Subcutaneous Panniculitis-Like T-Cell Lymphoma With Hemophagocytic Lymphohistiocytosis.

Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.

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.

Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine.

BACKGROUND: Small intestinal monomorphic-epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. METHODS: The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein-Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. RESULTS: Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. CONCLUSIONS: Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

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.

Clinical features and outcomes in patients with human immunodeficiency virus-negative, Castleman's disease: a single medical center study in Tunisia.

INTRODUCTION: Castleman's disease (CD), known as angiofollicular lymph node hyperplasia, is an uncommon condition. The two most common histological subtypes are hyaline vascular and plasma cell. We performed a retrospective analysis to define the clinic-pathological features and survival of CD, which is quite rare focusing on the particularities of our series with a review of the recent literature. METHODS: This is a retrospective study conducted in the department of internal medicine of Hedi Chaker hospital in Sfax, Tunisia over 25 years. The disease was histologically confirmed in all patients. For each file, we collected a set of data by filling in a pre-designed form. RESULTS: 18 patients were included. There were 8 men and 10 women with a mean age of 42.8 years. CD was monocentric in 5 cases (28%) and multicentric in 13 cases (72%). Clinically, peripheral adenopathy was present in 77.7% of patients and deep adenopathy in 72.2%. Systemic signs were found in 13 patients, including general condition (4.4%), fever (16.6%), serositis (27.7%), and skin involvement (33.3%). A biological inflammatory syndrome accompanied the clinical picture in 66% of patients. Abnormalities in the blood count were found in 12 cases (66%), with anemia in 11 cases, thrombocytosis in 3 cases, and hypereosinophilia in 3 cases. Cutaneous Kaposi's sarcoma was associated with Castleman's disease in 2 cases, Hodgkin's lymphoma, angioimmunoblastic T-cell lymphoma, and lymph node T-cell lymphoma were found in 1 case respectively. 3 of the patients had associated connective tissue diseases such as Sjögren's syndrome in 2 cases and rheumatoid arthritis in 1 case. HHV8 serology was positive in 1 case with a multicentric plasma cell form. Histologically, the plasma cell form represented 50% of cases, hyaline-vascular (39% of cases), and mixed (11% of cases). Therapeutically, high-dose corticosteroid therapy was initiated in 13 cases. As a second-line treatment, MOPP chemotherapy was used in 1 case due to transformation into Hodgkin's lymphoma, and biotherapy (rituximab) was used in 2 cases in the multicentric form. Surgical removal of superficial adenopathy was performed in 2 patients with monocentric CD. CONCLUSION: : Castleman's disease (CD) is a non-malignant lymphoproliferation of localized or multicentric form with a wide and heterogeneous clinical spectrum. Diagnosis can be difficult due to the lack of clinical and radiological specificity. Management depends on the clinical form involving surgical and/or medical management.

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.

Hepatosplenic T-cell lymphoma and inflammatory bowel disease

A 48-year-old man with a diagnosis of ulcerative colitis 18 years ago, under immunosuppressive treatment with azathioprine in the last 6 years due to corticosteroid dependence, was admitted to the Emergency Department due to fever of one week’s evolution. Blood tests showed thrombocytopenia, CRP 96.9mg/L, ferritin 3021ng/mL and hypertriglyceridemia. Blood and urine cultures were negative. Viral serologies (hepatitis B and C, HIV, parvovirus, CMV, HSV), atypical bacteria (Borrelia, Chlamydia, Coxiella) and screening for latent tuberculosis were also negative. Thoracoabdominal CT scan only showed splenomegaly. The bone marrow aspirate revealed immature lymphoid cells and a hemophagocyte figure, fulfilling the criteria for hemophagocytic syndrome, starting corticosteroid therapy at a dose of 1mg/Kg. Subsequently, the existence of an intrasinusoidal CD3 + CD5- lymphoid infiltrate and a FISH study with isochromosome 7q was reported, a characteristic pattern of hepatosplenic T-cell lymphoma (HSTCL). The study was completed with liver biopsy appreciating a 70% infiltration of T lymphocytes (50% gamma-delta) therefore the diagnosis was confirmed. Chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide) was started with the aim of considering hematopoietic stem cell transplantation. Unfortunately, the patient died 6 months later. (AU)

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.

Large T-cell extradural lymphoma with concurrent marked cerebrospinal fluid eosinophilia in a dog.

A 3-year-old male pit bull terrier was presented for a 4-day history of progressive tetraparesis and cervical pain. Magnetic resonance imaging confirmed an extradural mass within the left lateral vertebral canal extending from caudal C5 to mid-T2. Lumbar cerebrospinal fluid (CSF) demonstrated marked (90%) eosinophilic inflammation. A C6-7 dorsal laminectomy and C7-T2 left hemilaminectomy were done, with gross disease remaining. Histopathology revealed a large T cell lymphoma with marked eosinophilic infiltration. The dog underwent CHOP-based chemotherapy with resolution of clinical signs, with a similar course of therapy performed at recurrence 37 months after initial presentation. The dog was euthanized 39 months after presentation for multiorgan failure secondary to neutropenic sepsis and aspiration pneumonia. This represents a positive long-term response to multimodal treatment of extradural T-cell lymphoma within the vertebral canal associated with a marked CSF eosinophilia.

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.

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.

Hepatosplenic T-cell lymphoma presented with massive splenomegaly and pancytopenia - a case report.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma. Patients usually present with splenomegaly and pancytopenia but without lymphadenopathy. Immunohistochemistry (IHC) staining of bone marrow biopsy shows intra-sinusoidal infiltration of CD3 and CD56 T-lymphocytes. Current treatment strategy of HSTCL includes a CHOP regimen (cyclophosphamide, adriamycine, vincristine, prednisone) followed by autologous transplantation. CASE: A 28-year-old male presented with abdominal fullness, weight loss, and massive splenomegaly. Laboratory findings revealed pancytopenia. A CT scan of the abdomen displayed hepatomegaly and massive splenomegaly. The bone marrow pathology examination showed monotonous medium-sized lymphocytes with some cluster of atypical lymphocytes with loosely condensed chromatin and pale cytoplasm. The intra-sinusoidal location was more prominent after using IHC staining of CD3 and CD56, which are characteristics of HSTCL. We administered CHOP-based regiment every 3 weeks for 3 cycles; however, the response was a stable disease. Since the splenomegaly was still massive and compromised the patient, the multidisciplinary team decided to perform splenectomy. Unfortunately, the patient did not survive the surgery. CONCLUSION: Hepatosplenic T-cell lymphoma is a rare aggressive disease, which is part of peripheral T-cell lymphoma. CHOP-based chemotherapy appeared to be ineffective, and we need further studies to find the optimal treatment of HSTCL.

[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.