Malignant Perivascular Epithelioid Cell Tumor of the Uterus.

Perivascular epithelioid cell tumors (PEComa) are soft tissue tumors. They belong to the family of mesenchymal tumors and include angiomyolipomas, clear cell sugar tumors of the lung, and PEComas not otherwise specified (NOS). Tuberous sclerosis complex 1 (TSC1) and tuberous sclerosis complex 2 (TSC2) gene mutation is associated with PEComa, which causes hyperactivation of the mammalian target of rapamycin (mTOR) signaling pathway. In some cases, transcription factor E3 (TFE3) gene fusion is also observed. They are usually found in middle-aged women with clinical symptoms of abnormal uterine bleeding and pelvic pain. Radical surgical resection with clear margins is the mainstay of the treatment. We encountered a 54-year-old woman who had postmenopausal abnormal uterine bleeding. A hysterectomy was planned, but pelvic adhesions were discovered during the procedure. As a result, she underwent an exploratory laparotomy with hysterectomy, appendectomy, and total omentectomy. The biopsy of the uterus, left ovary, and a small bowel nodule revealed diffuse growth of epithelioid cells with eosinophilic granular cytoplasm with HMB45 staining, which indicated PEComa. A treatment plan with an mTOR inhibitor nab-sirolimus was proposed for the patient. Early detection, a multidisciplinary approach, and timely treatment are crucial for better disease prognosis.

Hairy Cell Leukemia: Hepatic Affinity Status Post Splenectomy.

Hairy cell leukemia (HCL) is a rare neoplasm of the B-cell lineage that is characterized by an indolent course and infiltration of the spleen, the bone marrow, and the reticuloendothelial system. Splenectomy is considered an effective treatment for peripheral cytopenia in patients with HCL. Hepatic involvement of hairy cells with infiltration of the sinusoidal endothelial cells is rarely reported in the literature and is not well understood. We present the case of an 88-year-old male with a history of traumatic splenectomy who was found to have a relapse of classic hairy cell leukemia within the hepatic portal system.

Acute Pancreatitis: A Rare Cause of Complement-Mediated Thrombotic Microangiopathy.

Disruption of the complement regulatory system can provoke thrombotic microangiopathy (TMA), leading to clinical manifestations of generalized fatigue from hemolytic anemia, purpura caused by thrombocytopenia, and acute kidney injury from end-organ ischemia. This particular classification of TMA is known as complement-mediated thrombotic microangiopathy (CM-TMA). In CM-TMA, an inciting event such as infection, surgery, vaccination, or pregnancy triggers an inflammatory response resulting in the expression of inherited mutations or the development of autoantibodies against complement regulatory proteins, which leads to microangiopathic hemolytic anemia, thrombocytopenia, and direct damage to renal endothelial cells. The diverse etiologies of CM-TMA make diagnostic and therapeutic decisions a challenging endeavor. We encountered a young male patient who presented with significant lethargy and confusion. The initial diagnosis was consistent with systemic inflammatory response syndrome secondary to acute pancreatitis; however, the hospital course was complicated by subsequent acute renal failure, hemolytic anemia, and thrombocytopenia, likely indicating CM-TMA. The patient was successfully treated with plasma exchange therapy and eculizumab. We suspect that our patient likely developed CM-TMA from an episode of acute pancreatitis. Prompt diagnosis and early intervention are essential to improving morbidity and mortality. This is underscored by the development of monoclonal antibody therapy that directly targets the pathogenic complement proteins, which have been shown to improve renal disease outcomes.

Efficacy and tolerability of isocitrate dehydrogenase inhibitors in patients with acute myeloid leukemia: A systematic review of clinical trials.

BACKGROUND: Acute myeloid leukemia (AML) is a hematological malignancy due to anomalous differentiation and proliferation of hematopoietic stem cells with myeloid blast buildup. Induction chemotherapy is considered the first line of treatment in most patients with AML. However, targeted therapy in the form of FLT-3, IDH, BCL-2, and immune checkpoint inhibitors, can be considered as the first line depending on their molecular profile, resistance to chemotherapy, comorbidities, etc. This review aims to assess the tolerability and efficacy of isocitrate dehydrogenase (IDH) inhibitors in AML. METHODS: We searched Medline, WOS, Embase, and clinicaltrials.gov. PRISMA guidelines were followed in this systematic review. 3327 articles were screened, and 9 clinical trials (N = 1119) were included. RESULTS: In randomized clinical trials (RCTs), objective response (OR) was reported in 63-74% of the patients with IDH inhibitors + azacitidine as compared to 19-36 % of the patients with azacitidine monotherapy in newly diagnosed (ND) medically unfit patients. Survival rates were significantly improved with the use of ivosidenib. OR was reported in 39.1-46 % of the patients who relapsed/refractory to chemotherapy. ≥Grade 3 IDH differentiation syndrome and QT prolongation were reported in 3.9-10 % and 2-10 % of the patients, respectively. CONCLUSION: IDH inhibitors (ivosidenib for IDH-1 and enasidenib for IDH-2) are safe and effective in treating ND medically unfit or relapsed refractory patients with IDH mutation. However, no survival benefit was reported with enasidenib. More randomized multicenter double-blinded clinical studies are needed to confirm these results and compare them with other targeting agents.

Safety and Efficacy of Tyrosine Kinase Inhibitors in Immune Thrombocytopenic Purpura: A Systematic Review of Clinical Trials.

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.