Sclerosing epithelioid fibrosarcoma associated with WRN gene variant presenting as chronic dyspnea and pathologic cervical fracture: a case report and review of the literature.

BACKGROUND: Sclerosing epithelioid fibrosarcoma is an aggressive sarcoma subtype with poor prognosis and limited response to conventional chemotherapy regimens. Diagnosis can be difficult owing to its variable presentation, and cases of sclerosing epithelioid fibrosarcoma are rare. Sclerosing epithelioid fibrosarcoma typically affects middle-aged individuals, with studies inconsistently citing gender predominance. Sclerosing epithelioid fibrosarcoma typically arises from the bones and soft tissues and often has local recurrence after resection and late metastases. Immunohistochemical staining typically is positive for mucin-4. Werner syndrome is due to an autosomal recessive mutation in the WRN gene and predisposes patients to malignancy. CASE PRESENTATION: A 37-year-old Caucasian female presented to the emergency department with 4 months of dyspnea and back pain. She had been treated for pneumonia but had persistent symptoms. A chest, abdomen, and pelvis computed tomography showed near-complete right upper lobe collapse and consolidation, mediastinal lymphadenopathy, lytic spinal lesions, and a single 15-mm hypodense liver nodule. The patient underwent a transthoracic right upper lobe biopsy, bronchoscopy, endobronchial ultrasound with transbronchial lymph node sampling, and bronchoalveolar lavage of the right upper lobe. The bronchoalveolar lavage cytology was positive for malignant cells compatible with poorly differentiated non-small cell carcinoma; however, the cell block materials were insufficient to run immunostains for further investigation of the bronchoalveolar lavage results. Consequently, the patient also underwent a liver biopsy of the liver nodule, which later confirmed a diagnosis of sclerosing epithelioid fibrosarcoma. Next-generation sequencing revealed a variant of unknown significance in the WRN gene. She was subsequently started on doxorubicin. CONCLUSION: Sclerosing epithelioid fibrosarcoma is a very rare entity, only cited approximately 100 times in literature to date. Physicians should be aware of this disease entity and consider it in their differential diagnosis. Though pulmonary involvement has been described in the context of sclerosing epithelioid fibrosarcoma, this malignancy may affect many organ systems, warranting extensive investigation. Through our diagnostic workup, we suggest a possible link between sclerosing epithelioid fibrosarcoma and the WRN gene. Further study is needed to advance our understanding of sclerosing epithelioid fibrosarcoma and its clinical associations as it is an exceedingly rare diagnosis.

The impact of impaired insulin regulation on severity of SARS-CoV-2 infection: a 2-year retrospective single-center analysis.

Background: The COVID-19 pandemic has caused an international healthcare crisis and produced a large healthcare burden. Diabetes mellitus (DM) is a common disease that can be controlled via pharmacologic agents; however, many patients have poor glycemic control, leading to disease-related complications. DM has been reported in the literature to be associated with increasing morbidity and mortality in COVID-19 patients. The authors aim to assess the associations between glucose homoeostasis and COVID-19 disease severity and mortality. Methods: A retrospective chart review of patients ages 18-100 years of age admitted with COVID-19 between January 2020 and December 2021 was performed. The primary outcome was COVID-19 mortality with respect to haemoglobin A1C levels of less than 5.7%, 5.7-6.4%, and 6.5% and greater. Disease severity was determined by degree of supplemental oxygen requirements (ambient air, low-flow nasal cannula, high-flow nasal cannula, non-invasive mechanical ventilation, and invasive mechanical ventilation). COVID-19 mortality and severity were also compared to blood glucose levels on admission as grouped by less than 200 mg/dl and greater than or equal to 200 mg/dl. Results: A total of 1156 patients were included in the final analysis. There was a statistically significant association between diabetic status and mortality (P=0.0002). Statistical significance was also noted between admission blood glucose ≥200 mg/dl and mortality (P=0.0058) and respiratory disease severity (P=0.0381). A multivariate logistic regression for predicting mortality showed increasing haemoglobin A1C was associated with increased mortality (odds ratio 1.72 with 95% CI of 1.122-2.635). Conclusions: In our 2-year retrospective analysis, there was an association between a diagnosis of DM and COVID-19-related mortality. Hyperglycaemia on admission was found to be statistically significant with mortality in patients diagnosed with COVID-19. Glucose homoeostasis and insulin dysregulation likely play a contributing factor to COVID-19 disease severity and mortality.

Primary Mediastinal B-Cell Lymphoma Presenting as Cardiac Tamponade.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of non-Hodgkin lymphoma. Typical symptoms include cough, chest pain, and dyspnea; however, cardiac tamponade as the primary manifestation is exceedingly rare. We hereby present a case of a 34-year-old male with a past medical history of obesity, who presented to our emergency department with a chronic dry cough for 4 months. On admission, computed tomography demonstrated a large 11.1-cm diameter anterior mediastinal mass, and echocardiography demonstrated cardiac tamponade physiology. The patient underwent further workup including pericardiocentesis, subsequent pericardial window, and mediastinal biopsy, which demonstrated histopathology consistent with PMBCL. Our case highlights the importance of a complete and thorough workup for patients with chronic untraditional symptoms. This case is unique in that PMBCL is rarely associated with cardiac tamponade as the primary clinical presentation. Additionally, we recommend an extensive cardiac workup for patients presenting with a large mediastinal mass, as failure to do so may result in patient morbidity and mortality.