Unusual cutaneous presentation of a T-cell lymphoproliferation
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1 Department of Pathology and Cytology University Hospital Centre Zagreb, Croatia Unusual cutaneous presentation of a T-cell lymphoproliferation Snjezana Dotlic, Stefan Dojcinov, Leticia Quintanilla-Fend
2 History Male 78 yo 9 month history Multiple cutaneous, aggressive looking, ulcerated nodules on lower legs, chest and arms Some nodules appear to spontaneously regress No B symptoms No evidence of systemic lymphadenopathy or hepatosplenomegaly Laboratory investigations: mild anaemia and elevated LDH (270 U/L) Excision skin biopsy of one of the nodules
3
4
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7 CD2 CD3 CD5 CD4 CD8
8 CD3 CD5
9 CD20 CD30
10 CD10 ICOS BCL6+ CXCL13+ BetaF1+ EBER-/+ PD1 CD21
11 Courtesy to Prof. Leticia Quintanilla de Fend Prof Falko Fend Molecular testing (Torrent PGM- Life Technology) (AIL panel: RHOA, IDH2, TET2, DNMT3A) Monoclonal PCR RHOA+ (codon 17) VAF 15% TET2+ (x3) VAF 55% (exon 3) VAF 10% (exon 7) VAF 37% (exon 10)
12 Diagnosis Cutaneous presentation of angioimmunoblastic T-cell lymphoma
13 Discussion points Extranodal (cutaneous) presentation of AIL Important differential diagnoses Utility of phenotypic and molecular testing for diagnosis
14 Angioimmunoblastic T-cell lymphoma (AIL) Definition and Classification Peripheral T-cell lymphoma of specialised CD4+ follicular T-helper cell (T FH ) Elderly patients Sytemic disease Slow insidious start Skin rash, hyperglobulinemia, autoantibodies Progressive disease with generalised lymphadenopathy Pathologically one of the most misdiagnosed lymphomas
15 AITL Morphological Patterns Pattern 1 Pattern 2 Pattern 3 Attygalle A, Blood 2002;99:
16 CD3 CD4 F-TH markers CD10 CXCL13 PD1 ICOS BCL6 SAP MAF CCR5 CD57 CD200 CD20 CD10
17 Molecular and GEP classification of AIL 14% of PTCL NOS are AIL by GEP AITL ALK- ALK+ ATL NK T PTCL-NOS TFH lymphomas - Common mutations RHOA, TET2, IDH2, DNMT3A (40-80%) Gene fusions CTLA4-CD28 (>50%) ITK-SYK (FTCL) Relative Level of Expression (x median value) Iqbal et al. Blood. 2014;123(19): Cairns et al. Blood. 2012;119(8): Palomero et al. Nat Genet Feb;46(2): Sakata-Yanagimato et al. Nat Genet Feb;46(2):171-5 Yoo et al. at Genet Apr;46(4):371-5 Yoo et al. Haematologica Jun;101(6): Lemonnier et al. Blood Aug 16;120(7) Dobay et al. Haematologica Apr;102(4):e148-e151
18 WHO 2016 TCL of TFH origin Gene expression profiling and mutational analysis Greater understanding of PTCL of follicular T- helper origin Nodal PTCL FH phen. Follicular variant AITL PC CD4+ S/MT LPD
19 AIL Skin manifestations Clinical skin manifestations in 50-90% of cases Maculopapular rash Also purpuric, petechial, nodular, plaque-like, urticarial, bullous Widespread, different parts of the body Minority present with clinical picture which suggests skin infiltration by lymphoma Balaraman et al. J Am Acad Dermatol Oct;65(4): Botros et al. Am J Dermatopathol Apr;37(4):274-83
20 AIL Skin manifestations Histological and molecular features Variable histological appearance when biopsied Perivascular infiltrate 47% Vascular hyperplasia or proliferation 44% Vasculitis 27% Combined patterns Molecular evidence of lymphoma more common than usually expected Clonal TCR 87% Cytologically atypical T-cell population 40% Balaraman et al. J Am Acad Dermatol Oct;65(4): Botros et al. Am J Dermatopathol Apr;37(4):274-83
21 Differential diagnosis of AIL in the skin Tfh phenotype 2 (3) of 5 Tfh markers (PD-1, CXCL-13, ICOS, BCL-6, and CD10): Peripheral T-cell lymphoma, not otherwise specified Mycosis fungoides Cutaneous CD30+ LPD Cutaneous CD4 + small/medium T-cell LP (CD4 + SMTCLP) Sezary syndrome Subcutaneous panniculitis-like TCL Bosisio and Cerroni. Am J Dermatopathol Feb;37(2):115-21
22 Primary cutaneous CD4+ small/medium T-cell LPD Solitary nodules on face, neck or upper trunk Patients otherwise asymptomatic Excellent prognosis with no treatment LPD rather than lymphoma Swerdlow et al. 2018
23 PTCL NOS, Cutaneous presentation CD3 CD30 PCRT monoclonal TCRbeta+ ICOS- CXCL13- BCL6- CD21 FDC- RHOA- IDH2- TET2- DNMT3A- CD4 CD10 CD8 PD1 PD1
24 Clinical follow up Chemotherapy: CEOP (1 cycle) in May 2018 Septic shock August 2018: alive, no visible skin lesions, no palpable lymphadenopathy or organomegaly
25 Concluding remarks Diagnosis of AIL in skin AIL rarely involves skin at initial presentation Cornerstone of diagnosis remains critical compilation of Clinical Morphological Immunophenotypic Molecular features But crucial novel tests, including mutational analysis, must be performed Specific mutations serve as indicators for ctdna useful for non invasive monitoring of mimimal resudal disease in AIL Sakata-Yanagimoto M et al, Ann Hematol 2017
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