Granulomatous scleromyxedema: case report and literature review.

Scleromyxedema is a rare and frequently disabling disease characterized by generalized waxy papules, skin induration, and cardinal histological features of dermal fibroblastic proliferation, thickened collagen, and mucin deposition. A monoclonal gammopathy is almost always present with rare progression to multiple myeloma. We describe the case of a 54-year-old man who presented with a rash in the setting of a new medication and histological features suggesting a granulomatous drug reaction. Despite discontinuation of the medication, the rash persisted and a second biopsy confirmed an interstitial granulomatous pattern. Serum protein electrophoresis identified the presence of a biclonal gammopathy leading to a diagnosis of granulomatous scleromyxedema. Review of the medical literature reveals only a handful of well-documented similar cases of this rare variant. It is important for pathologists and clinicians to be familiar with this condition to facilitate timely diagnosis and optimal clinical management of these patients.

α-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1.

The Hippo pathway regulates contact inhibition of cell proliferation and, ultimately, organ size in diverse multicellular organisms. Inactivation of the Hippo pathway promotes nuclear localization of the transcriptional coactivator Yap1, a Hippo pathway effector, and can cause cancer. Here, we show that deletion of αE (α epithelial) catenin in the hair follicle stem cell compartment resulted in the development of skin squamous cell carcinoma in mice. Tumor formation was accelerated by simultaneous deletion of αE-catenin and the tumor suppressor-encoding gene p53. A small interfering RNA screen revealed a functional connection between αE-catenin and Yap1. By interacting with Yap1, αE-catenin promoted its cytoplasmic localization, and Yap1 showed constitutive nuclear localization in αE-catenin-null cells. We also found an inverse correlation between αE-catenin abundance and Yap1 activation in human squamous cell carcinoma tumors. These findings identify αE-catenin as a tumor suppressor that inhibits Yap1 activity and sequesters it in the cytoplasm.