Top

Published in:

01-03-2018 | Case Report

Primary lymphomatous presentation of hairy cell leukemia as osteolytic vertebral lesions: a case report

Authors: Jinming Song, Hailing Zhang, Xiaohui Zhang, Lynn Moscinski, Haipeng Shao

Published in: Journal of Hematopathology | Issue 1/2018

Abstract

Hairy cell leukemia (HCL) is a rare and indolent mature B cell neoplasm. Most patients with HCL have excellent response to purine analogs and BRAF inhibitors. Therefore, it is clinically important to identify and differentiate HCL from other B cell neoplasms. HCL is predominantly found in the peripheral blood, bone marrow, or spleen. HCL presenting initially or solely in unusual sites is extremely rare (approximately ten or fewer). We hereby report a unique case of HCL presenting as vertebral osteolytic and epidural mass lesions without bone marrow, spleen, or peripheral blood involvement. The patient was a 53-year-old male with acute and chronic radicular pain down the posterior aspect of bilateral thighs. Imaging study with MRI demonstrated a L4 posterior vertebral osteolytic mass lesion, extending into the spinal canal, and a second right sacral S1 lesion extending into the sacral iliac joint. These two noncontiguous lesions were thought to be consistent with metastatic cancer or sarcoma, and the specimen was submitted to non-hematopoietic pathologist for diagnosis without flow cytometry. Initial immunohistochemical stains were ordered for solid tumor markers, which were all negative. As part of the workup, immunostain for BRAF V600E (VE1) was ordered for melanoma, and CD138 and cyclin D1 for myeloma, which returned positive and suggested the possibility of hairy cell leukemia. Additional workup for hairy cell leukemia confirmed the diagnosis. HCL typically presents with peripheral blood, bone marrow, or spleen involvement, while mass lesions in other sites are rare. High index of suspicion is essential for the correct diagnosis of HCL in mass lesions at unusual sites. In the absence of initial hematopathological workup and flow cytometry, HCL presenting as solid mass in unusual locations is misdiagnosed most likely as marginal zone B cell lymphoma (mucosa-associated lymphoid tissue (MALT) lymphoma). The expression of cyclin D1, TRAP, annexin A1, and BRAF V600E mutation would confirm the diagnosis of HCL. The main differentials include MALT lymphoma, mantle cell lymphoma (MCL), and hairy cell leukemia variant (HCLv). This case report will be interesting for the clinicians and pathologists alike and broaden the spectrum of clinical presentation of lymphomatous HCL.

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumors of haematopoietic and lymphoid tissues, 4th edn. International Agency for Research on Cancer, World Health Organization

Falini B, Martelli MP, Tiacci E (2016) BRAF V600E mutation in hairy cell leukemia: from bench to bedside. Blood 128(15):1918–1927. https://doi.org/10.1182/blood-2016-07-418434 CrossRefPubMed

Tallman MS, Hakimian D, Variakojis D, Koslow D, Sisney GA, Rademaker AW, Rose E, Kaul K (1992) A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. Blood 80(9):2203–2209PubMed

Jehn U, Bartl R, Dietzfelbinger H, Vehling-Kaiser U, Wolf-Hornung B, Hill W, Heinemann V (1999) Long-term outcome of hairy cell leukemia treated with 2-chlorodeoxyadenosine. Ann Hematol 78(3):139–144. https://doi.org/10.1007/s002770050490 CrossRefPubMed

Robak T, Blasinska-Morawiec M, Blonski J et al (1999) 2-chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia and hairy cell leukemia variant: 7-year experience in Poland. Eur J Haematol 62(1):49–56CrossRefPubMed

Tallman MS, Hakimian D, Rademaker AW, Zanzig C, Wollins E, Rose E, Peterson LC (1996) Relapse of hairy cell leukemia after 2-chlorodeoxyadenosine: long-term follow-up of the Northwestern University experience. Blood 88(6):1954–1959PubMed

Tadmor T, Polliack A (2011) Unusual clinical manifestations, rare sites of involvement, and the association of other disorders with hairy cell leukemia. Leuk Lymphoma 52(Suppl 2):57–61. https://doi.org/10.3109/10428194.2011.565395 CrossRefPubMed

Herold CJ, Wittich GR, Schwarzinger I, Haller J, Chott A, Mostbeck G, Hajek PC (1988) Skeletal involvement in hairy cell leukemia. Skelet Radiol 17(3):171–175. https://doi.org/10.1007/BF00351002 CrossRef

Pilichowska M, Shariftabrizi A, Mukand-Cerro I, Miller K (2014) Primary hairy cell leukemia/lymphoma of the breast: a case report and review of the literature. Case Rep Pathol 2014:497027. https://doi.org/10.1155/2014/497027 PubMedPubMedCentral

10.

Chandana SR, Kotecha R, Al-Janadi A, Chang HT, Conley BA (2013) Rare case of hairy cell leukemia with brain parenchymal involvement: a diagnostic dilemma. J Clin Oncol 31(11):e186–e188. https://doi.org/10.1200/JCO.2012.44.8787 CrossRefPubMed

11.

Hammond WA, Swaika A, Menke D, Tun HW (2017) Hairy cell lymphoma: a potentially under-recognized entity. Rare Tumors 9(1):6518. https://doi.org/10.4081/rt.2017.6518 CrossRefPubMedPubMedCentral

12.

Osman H, Roth T, Zhou J (2013) Hairy cell lymphoma: a unique presentation of hairy cell leukaemia. Br J Haematol 162(3):294. https://doi.org/10.1111/bjh.12420.CrossRefPubMed

13.

Rosen DS, Smith S, Gurbuxani S, Yamini B (2008) Extranodal hairy cell leukemia presenting in the lumbar spine. J Neurosurg Spine 9(4):374–376. https://doi.org/10.3171/SPI.2008.9.10.374 CrossRefPubMed

14.

Liu H, Wang W, Tang G, Yin CC, Muzzafar T, Medeiros LJ, Hu S (2015) Lymphomatous variant of hairy cell leukaemia: a distinctive presentation mimicking low-grade B-cell lymphoma. Histopathology 67(5):740–745. https://doi.org/10.1111/his.12694 CrossRefPubMed

15.

Yonal-Hindilerden I, Hindilerden F, Bulut-Dereli S, Yildiz E, Dogan IO, Nalcaci M (2015) Hairy cell leukemia presenting with isolated skeletal involvement successfully treated by radiation therapy and cladribine: a case report and review of the literature. Case Rep Hematol 2015:803921. https://doi.org/10.1155/2015/803921 PubMedPubMedCentral

16.

Waterfall JJ, Arons E, Walker RL, Pineda M, Roth L, Killian JK, Abaan OD, Davis SR, Kreitman RJ, Meltzer PS (2014) High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias. Nat Genet 46(1):8–10. https://doi.org/10.1038/ng.2828 CrossRefPubMed

17.

Akarca AU, Shende VH, Ramsay AD, Diss T, Pane-Foix M, Rizvi H, Calaminici MR, Grogan TM, Linch D, Marafioti T (2013) BRAF V600E mutation-specific antibody, a sensitive diagnostic marker revealing minimal residual disease in hairy cell leukaemia. Br J Haematol 162(6):848–851. https://doi.org/10.1111/bjh.12429 CrossRefPubMed

18.

Wang XJ, Kim A, Li S (2014) Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. Int J Clin Exp Pathol 7(7):4323–4328PubMedPubMedCentral

19.

Brown NA, Betz BL, Weigelin HC, Elenitoba-Johnson KS, Lim MS, Bailey NG (2015) Evaluation of allele-specific PCR and immunohistochemistry for the detection of BRAF V600E mutations in hairy cell leukemia. Am J Clin Pathol 143(1):89–99. https://doi.org/10.1309/AJCPDN4Q1JTFGCFC CrossRefPubMed

20.

Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M, Kreitman RJ (2012) Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation. Blood 119(14):3330–3332. https://doi.org/10.1182/blood-2011-09-379339 CrossRefPubMedPubMedCentral

21.

Turakhia S, Lanigan C, Hamadeh F, Swerdlow SH, Tubbs RR, Cook JR (2015) Immunohistochemistry for BRAF V600E in the differential diagnosis of hairy cell leukemia vs other splenic B-cell lymphomas. Am J Clin Pathol 144(1):87–93. https://doi.org/10.1309/AJCP5WVXJ2KTLODO CrossRefPubMed

22.

Tschernitz S, Flossbach L, Bonengel M, Roth S, Rosenwald A, Geissinger E (2014) Alternativer BRAF mutations in BRAF V600E-negative hairy cell leukaemias. Br J Haematol 165(4):529–533. https://doi.org/10.1111/bjh.12735 CrossRefPubMed

23.

Basso K, Liso A, Tiacci E, Benedetti R, Pulsoni A, Foa R, di Raimondo F, Ambrosetti A, Califano A, Klein U, Favera RD, 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(1):59–68. https://doi.org/10.1084/jem.20031175 CrossRefPubMedPubMedCentral

24.

Toth-Liptak J, Piukovics K, Borbenyi Z, Demeter J, Bagdi E, Krenacs L (2015) A comprehensive immunophenotypic marker analysis of hairy cell leukemia in paraffin-embedded bone marrow trephine biopsies—a tissue microarray study. Pathol Oncol Res 21(1):203–211. https://doi.org/10.1007/s12253-014-9807-5 CrossRefPubMed

25.

Pettirossi V, Santi A, Imperi E, Russo G, Pucciarini A, Bigerna B, Schiavoni G, Fortini E, Spanhol-Rosseto A, Sportoletti P, Mannucci R, Martelli MP, Klein-Hitpass L, Falini B, Tiacci E (2015) BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity. Blood 125(8):1207–1216. https://doi.org/10.1182/blood-2014-10-603100 CrossRefPubMedPubMedCentral

26.

Dietrich S, Hullein J, Lee SC et al (2015) Recurrent CDKN1B (p27) mutations in hairy cell leukemia. Blood 126(8):1005–1008. https://doi.org/10.1182/blood-2015-04-643361 CrossRefPubMed

27.

Sherman MJ, Hanson CA, Hoyer JD (2011) An assessment of the usefulness of immunohistochemical stains in the diagnosis of hairy cell leukemia. Am J Clin Pathol 136(3):390–399. https://doi.org/10.1309/AJCP5GE1PSBMBZTW CrossRefPubMed

28.

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(12):1308–1314. https://doi.org/10.1038/modpathol.3880239 CrossRefPubMed

29.

Federico M, Frassoldati A, Lamparelli T, Foà R, Brugiatelli M, Annino L, Baldini L, Capnist G, Chisesi T, di Celle PF, Invernizzi R, Lauria F, Truini M, Resegotti L, Silingardi V, Damasio EE (1994) Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL. Ann Oncol 5(8):725–731. https://doi.org/10.1093/oxfordjournals.annonc.a058977 CrossRefPubMed

30.

Spiers AS, Moore D, Cassileth PA et al (1987) Remissions in hairy-cell leukemia with pentostatin (2′-deoxycoformycin). N Engl J Med 316(14):825–830. https://doi.org/10.1056/NEJM198704023161401 CrossRefPubMed

31.

Ravandi F, O'Brien S, Jorgensen J, Pierce S, Faderl S, Ferrajoli A, Koller C, Challagundla P, York S, Brandt M, Luthra R, Burger J, Thomas D, Keating M, Kantarjian H (2011) Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood 118(14):3818–3823. https://doi.org/10.1182/blood-2011-04-351502 CrossRefPubMedPubMedCentral

32.

Dietrich S, Glimm H, Andrulis M, von Kalle C, Ho AD, Zenz T (2012) BRAF inhibition in refractory hairy-cell leukemia. N Engl J Med 366(21):2038–2040. https://doi.org/10.1056/NEJMc1202124 CrossRefPubMed

33.

Follows GA, Sims H, Bloxham DM, Zenz T, Hopper MA, Liu H, Bench A, Wright P, van’t Veer MB, Scott MA (2013) Rapid response of biallelic BRAF V600E mutated hairy cell leukaemia to low dose vemurafenib. Br J Haematol 161(1):150–153. https://doi.org/10.1111/bjh.12201 CrossRefPubMed

34.

Tiacci E, Park JH, De Carolis L, Chung SS, Broccoli A, Scott S, Zaja F, Devlin S, Pulsoni A, Chung YR, Cimminiello M, Kim E, Rossi D, Stone RM, Motta G, Saven A, Varettoni M, Altman JK, Anastasia A, Grever MR, Ambrosetti A, Rai KR, Fraticelli V, Lacouture ME, Carella AM, Levine RL, Leoni P, Rambaldi A, Falzetti F, Ascani S, Capponi M, Martelli MP, Park CY, Pileri SA, Rosen N, Foà R, Berger MF, Zinzani PL, Abdel-Wahab O, Falini B, Tallman MS (2015) Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med 373(18):1733–1747. https://doi.org/10.1056/NEJMoa1506583 CrossRefPubMedPubMedCentral

35.

Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, Cooper ZA, Chapman PB, Solit DB, Ribas A, Lo RS, Flaherty KT, Ogino S, Wargo JA, Golub TR (2012) Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487(7408):500–504. https://doi.org/10.1038/nature11183 CrossRefPubMedPubMedCentral

36.

Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS (2010) Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468(7326):973–977. https://doi.org/10.1038/nature09626 CrossRefPubMedPubMedCentral

37.

Marusiak AA, Edwards ZC, Hugo W et al (2014) Mixed lineage kinases activate MEK independently of RAF to mediate resistance to RAF inhibitors. Nat Commun 5:3901. https://doi.org/10.1038/ncomms4901 CrossRefPubMedPubMedCentral

38.

Shi H, Moriceau G, Kong X, Lee MK, Lee H, Koya RC, Ng C, Chodon T, Scolyer RA, Dahlman KB, Sosman JA, Kefford RF, Long GV, Nelson SF, Ribas A, Lo RS (2012) Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun 3:724. https://doi.org/10.1038/ncomms1727 CrossRefPubMedPubMedCentral

39.

Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, Gabay MT, Salton M, Dahlman KB, Tadi M, Wargo JA, Flaherty KT, Kelley MC, Misteli T, Chapman PB, Sosman JA, Graeber TG, Ribas A, Lo RS, Rosen N, Solit DB (2011) RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 480(7377):387–390. https://doi.org/10.1038/nature10662 CrossRefPubMedPubMedCentral

Title: Primary lymphomatous presentation of hairy cell leukemia as osteolytic vertebral lesions: a case report
Authors: Jinming Song
Hailing Zhang
Xiaohui Zhang
Lynn Moscinski
Haipeng Shao
Publication date: 01-03-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Hematopathology / Issue 1/2018
Print ISSN: 1868-9256
Electronic ISSN: 1865-5785
DOI: https://doi.org/10.1007/s12308-017-0315-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Primary lymphomatous presentation of hairy cell leukemia as osteolytic vertebral lesions: a case report

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

Isolated central nervous system post-transplant lymphoproliferative disorder in a pediatric patient: a case report with pathobiological perspective

A case of very rare co-occurrence of POEMS syndrome and JAK2 V617F positive MPN

Green inclusions in neutrophils—a case report and review of literature

Rare aggressive natural killer cell leukemia presented with leukopenia and disseminated intravascular coagulation—a diagnostic challenge

Greatly increased giant platelets mimicking blasts in flow cytometric analysis from a patient with primary myelofibrosis