	Kesler MV, Paranjape GS, Asplund SL, McKenna RW, Jamal S and Kroft SH: Anaplastic large cell lymphoma: a flow cytometric analysis of 29 cases. Am J Clin Pathol. 128:314–322. 2007. View Article : Google Scholar : PubMed/NCBI
10.	Muzzafar T, Wei EX, Lin P, Medeiros LJ and Jorgensen JL: Flow cytometric immunophenotyping of anaplastic large cell lymphoma. Arch Pathol Lab Med. 133:49–56. 2009.PubMed/NCBI
11.	Wright D, McKeever P and Carter R: Childhood non-Hodgkin lymphomas in the United Kingdom: findings from the UK Children’s Cancer Study Group. J Clin Pathol. 50:128–134. 1997.
12.	Jacobsen E: Anaplastic large-cell lymphoma, T-/null-cell type. Oncologist. 11:831–840. 2006. View Article : Google Scholar : PubMed/NCBI
13.	Stein H, Foss HD, Durkop H, et al: CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 96:3681–3695. 2000.
14.	Lamant L, McCarthy K, d’Amore E, et al: Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: Results of the ALCL99 study. J Clin Oncol. 29:4669–4676. 2011. View Article : Google Scholar : PubMed/NCBI
15.	Kinney MC, Higgins RA and Medina EA: Anaplastic large cell lymphoma: twenty-five years of discovery. Arch Pathol Lab Med. 135:19–43. 2011.PubMed/NCBI
16.	Creager AJ, Geisinger KR and Bergman S: Neutrophil-rich Ki-1-positive anaplastic large cell lymphoma: a study by fine-needle aspiration biopsy. Am J Clin Pathol. 117:709–715. 2002. View Article : Google Scholar : PubMed/NCBI
17.	Deutsch YE, Tadmor T, Podack ER and Rosenblatt JD: CD30: an important new target in hematologic malignancies. Leuk Lymphoma. 52:1641–1654. 2011. View Article : Google Scholar : PubMed/NCBI
18.	Costa V, Oliva T and Norton L: Successful treatment with daclizumab of refractory anaplastic lymphoma. Pediatr Blood Cancer. 53:1130–1131. 2009. View Article : Google Scholar : PubMed/NCBI
19.	Swerdlow SH, Campo E, Harris NL, et al: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; Lyon: pp. 326–329. 2008
20.	Craig FE and Foon KA: Flow cytometric immunophenotyping for hematologic neoplasms. Blood. 111:3941–3967. 2008. View Article : Google Scholar : PubMed/NCBI
21.	El-Sayed AM, El-Borai MH, Bahnassy AA and El-Gerzawi SM: Flow cytometric immunophenotyping (FCI) of lymphoma: correlation with histopathology and immunohistochemistry. Diagn Pathol. 3:432008. View Article : Google Scholar : PubMed/NCBI
22.	Shen H, Tang Y, Xu X, et al: Rapid detection of neoplastic cells in serous cavity effusions in children with flow cytometry immunophenotyping. Leuk Lymphoma. 53:1509–1514. 2012. View Article : Google Scholar : PubMed/NCBI
23.	Damm-Welk C, Schieferstein J, Schwalm S, Reiter A and Woessmann W: Flow cytometric detection of circulating tumour cells in nucleophosmin/anaplastic lymphoma kinase-positive anaplastic large cell lymphoma: comparison with quantitative polymerase chain reaction. Br J Haematol. 138:459–466. 2007. View Article : Google Scholar