Subcutaneous panniculitis-like T-cell lymphoma: fever and facial swelling with hemophagocytic syndrome.

We report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a young man presenting with fever and facial swelling. He had pancytopenia and hemophagocytic syndrome (HPS) on evaluation. The histopathological examination of skin punch biopsy from the face and chest wall showed SPTCL. Given the associated HPS, he was started on steroid and multidrug chemotherapy following which he had symptomatic improvement.

Gamma-delta T-cell lymphoma of the central nervous system: A case report and review of the literature.

Primary T-cell lymphoma (TCL) of the central nervous system (CNS) is a rare and potentially aggressive entity. We describe a case of TCL presenting in the basal ganglia with γδ receptor expression and a remarkably aggressive clinical course. To the best of our knowledge, this is the fifth reported case of γδ TCL presenting in the CNS. We review existing literature, including the previously reported cases of γδ TCL of the CNS. In our case, a 69-year-old male presented with acute onset dysarthria and right-sided weakness, with initial imaging concerning for stroke. Repeat imaging demonstrated a 2.6-cm mass in the left basal ganglia-corona radiata. Pathologic examination of a stereotactic biopsy revealed TCL with γδ receptor phenotype. The patient suffered rapid clinical decline and passed away within 6 weeks of initial diagnosis. This represents an important differential diagnosis and sheds light on the potentially poor prognosis conferred by γδ TCL of the CNS.

Angioimmunoblastic T-cell lymphoma involving the nasopharynx: An easily misdiagnosed disease with atypical histopathological features.

OBJECTIVES: To explore the clinicopathologic features, treatment, and survival outcomes of angioimmunoblastic T-cell lymphoma (AITL) involving the nasopharynx. METHODS: We retrospectively analyzed 73 cases of AITL. Among them, 64 cases with complete pre-treatment 18F-FDG positron emission tomography/computed tomography (PET/CT) images were integrated into the analysis of clinical characteristics and PET/CT findings of AITL involving the nasopharynx; 14 cases with both biopsies from lymph node and nasopharynx were included in the comparison of pathological characteristics of AITL in the two areas. Forty-six of the 73 patients who received first-line systemic treatment at our institute were included in the treatment efficacy and survival analyses. RESULTS: Nasopharyngeal involvement was seen in 44/64 (68.8%) patients. Histologically, lymph node and nasopharyngeal biopsies in 14 patients both showed small to medium-sized tumor cells, complex inflammatory infiltration, and Reed-Sternberg-like cells or B immunoblasts. However, tumor cells with clear cytoplasm, significant high endothelial venule (HEV) hyperplasia, and perivascular infiltration were observed in 5/14, 3/14, and 2/14 nasopharyngeal biopsies, respectively, but in all fourteen lymph node biopsies (P < 0.05). Immunophenotypic profiles and gene rearrangements were highly concordant. Treatment efficacy and survival were similar between patients with nasopharyngeal involvement and those without (P > 0.05), indicating nasopharyngeal involvement is not a prognostic factor for AITL patients. CONCLUSIONS: Nasopharyngeal involvement is common in AITL but can be easily misdiagnosed because of its atypical pathologic pattern, especially when a lymph node biopsy is unavailable. However, the patient's clinical presentation, PET/CT manifestations, the typical immunophenotype, and gene rearrangements help the diagnosis.

[Successful cord blood transplantation for refractory gamma-delta hepatosplenic T-cell lymphoma developed during treatment of Crohn's disease].

The patient was a 21-year-old man who had been diagnosed with Crohn's disease and received infliximab and azathioprine six years earlier. He was admitted with fever and fatigue. Peripheral blood examination showed LDH 2,473 U/l and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly. Bone marrow biopsy and liver biopsy showed CD4+CD56+TCRγδ＋CD8- atypical cells, leading to a diagnosis of hepatosplenic T-cell lymphoma (HSTCL). The patient was refractory to CHOP and DA-EPOCH, and therefore received cord blood transplantation with myeloablative conditioning. CT showed reduced in hepatosplenomegaly and peripheral blood examination showed LDH 165 U/l and plt 180,000/µl, so the patient was discharged on day117. HSTCL is a tumor of immature γδT cells with a Vδ1 mutation in the spleen, and immunodeficiency has been implicated in its pathogenesis. Patients with inflammatory bowel disease treated with azathioprine are known to have an increased risk of lymphoproliferative disease. In this case, use of immunosuppressive drugs for Crohn's disease may have caused malignant transformation of γδ cells in the intestinal epithelium. Although the patient was refractory to chemotherapy, he was able to achieve remission with early cord blood transplantation and long-term survival is expected.

Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application.

T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.

Indolent T-Cell/Natural Killer-Cell Lymphomas/Lymphoproliferative Disorders of the Gastrointestinal Tract-What Have We Learned in the Last Decade?

Primary gastrointestinal (GI) T-cell and natural killer (NK)-cell lymphomas/lymphoproliferative disorders (LPD) are uncommon, and they are usually aggressive in nature. However, T-cell and NK-cell lymphoma/LPD of the GI tract with indolent clinical course has been reported over the past 2 decades. Indolent T-cell LPD was formally proposed a decade ago in 2013 and 4 years later recognized as a provisional entity by the revised fourth edition of WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in 2017. Indolent T-cell LPD of the GI tract has been changed to indolent T-cell lymphoma of the GI tract as a distinct entity by the fifth edition of WHO Classification of Haematolymphoid Tumours, but the International Consensus Classification of mature lymphoid neoplasms prefers indolent clonal T-cell LPD of the GI tract instead. In the past decade, indolent lymphoma/LPD of the GI tract has been expanded to NK cells, and as such, indolent NK-cell LPD of the GI tract was recognized as an entity by both the fifth edition of WHO Classification of Haematolymphoid Tumours and the International Consensus Classification. The underlying genetic/molecular mechanisms of both indolent T-cell lymphoma/LPD of the GI tract and indolent NK-cell LPD of the GI tract have been recently discovered. In this review, we describe the history; salient clinical, cytohistomorphologic, and immunohistochemical features; and genetic/genomic landscape of both entities. In addition, we also summarize the mimics and differential diagnosis. Finally, we propose future directions with regard to the pathogenesis and clinical management.

Subcutaneous panniculitis-like T-cell lymphoma: Morphological, immunophenotypical and clonality assessment in six cats.

BACKGROUND: Primary cutaneous lymphoma represents 0.2%-3% of all feline lymphomas, with nonepitheliotropic lymphomas being the most common. In humans and dogs, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a primary nonepitheliotropic lymphoma with a T-cell phenotype developing in the subcutis and often mimicking inflammation. OBJECTIVE: The aim of this report is to describe pathological, phenotypical and clonal features of SPTCL in cats. ANIMALS: Six cats with SPTCL were included in this study. MATERIALS AND METHODS: Skin biopsies were formalin-fixed, routinely processed and stained. Histological and immunohistochemical investigation for anti-CD18, CD204, CD79a, CD20, CD3, FeLVp27and FeLVgp70 and clonality assessment were performed. RESULTS: Four male and two female domestic shorthair cats, mean age 11.2 years, developed SPTCL in the abdominal (three), inguinal (two) and thoracic (one) regions. Variably pleomorphic neoplastic lymphoid cells were present in the panniculus in percentages, expanding the septa (six of six) and extending into fat lobules in one of six cats. Tumours were associated with elevated numbers of neutrophils (five of six), lesser macrophages (six of six) and variable necrosis (six of six). Neoplastic cells expressed CD3+ (six of six), with clonal T-cell receptor rearrangement detected in five of six cats. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first description of SPTCL in cats. Lesions can be confused with panniculitis, leading to delay in diagnosis and therapy. Awareness of this neoplastic disease is relevant to avoid misdiagnoses and to gain greater knowledge about the disease in cats.

Mediastinal T-cell lymphoma in a free-ranging brown howler monkey (Alouatta guariba clamitans).

A free-ranging brown howler monkey (Atelidae: Alouatta guariba clamitans) was necropsied and a mediastinal T-cell lymphoma and esophageal dilation were diagnosed. The case report may contribute to the differential diagnosis of neoplastic and esophageal lesions in non-human primates and highlighted the importance of surveillance of cancer in wildlife.

[Cytologic evidence of hepatocytotropic T-cell-lymphoma in a 15-year-old male cat]. / Zytologischer Nachweis eines hepatozytotropen T-Zell-Lymphoms bei einem 15 Jahre alten Kater.

This case report describes the rare phenomenon of emperipolesis-like invasion of lymphatic blasts into the hepatocytes of a 15-year-old European Shorthair cat. The cat presented with nonspecific clinical signs (inappetence and weight loss). Cytologic examination of an ultrasound-guided fine-needle aspirate of the liver showed a subset of hepatocytes with emperipolesis-like invasion by lymphatic blasts. Few extracellularly located lymphatic blasts exhibited erythrophagia. Following the cytological diagnosis of large cell lymphoma and 2 weeks of monotherapy with prednisolone, the patient was euthanized due to his poor general condition. A post-mortem sample was obtained from the liver to confirm the suspected cytological diagnosis of hepatocytotropic lymphoma. Histopathology subsequently confirmed the cytologic findings. Immunohistochemically, the lymphatic blasts were positive for CD3 leading to a diagnosis of hepatocytotropic T-cell-lymphoma, which has rarely been described so far.

The expression and clinical significance of PLK1/p-PLK1 protein in NK/T cell Lymphoma.

AIMS: To investigate the expression of polo-like kinase 1 protein (PLK1) and its phosphorylation level (p-PLK1) in extranodal NK/T cell lymphoma (NKTCL) and their correlation with clinical characteristics and prognosis. METHODS: We collected 40 cases of NKTCL (referred to as the experimental group), which received diagnoses at the First Affiliated Hospital of Zhengzhou University between January 2018 and October 2022. Concurrently, we assembled a control group, including 20 cases afflicted with nasopharyngeal mucosal lymphoid hyperplasia diseases during the same timeframe. We utilized immunohistochemical techniques to evaluate the levels of PLK1 and p-PLK1 expression in both the experimental and control groups. Subsequently, we conducted an analysis to identify disparities in their expression and explore their relationships with clinical characteristics and patient prognosis. RESULTS: Among the 40 NKTCL patients, there were 27 males and 11 females, with a median age of 51 years (range 12-80 years). Compared to the control group, the tissue samples of NKTCL patients exhibited significantly elevated expression levels and active phosphorylation levels of PLK1 (P < 0.05). Correlation analysis of the immunohistochemical H score and Ki-67 positive rate of PLK1 and p-PLK1, revealed a significant positive correlation for both (P < 0.0001, each). No statistically significant differences were observed in the distribution of PLK1 and p-PLK1 expression in NKTCL patients with respect to gender, age, Ann Arbor stage, PINK-E score, B-symptoms, lactate dehydrogenase, ß2-microglobulin, blood EBV-DNA, bone marrow invasion, and lymph node metastasis (p > 0.05). Grouping based on PLK1 and p-PLK1 immunohistochemical H-scores revealed that the high expression of PLK1 and p-PLK1 was associated with poor prognosis. CONCLUSIONS: The expression levels and active phosphorylation levels of PLK1 were significantly increased in NK/T cell lymphoma, and patients with overexpression of PLK1 and p-PLK1 had a poorer prognosis.

High CD8+tumor-infiltrating lymphocytes indicate severe exhaustion and poor prognosis in angioimmunoblastic T-cell lymphoma.

Background: Exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs), characterized by the overexpression of immune checkpoints (IC), is a major impediment to anti-tumor immunity. However, the exhaustion status of CD8+TILs in angioimmunoblastic T cell lymphoma (AITL) remains unclear. Therefore, we aimed to elucidate the exhaustion status of CD8+TILs in AITL and its influence on prognosis. Methods: The correlation between CD8+TILs and IC expression in AITL was analyzed using single-cell RNA sequencing (n = 2), flow cytometry (n = 20), and RNA sequencing (n = 20). Biological changes related to CD8+TILs exhaustion at different cytotoxic T lymphocyte (CTL) levels (mean expression levels of CD8A, CD8B, GZMA, GZMB, and PRF1) in AITL were evaluated using RNA sequencing (n = 20) and further validated using the GEO dataset (n = 51). The impact of CD8 protein expression and CTL levels on patient prognosis was analyzed using flow cytometry and RNA sequencing, respectively. Results: Our findings demonstrated that the higher the infiltration of CD8+TILs, the higher was the proportion of exhausted CD8+TILs characterized by the overexpression of multiple IC. This was accompanied by extensive exhaustion-related biological changes, which suggested severe exhaustion in CD8+TILs and may be one of the main reasons for the poor prognosis of patients with high CD8+TILs and CTL. Conclusion: Our study comprehensively reveals the exhaustion status of CD8+TILs and their potential negative impact on AITL prognosis, which facilitates further mechanistic studies and is valuable for guiding immunotherapy strategies.

Updates in the Classification of T-cell Lymphomas and Lymphoproliferative Disorders.

PURPOSE OF REVIEW: Mature T/NK-cell neoplasms comprise a heterogeneous group of diseases with diverse clinical, histopathologic, immunophenotypic, and molecular features. A clinically relevant, comprehensive, and reproducible classification system for T/NK-cell neoplasms is essential for optimal management, risk stratification, and advancing understanding of these diseases. Two classification systems for lymphoid neoplasms were recently introduced: the 5th edition of World Health Organization classification (WHO-HAEM5) and the 2022 International Consensus Classification (ICC). In this review, we summarize the basic framework and updates in the classification of mature T/NK-cell neoplasms. RECENT FINDINGS: WHO-HAEM5 and ICC share basic concepts in classification of T/NK-cell neoplasms, emphasizing integration of clinical presentation, pathology, immunophenotype, and genetics. Major updates in both classifications include unifying nodal T-follicular helper-cell lymphomas into a single entity and establishing EBV-positive nodal T/NK-cell lymphoma as a distinct entity. However, some differences exist in taxonomy, terminology, and disease definitions. The recent classifications of mature T/NK-cell neoplasms are largely similar and provide new insights into taxonomy based on integrated clinicopathologic features.

Recommendations on prevention of infections in patients with T-cell lymphomas: a narrative review and synthesis.

T/Natural killer (NK) cell lymphomas (TCL) represent a heterogenous subgroup of non-Hodgkin lymphoma, associated with poorer prognosis and higher treatment toxicity. A cohesive synthesis of infection outcomes among TCL patients is lacking. International guidelines offer no specific recommendations regarding prophylaxis or supportive infection care for TCL patients. This systematic narrative review highlights infection outcomes in TCL patients treated with conventional, and novel therapies. Recommendations for infection screening, antimicrobial prophylaxis and vaccination strategies are outined.

Panniculitic primary cutaneous gamma delta T-cell lymphoma with concomitant features of autoimmune disease emphasizing a pathophysiologic continuum of lupus profundus with the panniculitic T cell lymphomas.

Certain T-cell lymphomas exhibit unique homing properties of the neoplastic lymphocytes for the subcutaneous fat. There are two primary forms of subcutaneous panniculitic lymphomas of T-cell origin. One falls under the designation of primary cutaneous gamma-delta T-cell lymphomas (PGD-TCL) whereby there is dominant involvement of the fat defininng a panniculitic form of PGD-TCL. The neoplastic cells are of the gamma-delta subset and are either double negative for CD4 and CD8 and/or can express CD8. They often have an aggressive clinical course. The other form of panniculitic T-cell lymphoma falls under the designation of subcutaneous panniculitis-like T-cell lymphoma (SPTCL). It represents a subcutaneous lymphoma derived from CD8+ T cells of the alpha-beta subset and typically has an indolent course. These two forms of panniculitic T-cell lymphoma exhibit overlapping histologic features with lupus profundus (LP), a putative form of panniculitic T-cell dyscrasia. We present three cases of PGD-TCL of the fat in the setting of lupus erythematosus (LE) (two cases) and dermatomyositis (DM) (one case), respectively. There were concurrent features of LE and DM in their lymphoma biopsies in two cases while a prior biopsy in one was interpreted as LP. In this latter case, the LP diagnosis presaged the diagnosis of panniculitic PGD-TCL by three years. One patient diagnosed with panniculitic PGD-TCL had hemophagocytic syndrome after developing a lupus-like complex including certain supportive serologies such as antibodies to double-stranded DNA following initiation of statin therapy. The second patient presented with PGD-TCL and concomitant features of anti-nuclear matrix 2 (NXP2) DM. The third patient presented in 2003 with LP and overlying skin features of acute LE, initially responding to Plaquenil, and then four years later was diagnosed with PGD-TCL heralded by Plaquenil treatment resistance. Two of the patients died of their lymphoma. All biopsies showed a characteristic histopathology of PGD-TCL. In two cases, the PGD-TCL was associated with overlying LE-cutaneous findings; another case had skin changes of lymphocyte-rich DM. In two cases, the MXA stain was strikingly positive, the surrogate type I interferon marker that is typically upregulated in biopsies of LE and DM. There are eight prior reported cases describing SPTCL with concomitant cutaneous changes of LE. In six cases there was an established history of LE, including LP responding initially to Plaquenil, similar to one of our cases. In the context of SPTCL or panniculitic PGD-TCL, panniculitic T-cell lymphomas can be associated with concomitant clinical and histologic features of LE or DM, including an upregulated type I interferon signature. Identifying histologic features associated with either of these prototypic autoimmune conditions should not be considered exclusionary to diagnosing any panniculitic T-cell lymphoma. A clinical, histomorphologic, and pathophysiologic continuum exists with LP, SPTCL and panniculitic PGD-TCL.

Angioimmunoblastic T-cell Lymphoma Mimicking Systemic Lupus Erythematosus: A Case Report and Literature Review.

Objective: This study aimed to investigate the clinical features of angioimmunoblastic T-cell lymphoma (AITL) mimicking systemic lupus erythematosus (SLE) and raise awareness about AITL among rheumatologists in order to prevent misdiagnosis and missed diagnosis. The study reports on a case of AITL mimicking SLE and provides a literature review. Methods: Using key words as search terms, relevant articles published in PubMed before 2022-05 were searched, and their clinical characteristics were collected and analyzed. Results: The literature review retrieved six case reports, including four cases initially diagnosed with SLE and then with AITL. The other two case diagnoses were SLE and AITL, respectively. The two diseases are pathogenically associated and share some common features. The clinical manifestations of AITL are complex. The disease is closely associated with abnormal immune functions and is highly heterogeneous. Conclusion: Patients with AITL generally have a poor prognosis. Rarely do reported cases show AITL mimicking SLE. AITL should be considered during clinical practice to prevent missed diagnoses or misdiagnoses.