Allogeneic hematopoetic stem cell transplant for patients with refractory T-Cell lymphomas.

OBJECTIVE: Allogeneic stem cell transplantation (allo-SCT) may have a curative potential due to the graft versus lymphoma effect. In this study, we aimed to compare transplant outcomes between refractory-T-NHL (ref-NHL) and Chemosensitive-T-NHL (CS-T-NHL). MATERIALS AND METHODS: We retrospectively reviewed the records of 26 ref-NHL and 29 CS-T-NHL consecutive patients who underwent allo-SCT at our center and compared the transplant outcomes between the groups. RESULTS: All patients were heavily pretreated with 27% of patients relapsing post-auto-SCT and two patients in the ref-T-NHL post-allo-SCT. Patients were transplanted mainly from unrelated donors. There were no differences in leucocytes and platelet engraftment between the two groups. At 3 years, the relapse incidence was 34% in Ref-TNHL and 19% in CS-TNHL (p = .33), with non-relapse mortality rates of 28% and 22%, respectively (p = .52). Female patients and those with a previous auto-SCT had lower relapse incidence (p = .045, p = .003). The 3-year overall survival was 39% in Ref-TNHL and 56% in CS-TNHL (p = .15). Trends for improved progression-free survival (PFS) and graft-versus-host disease relapse-free survival (GRFS) were observed in the CS-TNHL group (PFS: 60% vs. 30%, p = .075; GRFS: 38% vs. 21%, p = .1). CONCLUSION: Acknowledging the retrospective nature of our study, our results indicate that allo-SCT has a curative potential in patients with T-NHL even in refractory status.

Hematopoietic Bone Marrow Transplant to Treat Systemic EBV-positive T-cell Lymphoma of Childhood.

Systemic Epstein-Barr virus-positive T-cell lymphoma of childhood (S-EBV-TCL) is a rare disease for which there is no standard of care. S-EBV-TCL is often associated with hemophagocytic lymphohistiocytosis and is generally thought of on the spectrum of EBV-related disease. For the few reported cases of cure in the literature, hematopoietic stem cell transplant has been required because it is the only treatment that has induced complete remission in patients suffering from EBV-associated T-cell or natural killer cell lymphoproliferative diseases, except hemophagocytic lymphohistiocytosis. Here, we present the case of one patient who was successfully cured with a modified regimen of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), followed by hematopoietic stem cell transplant using a reduced-intensity conditioning regimen.

Extensive involvement of indolent T-cell lymphoma in a patient with ulcerative colitis.

Indolent T-cell lymphoma is a rare disease. Here we presented a 53-year-old male patient initially diagnosed as ulcerative colitis in 2000 that finally developed into extensive indolent T-cell lymphoma in 2022. We also described the differences between indolent T-cell lymphoma and inflammatory bowel disease, and the possible disease progression into lymphoma after biological therapy.

Linear IgA bullous dermatosis in the setting of angioimmunoblastic T-cell lymphoma.

We report an 80-year-old male developing linear IgA bullous dermatosis (LAD) in the setting of angioimmunoblastic T-cell lymphoma (AITL). This phenomenon is rare, as only three cases have been described in the literature. The pathophysiologic process can be attributed to dysregulation in somatic hypermutation and the expression of chemokine receptor 5 in AITL, contributing to increased IgA. Immunoglobulin production resulting from clonal plasma cell expansion may be because of the B-cell promotional effect by neoplastic follicular helper T-cells. Beyond providing a pathophysiologic platform for AITL-associated LAD, we also briefly summarized prior cases. This report demonstrates the importance of considering LAD in the differential diagnosis for patients with a bullous eruption in the setting of AITL.

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.

[RS3PE syndrome with angioimmunoblastic T-cell lymphoma early after the start of immunosuppressive therapy].

A 75-year-old man visited our Collagen Disease Department because of a fever, edema in the lower legs, and arthralgia. He presented with peripheral arthritis of the extremities and was negative for rheumatoid factor, leading to a diagnosis of RS3PE syndrome. A search for malignancy was performed, but no obvious malignant findings were found. After starting treatment with steroid, methotrexate, and tacrolimus, the patient's joint symptoms improved, but after five months, enlarged lymph nodes throughout the body were observed. A lymph node biopsy revealed a diagnosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders/angioimmunoblastic T-cell lymphoma (OI-LPD/AITL). After discontinuation of methotrexate and follow-up, no lymph node shrinkage was observed, and the patient had strong general malaise, so chemotherapy was started for AITL. After the start of chemotherapy, the patient's general symptoms improved quickly. RS3PE syndrome is a polyarticular, rheumatoid factor-negative, polyarticular synovitis with symmetric dorsolateral hand-palmar symmetric indentation edema that occurs mainly in elderly patients. It is also noted as a paraneoplastic syndrome, with 10%-40% of patients having malignant tumors. When our patient was diagnosed with RS3PE syndrome, a search for malignancy was performed, but there were no findings suggestive of malignant disease. However, after methotrexate and tacrolimus administration was started, the patient developed rapid lymph node enlargement, and the pathology showed AITL. The possibility of AITL as an underlying disease and RS3PE syndrome as a paraneoplastic syndrome, or conversely, OI-LPD/AITL associated with immunosuppressive therapy for RS3PE syndrome is considered. We herein report this case, as sufficient recognition is required for a proper diagnosis to be made and treatment of RS3PE syndrome to be performed.

Hepatosplenic T-cell lymphoma: a rare but challenging entity.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell neoplasm that most commonly arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. HSTCL is more common in adolescent and young adults and has a rapidly progressive clinical course and poor outcome due to its refractoriness to conventional chemotherapy regimens. Approximately 20% of the cases arise in the background of chronic immunosuppression or immune dysregulation. Patients commonly present with constitutional symptoms, hepatic and liver enlargement, and cytopenias; hematophagocytic syndrome can also occur. The most frequent chromosomal aberrations associated with HSTCL are isochromosome 7q and trisomy 8, and most cases harbor mutations in genes involved in chromatin modification or the JAK/STAT pathway. The rarity of this disease, along with lack of nodal involvement and presenting symptoms that mimic different entities including infectious etiologies, makes this lymphoma a significant diagnostic challenge. In this review, we highlight the clinical and pathologic features of HSTCL. Moreover, we summarize the results of recent molecular studies suggesting potential targets for novel therapeutics strategies.

Clinical characteristics and treatment of NK/T-cell lymphoma-associated HLH.

Natural killer (NK)/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHLH) is a rare and life-threatening disorder. Its clinical characteristics and appropriate treatment options are unclear. This study aimed to investigate the clinical characteristics and treatment options for this disease. We retrospectively analyzed the clinical data of 84 patients with NK/T-cell lymphoma and compared the characteristics, treatment, and survival between patients with and without HLH. Patients in the NK/T-LAHLH group were more likely to be younger age and have hepatosplenomegaly, B symptoms, neutropenia, anemia, thrombocytopenia, elevated lactate dehydrogenase levels, reduced serum albumin levels, bone marrow involvement, Ann Arbor stage III/IV, and International Prognostic Index score ≥ 3. After multivariate analysis, it was found that elevated lactate dehydrogenase and Ann Arbor stage III/IV were risk factors for HLH in patients with NK/T-cell lymphoma. After 2 weeks of therapy, 78.6% (11/14) patients who received the L-DEP/DEP regimen achieved an overall response rate of HLH, which was higher than that in 42.9% (9/21) patients who received the VP-16 + dexamethasone-based regimen. NK/T-LAHLH patients had poorer survival than non-HLH-NK/TCL patients. For NK/T-LAHLH, the L-DEP/DEP regimen may have a better response rate than the VP-16 + dexamethasone-based regimens.

Capillaritis as a Skin Manifestation of Hepatosplenic Gamma-Delta T-Cell Lymphoma.

We present the case of a 10-year-old boy who was admitted with 3 months of episodic febrile neutropenia and a new petechial rash. Routine bloods identified neutropenia, thrombocytopenia, and a raised alanine aminotransferase. The dermatology team was consulted in light of the symmetrical petechial eruption of the upper torso. A punch biopsy of the lesion was consistent with early capillaritis. The results showed superficial dermal red blood cell extravasation with mild perivascular lymphohistiocytic inflammatory infiltrate. There was no evidence of an atypical lymphoid infiltrate in the skin biopsy. An initial bone marrow aspirate showed an abnormal mature T-cell population consisting of CD4 and CD8 T cells with gamma-delta positivity. Karyotyping was also done, which demonstrated isochromosome 7q. These findings were consistent with a diagnosis of hepatosplenic T-cell lymphoma (HSTL). The patient underwent fourth-line chemotherapy due to refractory relapsing disease but sadly passed away within 12 months of diagnosis. HSTL is a rare and aggressive subset of peripheral T-cell lymphoma. Prognosis is poor with a median survival of <1 year from diagnosis. However, reports suggest improved outcomes if intensive, early, high-dose chemotherapy is used alongside hematopoietic stem cell transplantation. Therefore, there is an impetus to attain early diagnosis for aggressive early treatment and improved patient outcomes. Capillaritis, presenting as asymptomatic nonpalpable purpura, can be a rare presenting feature of HSTL. Dermatologists could play a pivotal role in the early recognition of this rare but aggressive hematological malignancy and promote prompt treatment resulting in better patient outcomes.

The Development of Chylothorax in a Child With T-cell Lymphoblastic Lymphoma and Ataxia Telangiectasia During Induction Therapy.

Chylothorax is an unusual complication of childhood cancer. It causes to additional morbidity and mortality during management. It should be kept in mind that chylothorax may occur due to mass shrinkage during treatment in patients with mediastinal mass and ductus thoracicus invasion at the initial diagnosis and necessary measures should be taken. This case was presented because of the rarity in pediatric oncology practice.

Cutaneous Involvement of Angioimmunoblastic T-Cell Lymphoma Masquerading as B-Cell Reactive Lymphoid Hyperplasia.

ABSTRACT: A 59-year-old woman presented with a persistent eruption manifested as multiple agminated miliary facial papules. Histopathological examination showed prominent nodular dermal lymphoid infiltrates with hyperplastic follicles that were initially interpreted as B-cell reactive lymphoid hyperplasia. Several years later, an additional biopsy showed a dense perifollicular infiltrate with reactive primary and secondary follicles. Accompanying T cells corresponded to CD3/CD4/PD1/CXCL13-positive cells and scattered Epstein-Barr virus-positive B cells were identified by in situ hybridization. A monoclonal T-cell population was demonstrated by TCRγ and TCRß Polymerase Chain Reaction amplification, as well as a minor abnormal circulating T-cell population by flow cytometry (0.62% of the white blood cells, CD4+CD3s-CD7-). A biopsy specimen from an enlarged right supraclavicular lymph node disclosed nodal involvement by angioimmunoblastic T-cell lymphoma. The observation of B-cell dermal nodular infiltrates with well-demarcated lymphoid aggregates forming primary lymphoid follicles may lead to overlook the T-cell component in some cases of angioimmunoblastic T-cell lymphoma. In such cases, a careful assessment of the apparently minor T-cell component is important to establish a correct diagnosis.

Rapidly progressive glomerulonephritis in a patient with angioimmunoblastic T-cell lymphoma: a rare autopsy case showing IgA vasculitis and cylinder-like deposits.

Angioimmunoblastic T-cell lymphoma (AITL), a hematological malignancy, originates from follicular helper T cells. The primary site of AITL is the lymph nodes, but extranodal presentation is frequent in patients with advanced stages. Here, we report a rare case of a patient with AITL presenting with rapidly progressive glomerulonephritis (RPGN). The patient underwent computed tomography, which showed systemic lymph node swelling. RPGN was noted at the time of admission. Livedo was observed in the lower limbs with purpura on the foot. The patient was diagnosed with AITL based on lymph node biopsy. Skin biopsy revealed vasculitis with immunoglobulin A (IgA) deposits. Renal biopsy revealed endocapillary proliferative glomerulonephritis with massive subendothelial deposits and intraluminal thrombi. Immunofluorescence showed IgA, IgG, and complement component 3c-predominant granular staining pattern in the capillary and mesangial areas. Electron micrographs demonstrated dense cylindrical-like deposits in the subendothelial space. Chemotherapy drugs were administered, but the patient's respiratory distress increased until death. Upon autopsy, membranoproliferative glomerulonephritis and extensive necrotizing cellular crescent formation were observed in the glomeruli. Taken together, this case is a rare combination of AITL and RPGN showing both cylinder-like deposits suggestive of cryoglobulinemic glomerulonephritis (CN) and IgA vasculitis.

[Patient with Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma with Small Intestinal Perforation Development during Chemotherapy].

Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is classified under type Ⅱ enteropathy-associated T-cell lymphoma(EATL). It is a rare disease with a low incidence rate. This study reports a case of a patient with MEITL who developed small intestinal perforation during chemotherapy. The patient was a 55-year-old woman who presented to a previous clinic with epigastric pain. Enteroscopy results showed a map-like ulcer in the jejunum. Examination of the tissue specimen collected from this site suggested T-cell lymphoma. The patient was referred to our hospital for chemotherapy. Seven days following the initiation of chemotherapy, an abdominal computed tomography(CT)revealed free air, leading to a diagnosis of gastrointestinal perforation. Emergency surgery was performed. Intraoperatively, bowel perforation and a degenerative ulcer were observed at 95 cm and 80 to 115 cm from the Treitz' ligament, respectively. In addition, all-layer intestinal necrosis was noted 150 and 90 cm from the terminal ileum. Total resection and anastomosis were performed. Postoperatively, the patient developed sepsis due to chemotherapy-related pancytopenia but recovered. She was discharged on postoperative day 24. Subsequently, positron emission tomography(PET)-CT revealed residual intestinal tumor cells and peritoneal dissemination. Chemotherapy was initiated, but there was no response. The patient died after 6.5 months. A radical treatment for MEITL has not yet been established. More case reports are needed to improve the prognosis of this disease.

Ruxolitinib as adjunctive therapy for secondary hemophagocytic lymphohistiocytosis: A case series.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm syndrome associated with mortality rates of up to 88%. Standard therapy with high-dose glucocorticoids and etoposide used in adults is extrapolated from pediatric trials, with significant toxicity in older patients and those with poor performance status. The JAK1/2 inhibitor ruxolitinib has recently gained attention as a treatment option for HLH due to its broad cytokine-modulating abilities and safety profile. Herein we report our center's experience using ruxolitinib in the treatment of adult-onset secondary HLH. CASE SERIES: We report four patients with profound secondary HLH provoked by diverse triggers, including invasive pulmonary aspergillosis on background systemic lupus erythematosus, disseminated tuberculosis, and T-cell lymphoma treated with ruxolitinib as monotherapy or combination therapy in upfront and salvage settings. RESULTS: All four patients had rapid, sustained improvement in clinical status, inflammatory markers, and hematological cell counts followed by durable remission. Three patients developed manageable infectious complications postruxolitinib. CONCLUSIONS: This series demonstrates the effective use of JAK inhibition with ruxolitinib to control pathological immune activation in critically ill patients with secondary HLH and otherwise limited therapeutic options. JAK inhibition is also an area of urgent investigation for the treatment of cytokine storm associated with COVID-19.

Hydroa Vacciniforme-like Lymphoproliferative disorder in an adult invades the liver and bone marrow with clear pathological evidence: a case report and literature review.

BACKGROUND: Hydroa Vacciniforme-like Lymphoproliferative Disorder (HV-LPD) is the name given to a group of Epstein-Barr virus (EBV)-associated diseases. It resembles hydroa vacciniforme (HV), the rarest form of photosensitivity, and is a T-cell disorder associated with an Epstein-Barr virus infection. The majority of diagnosed cases occur in East Asia and South America. It is rare in the United States and Europe. Multiple studies have revealed the clinical manifestation of an enlarged liver, but no gold standard such as pathology has yet supported this as a clinical sign of HV-LPD. CASE PRESENTATION: Here, we report a case of a 34-year-old Asian female with definite liver invasion. The patient had complained of a recurring facial rash for many years. The patient was admitted to the hospital because of an enlarged liver. After hospitalization, she was given an EB virus nucleic acid test. The EB virus nucleic acid test was positive, and pathological examination suggested that HV-LPD had invaded the skin, bone marrow, and liver. After being given antiviral treatment, the patient's symptoms were mitigated. CONCLUSIONS: Our case confirms the liver damage was caused by HV-LPD and the effectiveness of antiviral treatment.

Unraveling subcutaneous panniculitis-like T-cell lymphoma: An association between subcutaneous panniculitis-like T-cell lymphoma, autoimmune lymphoproliferative syndrome, and familial hemophagocytic lymphohistiocytosis.

Germline HAVCR2 mutations, recently identified in a large subset of patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). Discovery of this heritable HLH/SPTCL diathesis has expanded our understanding of a rare and molecularly heterogeneous lymphoma. Furthermore, patients with SPTCL have excellent survival unless they develop HLH. Therefore, through compiling data on SPTCL-related conditions that predispose patients to HLH, we are better able to predict which patients with SPTCL have the greatest risk of mortality. We present the first case of SPTCL with concomitant HLH and autoimmune lymphoproliferative syndrome (ALPS) in a patient who was subsequently diagnosed with familial HLH (F-HLH) attributable to a germline STXBP2 splice-site mutation. She had wild-type HAVCR2. Reports including ours show how SPTCL can evolve in the setting of an exaggerated host inflammatory response attributable to a variety of unusual underlying etiologies.

Intrapleural infections in patients with subcutaneous panniculitis-like T-cell lymphoma are susceptible to hemophagocytic lymphohistiocytosis.

Patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) are prone to the development of hemophagocytic lymphohistiocytosis (HLH). It is not known whether small infections in SPTCL patients can trigger the development of HLH. The clinical data were collected from 21 SPTCL patients admitted to our hospital from January 2006 to October 2019. Among 21 cases of SPTCL, six cases had HLH as the first manifestation (SPTCL/HLH), seven cases had intrathoracic infection (ITI), five cases were SPTCL/HLH, 13 cases had no ITI or HLH (SPTCL/no HLH). Two patients with SPTCL/noHLH healed spontaneously. We found that 28.6% of the SPTCL patients had HLH as the first presentation. ITI may cooperate with SPTCL to trigger HLH and a small number of SPTCL/noHLH can fully recover without treatment.

Concurrent Subcutaneous Panniculitis-like T-Cell Lymphoma and B-Cell Acute Lymphoblastic Leukemia in 2 Pediatric Patients.

Subcutaneous panniculitis-like T-cell lymphoma is a cutaneous lymphoma characterized by CD8+ T-cell infiltrate in the subcutis that is rare in children. Acute lymphoblastic lymphoma is the most common pediatric malignancy and often presents with fevers and pancytopenia. Herein, we report 2 pediatric patients presenting with subcutaneous panniculitis-like T-cell lymphoma and B-cell acute lymphoblastic lymphoma, distinct hematologic malignancies arising from different lymphoid lineages, with no identifiable germline cancer predisposition.

Subcutaneous Panniculitis-like T-Cell Lymphoma With Hemophagocytic Lymphohistiocytosis Syndrome in Children and Its Essential Role of HAVCR2 Gene Mutation Analysis.

BACKGROUND: We identified 3 adolescents with alpha-beta subtype subcutaneous panniculitis-like T-cell lymphoma. CASE PRESENTATION: Three patients presented with prolonged fever, abnormal skin lesions, and cytopenia described in the context. All had the same disease entity, which showed the prolonged duration of B systemic symptoms till diagnosis, difficulty to distinguish from autoimmune diseases, presence of hemophagocytic lymphohistiocytosis syndrome, good response, and remained on long-term remission with nonchemotherapy treatment, which included oral corticosteroid and cyclosporin. CONCLUSIONS: Although diagnosis can only be "highly suspected" with pathologic review, some cases may need multiple serial skin biopsy to clarify diagnosis because of the discrete distribution of specific histology. T-cell receptor gene rearrangement, which demonstrates a monoclonal pattern of alpha and beta chain gene, is the essential requirement for specific diagnosis. The role of molecular analysis by identification of germline hepatitis A virus cellular receptor 2 (HAVCR2) gene mutation can be much valuable in classifying susceptible patients.

Platelet-derived alpha-granules are associated with inflammation in patients with NK/T-cell lymphoma-associated hemophagocytic syndrome.

Due to the variable overlap of multiple symptoms, accurate early diagnosis of NK/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is difficult, making the prognosis extremely poor. Hemophagocytic syndrome (HPS) is now diagnosed primarily based on the hemophagocytic lymphohistiocytosis (HLH)-2004 diagnostic criteria, and platelet count is one of the baseline evaluations. However, in our study, the data showed that decreased platelets were not only a clinical feature of HPS but also the key cells that regulate inflammation by releasing α-granules containing upregulated platelet factor 4 (PF4) and downregulated platelet-derived growth factors (PDGFs). Furthermore, we found that angiopoietin-4 (ANG-4), which has significant differential expression, has been less reported, that may affect hematopoiesis and proinflammatory responses and can be used as diagnostic biomarkers together with PF4 and PDGFs.