The authors
state that there are no conflicts of interest to disclose. This
publication was funded by the CNIC. The CNIC is supported
by the Instituto de Salud Carlos III (ISCIII), the Ministerio de
Ciencia e Innovación (MCIN) and the Pro CNIC Foundation,
and is a Severo Ochoa Center of Excellence (grant CEX2020-
001041-S funded by MICIN/AEI/10.13039/501100011033).S

Cava-Valenciano, Fernando

Del Amo Del Arco, Nazaret

Guillén Santos, Raquel

Jiménez Rolando, Marta

Massó Asensio, Pilar

Álvarez Flores, María Beatriz

Pathology

English

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Pathology (- xxxx) xxx(xxx), xxxPrint ISSN 0031-Please cite this arj.pathol.2023.07.C O R R E S P O N D E N C EA rare finding of plasma cellleukaemia with hairy-cellmorphologyTo the Editor,Plasma cell leukaemia (PCL) is a very rare and typicallyhighly aggressive type of leukaemia. Prognosis is poor, withmedian survival below 6 months, and the disease is charac-terised by peripheral clonal plasmacytosis of peripheral blood(>2109/L PCs or PCs accounting for >20% of nucleatedblood cells).1 Within this rare disease, an even rarer mani-festation is the presence of circulating PCs with a villous or‘hairy’ lymphocyte morphology. Very few cases of thisvariant PCL have been described in the literature.2–11 How-ever, while the available reports do not describe the sameparameters [few include karyotype or fluorescence in situhybridisation (FISH) analysis], all of them coincide in thepresence of atypical villous cells with a lymphoid appearancethat would suggest a chronic B-lymphoproliferative disorderof the hairy-cell type rather than PCL.Here, we describe the case of a patient with PCL whosePCs had the appearance of villous lymphocytes (hairy plasmacell leukaemia; HPCL) and compare this case with the fewcases described in the literature to identify patterns in thelaboratory findings.A 73-year-old woman with a history of osteoporosistreated with calcium, bisphosphonate, and analgesics (para-cetamol and ibuprofen) presented at the emergency depart-ment with severe asthenia, dyspnoea, back pain, and pain inthe right arm after sudden movement. The patient also re-ported a worsening of her lower back pain during the pre-ceding 6 months. A physical examination revealedmucocutaneous pallor.A complete patient blood count revealed a leukocyte countof 106109/L containing 86.8% lymphocytes, markedanaemia with a haemoglobin of 54 g/L (reference range120–160) without reticulocytosis, and a platelet count of251109/L (130–450). Haemostasis tests revealed noremarkable alterations except for an elevated D-dimer con-centration of 3.87 mg/L (<0.5).Biochemical blood analysis gave results within the refer-ence range for glucose, urea, sodium, potassium and totalbilirubin and mildly elevated values for serum creatinine (124mmol/L, 44–106), urate (0.49 mmol/L, 0.14–0.35), lactatedehydrogenase (392 U/L, 81–234), ALT (45 U/L, <41), andAST (51 U/L, <31).Given the leukocytosis and anaemia, a peripheral bloodsmear was performed, revealing small cells with scantbasophilic cytoplasm. Most of these cells had small non-polarised cytoplasmic projections (Fig. 1A, green arrows),some had eccentric nuclei (Fig. 1B, red arrow), and a few ofthem were binucleated (Fig. 1C).We examined the immunophenotype of peripheral blooddue to the signs of chronic lymphoproliferative disorder inthe smear test. Initially an eight-colour screening tube was3025/Online ISSN 1465-3931  2023 Royal College of Patticle as: Álvarez Flores MB et al., A rare finding of plasma cell010used to rule out clonality and the presence of CD34þ pre-cursors. The tube contained the following antibody combi-nation: kappa FITC, lambda PE, CD34 PerCP-Cy5.5, CD19PE-Cy, CD10 APC, CD20APC-Cy7, CD45V450/HLA-DRV500. Cells were acquired in a FACSCanto Flow cytometer(BD Biosciences, USA) and analysed with Infinicyt software(Cytognos, Spain).The flow cytometry study revealed that 83% of total leu-kocytes consisted of a population with a CD45– , CD34– ,CD19– , CD20– , CD10– immunophenotype (Fig. 2A–C).This population was CD66, CD11b and CD33 negative andlacked expression of kappa and lambda surface immuno-globulin light chains, being CD200 positive (data not shown).Because the clonal population did not express CD19 andCD20 with high intensity as hairy cell leukaemia does,CD11c and CD103 were not analysed.An extension of the study to test for the presence of plasmacells showed that the abnormal cell population was CD38þ,CD138þ, CD19– , and CD56þþ, compatible with periph-eral plasma cells with an aberrant phenotype (Fig. 2D,E). Thepopulation was also positive for lambda clonality of veryweak intensity, detected intracellularly (Fig. 2F). The cellswere also negative for CD123 and HLA-DR. These findingsmeet the criteria for plasma cell leukaemia (>2109/L of PCsor >20% of the white blood cell count).A bone marrow smear revealed hypercellular bone marrowwith massive PC infiltration and the presence of plasmablasts.Some of the PCs had hairy cytoplasmic prolongations, whileothers were binucleated. Flow cytometry immunophenotyp-ing of bone marrow aspirate showed that 85.81% of bonemarrow cells were plasma cells (CD38þ, CD138þ) with anaberrant phenotype similar to that detected in peripheralblood: CD19– , CD56þþ, CD45– , and with low-intensitylambda light chain restriction detected by intracellularstaining.A conventional cytogenetic study of the BM aspiraterevealed normal karyotype cytogenetics (46 XX). FISHdetected deletions in chromosome 17p13 (p53) in 43% ofcells and in chromosome 13q14 in 68% of cells, the latterinvolving an IGH-BCL1 rearrangement. Complementarylaboratory studies determined total protein (82 g/L, 60–80)and immunoglobulins (IgG 18.9 g/L, 6.5–16; IgM <0.22 g/L, 0.41–2.4; IgA <0.05 g/L, 0.07–0.58). Serum proteinelectrophoresis detected a gamma monoclonal component at11.4 g/L. Serum immunofixation identified this component asan IgG lambdaþlambda light chain protein with no associ-ated heavy component. The b-2-microglobulin concentrationwas 10 mg/L (<2), and calcium and albumin were normal.Serum light chain concentrations were 0.32 mg/L for kappa(17–37) and 72.4 mg/L lambda (9–21). In a 24-hour urinesample, the concentration of free lambda light chain (BenceJones protein) was 6.3 g/24 h (<0.25).Whole-body computed tomography revealed osteopenia,small lytic lesions in the left scapula, a lytic lesion in the L2vertebra, and focal hypodense areas in the marrow of the iliacbones and vertebrae.hologists of Australasia. Published by Elsevier B.V. All rights reserved.leukaemia with hairy-cell morphology, Pathology, https://doi.org/10.1016/Fig. 1 (A–C) Wright–Giemsa staining of peripheral blood smears, showing atypical cells with a villous, ‘hairy-cell’ morphology.2 CORRESPONDENCE Pathology (xxxx), xxx(xxx), -The patient refused chemotherapy, transfusion with bloodproducts, and treatment with bortezomib, but accepteddexamethasone and EPO pulses. She had a torpid clinicalcourse, with severe anaemic syndrome, bone pain that wastreated with opioid analgesics, and subsequent generalisedfebrile syndrome. The patient died on day 13 day afteradmission.There are very few published reports of PCL with a hairy-cell morphology. All reported cases describe atypical hairycells with a lymphoid appearance, which would promptsuspicion of chronic B-lymphoproliferative syndrome ratherthan plasma cell leukaemia in the first instance. Haematolo-gists should be aware of the existence of this variant PCL toavoid delayed diagnosis.We aimed to compare the patient case presented here withthe others described in the literature. However, unfortunatelythe type of data presented varies between the different de-scriptions, and this heterogeneity makes it difficult to estab-lish shared patterns that distinguish the presentation of HPCLfrom that of classical PCL.Including the patient case presented here, we found 10case reports of HPCL.2–11 Of the patients, 60% were maleand all had leukocytosis (37.63109/L14.49, range13109/L to 106109/L). In 88.88% of patients, atypicalcells with a lymphoid appearance exceeded 40% of all pe-ripheral blood leukocytes. Most patients presented withanaemia (71.40%), elevated serum lactate dehydrogenasePlease cite this article as: Álvarez Flores MB et al., A rare finding of plasma cellj.pathol.2023.07.010(80%), and thrombocytopenia (83.33%). In addition, mostpatients had renal impairment, with w80% having serumcreatinine above the upper reference limit and a depressedestimated filtration rate (CKD-EPI equation). Uric acid waselevated in all patients, possibly reflecting the haematology-associated increase in nucleic acid production and thedepressed renal excretion. The aberrant PC population wasCD138þ, CD38þ, CD19– , and CD45– in all cases (exceptfor one patient with a dim CD45 signal). CD56 expressionwas detected in 50% of the atypical cell populations.Lambda light chain restriction was detected in 71% of cases(Table 1).Karyotypes were reported for only three of the patientsamples. Although the karyotypes were normal, in all threesamples FISH detected alterations in chromosome 13(monosomy 13 and two deletions in 13q).The key clinical and cytogenetic differences between pri-mary PCL and multiple myeloma were described byGundesen et al.12 Given the paucity of data on HPCL, it isdifficult to compare the features of classical PCL and HPCL.This study highlights the limited information available onHPCL and the current inability to determine if its prognosisdiffers from that of PCL with a classical morphology. Itwould be interesting to know the incidence of chromosome13 alterations in HPCL and to define their possible involve-ment in the development of the disease and responses totreatment for which a larger report of HPCL cases is needed.leukaemia with hairy-cell morphology, Pathology, https://doi.org/10.1016/Fig. 2 Peripheral blood immunophenotyping. (A–C) Flow cytometry dot plots revealing abnormal peripheral blood cells (magenta) negative for CD45, CD19, CD20,and CD10. (D,E) Flow cytometry detection of CD38þ and CD138þ clonal plasma cells with aberrant expression of CD56. (F) Intracellular staining revealing lambdalight-chain restriction. Polyclonal B lymphocytes are depicted in blue.Table 1 Flow cytometry immunophenotype, FISH, and karyotype analysisAuthors Light chain CD138 CD38 CD19 CD56 CD45 Karyotype FISHAlghasham11 Lambda þ þ – – ND 46, XX monosomy 13Kumar et al.3 Lambda þ þ – – ND ND NDLi et al.7 Kappa þ þ – þ – 46, XX 13q deletionSharma et al.2 Kappa þ þ – – dim ND NDTanioka et al.5 Lambda ND þ – ND – ND NDMajeed et al.8 ND þ þ – þ – ND NDÁlvarez et al. Lambda þ þ – þ – 46, XX del 17p13; del 13q14Hanbali et al.9 Lambda þ þ ND ND ND ND NDFISH, fluorescence in situ hybridisation; ND, not done.CORRESPONDENCE 3Acknowledgement: We thank Simon Bartlett for Englishediting, Marta Morado for her help with the photography ofthe cytological images and Ataulfo González and JesúsVillarrubia for their morphological consultancy. Thisresearch did not require additional funding and was carriedout with the resources used for patient diagnosis in theLaboratorio Central de la Comunidad de Madrid, BRSalud.Conflicts of interest and sources of funding: The authorsstate that there are no conflicts of interest to disclose. Thispublication was funded by the CNIC. The CNIC is supportedby the Instituto de Salud Carlos III (ISCIII), the Ministerio deCiencia e Innovación (MCIN) and the Pro CNIC Foundation,and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).Please cite this article as: Álvarez Flores MB et al., A rare finding of plasma cellj.pathol.2023.07.010María Beatriz Álvarez Flores1, Marta Jiménez Rolando2,Nazaret del Amo del Arco3, Pilar Massó Asensio4,Raquel Guillén Santos5, Fernando Cava-Valenciano51Unidad de Citometría de Flujo, Centro Nacional deInvestigaciones Cardiovasculares (CNIC), Madrid, Spain;2Servicio de Hematología, Hospital del Henares, Madrid,Spain; 3Servicio de Análisis Clínicos, Instituto de Medicinade Laboratorio Hospital Clínico San Carlos, Madrid, Spain;4Servicio de Hematología, Hospital Ramón y Cajal, Madrid,Spain; 5UR Salud, Laboratorio Central de la Comunidad deMadrid, Madrid, SpainContact Dr María Beatriz Álvarez Flores.E-mail: mbalvarez@cnic.esleukaemia with hairy-cell morphology, Pathology, https://doi.org/10.1016/4 CORRESPONDENCE Pathology (xxxx), xxx(xxx), -1. Criteria for the classification of monoclonal gammopathies, multiplemyeloma and related disorders: a report of the International MyelomaWorking Group. Br J Haematol 2003; 121: 749–57.2. Sharma P, Sachdeva MUS, Ahluwalia J, Malhotra P. Plasma cells withhairy projections and Auer rod-like inclusions in a patient with multiplemyeloma. BMJ Case Rep 2017; 2017: bcr2017221315.3. Kumar TN, Krishnamani K, Gandhi LV, Sadashivudu G,Raghunadharao D. Plasma cell leukaemia masquerading as hairy cellleukaemia: a case report. Indian J Hematol Blood Transfs 2014; 30: S33–5.4. Lesesve J-F, Broseus J. Confusing hairy cells in a case of IgG Kappaplasma cell leukemia. Clin Lab 2016; 62: 749–50.5. Tanioka F, Tamashima S, Shimizu S-I, Kobayashi H, Kobayashi Y,Sugimura H. A case of primary plasma cell leukemia with hairy-cellmorphology and lambda-type Bence-Jones protein. Immunohisto-chemical and molecular analysis. Jpn J Clin Oncol 2003; 33: 232–7.6. Lee HJ, Jo D-Y. Plasma cell leukemia with prominent hairy-cellmorphology. Am J Med Sci 2016; 352: 657.Please cite this article as: Álvarez Flores MB et al., A rare finding of plasma cellj.pathol.2023.07.0107. Li T, Zhang Y, Li K, Yang L, Wang Y. Plasma cell leukemiamorphologically resembling hairy cell leukemia variant. Int J LabHematol 2021; 43: 532–3.8. Memon A, Ali N. Plasma cell leukemia mimicking hairy cell leukemia:extended role of immunophenotyping in correct diagnosis. J ApplHematol 2019; 10: 108–9.9. Hanbali A, Alrajeh A, Rasheed W. Plasma cell leukemia mimickinghairy cell leukemia. Hematol Oncol Stem Cell Ther 2015; 8: 91–2.10. Bernier GM, Anku V, Graham RC, Johnson CA, Fanger MW. Hairyplasma-cell leukemia. Blood 1977; 50: 183.11. Alghasham N, Rawas W, Owaidah T, Hanbali A. Hairy-plasma cellleukemia. J Appl Hematol 2015; 6: 168–71.12. GundesenMT, LundT,Moeller HEH,AbildgaardN. Plasma cell leukemia:definition, presentation, and treatment. Curr Oncol Rep 2019; 21: 8.DOI: https://doi.org/10.1016/j.pathol.2023.07.010leukaemia with hairy-cell morphology, Pathology, https://doi.org/10.1016/

A rare finding of plasma cell leukaemia with hairy-cell morphology.

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A rare finding of plasma cell leukaemia with hairy-cell morphology.

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