TAFRO syndrome (TS) is a recently recognized and heterogenous systemic disease characterized by a confluence of symptoms: thrombocytopenia (T), anasarca (A), fever (F), reticulin myelofibrosis (R), and organomegaly (O). First described in Japan in 2010, the pathogenesis remains unclear and includes various clinical conditions such as malignancies, rheumatologic disorders, infections, and \"Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, and Skin changes\" (POEMS) syndrome. Due to its heterogeneous presentation and potential life-threatening delays in diagnosis, accurate diagnosis is crucial. According to the literature, no specific imaging modality has been recommended for the work-up of patients with suspected TS. Here, we report a case of TS and its management using 18F-FDG-PET/CT imaging as an attractive complementary diagnostic tool.

This systematic review article aims to investigate the clinical and radiological imaging characteristics of adrenal abnormalities in patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. We searched the literature in PubMed, the Cochrane Library, and the Web of Science Core Collection. Ultimately, we analyzed 11 studies with 22 patients plus our 1 patient, totaling 23 patients. The mean age was 47.0 ± 12.6 years. There were 20 male and 3 female patients, respectively. The histopathological analysis of lymph nodes was conducted in 15 patients (65.2%), and the diagnosis was consistent with TAFRO syndrome in all 15 patients. Among the 23 patients, 11 patients (18 adrenal glands) showed adrenal ischemia/infarction, 9 patients (13 adrenal glands) showed adrenal hemorrhage, and 4 patients (7 adrenal glands) showed adrenomegaly without evidence of concurrent ischemia/infarction or hemorrhage. One patient demonstrated unilateral adrenal hemorrhage and contralateral adrenomegaly. In patients with adrenal ischemia/infarction, the adrenal glands displayed poor enhancement through contrast-enhanced computed tomography (CT). In patients with adrenal hemorrhage, the adrenal glands revealed high attenuation through non-enhanced CT and hematoma through magnetic resonance imaging. Adrenomegaly, with or without adrenal ischemia/infarction or hemorrhage, was observed in all patients (23/23, 100%). The subsequent calcification of the affected adrenal glands was frequently observed (9/14, 64.3%) when a follow-up CT was performed. Abdominal pain was frequent (15/23, 65.2%), all of which occurred after the disease\'s onset, suggesting the importance of considering TAFRO syndrome as a cause of acute abdomen. Given the absence of evidence of adrenal abnormalities in non-TAFRO-idiopathic multicentric Castleman disease (iMCD), they may serve as diagnostic clues for differentiating TAFRO syndrome from non-TAFRO-iMCD.

We present a clinical case of a 79-year-old male admitted to inpatient care for longstanding asthenia and respiratory symptoms. Associated features were polyserositis, multiple enlarged lymphatic nodules, acute kidney injury, and heart failure. The patient\'s recent medical history revealed SARS-CoV-2 vaccination a week prior and an upper respiratory tract infection. The laboratory results from thoracentesis were compatible with a transudate, with no immunological stain. Epstein-Barr virus polymerase chain reaction (PCR) was positive. The thoracic, abdominal, and pelvic CT scans revealed multiple enlarged lymphatic nodules, worsening the pre-existent polyserositis and hepatosplenomegaly. The patient began to show signs of neurologic symptoms and deterioration of the global health status. An enlarged lymphatic nodule was excised and the pathology showed human herpesvirus 8 multicentric Castleman disease. The disease evolved rapidly into hematological dysfunction and blood transfusions were necessary. Even though the patient was started on high-dose rituximab therapy combined with etoposide, the disease evolved into multiorgan dysfunction with a fatal outcome.

BACKGROUND: Idiopathic Multicentric Castleman Disease (iMCD) is a complex and poorly understood pathophysiological entity, which encompasses a variety of conditions and can mimic or be associated with autoimmune/autoinflammatory diseases, making it challenging to diagnose and treat. Vacuoles, Enzyme E1, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is an adult-onset autoinflammatory disorder associated with hematological abnormalities and caused by acquired somatic mutations in the ubiquitin-like modifier activating enzyme 1 gene (UBA1) which shares several common clinical and biological signs with iMCD. In this article, we report a patient with VEXAS syndrome initially presenting as iMCD, questioning the link between these two entities.
METHODS: We report here a patient initially presenting as iMCD, proved on lymph node histology, which turns out to have a mutation at the splice acceptor site of exon 3 of UBA1 exhibiting VEXAS syndrome with Castleman-like lymph node.
CONCLUSIONS: This is only the second case of VEXAS syndrome presenting as iMCD. VEXAS syndrome should therefore be considered in the presence of iMCD suspicion, including in cases of compatible histology.

Multicentric Castleman disease (MCD) is a poorly understood, heterogeneous lymphoproliferative disorder with benign hyperplastic lymph nodes and systemic inflammatory symptoms. Human herpesvirus-8 (HHV-8) may be associated with MCD, whether or not the patient is infected with the human immunodeficiency virus (HIV). A 74-year-old man presented with anaemia, thrombocytopenia and bilateral axillary adenomegaly of unknown origin. The patient was admitted to the hospital two years ago with clinical signs of weight loss, asthenia, anorexia and a maculopapular rash on the trunk and back. Blood analysis showed pancytopenia (haemoglobin 7.7 g/dL, leucocytes 2.55 x 109/L and platelets 41 x 109/L), elevated acute phase reactants (such as C-reactive protein, erythrocyte sedimentation rate, ferritin and fibrinogen), hypoalbuminemia and hypergammaglobulinemia, and HIV serology was negative. Thoracic, abdominal and pelvic axial tomography showed generalised lymphadenopathy. The bone marrow biopsy showed only reactive changes, and the histology of an excisional biopsy of the adenopathy was consistent with the plasmablastic variant of MCD associated with HHV-8. The HHV-8 viral load was 3.8 x 104 copies/mL (4.5 log). He was started on prednisolone 60 mg/day and rituximab. He had a poor response to therapy, despite a reduction in the HHV-8 viral load, with clinical deterioration, transfusion-dependent anaemia and progression to multi-organ dysfunction leading to death three weeks after starting treatment. Our patient had a fulminant course of MCD despite treatment with rituximab. Further studies are needed to validate the different treatment modalities and to better understand the prognosis of this disease.

Herein, we report a rare case of Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8)-positive diffuse large B-cell lymphoma (DLBCL), which is characterized by malignant ascites and complex karyotypes. A 72-year-old male patient who tested negative for human immunodeficiency virus presented with thrombocytopenia and lymphadenopathies. He was diagnosed with KSHV/HHV8-associated multicentric Castleman disease (MCD). After three years, he developed progressive lymphadenopathies and massive ascites. The lymphoma cells in the ascitic fluid presented with characteristic immunophenotype and monoclonality, which support the diagnosis of KSHV/HHV8-positive DLBCL. Lymphadenopathies and massive splenomegaly are common manifestations of KSHV/HHV8-positive DLBCL. Nevertheless, peritoneal involvement, as observed in this case, is a rare presentation. This emphasizes the diagnostic complexities of KSHV/HHV8-associated lymphoproliferative disorders. Within the context of preexisting KSHV/HHV8-associated multicentric Castleman disease, the differential diagnosis of this disorder can be challenging.

Castleman disease (CD) is a rare lymphoproliferative disorder characterized by localized (unicentric) or systemic (multicentric) lymphadenopathy. This study presents a unique case of a 29-year-old female with a rare pelvic presentation of unicentric Castleman disease, specifically the hyaline vascular variant. Despite surgical resection, an unresectable residual lesion prompted adjuvant radiotherapy and subsequent chemotherapy. The literature highlights surgical resection as the primary treatment for localized Castleman disease; however, radiotherapy and combined chemotherapy regimens like cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) have shown promise in unresectable cases, emphasizing a multidisciplinary approach. This case underscores the importance of tailoring treatment strategies for uncommon Castleman disease presentations.

The diagnosis of adult-onset immunodeficiency syndrome associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents substantial challenges to clinicians and pathologists due to its nonspecific clinical presentation, absence of routine laboratory tests, and resemblance to certain lymphoma types, notably nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI). Some patients undergo lymphadenectomy for histopathological examination to rule out lymphoma, even in the absence of a preceding clinical suspicion of AIGA. This study aimed to identify reliable methods to prevent misdiagnosis of AIGA in this scenario through a retrospective case-control analysis of clinical and pathological data, along with immune gene transcriptomes using the NanoString nCounter platform, to compare AIGA and nTFHL-AI. The investigation revealed a downregulation of the C-X-C motif chemokine ligand 9 (CXCL9) gene in AIGA, prompting an exploration of its diagnostic utility. Immunohistochemistry (IHC) targeting CXCL9 was performed on lymph node specimens to assess its potential as a diagnostic biomarker. The findings exhibited a significantly lower density of CXCL9-positive cells in AIGA compared to nTFHL-AI, displaying a high diagnostic accuracy of 92.3% sensitivity and 100% specificity. Furthermore, CXCL9 IHC demonstrated its ability to differentiate AIGA from various lymphomas sharing similar characteristics. In conclusion, CXCL9 IHC emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and other similar conditions. This reliable diagnostic approach holds the potential to avert misdiagnosis of AIGA as lymphoma, providing timely and accurate diagnosis.

UNASSIGNED: Castleman disease (CD) is a rare lymphoproliferative disorder with various subtypes, including the HHV-8-negative/idiopathic multicentric CD (iMCD). The diagnosis of iMCD remains challenging due to its non-specific presentation, in the form of generalised lymphadenopathies and inflammation. Two clinical presentations have been recently defined: a severe form iMCD-TAFRO and a milder form of iMCD not otherwise specified (iMCD-NOS). identification of interleukin-6 (IL-6) as a major culprit of inflammatory symptoms led to the development of anti-IL-6 therapies, with siltuximab being the approved first-line treatment.
UNASSIGNED: A 16-year-old male presented with recurrent fever, night sweats and several other non-specific symptoms. After extensive evaluations, an excisional lymph node biopsy confirmed the iMCD-NOS diagnosis. The patient received high-dose steroid therapy followed by siltuximab for four years. This treatment was well tolerated with only mild neutropenia not leading to dose adjustment. On siltuximab, the patient developed two mild COVID-19 episodes. His response to siltuximab remained effective throughout four years.
UNASSIGNED: The absence of biomarker or causal agent identification poses a diagnostic challenge requiring lymph node histopathology for a definitive diagnosis of iMCD. Anti-IL 6 (siltuximab) is the recommended frontline therapy, suppressing inflammation and halting disease progression. Intravenous administration every 3 to 6 weeks can impact patient quality of life, prompting further research for alternative treatments. High-dose steroids, rituximab, cyclosporine, tacrolimus, lenalidomide or combined chemotherapy such as rituximab-bortezomib-dexamethasone are among the considered options according to disease severity.
UNASSIGNED: Overall, long-term siltuximab effectively controlled iMCD symptoms and was well tolerated by this young adult, who endured two mild COVID-19 episodes.
CONCLUSIONS: Lymph node biopsy rather than bone marrow biopsy is needed for the diagnosis of iMCD.We were able to control the patient\'s condition in the absence of cumulative toxicity during four years of siltuximab anti-IL6 therapy.Immunosuppressive anti-IL6 therapy did not worsen two episodes of COVID-19.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease often associated with pulmonary involvement. Recently, transbronchial lung cryobiopsy (TBLC) has been reported to be useful for the diagnosis of diffuse interstitial lung disease. However, there have been no reports of pathological assessment of TBLC for iMCD.
METHODS: To clarify the efficacy of TBLC in the diagnosis of iMCD, we retrospectively reviewed four iMCD patients who had undergone both TBLC and surgical lung biopsy (SLB).
RESULTS: The median age was 44 years; 2 males and 2 females. Two or three TBLC specimens were taken from each patient. All patients had no complications other than minimal bleeding. The size of the TBLC specimens was approximately 5-6 × 3-4 mm, and the alveolar region, and centrilobular and perilobular areas were adequately sampled. As with SLB, the extent of lung lesions and inflammatory cell infiltration could be sufficiently evaluated by TBLC. The presence of lymphoid follicles could also be assessed by TBLC; however, the germinal centers with lymphoid follicles were difficult to evaluate. The TBLC specimens could also be evaluated for immunostaining, especially IgG4 immunostaining, to rule out IgG4-related lung disease. Pulmonary pathological grading showed a high concordance rate between major pathological findings of TBLC and SLB. The pathologist\'s confidence level of TBLC for the diagnosis of iMCD was high in all cases.
CONCLUSIONS: TBLC exhibits a high concordance rate with SLB in the pathological evaluation of iMCD, which may be useful for the diagnosis of iMCD.