Stratification of Patients with Renal Cell Carcinoma by the Abundance of Sarcomatoid Features Reveals Differences in Survival and the Underlying Pathobiology.

Sarcomatoid renal cell carcinoma (sRCC) is histologically heterogeneous, with variable sarcomatoid amounts intermixed within epithelial carcinoma. However, the current classification for this aggressive disease is homogeneous and agnostic to the sarcomatoid proportion. We investigated whether sRCC subclassification has prognostic value and can reveal the biology underlying dedifferentiation and its clinical aggressiveness. On the basis of the intratumoral abundance of sarcomatoid features, cases were classified as sarcomatoid-high (≥10% sarcomatoid features) or sarcomatoid-low (<10% sarcomatoid features) in a cohort of 104 consecutive patients with sRCC undergoing nephrectomy at a single center. In comparison to sarcomatoid-low patients (n = 52), sarcomatoid-high patients (n = 52) had significantly shorter overall survival (median 14.5 vs 62.9 mo; p < 0.001), which was confirmed on multivariable analysis, and significantly shorter median metastasis-free survival among patients with clinically localized disease (10.7 vs 39.0 mo; p = 0.043). Transcriptomic analyses of 45 sRCC tumors revealed significant upregulation of nine hallmark pathways related to cell cycle/proliferation, epithelial-to-mesenchymal transition, reactive oxidative species, and interferon-α signaling among sarcomatoid-high (n = 24) versus sarcomatoid-low (n = 21) tumors. Categorization into transcriptomic clusters revealed predominance of proliferative, inflammatory, and immune effector phenotypes among sarcomatoid-high tumors, versus a hypoxia/angiogenesis phenotype among sarcomatoid-low tumors. Overall, these findings indicate prognostic value for sRCC subclassification into high versus low sarcomatoid groups and highlight key biology underlying the differences in clinical outcomes. PATIENT SUMMARY: Sarcomatoid renal cell carcinoma (sRCC) is a highly aggressive form of kidney cancer. The percentage of sarcomatoid features varies among tumors, but sRCC is still defined as a single kidney cancer type. Our results show that grouping patients according to their percentage of sarcomatoid features improves prediction of whether their tumors will become metastatic or lethal, and reveal molecular differences that may be important for this disease. Future assignment of sRCC to high and low sarcomatoid groups may help in guiding research and patient management.

A Narrative Review on the Monkeypox Virus: An Ongoing Global Outbreak Hitting the Non-Endemic Countries.

Monkeypox is a rare zoonotic DNA with lineage from the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. With a previous history of controlled and contained occasional outbreaks of the virus, currently, a widely erupted outbreak of monkeypox with progressively rising numbers has been reported since May 2022 in multiple countries of the western hemisphere that are not historically endemic for this infection, particularly the United Kingdom and European Union countries. We have written a comprehensive review article to help clinicians better understand the disease. The global cessation of smallpox vaccination has been hypothesized to cause the rise in monkeypox infections in recent years. Monkeypox, like any other viral infection, commences with prodromal symptoms; a maculopapular rash with centrifugal distribution usually follows. Polymerase chain reaction (PCR) confirms the diagnosis. Transmission in humans is possible through infected animals or humans. In the ongoing 2022 outbreak, the monkeypox virus has been undergoing novel mutations at an alarming rate. Treatment options for monkeypox are an area that still requires extensive research, and the utility of certain antiviral medications in treating monkeypox infection is currently being explored but is still controversial and debatable.

Bone marrow necrosis and fat embolism syndrome: a near fatal complication in previously undiagnosed sickle beta + thalassaemia.

Prevalence of haemoglobin sickle-ß+ thalassaemia (Hb S/ß+thal) is variable with geography ranging from 0.2% to 10% among sickle cell patients. Clinical presentation of Hb S/ß+thal patients depends on HbA level, with milder disease often going undiagnosed. However, rarely these patients can present with a fulminant vaso-occlusive crisis (VOC). Given VOC can present with non-specific symptoms, the diagnosis and treatment is often delayed. Here, we present a patient who initially developed altered mental status, pancytopenia and multiorgan failure due a critical VOC resulting in bone marrow necrosis and fat embolism. Subsequent workup confirmed that our patient had Sickle-ß+ thalassaemia, which had gone undiagnosed, despite subclinical evidence of haemolysis on routine lab work for years. Following diagnosis and initiation of RBC exchange, he improved significantly and was discharged home. High index of suspicion and bone marrow biopsy is vital for early diagnosis and management of this rare condition.

Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19).

Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.

Atypical Presentation of a Glomus Tumor in the Rearfoot: A Case Report.

Glomus tumors are rare and benign vascular soft-tissue masses commonly found subungually in the foot. A glomus tumor typically manifests with a classic triad of pain, point tenderness, and cold sensitivity. This case report describes an atypical presentation of a glomus tumor in the soft tissue of the rearfoot in a 77-year-old man in the setting of urosepsis. The mass had enlarged progressively for 6 months. Originally misdiagnosed as a hemangioma based on magnetic resonance imaging and clinical appearance, an excisional biopsy was performed. The lesion was subsequently diagnosed histopathologically as a glomus tumor. This article discusses the statistics of glomus tumor and discusses the importance of the need to recognize the symptoms and clinical findings of both typical and atypical presentation of this abnormality in differentiation and differential treatment and risk management of benign and malignant soft-tissue masses.

Necrotizing Myositis: A Rare Necrotizing Soft Tissue Infection Involving Muscle.

INTRODUCTION: Necrotizing myositis (NM) is an extremely rare necrotizing soft tissue infection involving muscle. Unlike similar infections (eg, necrotizing fasciitis, clostridial myonecrosis) that can be more readily diagnosed, NM can have a benign presentation then rapidly progress into a life-threatening condition with a mortality rate of 100% without surgical intervention. CASE REPORT: A 74-year-old man with a history of prostate cancer with radiation therapy, seed implants, and 2 transurethral resection procedures presented to the emergency department after a fall. He was initially diagnosed and treated for urosepsis. Sixteen hours after presentation, he complained of pain and swelling of his right groin. Computed tomography of the abdomen and pelvis showed gas findings suspicious for necrotizing infection of the bilateral thighs. Surgical exploration revealed NM. Separate cultures from the left thigh and bladder grew Streptococcus intermedius, Clostridium clostridioforme, and Peptostreptococcus, suggesting a possible common source of infection from the prostate gland or the osteomyelitic pubic symphysis, which subsequently spread to the bilateral thighs. CONCLUSIONS: To the best of the authors' knowledge, this is the first reported case of S intermedius and C clostridioforme causing NM. A high index of suspicion is required for extremely rare conditions like NM, because early diagnosis and surgical intervention significantly reduce mortality.