Abnormal Exacerbation of Moderately Differentiated Gastric Adenocarcinoma in a Patient with TAFRO Syndrome: An Impaired Tumor Immunity?

TAFRO syndrome is a relatively new disease entity first reported in 2010. We report a case of TAFRO syndrome accommodated by abnormal exacerbation of moderately differentiated gastric adenocarcinoma. The pathophysiology of TAFRO syndrome is largely unknown, but because the disease often responds to immunosuppressive therapy and also because T follicular helper (Tfh) cells are reported to be drastically decreased in TAFRO syndrome, involvement of a dysregulated immune system can be speculated. Growing evidence points toward a pivotal role of Tfh cells in tumor immunity through supporting ectopic lymphoid structures, which are recruitment sites for cells directly engaging in antitumor activity such as CD8⁺ T cells, NK cells, and macrophages. In fact, Tfh cells are reported to positively correlate with longer survival in human colorectal and breast cancer. Combined with our observations of hyperprogressive gastric cancer in the presented patient, an impaired tumor immunity is strongly indicated in TAFRO syndrome.

To and TAFRO – a cryptic cause of acute renal failure: a case report

Background TAFRO syndrome is a rare clinical subtype of idiopathic multicentric Castlemans disease characterised by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly. Renal involvement is common, sometimes requiring temporary renal replacement therapy. Due to the associated thrombocytopenia, renal biopsies are rarely performed limiting descriptions of the renal histopathology in this condition. This case describes a patient with TAFRO syndrome and the associated renal histology. Case presentation A 49-year-old Caucasian man presented to a tertiary hospital in Sydney with a six- week history of malaise, non-bloody diarrhoea, progressive shortness of breath, and drenching night sweats. A progressive bicytopenia and renal function decline necessitating temporary dialysis prompted a bone marrow aspirate and trephine, as well as a renal biopsy respectively. This noted a hypercellular bone marrow with increased granulopoiesis, reduced erythropoiesis, and fibrosis, with renal histology suggesting a thrombotic microangiopathic-like glomerulopathy. Alternate conditions were excluded, and a diagnosis of TAFRO syndrome was made. Glucocorticoids and rituximab were initiated with rapid renal recovery, and normalisation of his haematologic parameters achieved at six months. Conclusion This case describes an atypical thrombotic microangiopathy as the predominant histologic renal lesion in a patient with TAFRO syndrome. This was responsive to immunosuppression with glucocorticoids and rituximab, highlighting the importance of early recognition of this rarely described condition.

TAFRO syndrome: a case report

A man diagnosed as TAFRO syndrome was successfully responded to a novel immunosuppressive regimen containing methylprednisolone and mycophenolate mofetil. Blood cells firstly recovered, followed by the general situation and complete recover 1 month later, highlighting the danger of TAFRO syndrome and the importance of immunosuppressive agents in reversing pathological course

TAFRO Syndrome in a Kidney Transplant Recipient That Was Diagnosed on Autopsy: A Case Report

A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly and lymphadenopathy were observed, and development of prominent anasarca and worsening of renal function yielded the diagnosis of TAFRO syndrome. He was treated with high-dose steroids and plasmapheresis, and a thrombopoietin receptor agonist was administered for refractory thrombocytopenia. However, his general condition worsened, and he died on day 92. Histopathological analysis of a kidney autopsy specimen showed thrombotic microangiopathy characterized by glomerular endothelial swelling, mesangiolysis, and double contours of the glomerular capillary walls. His bone marrow showed megakaryocytic hyperplasia with mild reticulin fibrosis. Interestingly, these clinical and pathological features were remarkably similar to those the patient demonstrated before the kidney transplant, suggesting the recurrence of TAFRO syndrome. TAFRO syndrome is a rare systemic disorder whose concept has recently been established, but information on its long-term outcome is scarce. To our knowledge, this is the first case of TAFRO syndrome developing in a kidney transplant recipient, which suggests that disease recurrence occurs many years after the kidney transplant.

TAFRO syndrome: A case report with biopsy findings from three sites

Introduction/Objective TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) is a rare systemic inflammatory disorder. First reported in 2010, the majority of cases are from Japan, where it is currently regarded as a subtype of HHV8-negative Multicentric Castleman Disease. Methods/Case Report We report a case of TAFRO occurring in a 17-year old from Puerto Rico. She originally presented with abdominal pain, vomiting, and fever, and was also found to have splenomegaly, elevated sedimentation rate and C-reactive protein. Over the course of the next several days she developed respiratory distress, requiring ventilatory support, and anuric renal failure. Renal biopsy demonstrated evidence of thrombotic microangiopathy, which was interpreted as atypical hemolytic syndrome, requiring dialysis and treated with eculizumab. Because other diagnostic considerations at the time also included hemophagocytic lymphohistiocytosis and catastrophic antiphospholipid syndrome, bone marrow examination was performed which demonstrated increased megakaryocytes, without fibrosis or hemophagocytosis. Over the next two months, she developed anasarca with ascites, pleural effusion, pericardial effusion, multiple enlarged axillary and cervical lymph nodes, and persistence of splenomegaly. Biopsy of a left cervical lymph node demonstrated features suggestive of Castlemans disease, plasma cell variant. The constellation of symptoms, laboratory investigations and biopsy diagnoses support the diagnosis of TAFRO syndrome. The patient received rituximab, high dose steroids, and hemodialysis with clinical improvement. At 16 months follow up, the patient is in remission. Results (if a Case Study enter NA) NA Conclusion From a pathology standpoint, the case provides biopsy findings of three distinct organ systems all with relatively unusual findings that together are characteristic of TAFRO syndrome. It highlights the risk of accepting “biopsy proven” diagnoses such as atypical hemolytic uremic syndrome that also require significant laboratory and clinical correlation for true confirmation, and points out the importance and opportunity for pathologists to see the forest along with the trees in order to recognize rare diseases such as TAFRO.

TAFRO Syndrome and Elusive Diagnosis of Idiopathic Multicentric Castleman Disease Treated with Empiric Anti-Interleukin-6 Therapy

TAFRO syndrome is defined by the presence of thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal dysfunction (R), and organomegaly (O) and can be seen with idiopathic multicentric Castleman disease (iMCD) or as an isolated process without iMCD. Although the diagnosis of iMCD in patients with TAFRO can be challenging to make, iMCD should remain high on the differential diagnosis. Similar to iMCD, the pathophysiology of TAFRO is not well understood but is thought to be related to hypercytokinemia, with interleukin (IL)-6 playing a pivotal role. Anti-IL-6 monoclonal antibody therapy is an effective treatment modality for iMCD, but to date, there is no clear guidance on treatment of TAFRO in the absence of definitive diagnosis of iMCD, leading to suboptimal management and high morbidity. We report a case of TAFRO syndrome and demonstrate benefit with the empiric use of anti-IL-6 antibody therapy in the context of delayed diagnosis of iMCD.

Intracranial Hemorrhage in a Patient with TAFRO Syndrome Treated with Cyclosporine A and Rituximab

TAFRO syndrome, a rare subtype of idiopathic multicentric Castleman disease, manifests as thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Thrombotic microangiopathy, including renal dysfunction, is frequently associated with this syndrome. TAFRO syndrome can be life threatening and show rapid progression, and the diagnosis and management of this disorder remain challenging. A 48-year-old woman was diagnosed with TAFRO syndrome complicated by thrombotic microangiopathy based on the clinical and histopathological findings. After receiving high-dose steroids, her thrombocytopenia and anasarca did not improve. The patient subsequently received a combination of cyclosporine A and rituximab as second-line therapy, which resulted in a significant gradual improvement in the clinical symptoms. Meanwhile, her platelet count increased to more than 40 × 109/L; however, she developed intracranial hemorrhage. Following surgical evacuation, the patient recovered with an achievement of sustained remission. Based on these findings, attention should be paid to life-threatening bleeding associated with local thrombotic microangiopathy even when intensive treatment is administered for TAFRO syndrome.