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Alemtuzumab is a potent lymphocyte-depleting immunotherapy used in solid organ transplan-tation (SOT), that is increasingly being applied in diverse lymphoproliferative disorders (LPDs). However, a significant toxicity limiting expanded usage is cytomegalovirus (CMV) infection, for which standardized preventive strategies exist in SOT but not in LPDs due to a poor understanding of infection risk in this population, with early LPD studies largely limited to stem cell transplantation. Using one of the most diverse arrays of LPDs studied to date, our retrospective cohort study of non-transplant patients receiving alemtuzumab over a ten-year period at a large regional cancer center examines the incidence and clinical profile of infected patients. Among 24 patients, we identified a composite CMV infection rate of 42% with a symptomatic rate of 21%. We also noted significant variations in preventive strategies, which alongside a high infection rate presents an opportunity to improve outcomes through further work in standardization. [ABSTRACT FROM AUTHOR]

Background. Patients with lymphoproliferative disorders (LPD) are at increased risk of developing venous thromboembolic complications (VTEC). Existing risk assessment systems for VTEC (Khorana, Vienna, ThroLy, etc.) do not have sufficient prognostic accuracy in this patient population. The thrombodynamics test may improve the prognosis of VTEC and optimize the prophylactic use of anticoagulants in these patients.Aim. To evaluate thrombodynamics test efficacy in assessing the risk of venous VTEC in LPD patients.Materials and methods. Medical data of 990 patients with LPD who received treatment at the Kirov Research Institute of Hematology and Blood Transfusion from 2019 to 2021 were analyzed. Coagulation parameters were evaluated at admission, as well as the risk of developing VTEC by prognostic scales Khorana, Vienna, ThroLy, SAVED, and Padua. Data are presented as median and interquartile range. Mann–Whitney U test was used to compare two independent groups. Correlation was determined using Spearman’s rank correlation. Logistic regression was used to determine dependencies. The diagnostic value of laboratory tests was established through ROC analysis.Results. In the overall cohort of LPD patients, the incidence of VTEC was 2.1 %. Screening coagulogram parameters in these patients did not exceed reference values. Patients with LPD who developed VTEC initially showed a significant increase in clot velocity (V), initial growth velocity (Vi), and clot size (Cs). It was found that the presence of spontaneous clots significantly increased the chances of developing a thrombotic event (odds ratio 3.99; 95 % confidence interval 1.56–10.22; p = 0.004). It was also determined that V velocity is an independent predictor of VTEC (adjusted odds ratio 1.053; 95 % confidence interval 1.016–1.090; p = 0.0046). The AUC determined by ROC analysis for the V parameter was 0.722 (threshold value 30.7 μm/min sensitivity 81 %, specificity 57.4 %).Conclusion. Clot growth velocity is the most informative parameter of thrombodynamics test in predicting VTEC.

Abstract Background Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is a rare disease characterized by a persistent increase in NK cells in peripheral blood and is generally asymptomatic. If present, symptoms may include fatigue, B symptoms (fever, night sweats, and unintentional weight loss), autoimmune-associated diseases, splenomegaly, and infection due to neutropenia. Peripheral neuropathy, however, is uncommon with an incidence of 3%. Neurolymphomatosis is a neurological manifestation of non-Hodgkin lymphoma and leukemia in which neurotropic neoplastic cells infiltrate the nerves. Moreover, neurolymphomatosis caused by CLPD-NK is extremely rare, with even fewer cases of autonomic dysfunction. We report a case of neurolymphomatosis associated with CLPD-NK and developed autonomic dysfunction, including orthostatic hypotension and gastrointestinal symptoms. Case presentation The patient was a 61-year-old male who was referred to our hospital for leukocytosis. He was diagnosed with CLPD-NK; however, was untreated since he had no hepatosplenomegaly, and other systemic symptoms. He later developed numbness in his lower extremities. Cerebral spinal fluid examination revealed a markedly elevated protein level of 140 mg/dL, and contrast-enhanced magnetic resonance imaging showed bilateral L4 and 5 nerve roots with enlargement and contrast effect. An immune-mediated polyradiculoneuropathy was suspected, and he was treated with intravenous methylprednisolone and immunoglobulin followed by oral prednisolone and cyclosporine. Although his symptoms were relieved by the immunotherapy, significant autonomic dysfunction, including intractable diarrhea, decreased sweating, and orthostatic hypotension, appeared. Additionally, tests for onconeuronal antibodies, ganglionic nicotinic acetylcholine receptor (gAChR) antibody, NF155, CNTN1, Caspr1 antibody, and anti-ganglioside antibodies were all negative. A sural nerve biopsy revealed lymphocytic infiltration, and immunohistochemical staining of lymphocytes confirmed the infiltration of NK and T cells. Therefore, a diagnosis of neurolymphomatosis caused by CLPD-NK was made, and chemotherapy led to partial symptom improvement. Conclusions We experienced a case of pathologically diagnosed neurolymphomatosis with autonomic dysfunction associated with CLPD-NK. In cases of subacute to chronic autonomic dysfunction, paraneoplastic neuropathy, amyloidosis, and autoimmune autonomic ganglionopathy are considered; however neurolymphomatosis caused by CLPD-NK, an important cause of autonomic dysfunction, is not. In difficult to make diagnosis, aggressive nerve biopsy is required.

Background: Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is a rare disease characterized by a persistent increase in NK cells in peripheral blood and is generally asymptomatic. If present, symptoms may include fatigue, B symptoms (fever, night sweats, and unintentional weight loss), autoimmune-associated diseases, splenomegaly, and infection due to neutropenia. Peripheral neuropathy, however, is uncommon with an incidence of 3%. Neurolymphomatosis is a neurological manifestation of non-Hodgkin lymphoma and leukemia in which neurotropic neoplastic cells infiltrate the nerves. Moreover, neurolymphomatosis caused by CLPD-NK is extremely rare, with even fewer cases of autonomic dysfunction. We report a case of neurolymphomatosis associated with CLPD-NK and developed autonomic dysfunction, including orthostatic hypotension and gastrointestinal symptoms. Case presentation: The patient was a 61-year-old male who was referred to our hospital for leukocytosis. He was diagnosed with CLPD-NK; however, was untreated since he had no hepatosplenomegaly, and other systemic symptoms. He later developed numbness in his lower extremities. Cerebral spinal fluid examination revealed a markedly elevated protein level of 140 mg/dL, and contrast-enhanced magnetic resonance imaging showed bilateral L4 and 5 nerve roots with enlargement and contrast effect. An immune-mediated polyradiculoneuropathy was suspected, and he was treated with intravenous methylprednisolone and immunoglobulin followed by oral prednisolone and cyclosporine. Although his symptoms were relieved by the immunotherapy, significant autonomic dysfunction, including intractable diarrhea, decreased sweating, and orthostatic hypotension, appeared. Additionally, tests for onconeuronal antibodies, ganglionic nicotinic acetylcholine receptor (gAChR) antibody, NF155, CNTN1, Caspr1 antibody, and anti-ganglioside antibodies were all negative. A sural nerve biopsy revealed lymphocytic infiltration, and immunohistochemical staining of lymphocytes confirmed the infiltration of NK and T cells. Therefore, a diagnosis of neurolymphomatosis caused by CLPD-NK was made, and chemotherapy led to partial symptom improvement. Conclusions: We experienced a case of pathologically diagnosed neurolymphomatosis with autonomic dysfunction associated with CLPD-NK. In cases of subacute to chronic autonomic dysfunction, paraneoplastic neuropathy, amyloidosis, and autoimmune autonomic ganglionopathy are considered; however neurolymphomatosis caused by CLPD-NK, an important cause of autonomic dysfunction, is not. In difficult to make diagnosis, aggressive nerve biopsy is required. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 73-year-old woman with rheumatoid arthritis who developed a lymphoproliferative disorder after discontinuing immunosuppressive drugs. The patient initially showed improvement but later experienced a relapse of symptoms. The article highlights the importance of closely monitoring rheumatoid arthritis patients with lymphoproliferative disorders and promptly initiating chemotherapy. It also discusses the classification and prognosis of these disorders and the significance of monitoring lymphocyte counts and serum markers. The article provides case reports and references to support its findings. [Extracted from the article]

Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop as a consequence of immunosuppression in transplant recipients. We sought to determine if subtypes of PTLD correlated with different outcomes. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients. A total of 558 children and infants underwent cardiac transplantation at our institution between 1985 and 2019 and were followed until March 2021. Forty-nine of 558 patients developed PTLD (8.8%). As compared to older children (>one year of age), infant recipients (p = 0.04). Although not reaching statistical significance, patients with a shorter time to PTLD diagnosis showed a trend toward higher rates of M-PTLD or cHL. As expected, the overall survival (OS) of patients with M-PTLD or cHL was significantly lower than patients with non-destructive or polymorphic PTLD.

Background: Previous studies have shown that at least a of intraoral eosinophilic ulcer is best classified as a CD30 + T-cell lymphoproliferative disorder (LPD), with histopathology reminiscent of lymphomatoid papulosis (LyP) of the skin. Microscopically, a mixed population of inflammatory cells, often including eosinophils and varying numbers of atypical lymphoid cells, frequently expressing CD30, is typical for LyP, whose clinicopathological spectrum includes type A, B, C, D, E, and LyP with DUSP22/IRF4 rearrangement. To date, about 27 intraoral LyP cases have been reported. Of them, 7 cases were diagnosed as LyP type C, which is frequently confused with anaplastic large cell lymphoma (ALCL) on histopathology. Methods: A 60-year-old male was referred for a one-month history of a tongue ulcer. Results: Microscopy showed numerous subepithelial atypical large lymphoid cells, which expressed CD4 (with partial loss of CD3, CD5, and CD7), CD8 (few cells), CD30 (about 50%, in non-diffuse pattern with size variability), TIA-1, and Ki-67 (85%), without staining for CD56, ALK, LMP1, and EBER1/2, concerning for a diagnosis of ALCL. However, after three weeks, the lesion completely healed. Conclusion: We present here a rare case of intraoral CD30+ T-cell LPD that we believe is the oral counterpart of cutaneous LyP type C. [ABSTRACT FROM AUTHOR]

Methotrexate is a commonly employed folate antagonist used as a disease modifying antirheumatic drug. It is recommended by the European League Against Rheumatism Guidelines as an add-on therapy for the treatment of polymyalgia rheumatica. Lymphoproliferative disease developing during methotrexate treatment is recognised as methotrexate-associated lymphoproliferative disorder. We describe a patient with polymyalgia rheumatica on long-term methotrexate treatment presenting with double vision and systemic symptoms concerning for giant cell arteritis. Two months prior, she had noticed a mass of the right nasal dorsum. Neuroimaging showed several lesions of the nasal cavity and a clival lesion. Nasal cavity biopsy revealed diffuse large B-cell lymphoma, and FDG-PET/CT 3 weeks after methotrexate cessation showed significant interval disease regression, confirming the diagnosis of methotrexate-associated lymphoproliferative disorder. Follow-up FDG-PET/CT 4 months after methotrexate cessation showed complete radiological regression of lymphoproliferative lesions. The cumulative incidence of methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis treated with methotrexate has been reported to be up to 4.7% at 10 years in a retrospective study. Cessation of methotrexate resulted in spontaneous regression in 59% of patients. It is important to include methotrexate-associated lymphoproliferative disorder on the differential diagnosis for patients on long-term methotrexate treatment who present with neuro-ophthalmic symptoms and signs as tissue diagnosis prior to commencing steroid treatment is essential to secure the diagnosis and guide treatment. [ABSTRACT FROM AUTHOR]

In the 1980s, immunohistochemistry and clonality analyses became instrumental in the recognition and definition of new types of cutaneous T‐cell lymphoma (CTCL) and cutaneous B‐cell lymphoma (CBCL) and the development of new classifications. By accepting loss of pan‐T‐cell antigens and clonal T‐cell receptor gene rearrangements as important criteria to differentiate between benign and malignant T‐cell proliferations, and monotypic immunoglobulin light‐chain expression and clonal immunoglobulin gene rearrangements as crucial criteria to distinguish between benign and malignant B‐cell proliferations, many cases, until then diagnosed as cutaneous lymphoid hyperplasia or pseudolymphoma, were reclassified as primary cutaneous CD4+ small/medium T‐cell lymphoma (PCSM‐TCL) or primary cutaneous marginal zone lymphoma (PCMZL), respectively. However, in recent years there is growing awareness that neither these immunohistochemical criteria nor demonstration of T‐cell or B‐cell clonality is specific for malignant lymphomas. In addition, many studies have reported that these low‐grade malignant CTCL and CBCL have an indolent clinical behavior and an excellent prognosis with disease‐specific survival rates of or close to 100%. As a result, recent classifications have downgraded several low‐grade malignant cutaneous lymphomas to lymphoproliferative disorder (LPD). Both the 5th edition of the WHO classification (2022) and the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms reclassified PCSM‐TCL as primary cutaneous CD4+ small/medium T‐cell LPD and primary cutaneous acral CD8+ T‐cell lymphoma as primary cutaneous acral CD8+ T cell LPD. While the 2022 ICC introduced the term "primary cutaneous marginal zone LPD," in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs. [ABSTRACT FROM AUTHOR]

Rosai Dorfman disease is a benign lymphoproliferative disorder. Isolated extranodal involvement is rarely encountered. The causation has not been attributed to any particular factor and the clinical progress of the disease is varied. Treatment options range from observation to medical therapy to surgical excision. Long term follow up is advocated. We report an elderly female with complaints of nasal obstruction who underwent ESS and was diagnosed with this disease on account of histopathology. Follow up period has been uneventful. The case report illustrated here is aimed at highlighting high index of suspicion as well as creating awareness regarding diagnosis and management of a rarely seen pathology. [ABSTRACT FROM AUTHOR]

Purpose of Review: The treatment of Waldenström macroglobulinemia (WM) has evolved over the past decade. With the seminal discoveries of MYD88 and CXCR warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) mutations in WM cells, our understanding of the disease biology and treatment has improved. The development of a new class of agents, Bruton tyrosine kinase inhibitors (BTKi), has substantially impacted the treatment paradigm of WM. Herein, we review the current and emerging BTKi and the evidence for their use in WM. Recent Findings: Clinical trials have established the role of covalent BTKi in the treatment of WM. Their efficacy is compromised among patients who harbor CXCR4WHIM mutation or MYD88WT genotype. The development of BTKC481 mutation-mediated resistance to covalent BTKi may lead to disease refractoriness. Novel, non-covalent, next-generation BTKi are emerging, and preliminary results of the early phase clinical trials show promising activity in WM, even among patients refractory to a covalent BTKi. Summary: Covalent BTK inhibitors have demonstrated meaningful outcomes in treatment-naïve (TN) and relapsed refractory (R/R) WM, particularly among those harboring the MYD88L265P mutation. The next-generation BTKi demonstrate improved selectivity, resulting in a more favorable toxicity profile. In WM, BTKi are administered until progression or the development of intolerable toxicity. Consequently, the potential for acquired resistance, the emergence of cumulative toxicities, and treatment-related financial burden are critical challenges associated with the continuous therapy approach. By circumventing BTK C481 mutations that alter the binding site to covalent BTKi, the non-covalent BTKi serve as alternative agents in the event of acquired resistance. Head-to-head comparative trials with the conventional chemoimmunotherapies are lacking. The findings of the RAINBOW trial (NCT046152), comparing the dexamethasone, rituximab, and cyclophosphamide (DRC) regimen to the first-generation, ibrutinib are awaited, but more studies are needed to draw definitive conclusions on the comparative efficacy of chemoimmunotherapy and BTKi. Complete response is elusive with BTKi, and combination regimens to improve upon the efficacy and limit the treatment duration are also under evaluation in WM. [ABSTRACT FROM AUTHOR]

We herein report a case of methotrexate‐associated lymphoproliferative disorder (MTX‐LPD) showing fibrin‐associated large B‐cell lymphoma‐like heart valve lesions, and Epstein‐Barr virus (EBV)‐positive mucocutaneous ulcer‐like cutaneous and oral mucosal lesions. MTX‐LPD is a critical complication that can occur in RA patients who are treated with MTX. EBV also plays a defining or important role in LPDs. Among the sites of MTX‐LPD, 40−50% occur in extranodal sites, including the gastrointestinal tract, skin, liver, lung, and kidney. There are few reports of MTX‐LPDs involving the heart valves, and to the best of our knowledge, this is the first case to be reported in the English literature. The possibility of EBV‐positive LPD should be considered in RA patients, even in patients with an atypical site, as in this case. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 5-year-old boy with widespread dyspigmentation. The boy had a history of atopic dermatitis and presented with hypopigmented and hyperpigmented patches on his torso, face, and limbs. Various tests were conducted, including blood tests and skin scrapings, which all came back normal. Biopsies were taken from different types of lesions, and histopathology revealed atypical superficial dermal lymphoid infiltrate. The diagnosis was determined to be hypopigmented interface T-cell dyscrasia, a distinct form of lymphoid dyscrasia. The article discusses the clinical features, histopathological findings, and treatment options for this condition. [Extracted from the article]

Syphilis can mimic, clinically and microscopically, many other diseases. By microscopy, typically syphilis presents with plasma cell infiltration, admixed with lymphocytes and macrophages, in lichenoid and/or perivascular/perineural distribution pattern. When exuberant, this inflammatory infiltrate can mimic a lymphoproliferative disorder (LPD), notably plasma cell neoplasia or lymphoma. To date, about 12 cases of secondary syphilis, all but one in extraoral location, suggesting initially a LPD, have been published. Here, to our knowledge, we report an unusual case of intraoral primary syphilis initially suggesting LPD, notably lymphoid hyperplasia (pseudolymphoma); however, mucosa‐associated lymphoid tissue (MALT) lymphoma and follicular lymphoma could not be disregarded. Polyclonality of plasma cells on immunohistochemistry, in strict clinical correlation, was essential to arrive at the correct diagnosis. [ABSTRACT FROM AUTHOR]

EBV+ lymphomas constitute a significant cause of morbidity and mortality in recipients of allogeneic hematopoietic cell (HCT) and solid organ transplants (SOT). Phase I and II trials have shown that in HCT recipients, adoptive transfer of EBV-specific T-cells from the HCT donor can safely induce durable remissions of EBV+ lymphomas including 70->90% of patients who have failed to respond to treatment with Rituximab. More recently, EBV-specific T-cells generated from allogeneic 3rd party donors have also been shown to induce durable remission of EBV+ lymphomas in Rituximab refractory HCT and SOT recipients. In this review, we compare results of phase I and II trials of 3rd party and donor derived EBVspecific T-cells. We focus on the attributes and limitations of each product in terms of access, safety, responses achieved and durability. The limited data available regarding donor and host factors contributing to T cell persistence is also described. We examine factors contributing to treatment failures and approaches to prevent or salvage relapse. Lastly, we summarize strategies to further improve results for virus-specific immunotherapies for post-transplant EBV lymphomas. [ABSTRACT FROM AUTHOR]

Primary cutaneous CD4+ small to medium T-cell lymphoproliferative disorder is rare, accounting for only 2-3% of all primary cutaneous lymphomas. Patients usually present in their 50s with a rapidly growing yet asymptomatic nodule on the face or neck. In this report, we describe the case of a 50-year-old man with an asymptomatic, small, round nodule on his temple area appearing in the preceding two months without any systemic involvement. Surgical excision was done, and histopathological and immunohistochemical studies revealed high infiltration of CD4+ lymphocytes in the dermis, confirming the diagnosis of primary cutaneous CD4+ small to medium T-cell lymphoproliferative disorder. An excellent outcome was achieved, with no signs of recurrence after two months of follow-up. As the disease is often overlooked in the differential diagnoses of suddenonset, rapidly growing lesions, this report reminds physicians to keep it in mind and avoid unnecessary aggressive interventions. [ABSTRACT FROM AUTHOR]

Background: High dose chemotherapy (HDCT) preceding autologous hematopoietic stem cell transplantation (autoSCT) can be toxic for cardiovascular system, which can be mediated with the development of endothelial dysfunction. No studies on the assessment of arterial stiffness and endothelial function after HDCT and autoSCT have been performed before. Aim: To evaluate endothelial function and arterial rigidity parameters by photoplethysmography in patient candidates for HDCT with autoSCT, to identify associated factors and to analyze changes of these parameters over time after HDCT and autoSCT. Materials and methods: In this cohort prospective observational study in 71 patients with verified hemoblastosis (mean age 43.8 ± 12.6 years) we assessed endothelial function and stiffness by photoplethysmography (AngioScan-01, Russia) before and after HDCT with autoSCT. Thirty two (32, 45%) patients had multiple myeloma (ММ), 39 (55%), lymphoproliferative disorders (LPD). We measured the stiffness index (SI), reflection index (RI), augmentation index normalized by heart rate of 75 beats per minute (AIp75) and performed the occlusion test with measurement of occlusion index (ОI) and phase shift (PS). Results: Mean RI in the total study group before HDCT with autoSCT was increased to RI 34.9% [24.5; 50.6], OI decreased to OI 1.5 [1.25; 1.80], and PS module decreased to PS 6.7 ms [3.9; 8.9]. After HDCT with autoSCT the PS module increased to 8.4 ms [5.0; 12.4] (p = 0.001) and OI increased to 1.7 [1.3; 2.2] (p = 0,007), which indicates an improvement in endothelial function. Changes in other parameters of arterial function were non-significant. We also analyzed a selected group of the patients with MM who had higher cardiovascular risk, compared to the LPD patients: they were older (53 vs 36.1 years; p 0.001), had higher rates of arterial hypertension (p 0.001) and diabetes mellitus (p = 0.048). Compared to the LPD patients, the MM patients had higher baseline values of SI (7.5 m/s [7.3; 7.9]), RI (42.9% [32.1; 53.6]), and AIp75 (6.3% [-1.65; 13.8]), indicating higher vascular stiffness. They also had lower PS module values (5.0 ms [2.1; 8.5]). The LPD patients had been more frequently treated with anthracyclines (p 0.001) and radiation (p = 0.002). After HDCT with autoSCT, they had a higher increment of OI, namely, from 1.4 [1.3; 1.8] to 1.7 [1.4; 2.1] (p = 0.003). Conclusion: This study was the first to show a high rate of endothelial dysfunction and vascular stiffness abnormalities in patients with hemoblastoses who were candidates for HDCT with autoSCT. After HDCT with autoSCT, changes of endothelial function and stiffness were multidirectional. Despite a significant improvement, endothelial function parameters were not normalized. We were unable to find any predictors of the abnormalities. Thus, the identified baseline abnormalities in stiffness and endothelial function cannot be a contraindication to HDCT with autoSCT.

Monoclonal T-cell lymphocytosis has been reported in patients with concomitant autoimmune diseases, viral infections, or immunodeficiencies. Referred to as T-cell large granular lymphocytic leukemia (T-LGLL), most cases cannot identify the triggering cause. Only small case series have been reported in the literature, and no treatment consensus exists. T-cell lymphocytosis may also appear after the transplant of hematopoietic stem cells or solid organs. Rare cases have been reported in patients undergoing autologous stem cell transplant (ASCT) for hematological diseases (including multiple myeloma or non-Hodgkin’s lymphoma). Here, we describe the singular case of a patient who underwent ASCT for Hodgkin’s lymphoma and displayed the onset of T-LGLL with an uncommonly high number of lymphocytes in peripheral blood and their subsequent spontaneous remission.

Abstract Background Histiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed. Methods In our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included. Result Based on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality. Conclusion Despite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+PCSM-LPD) is a low-grade cutaneous T cell disorder. There is no standardized approach to treatment of CD4+ PCSM-LPD due to its rarity. Herein, we discuss a 33-year-old woman with CD4+PCSM-LPD which resolved after a partial biopsy. We highlight that conservative and local treatment modalities should be considered prior to utilizing more aggressive and invasive treatment options.

Abstract Background Chronic active Epstein-Barr virus infection (CAEBV) is a systemic EBV-positive lymphoproliferative disorder (EBV-LPD) considered to be associated with a genetic immunological abnormality, although its cause is still unclear. EBV is usually detected in T cells or NK cells in CAEBV patients with only a few cases involving B cells described in East Asia, which may be due to differences in genetic and environmental factors. Case description A 16-year-old boy who seemed to be diagnosed as CAEBV of B cell type was studied. The patient had IM-like symptoms persisting for more than 3 months, high levels of EBV DNA in the PB, and positive EBER in situ hybridization in B cells. In addition, to exclude underlying genetic disorders, we performed next-generation sequencing (NGS) and whole-exome sequencing (WES), which identified the missense mutation in PIK3CD (E1021K), ADA (S85L) and CD3D (Q140K) in the patient while no same genetic mutation was detected in his parents and sister. However, there is no diagnosis of CAEBV of B cell type in the most recent World Health Organization classification of tumors of hematopoietic and lymphoid tissues, therefore we finally diagnosed this patient as EBV-B-LPD. Conclusions This study shows a rare case of a patient meeting the definition of CAEBV B-cell disease in East Asia. Meanwhile, the case indicates that the missense mutation and the disease are related.

Heuristics are cognitive strategies used to facilitate decision‐making. They can be helpful tools for expediting pathologic diagnoses, however, they can also affect judgment and lead to biases that guide the pathologist astray. We report the case of a 52‐year‐old female who presented with two unusual pigmented lesions on the wrist and thigh that clinically and histopathologically resembled an atypical melanocytic proliferation. A biopsy of the thigh revealed a broad proliferation of large, atypical cells forming nests within a heavily pigmented epidermis. The lesion was initially misdiagnosed as melanoma in situ, despite equivocal staining for melanocytic markers, likely due to anchoring and adjustment as well as availability biases, which restricted the differential diagnosis and limited the selection of immunohistochemical stains. It was later discovered through chart review that the patient had a prior history of a cutaneous CD30+ lymphoproliferative disorder, which eventually led to the appropriate diagnosis in this case. Herein, we highlight a rare and unusual presentation of a pigmented epidermotropic CD30+ lymphoproliferative disorder, along with the biases leading to its misdiagnosis and the steps leading to the revelation of the actual diagnosis. [ABSTRACT FROM AUTHOR]

Monoclonal T-cell lymphocytosis has been reported in patients with concomitant autoimmune diseases, viral infections, or immunodeficiencies. Referred to as T-cell large granular lymphocytic leukemia (T-LGLL), most cases cannot identify the triggering cause. Only small case series have been reported in the literature, and no treatment consensus exists. T-cell lymphocytosis may also appear after the transplant of hematopoietic stem cells or solid organs. Rare cases have been reported in patients undergoing autologous stem cell transplant (ASCT) for hematological diseases (including multiple myeloma or non-Hodgkin’s lymphoma). Here, we describe the singular case of a patient who underwent ASCT for Hodgkin’s lymphoma and displayed the onset of T-LGLL with an uncommonly high number of lymphocytes in peripheral blood and their subsequent spontaneous remission. [ABSTRACT FROM AUTHOR]

Purpose of Review: Epstein-Barr Virus (EBV) is a ubiquitous herpesvirus that affects almost all humans and establishes lifelong infections by infecting B-lymphocytes leading to their immortalization. EBV has a discrete life cycle with latency and lytic reactivation phases. EBV can reactivate and cause lymphoproliferation in both immunocompetent and immunocompromised individuals. There is sparse literature on monitoring protocols for EBV reactivation and no standardized treatment protocols to treat EBV-driven lymphoproliferation. Recent Findings: While there are no FDA-approved therapies to treat EBV, there are several strategies to inhibit EBV replication. These include immunosuppression reduction, nucleoside analogs, HDAC inhibitors, EBV-specific cytotoxic T-lymphocytes (CTLs), and monoclonal antibodies, such as rituximab. There is currently an open clinic trial combining the use of a HDAC inhibitor, nanatinostat, and ganciclovir to treat refractory/relapsed EBV lymphomas. Another novel therapy includes tabelecleucel, which is an allogenic EBV-directed T-cell immunotherapy that was approved by the European Medicines Agency, but is currently only available in the US for limited use in relapsed or refractory EBV-positive PTLD. Summary: Further research is needed to establish EBV monitoring protocols in high-risk populations, such as those with autoimmune disease, cancer, HIV, or receiving immunosuppressive therapy. Additionally, standardized treatments for both the prevention of EBV reactivation in high-risk populations and treatment of EBV reactivation and lymphoproliferation need to be established. [ABSTRACT FROM AUTHOR]

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. Summary: The recent classifications of mature T/NK-cell neoplasms are largely similar and provide new insights into taxonomy based on integrated clinicopathologic features. [ABSTRACT FROM AUTHOR]

Methotrexate is an immunosuppressant commonly used to treat inflammatory conditions, such as rheumatoid arthritis. However, albeit exceedingly rare, it can have serious adverse effects within the central nervous system (CNS), such as methotrexate-associated lymphoproliferative disorder (MTX-LPD). Literature describing the natural history, treatment options, and clinical outcomes of patients with CNS MTX-LPD remains sparse. We present a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a case illustration of CNS MTX-LPD. A systematic review of the literature revealed 12 published cases of CNS MTX-LPD, plus the case presented herein, for a total of 13 included cases. The most common indication for MTX was rheumatoid arthritis. The most common treatment for the LPD was MTX cessation (12, 92.3%), adjunct chemotherapy (2, 15.4%), total tumor resection (3, 23.1%), or steroid therapy (1, 7.7%). Treatment usually led to improvement of neurological symptoms (9, 69.2%) along with regression of the lesions (3, 23.1%) with no recurrence (6, 46.2%). Death was reported in four cases (30.8%) with a mean time from onset of 11 months. CNS MTX-LPD should be considered in the differential diagnosis for patients who are taking MTX presenting with neurologic symptoms, as immediate withdrawal of MTX has demonstrated good prognosis. [ABSTRACT FROM AUTHOR]

Objectives: To elucidate the efficacy and safety of rituximab in special types of rheumatoid arthritis. Methods: We retrospectively reviewed all patients with rheumatoid arthritis with lymphoproliferative disorder or vasculitis treated with rituximab between April 2010 and June 2022 at Keio University Hospital. We assessed the effectiveness of rituximab using the Disease Activity Score for 28 joints‐erythrocyte sedimentation rate (DAS28‐ESR), Clinical Disease Activity Index (CDAI), and safety of rituximab during the disease course. We also assessed the glucocorticoid‐sparing effects of rituximab. Results: We included eight patients with a history of lymphoproliferative disorder and five patients with rheumatoid vasculitis. They were treated with rituximab without high‐dose glucocorticoid. The mean DAS28‐ESR and CDAI scores significantly improved 12 months after rituximab administration (DAS28‐ESR, 4.7 vs. 2.7, p <.001; CDAI, 16.0 vs. 5.1, p =.006, respectively), and the dose of prednisolone was reduced from a mean of 7.4 mg/day to 4.0 mg/day at 12 months (p =.05) and 3.2 mg/day at the last visit (p =.04). During the mean follow‐up period of 52 months, we recorded one recurrence of lymphoproliferative disorder (not B‐cell type) in patients with a history of lymphoproliferative disorder and remarkable improvement of skin ulcers in patients with vasculitis. Conclusion: B‐cell depletion by rituximab may be a useful treatment option for patients with lymphoproliferative disorder and rheumatoid vasculitis. [ABSTRACT FROM AUTHOR]

Background: Histiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed. Methods: In our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included. Result: Based on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality. Conclusion: Despite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma. [ABSTRACT FROM AUTHOR]

Abstract Background Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described. Case presentation A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and “other iatrogenic immunodeficiency-associated lymphoproliferative disorder” (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD. Conclusions This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.

The article discusses a rare case of Hydroa vacciniforme-like lymphoproliferative disorder (HVLLPD) in a Cook Island Māori child, which is a rare Epstein-Barr virus-associated disease. The case study highlights the clinical presentation, histological findings, and treatment approach for this condition, emphasizing the need for close clinical follow-up due to the risk of systemic involvement and lymphoma transformation. The article also notes the genetic similarities between Pacific Island and East Asian populations, suggesting a possible link to historic migration patterns. [Extracted from the article]

Introduction: Primary cutaneous CD8+ acral T-cell lymphoproliferative disorder (CD8+ ATCLPD) is a rare form of cutaneous T-cell lymphoma that commonly presents on the acral regions of the body. We report a case of a 61-year-old man diagnosed with primary cutaneous CD8+ ATCLPD of the ear. Case presentation: A 61-year-old man presented with a non-healing, erythematous painful macule on the ear that had been evolving for the past 3 months. The lesion was resected, and histopathological examination revealed a primary cutaneous CD8+ ATCLPD with acral localization. Further investigations including CT scan of the thorax, abdomen and pelvis were done to stage the disease. The results showed no extracutaneous involvement. Conclusion: Accurate identification of primary cutaneous CD8+ ATCLPD is crucial due to its distinct prognostic and therapeutic implications compared to other CD8+ cytotoxic lymphoid proliferations. Primary cutaneous CD8+ ATCLPD can be treated conservatively and typically follows a slow clinical course, regardless of the treatment method. Understanding the clinical context, as well as the morphological and immunophenotypic characteristics, can assist in making a precise diagnosis. [ABSTRACT FROM AUTHOR]

Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract is a new provisional entity listed in the structure of the forthcoming fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors. It was first named as "NK-cell enteropathy" and "Lymphomatoid gastropathy" by two independent series a decade ago. Molecular or cytogenetic studies have lent support to the clonal/neoplastic nature of this entity. Herein we add two of such cases that still challenge pathologists and were previously diagnosed as aggressive lymphomas of NK/T derivation. [ABSTRACT FROM AUTHOR]

Background: Chronic active Epstein-Barr virus infection (CAEBV) is a systemic EBV-positive lymphoproliferative disorder (EBV-LPD) considered to be associated with a genetic immunological abnormality, although its cause is still unclear. EBV is usually detected in T cells or NK cells in CAEBV patients with only a few cases involving B cells described in East Asia, which may be due to differences in genetic and environmental factors. Case description: A 16-year-old boy who seemed to be diagnosed as CAEBV of B cell type was studied. The patient had IM-like symptoms persisting for more than 3 months, high levels of EBV DNA in the PB, and positive EBER in situ hybridization in B cells. In addition, to exclude underlying genetic disorders, we performed next-generation sequencing (NGS) and whole-exome sequencing (WES), which identified the missense mutation in PIK3CD (E1021K), ADA (S85L) and CD3D (Q140K) in the patient while no same genetic mutation was detected in his parents and sister. However, there is no diagnosis of CAEBV of B cell type in the most recent World Health Organization classification of tumors of hematopoietic and lymphoid tissues, therefore we finally diagnosed this patient as EBV-B-LPD. Conclusions: This study shows a rare case of a patient meeting the definition of CAEBV B-cell disease in East Asia. Meanwhile, the case indicates that the missense mutation and the disease are related. [ABSTRACT FROM AUTHOR]

Sadan Mohammed Al Harbi,1 Nada Jomaan Al Ghamdi,1 Tarek Mohamed Elsharkawy,2 Mohammad Abdelqader Al Hamad,2 Sultan Bajawi1 1Department of Dermatology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia; 2Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi ArabiaCorrespondence: Sadan Mohammed Al Harbi, Department of Dermatology, College of Medicine, Imam Abdulrahman Bin Faisal University, Post Box No. 1982, Dammam, 31441, Saudi Arabia, Email Smharbi@iau.edu.saAbstract: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a lymphoproliferative disorder in which the majority of cells are reactive T cells with only a minor population of neoplastic large B cells. THRLBCL is a very rare lymphoma, and most cases are nodal THRLBCL; an extranodal case of THRLBCL presenting primarily on the skin is an extremely rare occurrence with only a few cases reported in the literature. Here, we report a case of a primary cutaneous THRLBCL in a 41-year-old Saudi male who presented unusually with multiple skin lesions. He was successfully treated with electron beam radiotherapy and had a complete resolution with no recurrence as of his 24-month follow-up.Keywords: T-cell-rich B-cell lymphoma, lymphoproliferative disorder, radiotherapy, neoplastic B cells

Sadan Mohammed Al Harbi,1 Sahar Al Natour,1 Nasser Mohammed Al Saif,1 Noura Al Saif,1 Methal Isam Al Bayat2 1Department of Dermatology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Sadan Mohammed Al Harbi, Department of Dermatology, College of Medicine, Imam Abdulrahman Bin Faisal University, Post Box No. 1982, Dammam, 31441, Saudi Arabia, Email Smharbi@iau.edu.saAbstract: Primary cutaneous B-cell lymphomas (PCBCLs) are very rare to be seen in pediatric and adolescent age group, especially primary cutaneous follicle center lymphoma (PCFCL) which is considered the least occurring main subtype. Here, we describe a 16-year-old girl who developed a slowly growing solitary firm smooth surfaced erythematous nodule over her forearm. Histopathological examination showed a dense dermal nodular, periadnexal and perivascular lymphoid infiltrate extending deep to the subcutis. Immunohistochemical staining showed a B-cell population with positivity for CD20, variable staining for BCL6 and CD10 and uniquely staining for BCL2. Although a primary cutaneous marginal zone lymphoma (PCMZL) was considered but the presences of interfollicular BCL6 and CD10 positivity established the diagnosis of PCFCL. To our knowledge, only 12 cases of pediatric and adolescent PCFCL have been described in the literature.Keywords: B-cell lymphoma, skin cancer, pediatric, juvenile, lymphoproliferative disorder

Hidradenitis suppurativa is a chronic inflammatory disease associated with multiple comorbidities, and its association with lymphoma has recently been a topic of debate. However, it is still controversial whether this risk can be attributed to the disease itself or whether it has any relationship with immunosuppressive treatment. Here, we describe the case of a patient with severe perianal hidradenitis suppurativa treated with methotrexate and infliximab, whose exacerbation with persistence of severe symptoms refractory to adequate treatment led to the diagnosis of diffuse large non-Hodgkin B-cell lymphoma. It was decided to perform a colostomy to improve perianal sepsis, and immunochemotherapy was proposed.

Background: Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described. Case presentation: A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and "other iatrogenic immunodeficiency-associated lymphoproliferative disorder" (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD. Conclusions: This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified. [ABSTRACT FROM AUTHOR]

Castleman disease (CD) is a rare lymphoproliferative disorder that includes various clinico-pathological subtypes. According to clinical course, CD is divided into unicentric CD (UCD) and multicentric CD (MCD). MCD is further distinguished based on the etiological driver in herpes virus-8-related MCD (that can occur in the setting of HIV); in MCD associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes); and idiopathic MCD (iMCD). The latter can also be divided in iMCD-TAFRO (thrombocytopenia, anasarca, fever, myelofibrosis, organomegaly) and iMCD not otherwise specified. To date, CD pathogenesis is still uncertain, but CD may represent the histological and clinical result of heterogeneous pathomechanisms. Transcriptome investigations in CD lymph nodes have documented the expression and up-regulation of different cytokines; furthermore, few recent studies have shown alterations of different T-cell subsets in CD patients, suggesting a possible role of the nodal microenvironment in CD development. On this basis, our study aimed to investigate the distribution of T-cell subsets in the clinico-pathological spectrum of CD. We evaluated the CD4/CD8 ratio and the number of T-regulatory (T-reg) FOXP3+ cells in 28 CD cases. In total, 32% of cases showed a decreased CD4/CD8 ratio due to increased CD8+ T-cells, including both UCD, iMCD, and HHV8+ MCD cases. The T-reg subset analysis revealed a statistically significant (p < 0.0001) lower mean number of FOXP3+ T-reg cells in CD cases when compared with non-specific reactive lymph nodes. We did not find statistically significant differences in T-reg numbers between the different CD subtypes. These findings may suggest that alterations in T-cell subpopulations that can lead to disruption of immune system control may contribute to the numerous changes in different cellular compartments that characterize CD. [ABSTRACT FROM AUTHOR]

Abstract is missing (Quiz)

Objective: To assess the spectrum and clinico-haematological profile of chronic lymphoproliferative disorders in patients presenting with lymphocytosis. Method: The cross-sectional, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data related to cases of bone marrow aspirate and trephine from January to November 2020. Patients for whom the bone marrow was done for lymphocytosis were studied for the presence of lymphoproliferative disorders, sub-types and patients’ characteristics. The diagnosis and classification were based on the World Health Organisation criteria for tumours of haematopoietic and lymphoid tissues. Data was analysed using SPSS 21. Results: Of the 3,334 bone marrow specimens tested, 103(3%) were related to lymphocytosis. Of these, 84(82%) were diagnosed with lymphoproliferative disorders, while diagnosis remained undetermined in 19(18%) cases. Male:female ratio was 3.6:1 and median age was 60 years (range: 21-85 years). Constitutional symptoms were found in 61(73%) patients. Median absolute lymphocyte count was 45x109/L (range: 5.3-480). All 84(100%) patients were classified as B-cell lymphoproliferative disorder. Chronic lymphocytic leukaemia was the most common form, 61(73%), and 31(51%) of them presented with advanced stage disease. Conclusion: A huge majority of patients presenting with lymphocytosis had underlying lymphoproliferative disorders of which B-cell chronic lymphocytic leukaemia was found to be the most common. Key Words: Lymphoproliferative disorder, Lymphocytosis, Chronic lymphocytic leukaemia, Bone marrow, Pakistan.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is indolent clinical behaviour and uncertain malignant potential. Histologically, these lesions show a predominance of small to medium-size CD4+ pleomorphic T-cell expressing follicular helper T-cell markers. We report the case of a 59-year-old female who presented with nodules on the left chest for 3 years. Dermatological examination showed four red nodules localized on the left chest with angiotelectasis without tenderness. The histopathological manifestation was consistent with the diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. We focus on the clinical appearance, histopathological features, diagnosis, and differential diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSMLPD) is an uncommon T-cell proliferation, which generally presents as an asymptomatic solitary slow-growing erythematous papule or plaque in the head and neck region. Keywords: cutaneous; T-cell; lymphoproliferative disorder; genetics; genomics; molecular; sequencing EN cutaneous T-cell lymphoproliferative disorder genetics genomics molecular sequencing 768 770 3 10/10/23 20231001 NES 231001 PEER REVIEW The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1002/hon.3133. 2022; 140 (11): 1229 - 1253. https://doi.org/10.1182/blood.2022015851 3 Çetinözman F, Jansen PM, Willemze R. Expression of programmed death-1 in primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, cutaneous pseudo-T-cell lymphoma, and other types of cutaneous T-cell lymphoma. [Extracted from the article]

Abstract Background This case reveals a novel presentation of drug rash with eosinophilia and systemic symptoms syndrome that mimics a lymphoproliferative disorder. The heterogeneous clinical presentation of drug rash with eosinophilia and systemic symptoms syndrome gives rise to a broad differential diagnosis that includes a multitude of infectious, inflammatory, and autoimmune conditions. This patient was diagnosed with drug rash with eosinophilia and systemic symptoms syndrome 4 weeks after starting sulfasalazine and 5 weeks after starting hydroxychloroquine for rheumatoid arthritis. Both of these medications have been shown to cause drug rash with eosinophilia and systemic symptoms syndrome, albeit more rarely in the context of hydroxychloroquine. This patient’s history, physical examination, and workup illuminate a case of drug rash with eosinophilia and systemic symptoms syndrome that masquerades as a lymphoproliferative disorder despite its adherence to the RegiSCAR criteria. Case presentation A 22-year-old African-American female with an atopic history and rheumatoid arthritis presented for evaluation of a rash, unremitting fevers, and syncope. She was found to have drug rash with eosinophilia and systemic symptoms syndrome. A syncope workup was unremarkable. Computed tomography of the chest/abdomen/pelvis confirmed extensive lymphadenopathy and revealed a small right pleural effusion (Fig. 5). These imaging findings accompanied by fevers and a rash in the setting of eosinophilia, leukocytosis, and transaminitis led to the clinical suspicion for drug rash with eosinophilia and systemic symptoms syndrome. Steroids were subsequently initiated. Broad-spectrum antibiotic therapy was implemented to cover for possible skin/soft tissue infection due to initial paradoxical worsening after discontinuation of the culprit drugs. Lymph node biopsy ruled out a lymphoproliferative disorder and instead demonstrated necrotizing lymphadenitis. An extensive infectious and autoimmune workup was noncontributory. Clinical improvement was visualized, antibiotics were discontinued, and she was discharged on a steroid taper. Conclusion This case reflects how drug rash with eosinophilia and systemic symptoms syndrome can masquerade as a lymphoproliferative disorder. Additionally, it highlights the extent to which rapid identification and treatment optimized the patient’s outcome. It calls into question how immunogenetics may factor into a patient’s susceptibility to acquire drug rash with eosinophilia and systemic symptoms syndrome. This case is unique because of the early onset of visceral organ involvement, the type of internal organ involvement, the hematopoietic features, and the lymphadenopathy associated with a disease-modifying antirheumatic drug.

Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.

The diagnosis of leukemic B-cell lymphoproliferative disorders (B-LPDs) is made by integrating clinical, cytological, cytometric, cytogenetic, and molecular data. This leaves room for differences and inconsistencies between experts. In this study, we examine methodological and conceptual aspects of the flow cytometric classification of leukemic B-LPDs that could explain them. Among methodological aspects, we discuss (1) the different statistical tests used to select and evaluate markers, (2) how these markers are analyzed, (3) how scores are interpreted, (4) different degrees to which diagnostic information is used, and (5) and the impact of differences in study populations. Among conceptual aspects, we discuss (1) challenges to integrating different biological data points, (2) the under examination of the costs of misclassification (false positives and false negatives), and finally, (3) we delve into the impact of the lack of a true diagnostic gold standard and the indirect evidence suggesting poor reproducibility in the diagnosis of leukemic B-LPDs. We then outline current harmonization efforts and our personal approach. We conclude that numerous flow cytometry scores and diagnostic systems are now available; however, as long as the considerations discussed remain unaddressed, external reproducibility and interobserver agreement will not be achieved, and the field will not be able to move forward if a true gold standard is not found. [ABSTRACT FROM AUTHOR]

Primary, acute Epstein--Barr virus (EBV) infection is associated with a variety of cutaneous eruptions, including the viral exanthem of infectious mononucleosis and erythema multiforme. Latent, chronic EBV infection can rarely result in development of lymphoproliferative disorders with cutaneous manifestations; however, these disorders do not arise from primary infection. In this report, we present a case of primary, acute EBV infection presenting with histopathologic features closely mimicking aggressive cytotoxic cutaneous T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Summary: Burkitt lymphoma arising in paediatric post‐solid‐organ transplantation‐Burkitt lymphoma (PSOT‐BL) is a clinically aggressive malignancy and a rare form of post‐transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT‐BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1–14) and age at PSOT‐BL diagnosis was 8.0 years (range: 1–17). All but one patient had late onset of PSOT‐BL (≥2 years post‐transplant), with a median interval from transplant to PSOT‐BL diagnosis of 4.0 years (range: 0.4–12). Heart (n = 18 [51.4%]) and liver (n = 13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment‐related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma‐specific French–American–British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low‐intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow‐up was 6.7 years (range: 0.5–17). Three‐year event‐free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT‐BL patients receiving BL‐specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi‐institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT‐BL. [ABSTRACT FROM AUTHOR]

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a lymphoproliferative disorder in which the majority of cells are reactive T cells with only a minor population of neoplastic large B cells. THRLBCL is a very rare lymphoma, and most cases are nodal THRLBCL; an extranodal case of THRLBCL presenting primarily on the skin is an extremely rare occurrence with only a few cases reported in the literature. Here, we report a case of a primary cutaneous THRLBCL in a 41-year-old Saudi male who presented unusually with multiple skin lesions. He was successfully treated with electron beam radiotherapy and had a complete resolution with no recurrence as of his 24-month follow-up. [ABSTRACT FROM AUTHOR]