Atypical T-cell Research Articles

Cord compression due to atypical T-cell lymphoma from paraspinal soft tissue: report of a case

Cord compression due to atypical T-cell lymphoma from paraspinal soft tissue: report of a case

Granulomatous Slack Skin With Lung and Esophagus Involvement: A Case Report and Molecular Analysis.

Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.

Atypical Intralymphatic T-Cell Proliferation during DRESS Mimicking Intravascular Lymphoma: Case Report

Drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced reaction that represents a life-threatening condition. The histopathologic appearance of the skin biopsy is nonspecific but may exceptionally show an atypical intralymphatic lymphocytic infiltrate, and mimic an intravascular lymphoma. Through this article, we will report an exceptional case of a patient presenting with skin lesions pointing to a dress, but whose histological appearance, in the presence of adenopathy during physical examination, can lead, by mistake, to the diagnosis of an intralymphatic lymphoma. We aim to highlight the various diagnostic indices allowing the distinction between these two entities, including the immunohistochemical study, the search for the TcR clonal rearrangement and the anatomo-clinical correlation.

Angioimmunoblastic T-Cell Lymphoma with Concurrent EBV Viremia: A Challenging Case

Abstract Introduction/Objective Angioimmunoblastic T-cell lymphoma (AITL) represents only 1-2% of all non-Hodgkin lymphomas but is one of the most common non-cutaneous T-cell lymphomas. Although typically associated with latent Epstein Barr Virus (EBV) infection, recent studies have demonstrated the presence and prognostic impact of EBV viremia at the time of diagnosis. Here, we present a case of AITL in which the diagnosis was complicated by EBV viremia. Methods/Case Report A 41-year-old male presented to our hospital with generalized abdominal pain, diffuse lymphadenopathy, hepatomegaly, ascites, and diffuse body wall edema. A recent retroperitoneal lymph node biopsy reportedly demonstrated features suggesting an infectious process, and EBV PCR revealed a viral load of 141,050 copies/mL. A left axillary lymph node was excised, which demonstrated vascular proliferation and diffuse architectural effacement by a polymorphous infiltrate including variably sized lymphocytes with moderate to abundant clear cytoplasm, and occasional admixed neutrophils, plasma cells, and eosinophils. Immunohistochemical staining demonstrated an atypical CD4-positive, CD7-negative T-cell population in a vaguely nodular distribution, expressing Bcl-6, PD-1, ICOS, and CXCL13 without definite CD10 expression. CD21 immunostaining demonstrated markedly expanded follicular dendritic cell meshworks in a distribution similar to the atypical T-cell population. No B-cell or cytotoxic T-cell proliferation was seen, and in situ hybridization for EBV-encoded RNA (EBER ISH) demonstrated only scattered EBV- positive cells. Taken together, these findings supported a diagnosis of AITL over an atypical reaction to EBV infection. Next-generation sequencing demonstrated mutations in TET2, IDH2, and RHOA, further confirming the diagnosis. Results (if a Case Study enter NA) NA Conclusion AITL manifests with a diverse range of clinical symptoms and pathological features and may mimic infection. Additionally, acute EBV infection is well-known to mimic various lymphomas and has rarely been reported to mimic AITL. We present this case to raise awareness of the concurrent presentation of AITL with EBV viremia and to highlight features that may be helpful in distinguishing between the two.

Atypical Stem Cell, Pre-B-Cell, T-Cell and Myeloid Gene Expression Characterizes Early Waldenstrom's Macroglobulinemia Clones Which Diminishes with Advancing Disease and Has Therapeutic Implications

Background: In previous studies using multi-omic data for 253 treatment-naive patients with Waldenstrom's Macroglobulinemia (WM), we identified three subtypes of WM: B-cell like (BCL), Plasma cell like (PCL), and an intermediate clone enriched for early/smoldering WM from which the other two evolved (Hunter et al, ASH 2022). The BCL and PCL subtypes show distinct mutation and transcriptional signatures, as well as clinical characteristics. Diffusion pseudo-time (DPT) analysis suggests all patient tumors, regardless of subtype have a shared evolutionary path and can be divided into Early and Late DPT determined stages that mirror disease progression. Additional analysis of DPT suggests it represents a continuous process akin to clonal evolution. We therefore sought to further characterize the DPT signal in MYD88 mutated WM. Methods: RNASeq was performed on CD19-selected bone marrow (BM) samples from 249 of the 253 treatment-naive WM patients who were MYD88 mutated, as well as 13 paired CD19+CD27- and CD19+CD27+ selected healthy donor (HD) peripheral blood samples. Whole exome sequencing of CD19-selected BM cells along with CD19-depleted peripheral blood mononuclear controls was also performed for 215 of the WM samples. To assess BM histology, slides from 66 BM paraffin blocks from these WM patients were analyzed. Results: WM patients had median age of 66 (range 31-95 years), BM involvement of 50% (5-95%) and serum IgM level of 3,162 (104-10,321 mg/dL). The median follow-up for the study cohort was 8.8 (range 0.2 - 33.8 years). Patients were stratified into 5 cohorts by DPT values. Analysis of BM involvement by DPT cohorts revealed a stepwise increase with the median involvement rising from 20% in the lowest to 80% in the highest cohort (p<0.0001). Increasing DPT predicted for shorter time from biopsy to first therapy (p=0.0003) but was not predictive of time from diagnosis to first therapy consistent with DPT alignment by stage of WM development. RNASeq analysis revealed high expression of genes atypical of mature B-cells that diminished with increasing DPT ( Figure 1). Among these were the myeloid chemo-attractants CXCL1, CXCL8 and CXCL12 which fell from a median of 4.4, 67.2 and 41.1 to 0.1, 3.6 and 0.8 transcripts per million (TpM) in the lowest and highest DPT cohorts, respectively (p<0.0001). Accordingly, all the top 20 gene ontology (GO) terms associated with DPT were related to activation, degranulation, and migration of myeloid cells and leukocytes. Pathological review of the 66 BM slides ranked by DPT, showed increased early myeloid cells and eosinophils clustering near small lymphoid aggregates, and as DPT increased, increased lymphocytes and mast cells with decreased myeloid cell involvement was observed. By RNASeq, pre-B-cell genes including MYB, the VDJ recombination genes RAG1, RAG2 and DNTT as well as the surrogate light chain genes IGLL1 and VPREB1 fell from 22.5, 10, 13.5, 61.1, 144 and 38.3 to 2.2, 1, 1.1, 9.1, 12.2 and 4.3 TpM, respectively (p<0.0001). T-cell and myeloid genes including CD4, CD8A, FCGR3A (CD16), CD14 and CD33 also decreased with increased DPT from 67.6, 7.1, 80.5, 200, and 23.2 to 2.4, 0.9, 1.7, 3.6 and 0.7 TpM, respectively (p<0.0005). A subclonal stem cell signature was also detected, including CD34 and KIT (CD117), which fell from 1.67 and 0.64 to 0.15 and 0.06 TpM, respectively (0<0.0001). CD34, KIT, preBCR, CD4, CD8A, FCGR3A, CEACAM8 (CD66b), and CD33 expression was confirmed by CD19+ light chain restricted flow cytometry in WM but not in HD samples. In addition, the MB and plasma blast genes PRDM1 and XBP1 were elevated in all samples regardless of DPT, consistent with a putative memory B-cell origin. Progression free survival (PFS) in response to proteasome inhibitors revealed strong stratification by subtype (p=0.001), as well as inferior PFS with BTK-inhibitors in low DPT patients (p= 0.044; Figure 2), suggesting less BTK dependence in the early DPT clones. Consistent with this finding, gene set enrichment identified increased BCR signaling with increased DPT. Conclusions: This analysis suggests that stem cell program reactivation and atypical marker expression characterize early WM clones that are ultimately replaced by clones exhibiting more typical B-cell markers with disease progression. The findings may be relevant to treatment selection and provide a framework for investigating subtype and early/late evolutionary staging in the treatment approach to WM.

Polytypic B-Cells, B-Cell Lymphoproliferative Disorders/Lymphomas, and Neoplastic T-Cells Divergently Differentiate from TET2-/ DNMT3A-Mutated Clonal Hematopoiesis in Patients with Follicular Helper T-Cell Lymphomas/Lymphoproliferative Disorders

Introduction: Patients with follicular helper T-cell lymphomas/lymphoproliferative disorders (TFH-LPDs) commonly develop B-cell lymphoproliferative disorders and lymphomas (B-LPDs), but the pathophysiology is incompletely understood. TFH-LPDs often arise from TET2-/ DNMT3A-mutated clonal hematopoiesis (CH). Here we show TET2/ DNMT3A mutations are commonly shared by polytypic B-cells (PBCs), B-LPDs, and TFH-LPDs, with the latter two often carrying additional unique mutations. Methods: Pathology database search at Memorial Sloan Kettering identified patients with TFH-LPDs and PBCs or B-LPDs available for genotyping. If available, myeloid cells were also genotyped. PBCs lacked aberrancies by morphology and flow cytometry (FC) immunophenotyping (including polytypic light chain expression). TFH-LPDs and B-LPDs were defined using International Consensus Classification criteria. Genotyping assays included targeted next-generation sequencing (NGS) with (n=13) or without (n=8; cases 1, 4, 9, 10, 15, 16, 17, 22) a matched germline control and droplet digital PCR (n=4; cases 2, 3, 5, 6). Genotyping was performed on bulk samples or FC-sorted cells, including T-, B-, and myeloid as available. In bulk samples, mutations with allele frequencies (VAFs) >2x the percentage of neoplastic T- and myeloid cells combined in B-LPD samples and of neoplastic T- and total B-cells in bulk blood (PB)/bone marrow (BM) samples were considered present in B-LPD or myeloid compartments, respectively. A >2% VAF cutoff was utilized. EBV status was assessed using EBER in situ hybridization on tissues, serum EBV DNA by quantitative PCR, and/or evaluation of off target EBV reads by NGS. Statistical analyses utilized Mann-Whitney U tests. Results: In total, 25 patients (10 female, 15 male; median age 70 [range 38-82] years) with TFH-LPDs (19 TFH lymphoma, angioimmunoblastic type, 4 TFH lymphoma, NOS, 2 T-LPD with TFH phenotype [defined by morphologically and/or immunophenotypically atypical T-cells with both TFH-like phenotypes and genomic alterations that did not fulfill morphologic criteria for diagnosis of lymphoma]) were identified. The TFH-LPDs harbored TET2 (25/25, 100%), DNMT3A (12/25, 48%), RHOA p.G17 (15/25, 60%), and IDH2 p.R172 (9/25, 36%) mutations (Figure 1A). PBCs from 11 patients were evaluated (7 EBV+, 3 EBV-, 1 EBV unknown; 5 from lymph node, 4 PB, 2 BM). PBCs from 7/11 (64%) shared identical TET2 (n=6; median VAF 0.11 [range 0.02 - 0.27]) and/or DNMT3A (n=3; median VAF 0.05 [range 0.03-0.49]) mutations with corresponding TFH-LPDs. PBCs in 1 patient harbored a unique mutation ( TET2). Four of 8 (50%) patients in which myeloid cells were assessed harbored identical TET2 and/or DNMT3A mutations in the myeloid, PBC, and TFH-LPD compartments. B-LPDs were evaluated from 14 patients (5 diffuse large B-cell lymphoma, 5 polymorphic B-LPD, 2 follicular lymphoma, 1 B-LPD, NOS, 1 plasma cell myeloma; 11 EBV+, 3 EBV-; 9 from tissue, 4 PB, 1 BM). Polymorphic B-LPDs showed atypical polymorphic morphology and an abnormal B-cell immunophenotype by FC and/or a clonal IgH gene rearrangement. The B-LPD, NOS showed an abnormal CD5-/CD10- immunophenotype with light chain restriction by FC without available tissue for morphologic evaluation. Nine of 14 (64%) B-LPDs shared identical mutations with corresponding TFH-LPDs ( TET2 [n=9; median VAF 0.42 (range 0.10- 0.56)], DNMT3A [n=5; median VAF 0.27 (range 0.05-0.50)], TET3 [n=1; VAF 0.32]). Myeloid compartments in 9/12 (75%) patients shared identical TET2 and/or DNMT3A mutations with B- and/or T-LPDs. B-LPDs more commonly harbored additional mutations absent in corresponding TFH-LPDs than PBCs (12/14 [86%] vs 1/8 [13%] evaluated by NGS; p=0.001). Unique mutations in B-LPDs involved epigenetic/transcriptional regulation (n=14, e.g. TET2, KMT2D, SETD5), signaling pathways (n=22, e.g. DTX1, KRAS, EPHA5), and DNA damage response (n=3, e.g. ATM, CHEK2, BRCA2). Incidences of shared and unique mutations did not significantly differ among EBV+ and EBV- cases. Conclusions: Both PBCs and B-LPDs in TFH-LPD patients are commonly EBV+ and share TET2/ DNMT3A mutations with TFH-LPDs, consistent with common origin from CH. B-LPDs more often harbor additional unique mutations than PBCs. Thus, CH mutations and EBV activation in B-cells may predispose TFH-LPD patients to B-LPDs, which may develop with additional private genomic aberrations aiding transformation (Figure 1B).

Primary cutaneous T-cell lymphoma: a review of the most common entities with focus on recent updates

Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between dermatologists, pathologists and hematologists/oncologists. This article reviews the most common cutaneous T-cell lymphomas: mycosis fungoides (both classic and variant forms) as well as its leukemic counterpart Sézary syndrome, CD30+ T-cell lymphoproliferative disorders including the ever-expanding group of lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, and primary cutaneous CD4+ small/medium lymphoproliferative disorder. We discuss the classic clinical and histopathologic features of these lymphomas and review how they can be distinguished from reactive entities. In particularly, updates to these diagnostic categories and current controversies in classification are highlighted. Moreover, we review the prognosis and treatment for each entity. These lymphomas exhibit variable prognosis, and therefore it is important to correctly classify atypical cutaneous T-cell infiltrates for appropriate patient treatment and prognosis. Cutaneous T-cell lymphomas are at the interface of several medical specialties; this review seeks to summarize key features of these lymphomas and highlight new and emerging insights into these lymphomas.

Primary cutaneous T-cell lymphoma: a review of the most common entities with focus on recent updates

Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between dermatologists, pathologists and hematologists/oncologists. This article reviews the most common cutaneous T-cell lymphomas: mycosis fungoides (both classic and variant forms) as well as its leukemic counterpart Sézary syndrome, CD30+ T-cell lymphoproliferative disorders including the ever-expanding group of lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, and primary cutaneous CD4+ small/medium lymphoproliferative disorder. We discuss the classic clinical and histopathologic features of these lymphomas and review how they can be distinguished from reactive entities. In particularly, updates to these diagnostic categories and current controversies in classification are highlighted. Moreover, we review the prognosis and treatment for each entity. These lymphomas exhibit variable prognosis, and therefore it is important to correctly classify atypical cutaneous T-cell infiltrates for appropriate patient treatment and prognosis. Cutaneous T-cell lymphomas are at the interface of several medical specialties; this review seeks to summarize key features of these lymphomas and highlight new and emerging insights into these lymphomas.

Coexpression of natural killer cell antigens by T-cell large granular lymphocytes in hydroa vacciniforme lymphoproliferative disorder and the involvement of Vδ1 + epithelial-type γδT cells

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) is a cutaneous variant of chronic active Epstein–Barr virus disease. We examined the coexpression of T- and natural killer (NK)-cell antigens in five patients with classic HV (cHV) and five with systemic HV (sHV). T-cell receptor (TCR) repertoire analysis was performed with high‑throughput sequencing. All five cHV patients had increased γδT cells (> 5%), whereas five sHV patients showed γδT- and αβT-cell dominance in two patients each, and a mixture of abnormal γδT and αβT cells in one. Circulating CD3 + T cells expressed CD16/CD56 at 7.8–42.3% and 1.1–9.7% in sHV and cHV, respectively. The percentage of CD16/CD56 + T cells was higher in the large granular lymphocyte or atypical T-cell fractions in sHV, but no TCR Vα24 invariant chain characteristic of NKT cells was detected. Considerable numbers of CD3 + cells expressing CD56 were observed in sHV skin infiltrates. Of the circulating γδT cells tested, TCR Vδ1 + cells characteristic of the epithelial type of γδT cells were dominant in two sHV cases. Thus, atypical αβT and γδT cells in HV-LPD can express NK-cell antigens, such as CD16 and CD56, and Vδ1 + epithelial-type γδT cells are a major cell type in some HV-LPD cases.

Cord compression due to atypical T-cell lymphoma from paraspinal soft tissue: Report of a case

Background: During lymphomas natural history of the disease, 5-10% of cases may develop Central Nervous affectation.

A Novel Fusion Partner in a Case of Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement

Abstract Introduction/Objective Myeloid/lymphoid neoplasms with rearrangement of FGFR1 are uncommon and heterogeneous group of hematological malignancies that may present as myeloproliferative neoplasm, acute myeloid leukemia, T or B lymphoblastic lymphoma/leukemia, or mixed phenotypic acute leukemia. Patients can present with lymphadenopathy, mediastinal mass, or systemic symptoms. Eosinophilia is common in peripheral blood or bone marrow. Several chromosomal rearrangements and fusion genes have been described with FGFR1 rearrangement and all of them encode an aberrant tyrosine kinase. Tyrosine kinase inhibitors may offer a prospective therapeutic approach although specific targeted therapies have yet to be established. Methods/Case Report We present a case of a 14-year-old male who presented with rapid neck pain and swelling. Imaging revealed a 15 x 8 x 6 cm neck mass extending into the anterior mediastinum. Laboratory evaluation revealed anemia, thrombocytopenia, and leukocytosis (41.7 K/mm3), with absolute eosinophilia and blasts of 50%. Flow cytometry of peripheral blood demonstrated a population of T-lymphoblasts comprising about 60% of the cellularity with dim CD45, cytoplasmic CD3, CD7, TdT, CD38, CD4, CD5, CD10, and CD15, supporting T-lymphoblastic leukemia/lymphoma. The patient received induction chemotherapy, and subsequent bone marrow biopsy showed morphologic remission. Six weeks from diagnosis, the patient developed a gluteal mass with an atypical T-cell infiltrate that was negative for TdT; and at 15 weeks from diagnosis, developed an enlarging abdominal mass, also with an atypical T-cell infiltrate also negative for TdT and CD1a. At that time molecular diagnostic studies of the abdominal wall mass discovered a previously unpublished ATG16L1-FGFR1 fusion, supporting myeloid/lymphoid neoplasm with FGFR1 rearrangement, T-lymphoblastic leukemia/lymphoma. Results (if a Case Study enter NA) NA. Conclusion Although a variety of translocations have been identified with FGFR1 rearrangement, the novel fusion partner ATG16L1 has not been previously reported. The case also illustrates an unusual extramedullary recurrence of the T-cell lymphoblastic leukemia/lymphoma with significant antigenic shift including loss of TdT and CD1a.

Renal infiltration of peripheral T-cell lymphoma, not otherwise specified, mimicking drug-induced acute interstitial nephritis.

Renal invasion of T-cell lymphoma does not usually occur. The renal infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is rare. Therefore, the detailed pathology, clinical features, and effective therapy of this type of extranodal disease remain uncovered. Here, we report the rare case of acute kidney injury (AKI) caused by the renal infiltration of PTCL-NOS with no evidence of lymphadenopathy and extranodal lesions, except for the kidney. We mistakenly diagnosed our patient with drug-induced acute interstitial nephritis (AIN) at first, because his clinical features were similar to those of drug-induced AIN; however, we reached the correct diagnosis by detecting atypical T-cells in his urine. After the introduction of cyclophosphamide, doxorubicin, vincristine, and prednisone therapy his general condition improved rapidly. When suspecting drug-induced AIN as the cause of AKI, PTCL-NOS should also be recognized as one of the causes, and urine cytology may be useful to noninvasively distinguish between the two diseases.

Sézary Syndrome: Different Erythroderma Morphological Features with Proposal for a Clinical Score System.

Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, peripheral lymphadenopathies, and circulating atypical cerebriform T-cells. To date, no definite staging system has been developed for these patients. In this retrospective analysis of the archive of the Dermatological Clinic of the University of Turin, Italy, erythrodermic SS patients were classified according to clinical records and photographs into three main presentations: erythematous, infiltrated, or melanodermic. The pattern of erythroderma was found to be associated with disease outcome, as better survivals were recorded in patients with erythematous and infiltrative erythroderma. Patients in the melanodermic group, though less represented in our investigation, seemed to show a worse trend in survival. According to this preliminary evidence, a new prognostic classification, with a revised score specific for Sézary syndrome patients, can be proposed to usefully integrate the current staging system. The correlation displayed in our research will be hopefully confirmed by prospective studies with larger cohorts, with the aim of identifying significant prognostic features in this subset of cutaneous T-cell lymphoma patients.

Clinical manifestations and treatment outcomes of pyoderma gangrenosum following rituximab exposure: A systematic review

Clinical manifestations and treatment outcomes of pyoderma gangrenosum following rituximab exposure: A systematic review

Tre-P-05 - Use of mogamulizumab for refractory Sézary syndrome in real clinical practice: report of three cases

Sézary syndrome (SS) is a cutaneous T cell lymphoma (CTLC) with poor prognosis which can present de novo or secondary to mycosis fungoides (MF). We report our experience treating patients with SS with mogamulizumab (n=3). <h3>Case 1:</h3> A 76-year-old woman presented with an 8-year history of refractory erythroderma. Skin biopsy showed dermal lymphocytic infiltrate with aberrant phenotype. Blood flow cytometric analysis detected 77% pathologic T-lymphocytes (TL) with SS phenotype and positive T-cell receptor (TCR) ϒ gene rearrangement. Lymph node biopsy showed SS infiltration. She was diagnosed with stage IVA1 SS (T4N1M0B2). Due to disease progression after treatment with bexarotene, mogamulizumab was started following the usual protocol. Patient achieved complete clinical response (CR) since the 2nd infusion in skin, blood and lymph nodes. She presented grade IV neutropenia after the 6th infusion which resolved with filgastrim, and a grade II lymphopenia after the 5th infusion which resolved with posology spaced to every 6 weeks. Patient continues disease-free after 12 months of treatment. <h3>Case 2:</h3> A 66-year-old woman presented with a 1-year history of erythroderma. Skin biopsies were consistent with MF. Blood flow cytometric analysis detected 59.2% of pathological TL with SS phenotype and positive TCR ϒ gene rearrangement. Lymph node biopsy showed SS infiltration. Diagnosis of stage IVA2 SS (T4N3M0B2) was stablished. She was treated with extracorporeal photopheresis, interferon α-2B, bexarotene and gemcitabine with partial response. Treatment with mogamulizumab was started with complete CR after the 4th infusion in skin, lymph nodes, and blood with good tolerability. She received an allogeneic bone marrow transplant after the 5th cycle and continues disease-free after 100 days post-transplant. CASE 3 A 36-year-old man presented with follicular infiltrated papules and alopecia affecting most of the body surface. Blood flow cytometric analysis showed 93% of pathological TL and positive TCR ϒ gene rearrangement. Skin biopsy was consistent with MF. Lymph nodes showed SS infiltration. Patient was diagnosed with Stage IVA2 SS (T2N3M0B2). He was treated with bexarotene and brentuximab with initial CR but disease progression after 10 cycles. Treatment with mogamulizumab was started with initial improvement but failure after 6 months. Mogamulizumab is a monoclonal antibody that selectively binds to CCR4 present on atypical TL. To date, only a series of 13 patients with CTCL treated with mogamulizumab in clinical practice has been reported, with good tolerability and CR in blood and skin. In our series 2 out of 3 patients presented an impressive CR in all aspects of the disease. One patient developed neutropenia and lymphopenia in relation to mogamulizumab, which resolved after specific treatment. This series supports the use of mogamulizumab in patients with refractory SS. Larger series are needed to evaluate the use mogamulizumab for CTCL in routine clinical practice.

Acute Liver Injury Due to T-cell Infiltration into the Liver as an Initial Clinical Finding of Adult T-cell Leukemia/Lymphoma.

Acute liver injury (ALI) has been rarely reported as a clinical finding of adult T-cell leukemia/lymphoma (ATLL). A 74-year-old Japanese female patient who was histologically diagnosed as having autoimmune hepatitis (AIH) one year earlier, showed elevations in her aminotransferase and total bilirubin levels, and this was considered to be an exacerbation of AIH. Liver biopsy revealed interface hepatitis. Because atypical lymphocytes and human T-cell leukemia virus 1 immunoglobulin G antibody were positive, the patient was diagnosed to have ATLL. The biopsy revealed CD4+ and CD8+, but not CD20+ lymphocytes. Thus, the ALI in the patient was due to T-cell infiltration into the liver, and not due to an exacerbation of AIH.

Germline Mutations in CTLA4 and Spectrum of Bone Marrow Features Overlapping with Aplastic Anemia and Large Granular Lymphocyte Lymphocytosis

Introduction: CTLA4 haploinsufficiency due to germline heterozygous mutations in the cytotoxic T-lymphocyte antigen-4 gene (CTLA4) results in severe systemic immune dysregulation; infiltrative lymphocytic lesions of lungs (e.g. lymphocytic pneumonitis), GI tract (e.g.lymphocytic colitis), and CNS; and a spectrum of autoimmunity, immunodeficiency and peripheral blood cytopenias. We describe the hematologic, bone marrow (BM), and flow cytometry (FC) features of CTLA4 haploinsufficiency of a cohort of 14 patients, which show overlapping morphologic features with acquired aplastic anemia (acAA), and large granular lymphocyte lymphocytosis (LGL) in a subset of patients. We compared the findings to those in a separate cohort of 20 age matched patients diagnosed with acAA. There were significant differences between acAA and CTLA4 deficiency based on analysis of BM lymphocyte subsets and marrow lymphocyte infiltration patterns.Materials and Methods: Peripheral blood (PB), BM and FC analysis of patients with germline mutations in CTLA4, and acAA was performed along with review of clinical, molecular and laboratory data. Statistical comparisons were made using Mann Whitney test, with p < 0.05 for significance.Results: Median age at initial evaluation for patients with CTLA4 haploinsufficiency was 23.5 years (range 11-71 years), with a male-to-female ratio of 11:3. 11 out of 14 patients had cytopenias. Of those with cytopenias 2/11 had pancytopenia, 4/11 had bicytopenia and 5/11 had unilineage cytopenia. Hypogammaglobulinemia was common (13/14). In some cases cytopenias were recognized as autoimmune in etiology with immune thrombocytopenic purpura and autoimmune hemolytic anemia, among the most common hematologic manifestations. Three patients met criteria for a diagnosis of moderate AA, 1 for severe AA, and 1 for LGL. Overall bone marrow biopsies were hypocellular for age (10/14) with a subset (29% [4/14]) showing severe trilineage hypoplasia with ≤20% cellularity. Atypical interstitial CD8-positive T-cell infiltrates with prominent non-paratrabecular CD4-positive T-cell aggregates were evident by immunohistochemistry in most cases (10/14), accompanied by a near absence of B-cells. T-cell clonality was assessed by T-cell receptor (TCR) gamma PCR and showed abnormal oligoclonal T-cell populations in 3/8, and one case with a clonal T-cell receptor gene rearrangement. B-cell IgH PCR reactions were polyclonal. In all cases, cytogenetic studies were either negative or showed only minor abnormalities (i.e. loss of Y chromosome). Given the morphologic overlap of a subset of CTLA4 cases with acAA, we compared bone marrow flow cytometry analysis of 8 CTLA4 cases with 20 acAA cases. CTLA4 patients showed >5 fold reduction in the median percentage of B-cells in comparison to acAA (p=0.0005). While acAA cases demonstrated relative preservation the B-cell compartment with intact B-cell maturation sequence; in contrast CTLA4 cases showed abnormal B-cell maturation patterns in half of cases characterized by few detectable early B-cell precursors, and progressive loss of intermediate and mature forms. T-cell populations in CTLA4 showed inverted CD4:CD8 ratios with relatively increased CD57+ T-cells, and atypical dim expression of CD20 on T-cells. Morphologically, when the markedly hypocellular CTLA4 cases were compared to acAA on core biopsies, little difference in marrow cellularity was seen; however, the CTLA4 cases showed multiple large atypical T-cell aggregates and near total absence of B-cells, which was not seen in acAA; acAA cases showed scattered background T-cells and B-cells.Conclusions: CTLA-4 deficiency presents with cytopenias, autoimmunity, and immunodeficiency with a subset of patients that have features overlapping with bone marrow failure, specifically AA and LGL. Herein we demonstrate a combination of abnormal BM findings, previously unreported, comprising hypocellularity, CD8-positive interstitial T-cell infiltrates with atypical CD4-positive T-cell aggregates, marked B-cell lymphopenia, increased LGLs and abnormal T-cell clonality patterns by PCR. These features may help identify patients harboring CTLA4 mutations for early detection and optimal therapeutic management. DisclosuresYoung:Novartis/GSK to institute: Research Funding. Townsley:Novartis/GSK to institute: Research Funding.

T-cell lymphoproliferative processes in the spleen.

T-cell lymphoproliferative processes in the spleen are rare and it is important to study normal T cell subsets in the spleen to understand the splenic milieu in which they arise. True malignant T-cell processes including hepatosplenic T-cell lymphoma and T-cell large granular lymphocytic leukemia occur in the spleen, but other atypical reactive T-cell proliferations and those of uncertain significance also have been described. Proper distinction of florid T cell responses from malignant T-cell neoplasms has important therapeutic implications for the patient.

A Novel Method for Identifying Transgender and Gender Diverse Patients with Lymphoma: A Single Center Experience

Background: 0.6% of the population is transgender or gender diverse (TGD) and have a gender that differs from their sex assigned at birth (Flores et al., Williams Institute, 2016). TGD people face mistreatment and discrimination, and represent a vulnerable population which is understudied and not well-captured in large cohorts (James et al., National Center for Transgender Equality, 2015). Thus, little is known regarding their cancer risks, prevalence, and outcomes, particularly in the realm of hematologic malignancies. Efforts to study malignancy prevalence in TGD populations are of utmost importance to improve patient care. Limited data suggests TGD patients have higher rates of certain cancers, including lymphoma, compared to other patients, but require validation (Braun et al., Epidemiol Rev, 2017). To accomplish this goal, we sought to design and implement a reproducible data collection strategy to identify TGD patients within a cohort of patients with lymphoproliferative disorders at the Wilmot Cancer Center. Methods: We reviewed the charts of 2200 unselected, consecutive patients with any lymphoproliferative disorder from a single-center, regionally representative, database at the University of Rochester. Our algorithm included searching the following variables for suggestion of TGD identity: demographics, preferred name/alias, medications, problem list, medical/surgical history, social history, an electronic medical record (EMR) lesbian, gay, bisexual, and transgender (LGBT) tab, and karyotype data if available. Additionally, we searched each chart for the following terms: "transgender," "trans," "transsexual," "gender," "genderqueer," "non-binary," "non-conforming," "male to female," "MTF," "female to male," "FTM," "male," and "female" to identify TGD patients. Data on diagnosis, treatment, and more detailed demographics were collected for patients identified as TGD. We report descriptive analyses of our results. Results: Three transgender patients with lymphoproliferative disorders were identified, comprising 0.1% of the database (95% CI 0%, 0.4%). All were white, transgender women with diagnoses of follicular lymphoma, chronic lymphocytic leukemia, and atypical angiotrophic t-cell infiltrate concerning for lymphomatoid papulosis. All three were identified by medication history and searches for the terms "female" and "transgender" as well as aliases differing from legal name. Conclusions: More oncologic research must be done to explore the prevalence of specific malignancies in TGD populations. Such research is limited by inconsistent documentation of gender identity in EMRs resulting in lack of basic epidemiologic data on TGD people with cancer. Our chart review successfully identified three transgender patients. Among the methods used, medication histories, discrepancies between legal name and alias, and searches for the words "transgender" and "female" provided the most fruitful results. We expected diagnoses related to transgender identity, documentation of transgender identity, and the LGBT tab to yield significant results. However, these were low-yield sources in our study. Our inability to identify a percentage of TGD patients similar to prior data was likely multifactorial: 1) TGD patients may not want their gender identities known to oncologists and may not share related information; 2) oncologists may not ask about gender identity or related histories; and/or 3) TGD patients may seek care at outside institutions. Alternatively, the prevalence of lymphoma may be low in TGD populations, conflicting with prior data. Further research regarding TGD patients with hematologic malignancies necessitates specific collection of gender identity data within the EMR and large datasets such as the cooperative groups. More research is needed regarding the optimum questions regarding gender identity which will yield accurate data and maintain strong relationships between patients and providers. Disclosures Casulo: Celgene: Research Funding; Gilead: Honoraria, Other: Travel, accommodation, expenses; Roche: Other: Travel, accommodation, expenses.

1505 Relapsed Angioimmunoblastic T-Cell Lymphoma Presenting as Severe Colitis With Bowel Perforation

INTRODUCTION: Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of the uncommon peripheral T-cell lymphomas that usually presents as acute onset of systemic B symptoms and generalized lymphadenopathy. Here, we report a case of a woman with relapsed AITL involving the descending, sigmoid colon, and rectum, presenting as persistent diarrhea and bowel perforation. CASE DESCRIPTION/METHODS: A 78-year-old woman who was diagnosed with AITL in 2002 and had been stable on continuous therapy of romidepsin for the past 2.5 years for relapsed disease, presented with a 6-week history of diarrhea, fatigue, and decreased appetite. The diarrhea was watery, non-bloody, occurred 4-5 times a day, with fecal urgency and incontinence. The patient denied any abdominal pain, nausea, vomiting, or fever. There was no recent change in her medications, and no recent history of travel or contact with children or pets. During the 6-week period, she was hospitalized twice and was initially thought to have infectious colitis, for which she was given ciprofloxacin, metronidazole, and re-hydration therapy. Abdominal CT showed severe left-sided colitis with multiple enlarged perirectal and mesenteric lymph nodes. Upon her third admission, infectious etiologies were ruled-out and sigmoidoscopy showed markedly edematous and erythematous rectum. Biopsies from the rectum and sigmoid colon showed dense atypical T-cell infiltration consistent with involvement of her previous AITL. Her hospital course was further complicated by bowel perforation and polymicrobial positive blood cultures. She refused surgery and was referred to home hospice for palliative care. DISCUSSION: AITL is an aggressive peripheral T-cell lymphoma that is believed to arise from CD4 positive follicular helper T-cells. It accounts for 1-2% of non-Hodgkin lymphoma cases and has a higher incidence among Asian/Pacific Islanders and Hispanic Whites in the United States. Initial presentation commonly includes generalized lymphadenopathy, fever, unintentional weight loss, and night sweats. With progression, it can commonly involve the bone marrow, spleen, skin and soft tissues. However, gastrointestinal involvement is rare. In 1996, Goenka et al. reported AITL presenting as colonic polyps. We are reporting a case of AITL progressing to involve the descending, sigmoid colon, and rectum, whose presentation was initially mistaken for infectious colitis. However, due to high clinical suspicion, sigmoidoscopy was performed and biopsies confirmed the diagnosis of AITL of the colon.