letter to editor

Primary cutaneousT cell lymphoma withbone marrow infiltrationand erythroblastopenia –A rare association

To the Editor: Pure red cell apla-sia (PRCA) is associated with var-ious mature and precursor B andT lymphoproliferative disorders.However, its association with pri-mary cutaneous T cell lymphoma(CTCL) is distinctly rare. We re-port an uncommon association ofprimary CTCL with erythroblas-topenia and bone marrow (BM)infiltration with overall featuressuggestive of a paraneoplasticPRCA.

A 30-year-old female presentedwith history of gradually progres-sive ulcero-nodular lesion overher lower limb (Figure 1A). Theskin biopsy showed features con-sistent with primary CTCL con-firmed by immunohistochemistry(Figure 1B–E) Positron emissiontomography scan showed extensiveinvolvement of subcutaneous andintramuscular planes of the legand thigh, as well as the underlyingbone. The external iliac, inguinal,and femoral lymph nodes alsoshowed involvement. During hos-pital stay, her general conditionworsened, and she developed asudden drop in hemoglobin(105–40 g/L), reticulocytopenia(0.44%) and thrombocytopenia(84 · 109/L). Total leukocytecount was normal (4.6 · 109/L).Peripheral smear showed neutro-philia with occasional myelocytesand nucleated RBCs. However,there were no atypical cells. BMexamination showed erythroblas-topenia (Figure 1F) and matura-

Hematol Oncol Stem Cell Ther 7(2) Second Quarter 2

tion arrest at proerythroblaststage, which constitute around4% of all nucleated cells in theBM. There were no viralcytopathic changes. Trephinebiopsy showed focal infiltrationby CTCL (Figure 1G–I) withthe rest of the areas showing pre-served hematopoiesis except formarked erythroblastopenia. Thepatient succumbed to her illnessbefore starting definite chemother-apy and died of multiorgandysfunction.

PRCA is an inherited or ac-quired condition characterized byreticulocytopenia (<1%) anderythroblastopenia (<0.5%) withnormal production of myeloidand megakaryocytic lineages.1

PRCA can be classified as congen-ital, primary or idiopathic and sec-ondary. PRCA is reported to beassociated with chronic lympho-cytic leukemia, diffuse large celllymphoma, splenic marginal zonelymphoma, T cell large granularleukemia (T-LGL), angioimmun-oblastic T cell lymphoma (AITL),follicular lymphoma, myelomas,myelodysplastic syndrome, acuteleukemia, Hodgkin’s lymphoma,Waldenström’s macroglobuline-mia, chronic myelogenous leuke-mia, primary myelofibrosis andessential thrombocythemia.1,2 Inone of the largest studies fromJapan, lymphoma was seen in eightout of 185 patients with PRCA.3

A previous study from our insti-tute had one case of NHL out ofnine cases with PRCA.4 One ofthe recent reviews shows that themost common lymphoproliferativedisorder associated with PRCA isT-LGL followed by AITL.2

Primary CTCLs are uncommon

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lymphomas, which present aspatches, plaques or nodular lesionswith or without ulceration. Someof them can lead to hematologicalmanifestations, especially cd T celllymphomas which can presentwith secondary hemophagocyto-sis.5 BM involvement can occurin these tumors in up to 12–20%of cases.6,7 There is only a singlecase of mycosis fungoides associ-ated with PRCA in the literature.3

Possible mechanisms of PRCA inlymphoproliferative disorders in-clude antibody mediated cytotoxicor complement mediated injuryto erythroid precursors, cytotoxicor cytokine mediated injuryinduced by monoclonal or poly-clonal expansion of T cells orNK cells.2 Our case showed infil-tration of BM by CTCL associatedwith erythroblastopenia and clini-cally behaving like a PRCA. Therewas only a patchy involvement ofthe BM by CTCL with preservedareas showing marked erythroblas-topenia and preservation of allother hematopoietic elements,which suggests that the erythro-blastopenia is probably an indirector paraneoplastic effect, and notdue to direct BM infiltration.Though there are reports and re-views associating PRCA with lym-phomas, the association of CTCLwith erythroblastopenia isdistinctly rare. Moreover, the exactincidence and clinical impact oferythroblastopenia in such asituation is unclear in theliterature.

CONFLICT OF INTEREST

The authors have no conflict ofinterest to declare.

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Figure 1. Ulcero-nodular lesions over lower limb (A). Skin biopsy shows dermal and subcutaneous nodular aggregates and sheets of atypicallymphoid cells without epidermotropism (H&E, 4· & 20·) (B & C); cells are positive for CD3 (D) and LCA (not shown); negative for CD20 (E), CD4,CD8, CD79a, CD30, CD138, CD38, and CD56 (not shown). Bone marrow aspirate shows occasional proerythroblasts (MGG, 100·) (F). Bone marrowtrephine biopsy shows infiltration by atypical lymphoid cells admixed with histiocytes, plasma cells and eosinophils (H & E, 20·) (G) which werepositive for CD3 (H), in a background of fibrosis (reticulin stain, 20·) (I).

100 Hematol Oncol Stem Cell Ther 7(2) Second Quarter 2014 hemoncstem.edmgr.com

letter to editor

letter to editor

Sreejesh Sreedharanunni a, Man Updesh SinghSachdeva a,*,Bishan Radotra b,Anusree Prabhakaran c,Gaurav Prakash c

a Department of Hematology, Post

Graduate Institute of Medical

Education and Research, Chandigarh,

India, b Department of Histopathology,

Post Graduate Institute of Medical

Education and Research, Chandigarh,

India, c Department of Internal

Medicine, Post Graduate Institute of

Medical Education and Research,

Chandigarh, India* Corresponding author. Address:

Department of Hematology, Post

Hematol Oncol Stem Cell Ther 7(2) Second Quarter 2

Graduate Institute of Medical

Education and Research, Chandigarh

160012, India. Tel.: +91 172 2755128;

fax: +91 172 2744401

drmanupdeshpgi@yahoo.co.in

ª 2014 King Faisal Specialist Hospital &Research Centre. Published by Elsevier Ltd.All rights reserved.DOI: http://dx.doi.org/10.1016/j.hemonc.2014.01.003

REFERENCES

1. Dessypris EN, Lipton JM. Pure red cell aplasia.In: Greer JP, Foerster J, Rodgers GM, et al., editors.Wintrobe's clinical hematology, 1. PhiladelphiaPA: Lippincot Williams & Wilkins; 2009. p.1196–207.2. Vlachaki E, Diamantidis MD, Klonizakis P, Haral-ambidou-Vranitsa S, Ioannidou-Papagiannaki E,Klonizakis I. Pure red cell aplasia and lymphoprolif-

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erative disorders: an infrequent association. SciWorld J 2012:475313 Epub 2012 April 19.PMC3349208.3. Hirokawa M, Sawada K, Fujishima N, Kawano F,Kimura A, Watanabe T, et al. Acquired pure red cellaplasia associated with malignant lymphomas: anationwide cohort study in Japan for the PRCACollaborative Study Group. Am J Hematol2009;84(3):144–8.4. Malhotra P, Muralikrishna GK, Varma N, KumariS, Das R, Ahluwalia J, et al. Spectrum of pure redcell aplasia in adult population of north-west India.Hematology 2008;13(2):88–91.5. Swerdlow SH, Campo E, Harris NL, Jaffe ES,Pileri SA, Stein H, et al., editors. WHO classificationof tumours of haematopoietic and lymphoid tis-sues. Lyon: France, IARC Press; 2008.6. Mart� RM, Estrach T, Reverter JC, Campo E,Brugues R, Bruguera M, et al. Utility of bonemarrow and liver biopsies for staging cutaneous T-cell lymphoma. Int J Dermatol 1996;35(6):450–4.7. Salhany KE, Greer JP, Cousar JB, Collins RD.Marrow involvement in cutaneous T-cell lymphoma.A clinicopathologic study of 60 cases. Am J ClinPathol 1989;92(6):747–54.

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