Hemorrhagic Bullous Dermatosis

Introduction The patient is a 64 year old man with active primary central nervous system B-cell lymphoma who was hospitalized for management of a right lower extremity traumatic injury complicated by a calf hematoma. During the hospital stay, the patient was diagnosed with a provoked left lower extremity deep vein thrombosis (DVT) and treated initially with therapeutic dosing of enoxaparin. Five days after low molecular weight heparin (LMWH) initiation, gradual development of tense, well-circumscribed bullae were noted to appear on his arms and hands bilaterally, ranging from 0.5 cm to 1.5 cm in diameter. These lesions were both nonpruritic and nontender with no significant surrounding erythema (Figure 1). Bullae were located distal to the site of enoxaparin injections. Aside from a normocytic normochromic anemia related to chronic medical conditions, results of platelet counts, creatinine levels, and coagulation profiles remained unremarkable. A shave biopsy of one of the lesions revealed an intraepidermal collection of red blood cells without evidence of thrombotic or vasculitic changes (Figures 2 & 3). enoxaparin dose was reduced several days after lesion onset due to increasing calf hematoma size, in an effort to balance anticoagulation benefit for the DVT with risk of continued bleeding into the hematoma. The bullae started to regress approximately two weeks after onset, eventually crusting over. The patient was eventually discharged home

Silencing the GUCA2A-GUCY2C tumor suppressor axis in CIN, serrated, and MSI colorectal neoplasia.

Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI). Transformation through the APC pathway involves loss of the hormone GUCA2A that silences the tumor-suppressing receptor GUCY2C. Indeed, oral hormone replacement is an emerging strategy to reactivate GUCY2C and prevent CRC initiation and progression. Moreover, retained expression by tumors arising from TAs has established GUCY2C as a diagnostic and therapeutic target to prevent and treat metastatic CRC. Here, we defined the potential role of the GUCA2A-GUCY2C axis and its suitability as a target in tumors arising through the SA and MSI pathways. GUCA2A hormone expression was eliminated in TAs, SAs, and MSI tumors compared to their corresponding normal adjacent tissues. In contrast to the hormone, the tumor-suppressing receptor GUCY2C was retained in TA and MSI tumors. Surprisingly, GUCY2C expression was nearly eliminated in SAs, reflecting loss of the transcription factor CDX2. Changes in the GUCA2A-GUCY2C axis in human SAs and MSI tumors were precisely recapitulated in genetic mouse models. These data reveal the possibility of GUCA2A loss silencing GUCY2C in the pathophysiology of, and oral hormone replacement to restore GUCY2C signaling to prevent, MSI tumors. Also, they highlight the potential for targeting GUCY2C to prevent and treat metastases arising from TA and MSI tumors. In contrast, loss of GUCY2C excludes patients with SAs as candidates for GUCY2C-based prevention and therapy