Angioimmunoblastic T-cell lymphoma and Kaposi sarcoma: A fortuitous collision?

AIMS: Follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic-type (AITL), one of the most prevalent T-cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein-Barr virus-positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. METHODS AND RESULTS: Three male patients aged 49-76 years, HIV-negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10+ (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31+ and/or CD34+ , HHV8+ spindle cells. High-throughput sequencing showed AITL-associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. CONCLUSION: Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open.

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.

Spontaneous remission of angioimmunoblastic T-cell lymphoma in a child with ataxia-telangiectasia: a case report.

BACKGROUND: Angioimmunoblastic T-cell lymphoma is an uncommon subtype of peripheral T-cell lymphoma in children with fewer than 20 cases reported in literature. CASE PRESENTATION: A 3-year-old Omani boy was diagnosed with ataxia-talengectasia presenting with fever and generalized lymphadenopathy. His biopsy revealed atypical lymphocytic infiltrate consistent with the diagnosis of angioimmunoblastic T-cell lymphoma. Within 3 weeks from the initial presentation and without any neoadjuvant therapy, he showed complete recovery of symptoms with absence of fever and regression of all previously affected lymph nodes. He has remained in remission ever since. CONCLUSION: This is the first report of spontaneous improvement of angioimmunoblastic T-cell lymphoma in a patient with ataxia-telangiectasia who was 3 years old at presentation. Owing to the paucity of similar cases, this report adds valuable diagnostic, therapeutic, and monitoring data.

[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.

Cardiac Tamponade as a Recurrence of Angioimmunoblastic T-Cell Lymphoma with the Detection of a p.Gly17Val RHOA Mutation in the Pericardial Effusion.

Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL. He was diagnosed with cardiac tamponade caused by AITL recurrence in the presence of the p.Gly17Val RHOA mutation as well as T-lineage cells with an aberrant immune-phenotype in the pericardial effusion. This case suggests that a precision medicine approach by detecting the presence of a p.Gly17Val RHOA mutation is useful for the management of AITL.

Plasmacytic Pleural Effusion as a Major Presentation of Angioimmunoblastic T-Cell Lymphoma: A Case Report.

Angioimmunoblastic T-cell lymphoma is one of the peripheral T-cell lymphomas. Reactive plasma cells can occasionally be observed in AITL patients' peripheral blood and bone marrow. Plasmacytic pleural effusion as the presentation of AITL has not been reported before. The mechanisms of plasmacytic pleural effusion are not fully understood. Here we present an 82-year-old male with exuberant plasma cells in his pleural effusion in addition to his peripheral blood and bone marrow aspiration. By presenting this case, we would like to expand the spectrum of disease presentations in AITL and discuss the significance of flow cytometry in the differential diagnosis of pleural effusion. To our knowledge, this is the first case report in the literature, which will be crucial to assist the hematopathologist in accurate diagnosis and treatment.

Angioimmunoblastic T-cell lymphoma with elevated serum IgA and infiltration of IgA-positive plasma cells into a skin lesion.

Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common types of peripheral T-cell lymphoma. Laboratory examination exhibits immunological abnormalities, such as polyclonal hypergammaglobulinemia and hemolytic anemia. Skin lesions are also observed in approximately half of AITL cases. However, the relationship of skin involvement with the clinical course and prognosis is unknown. Herein, we report the case of a patient with AITL with elevated serum immunoglobulin A (IgA) level, which was a predictive element of poor prognosis, and infiltration of IgA-positive plasma cells into the skin lesions. Based on this case, we believe that skin manifestations could be used to identify the characteristics of immune disorders and prognosis of AITL.

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.

CD56-positive Angioimmunoblastic T-cell Lymphoma Complicated by Chylothorax.

A 77-year-old woman presented with systemic lymphadenopathy and bilateral pleural effusion. Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed based on the results of a lymph node biopsy. AITL cells expressed the aberrant antigen of CD56. The bilateral pleural effusion was attributed to chylothorax, not the infiltration of lymphoma cells into the pleura, as determined by the pleural fluid analysis. We therefore diagnosed her with CD56-positive AITL complicated by chylothorax. She achieved complete remission by multidrug chemotherapy. AITL is commonly complicated by pleural effusion, but rarely by chylothorax. This is the first case of CD56-positive AITL complicated by chylothorax.

Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma.

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. Pathological exam revealed granulomatous vasculitis of small and medium arterioles with infiltrating malignant T lymphocytes. Although skin manifestations are common in AITL, necrotizing granulomatous vasculitis with accompanying tumor cells leading to severe digital ischemia appears rare. Subsequently the patient developed profound pancytopenia with bone marrow confirming severe aplastic anemia. To our knowledge only one other case of aplastic anemia has been reported in a patient with AITL. We discuss the diagnostic and management considerations involved in this patient care and review similar reported cases.

Emergence of anti-mitochondrial M2 antibody in patient with angioimmunoblastic T-cell lymphoma.

A 68-year-old woman was referred to our hospital due to fever and rash on the neck and extremities. Laboratory findings revealed hepatic dysfunction and positivity for anti-mitochondrial M2 antibody (AMA-M2). Hepatosplenomegaly and systemic lymphadenopathy were detected by enhanced computed tomography. One week after her first visit, hypoxemia, ascites, and Coomb test-positive autoimmune hemolytic anemia had newly appeared in addition to worsened fever, hepatosplenomegaly, and lymphadenopathy. Results of axillary lymph node, skin, and bone-marrow biopsies led to the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), for which CEPP therapy (cyclophosphamide, etoposide, procarbazine, and prednisolone) was initiated. Her serum levels of hepatobiliary enzymes normalized and AMA-M2 became negative after treatment. The unexpected positivity for AMA-M2 might have been caused by AITL cell-activated intrahepatic immune cells or the tumor cells themselves inflicting bile duct injury that mimicked primary biliary cholangitis. Alternatively, cross reactivity due to the overproduction of immunoglobulins may have caused this phenomenon. The present case may shed light on of the mechanisms of liver dysfunction accompanying AITL.

Immunoglobulinopathies in patients with angioimmunoblastic T-cell lymphoma.

AIM: The aim of the study was to characterize quantitative and qualitative immunoglobulinopathies in patients with AITL at the onset of the disease. MATERIALS AND METHODS: 55 patients with newly diagnosed AITL were enrolled in the study, the male/female ratio was 30/25; median age was 61 (29-81) years. Diagnosis was based on standard WHO criteria. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay. RESULTS: Quantitative and qualitative immunoglobulinopathies were determined in 49 (89,1%) of 55 pts. Quantitative immunoglobulinopathies were revealed in 47 (85.5%) of 55 cases, qualitative - in 14 (25,5%). Combination quantitative and qualitative immunoglobulinopathies was observed in 12 (21,8%) of 55 pts. The detected immunoglobulinopathies were divided into 4 groups: polyclonal hypergammaglobulinaemia, hypogammaglobulinaemia, oligoclonal gammapathy, and monoclonal gammapathy. Polyclonal hypergammaglobulinaemia was marked in 41 (74.5%) of 55 pts, elevated level of IgG was determined in 27 (49,15%) of 55 cases, IgM - in 18 (32,7%) and IgA - in 21 (38.2%). Interestingly, polyclonal IgE hypergammaglobulinaemia was detected in 12 (48,0%) of 25 cases of performed studies. Hypogammaglobulinaemia was detected in 8 (14,5%) of 55 cases. Oligoclonal gammapathy was determined in 4 (7.3%) of 55 pts. Monoclonal gammapathy was revealed in 11 (20,0%) of 55 cases. The amount of monoclonal immunoglobulin varied from 2.6 to 14.1 g/l. Monoclonal immunoglobulin Gk was detected in 5 of 11 pts, Gλ - in 2, Mλ - in 2, Mk - in 2. Monoclonal gammapathy was accompanied by polyclonal hypergammaglobulinaemia in 9 of 11 cases, hypogammaglobulinaemia - in 2. CONCLUSION: Quantitative and qualitative immunoglobulinopathies are observed in most patients at the onset of AITL. Quantitative abnormalities were determined more often than qualitative. Monoclonal gammapathy can be a manifestation of lymphoproliferation and other concomitant disorders. The prognostic value of immunochemical parameters is still unclear and requires dynamic observation and study.

Hyponatremia as presentation in a patient with neurosarcoidosis / Hiponatremia como presentación en un paciente con neurosarcoidosis

Sarcoidosis is an inflammatory disease with unknown cause characterized by non-caseating granuloma formations. It may present with bilateral hilar lymphadenopathy, skin lesions, eye and musculoskeletal system involvement. Hypercalcemia and hypercalciuria are important electrolyte imbalances resulting from sarcoidosis and sometimes they may cause nephrolitiasis and kidney failure. Hyponatremia, although being quite rare, has been found in some patients with sarcoidosis. Herein, we have reported a patient with neurosarcoidosis who presented with hyponatremia and responded well to corticosteroid treatment (AU)

La sarcoidosis es una enfermedad inflamatoria, de causa desconocida, que se caracteriza por la formación de granulomas no caseificantes. Se puede presentar con linfadenopatía hiliar bilateral, lesiones en la piel, en los ojos, y la implicación del sistema musculoesquelético. La hipercalcemia y la hipercalciuria son importantes desequilibrios electrolíticos resultantes de la sarcoidosis, y algunas veces pueden causar nefrolitiasis e insuficiencia renal. La hiponatremia, a pesar de ser bastante rara, se ha encontrado en algunos pacientes con sarcoidosis. Aquí, hemos informado de un paciente con neurosarcoidosis que se presentó con hiponatremia y respondió bien al tratamiento con glucocorticoides (AU)

Cardiac Tamponade as Initial Presentation of Angioimmunoblastic T-Cell Lymphoma.

A 21-year-old man presented initially with impending cardiac tamponade secondary to an angioimmunoblastic T-cell lymphoma (AITL). Following unsuccessful pericardiocentesis and subxiphoid pericardiostomy, the patient's deteriorating hemodynamics prompted an urgent sternotomy. Histopathological diagnosis confirmed AITL. While chemotherapy remains the most effective treatment of AITL, life-threatening complications of the tumor necessitates surgical intervention.

Systemic lupus erythematosus as the concomitant manifestation of angioimmunoblastic T-cell lymphoma.

Herein we report a case of the simultaneous occurrence of angioimmunoblastic T-cell lymphoma (AITL) and systemic lupus erythematosus (SLE) in a 76-year-old woman. She presented with fever, night sweats, and general malaise. A laboratory examination revealed leukopenia, anemia, polyclonal hypergammaglobulinemia, hypocomplementemia, positive results for anti-nuclear antibodies and anti-double strand DNA (anti-dsDNA) antibodies, and mild proteinuria. A computed tomography scan of the abdominal cavity showed multiple swollen intra-abdominal and intra-pelvic lymph nodes. A biopsy specimen obtained from the peri-iliac lymph node confirmed the diagnosis of AITL, while renal biopsy results were consistent with lupus nephritis, International Society of Nephrology and Renal Pathology Society class V. These results indicated that our patient developed SLE concomitantly with AITL. These findings will lead to further understanding of the pathogenic mechanism of SLE.