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Pathology & Oncology Research
Published in: Pathology & Oncology Research 1/2015

01-01-2015 | Research

A Comprehensive Immunophenotypic Marker Analysis of Hairy Cell Leukemia in Paraffin-Embedded Bone Marrow Trephine Biopsies–A Tissue Microarray Study

Authors: Judit Tóth-Lipták, Klára Piukovics, Zita Borbényi, Judit Demeter, Enikő Bagdi, László Krenács

Published in: Pathology & Oncology Research | Issue 1/2015

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Abstract

Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferation characterized by a unique immunophenotype. Due to low number of circulating neoplastic cells and ‘dry tap’ aspiration, the diagnosis is often based on BM trephine biopsy. We have performed a consecutive immunohistochemical analysis to evaluate diagnostic usefulness of various HCL markers (CD11c, CD25, CD68, CD103, CD123, CD200, annexin A1, cyclin D1, DBA.44, HBME-1, phospho-ERK1/2, TRAP, and T-bet) currently available against fixation resistant epitopes. We analyzed tissue microarrays consisting of samples gained from 73 small B-cell lymphoma cases, including hairy cell leukemia (HCL) (n = 32), HCL variant (HCL-v) (n = 4), B-cell chronic lymphocytic leukemia (B-CLL) (n = 11), lymphoplasmacytic lymphoma (LPL) (n = 3), mantle cell lymphoma (MCL) (n = 10), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 2), splenic B cell marginal zone lymphoma (SMZL) (n = 8), and splenic B cell lymphoma/leukemia, unclassifiable (SBCL) (n = 3) cases. The HCL cases were 100 % positive for all but 2 (DBA.44 and CD123) of these markers. Annexin A1 showed 100 % specificity and accuracy, which was followed by CD123, pERK, CD103, HBME-1, CD11c, CD25, CD68, cyclin D1, CD200, T-bet, DBA.44, and TRAP, in decreasing order. In conclusion, our results reassured the high specificity of annexin A1 and pERK, as well as the diagnostic value of standard HCL markers of CD11c, CD25, CD103, and CD123 also in paraffin-embedded BM samples. Additional markers, including HBME-1, cyclin D1, CD200, and T-bet also represent valuable tools in the differential diagnosis of HCL and its mimics.
Literature
1.
Foucar K, Falini B, Catovsky D, Stein H (2008) Hairy cell leukemia. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, vol 2, 4th edn. WHO classification of tumours. IARC, Lyon, pp 188–190
2.
Robbins BA, Ellison DJ, Spinosa JC, Carey CA, Lukes RJ, Poppema S, Saven A, Piro LD (1993) Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia. Blood 82:1277–1287PubMed
3.
Sánchez ML, Almeida J, Vidriales B, López-Berges MC, García-Marcos MA, Moro MJ, Corrales A, Calmuntia MJ, San Miguel JF, Orfao A (2002) Incidence of phenotypic aberrations in a series of 467 patients with B chronic lymphoproliferative disorders: basis for the design of specific four-color stainings to be used for minimal residual disease investigation. Leukemia 16:1460–1469PubMedCrossRef
4.
Del Guidice I, Matutes E, Morilla R, Owusu-Ankomah K, Rafiq F, A’Hern R, Delgado J, Bazerbashi MB, Catovsky D (2004) The diagnostic value of CD123 in B cell disorders with hairy or villous lymphocytes. Haematologica 89:303–308
5.
6.
7.
Venkataraman G, Aguhar C, Kreitman RJ, Yuan CM, Stetler-Stevenson M (2011) Characteristic CD103 and CD123 expression pattern defines hairy cell leukemia: usefulness of CD123 and CD103 in the diagnosis of mature B-cell lymphoproliferative disorders. Am J Clin Pathol 136:625–630. doi:10.​1309/​AJCPKUM9J4IXCWEU​ PubMedCrossRef
8.
Matutes E, Wotherspoon A, Brito-Babapulle V, Catovsky D (2001) The natural history and clinico-pathological features of the variant form of hairy cell leukemia. Leukemia 15:184–186PubMedCrossRef
9.
10.
Piris M, Foucar K, Mollejo M, Campo E, Falini B (2008) Splenic B-cell lymphoma/leukaemia, unclassifiable. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, WHO classification of tumours, vol 2, 4th edn. IARC Press, Lyon, pp 191–193
11.
Kanellis G, Mollejo M, Montes-Moreno S, Rodriguez-Pinilla SM, Cigudosa JC, Algara P, Montalban C, Matutes E, Wotherspoon A, Piris MA (2009) Splenic diffuse red pulp small B-cell lymphoma: revision of a series of cases reveals characteristic clinico-pathological features. Haematologica 95:1122–1129. doi:10.​3324/​haematol.​2009.​013714 CrossRef
12.
Isaacson PG, Piris MA, Berger F, Swerdlow SH, Thieblemont C, Pittaluga S, Harris NL (2008) Splenic B-cell marginal zone lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn, WHO classification of tumours, vol 2. IARC Press, Lyon, pp 185–187
13.
Else M, Ruchlemer R, Osuji N, Del Giudice I, Matutes E, Woodman A, Wotherspoon A, Swansbury J, Dearden C, Catovsky D (2005) Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years. Cancer 104:2442–2448PubMedCrossRef
14.
15.
Hounieu H, Chittal SM, al Saati T, de Mascarel A, Sabattini E, Pileri S, Falini B, Ralfkiaer E, Le Tourneau A, Selves J et al (1992) Hairy cell leukemia. Diagnosis of bone marrow involvement in paraffin-embedded sections with monoclonal antibody DBA.44. Am J Clin Pathol 98:26–33PubMed
16.
Janckila AJ, Cardwell EM, Yam LT, Li CY (1995) Hairy cell identification by immunohistochemistry of tartrate-resistant acid phosphatase. Blood 85:2839–2844PubMed
17.
Hoyer JD, Li CY, Yam LT, Hanson CA, Kurtin PJ (1997) Immunohistochemical demonstration of acid phosphatase isoenzyme 5 (tartrate-resistant) in paraffin sections of hairy cell leukemia and other hematologic disorders. Am J Clin Pathol 108:308–315PubMed
18.
Went PT, Zimpfer A, Pehrs AC, Sabattini E, Pileri SA, Maurer R, Terracciano L, Tzankov A, Sauter G, Dirnhofer S (2005) High specificity of combined TRAP and DBA.44 expression for hairy cell leukemia. Am J Surg Pathol 29:474–478PubMedCrossRef
19.
Bosch F, Jares P, Campo E, Lopez-Guillermo A, Piris MA, Villamor N, Tassies D, Jaffe ES, Montserrat E, Rozman C, Cardesa A (1994) PRAD-1/cyclin D1 gene overexpression in chronic lymphoproliferative disorders: a highly specific marker of mantle cell lymphoma. Blood 84:2726–2732PubMed
20.
Miranda RN, Briggs RC, Kinney MC, Veno PA, Hammer RD, Cousar JB (2000) Immunohistochemical detection of cyclin D1 using optimized conditions is highly specific for mantle cell lymphoma and hairy cell leukemia. Mod Pathol 13:1308–1314PubMedCrossRef
21.
22.
Jöhrens K, Happerfield LC, Brown JP, Erber WN, Stein H, Anagnostopoulos I (2008) A novel CD11c monoclonal antibody effective in formalin-fixed tissue for the diagnosis of hairy cell leukemia. Pathobiology 75:252–256. doi:10.​1159/​000132386 PubMedCrossRef
23.
24.
25.
Falini B, Tiacci E, Liso A, Basso K, Sabattini E, Pacini R, Foa R, Pulsoni A, Dalla Favera R, Pileri S (2004) Simple diagnostic assay for hairy cell leukaemia by immunocytochemical detection of annexin A1 (ANXA1). Lancet 363:1869–1870PubMedCrossRef
26.
27.
Tiacci E, Schiavoni G, Martelli MP, Boveri E, Pacini R, Tabarrini A, Zibellini S, Santi A, Pettirossi V, Fortini E, Ascani S, Arcaini L, Inghirami G, Paulli M, Falini B (2013) Constant activation of the RAF-MEK-ERK pathway as a diagnostic and therapeutic target in hairy cell leukemia. Haematologica 98:635–639. doi:10.​3324/​haematol.​2012.​078071 PubMedCentralPubMedCrossRef
28.
Morgan EA, Yu H, Pinkus JL, Pinkus GS (2013) Immunohistochemical detection of hairy cell leukemia in paraffin sections using a highly effective CD103 rabbit monoclonal antibody. Am J Clin Pathol 139:220–230. doi:10.​1309/​AJCPHW7RULIZT2GB​ PubMedCrossRef
29.
Krenács L, Tóth-Lipták J, Demeter J, Piukovics K, Borbényi Z, Gogolák P, Sári E, Bagdi E (2013) Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes. Virchows Arch 463:787–794. doi:10.​1007/​s00428-013-1490-52013 PubMedCrossRef
30.
Frisch B, Bartl R (eds) (1999) Biopsy interpretation of bone and bone marrow, 2nd edn. Arnold, London-Sidney-Auckland, p 350
31.
Erber WN, Mason DY (1988) Expression of the interleukin-2 receptor (Tac antigen/CD25) in hematologic neoplasms. Am J Clin Pathol 89:645–648PubMed
32.
Micklem KJ, Dong Y, Willis A, Pulford KA, Visser L, Dürkop H, Poppema S, Stein H, Mason DY (1991) HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the beta 7 subunit. Am J Pathol 139:1297–1301PubMedCentralPubMed
33.
Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D, Marais R (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116:855–867PubMedCrossRef
34.
Dorfman DM, Hwang ES, Shahsafaei A, Glimcher LH (2004) T-bet, a T-cell-associated transcription factor, is expressed in a subset of B-cell lymphoproliferative disorders. J Clin Pathol 122:292–297. doi:10.​1309/​AQQ2DVM75DVY0PWP​ CrossRef
35.
Muñoz L, Nomdedéu JF, López O, Carnicer MJ, Bellido M, Aventín A, Brunet S, Sierra J (2001) Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Haematologica 86:1261–1269PubMed
36.
Li WV, Kapadia SB, Sonmez-Alpan E, Swerdlow SH (1996) Immunohistochemical characterization of mast cell disease in paraffin sections using tryptase, CD68, myeloperoxidase, lysozyme, and CD20 antibodies. Mod Pathol 9:982–988PubMed
37.
38.
Sainati L, Matutes E, Mulligan S, de Oliveira MP, Rani S, Lampert IA, Catovsky D (1990) A variant form of hairy cell leukemia resistant to alpha-interferon: clinical and phenotypic characteristics of 17 patients. Blood 76:157–162PubMed
39.
Basso K, Liso A, Tiacci E, Benedetti R, Pulsoni A, Foa R, Di Raimondo F, Ambrosetti A, Califano A, Klein U, Dalla Favera R, Falini B (2004) Gene expression profiling of hairy cell leukemia reveals a phenotype related to memory B cells with altered expression of chemokine and adhesion receptors. J Exp Med 199:59–68PubMedCentralPubMedCrossRef
40.
Tiacci E, Schiavoni G, Forconi F, Santi A, Trentin L, Ambrosetti A, Cecchini D, Sozzi E, di Francia CP, Di Bello C, Pulsoni A, Foà R, Inghirami G, Falini B (2012) Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation. Blood 119:192–195. doi:10.​1182/​blood-2011-08-371179 PubMedCrossRef
41.
Visser L, Shaw A, Slupsky J, Vos H, Poppema S (1989) Monoclonal antibodies reactive with hairy cell leukemia. Blood 74:320–325PubMed
42.
Schwarting R, Stein H, Wang CY (1985) The monoclonal antibodies alpha S-HCL 1 (alpha Leu-14) and alpha S-HCL 3 (alpha Leu-M5) allow the diagnosis of hairy cell leukemia. Blood 65:974–983PubMed
43.
Armitage RJ, Cawley JC (1986) Normal and certain leukaemic B cells express IL-2 receptors without in vitro activation. Clin Exp Immunol 63:298–302PubMedCentralPubMed
44.
Sheibani K, Winberg CD, van de Velde S, Blayney DW, Rappaport H (1987) Distribution of lymphocytes with interleukin-2 receptors (TAC antigens) in reactive lymphoproliferative processes, Hodgkin’s disease, and non-Hodgkin’s lymphomas. An immunohistologic study of 300 cases. Am J Pathol 127:27–37PubMedCentralPubMed
45.
De Boer CJ, Kluin-Nelemans JC, Dreef E, Kester MGD, Kluin PM, Schuuring E, van Krieken JHJM (1996) Involvement of the CCND1 gene in hairy cell Leukemia. Ann Oncol 7:251–256PubMedCrossRef
46.
Kreft A, Büsche G, Bernhards J, Georgii A (1997) Immunophenotype of hairy-cell leukaemia after cold polymerization of methyl-methacrylate embeddings from 50 diagnostic bone marrow biopsies. Histopathology 30:145–151PubMedCrossRef
47.
Brunetti L, Di Noto R, Abate G, Gorrese M, Gravetti A, Raia M, Scalia G, Pascariello C, Camera A, Del Vecchio L (2009) CD200/OX2, a cell surface molecule with immuno-regulatory function, is consistently expressed on hairy cell leukemia neoplastic cells. Br J Haematol 145:665–667. doi:10.​1111/​j.​1365-2141.​2009.​07644.​x PubMedCrossRef
48.
Palumbo GA, Parrinello N, Fargione G, Cardillo K, Chiarenza A, Berretta S, Conticello C, Villari L, Di Raimondo F (2009) CD200 expression may help in differential diagnosis between mantle cell lymphoma and B-cell chronic lymphocytic leukemia. Leuk Res 33:1212–1216. doi:10.​1016/​j.​leukres.​2009.​01.​017 PubMedCrossRef
Metadata
Title
A Comprehensive Immunophenotypic Marker Analysis of Hairy Cell Leukemia in Paraffin-Embedded Bone Marrow Trephine Biopsies–A Tissue Microarray Study
Authors
Judit Tóth-Lipták
Klára Piukovics
Zita Borbényi
Judit Demeter
Enikő Bagdi
László Krenács
Publication date
01-01-2015
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 1/2015
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-014-9807-5

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