Folliculin mutation-negative trichodiscomas in a patient with multiple endocine neoplasia type I syndrome

Multiple endocrine neoplasia (MEN) type I, an autosomal dominant disorder caused by mutations in the MEN1 gene, is classically associated with parathyroid, pituitary, and pancreatic tumors. Patients with MEN type I also frequently exhibit multiple cutaneous lesions, specifically facial angiofibromasand collagenomas. Herein we describe a patient with genetically confirmed MEN type I syndrome who presented with trichodiscomas, skin tumorscharacteristic of Birt-Hogg-Dubé (BHD) syndrome. Although BHD is associated with mutations in the folliculin (FLCN) gene, this patient with trichodiscomaswas negative for the FLCN mutation

A pink enlarging plaque on the plantar foot: amelanotic acral lentiginous melanoma

Acral lentiginous melanomas account for less than 5% of all melanomas, whereas amelanotic melanomas account for around 2-8% of all melanomas. Amelanotic acral lentiginous melanomas are even less common and can often be mistaken for other clinical entities, including pyogenic granulomas, non-melanoma skin cancers, and warts. We describe a man in his 50s with a twenty-year history of a skin-colored plaque on the right plantar foot; after enlargement and failure of wart treatment, a shave biopsy revealed an amelanotic melanoma. A subsequent wide local excision and sentinel lymph node biopsy revealed melanoma in 4 lymph nodes and the patient underwent an abbreviated course of interferon-alpha therapy. The patient remained stable until 2 ? years after diagnosis, at which time he presented with in-transit metastases on the foot and right thigh; he has since been stable on nivolumab. This case represents the challenge of diagnosing amelanotic melanomas on acral surfaces and highlights the importance of considering a skin biopsy for diagnosis of any changing, atypical amelanotic lesions on the feet or hands

Chronic Q-Fever (Coxiella burnetii) Causing Abdominal Aortic Aneurysm and Lumbar Osteomyelitis: A Case Report

Coxiella burnetii is a rare cause of chronic infection that most frequently presents as endocarditis. We report a case of C burnetii causing an infected abdominal aortic aneurysm with contiguous lumbar osteomyelitis resulting in spinal cord compromise. The diagnosis was established by serologic studies consistent with chronic Q-fever (ratio of C burnetii immunoglobulin [Ig]G phase II titer to IgG phase I titer <1) and was confirmed by positive C burnetii polymerase chain reaction of vertebral tissue in addition to pathology of vertebral bone showing intracellular Gram-negative coccobacillary bacteria. The patient clinically improved after surgical decompression and prolonged treatment with doxycycline and hydroxychloroquine

Cellular Senescence as a Possible Mechanism for Halting Progression of Keloid Lesions

Keloid scarring is a consequence of aberrant wound healing that leads to expansion of the scar beyond the confines of the skin injury. Keloid scars are characterized by excessive extracellular matrix disposition, prolonged proliferation of fibroblasts, increased angiogenesis, and inflammatory cell infiltration. There is no single satisfactory treatment for keloid, and it can lead to severe disfigurements and bodily dysfunction. Thus, clarification of the mechanisms underlying keloid formation, as well as those that prevent it from behaving as a malignant tumor, has significant consequences not only for treatment of keloid but also for the prevention of malignant tumor formation. Senescence is an irreversible form of growth arrest that has been shown to play a role, both in vitro and in vivo, in preventing malignant tumorigenesis upon oncogenic stress. In this study it is shown that fibroblasts embedded inside keloid scars proliferate at a slower rate compared with either those residing at the proliferative edges of the scar or normal fibroblasts. Likewise it is demonstrated that keloid fibroblasts exhibit a cell-cycle arrest with a G2/M DNA content and a higher rate of senescence. The results also indicate that levels of the tumor suppressor protein PML are higher in the active regions of keloid. The study therefore suggests that senescence is one possible mechanism by which keloid is maintained in a benign state. On this basis, “pro-senescence therapy” should be taken into consideration when designing treatment strategies for keloid

Alterations in thromboxane synthase and thromboxane A2 receptors in experimental alcoholic liver disease. J Pharmacol Exp Ther 282: 1037–1043

ABSTRACT We have previously shown that hepatic thromboxane production is increased in experimental alcoholic liver disease. The present study was designed to investigate the cell type in liver responsible for increased thromboxane synthesis and the role of the thromboxane receptor system in the pathogenesis of liver injury. Male Wistar rats were divided into four groups and fed a liquid diet with dextrose or ethanol for 2, 4 and 8 weeks. Medium chain triglycerides or corn oil provided the dietary fatty acids. Kupffer cells, endothelial cells and hepatocytes were isolated from rats fed the different diets for 4 weeks. Liver histopathology, thromboxane synthase mRNA and protein, thromboxane levels and thromboxane receptor mRNA were evaluated in each group. In rats fed corn oil and ethanol, an increase in thromboxane synthase and liver levels of thromboxane metabolites were significantly higher than in the corn oildextrose-fed group and were correlated with the presence of pathological changes in the liver. Kupffer cells showed increased expression of thromboxane synthase. In rats fed medium chain triglycerides and ethanol, the levels of thromboxane synthase mRNA and protein were significantly lower than in the corn oil-ethanol-fed groups (P Ͻ .01) and liver injury was absent. However, the levels of thromboxane synthase mRNA, protein and thromboxane were significantly higher in the medium chain triglyceride-ethanol-fed rats than in the respective dextrose-fed controls. Among the different cell types, thromboxane A 2 -receptor mRNA levels were highest in the Kupffer cells in corn oil-ethanol-fed rats. The increase in thromboxane synthase in Kupffer cells together with an increase in thromboxane receptor levels suggests than thromboxanes may contribute to liver injury in ethanol-fed rats