Vitamin D Receptor and Retinoid X Receptor Alpha in Melanocytic Benign Lesions and Melanoma.

ABSTRACT: Vitamin D receptor (VDR) exerts its biological effects when it heterodimerizes to a nuclear receptor of the retinoid family called retinoid X receptor α (RXRα), stimulating or inhibiting DNA transcription. VDR stimulation by vitamin D analogs led to in vitro antiproliferative effects, and experimental RXRα knockout led to loss of proliferation control in melanoma cells. The aim of this study was to determine VDR and RXRα positivity in melanocytic lesions, compared with normal skin species. By immunohistochemistry assays, nuclear VDR, cytoplasmic VDR, and RXRα and RXRα in keratinocytes surrounding melanocytes were evaluated in 77 controls, 92 intradermal nevi, 54 dysplastic nevi, and 83 melanomas in this retrospective cross-sectional study. Nuclear VDR, cytoplasmic VDR, and RXRα were less expressed in exposed areas ( P < 0.001, P = 0.0006, and P < 0.001, respectively) than covered areas. All melanocytic lesions had loss of VDR and RXRα comparing with the control group. In the melanoma group, nuclear VDR tended to inversely correlate with the Breslow index (r = -0.11, P = 0.29) but directly correlated with histological regression ( P = 0.0293). RXRα inversely correlated with mitosis (r = -0.245; P = 0.0263). We can suggest that sun exposure affected VDR and RXRα immunopositivity. Nuclear VDR tendency of inverse correlation with the Breslow index showed that worse melanomas have a greater loss of VDR. RXRα inversely correlated with mitosis, indicating that RXRα can have a role in proliferation control. VDR and RXRα may participate in the development of melanocytic lesions and be a future target of new studies and directed therapies.

Clinical diagnostic approach for oral lymphomas: a multi-institutional, observational study based on 107 cases.

OBJECTIVE: To evaluate oral lymphomas' clinical manifestations and investigate whether clinical features are associated with lymphoma subtypes. STUDY DESIGN: Oral lymphomas with at least 1 representative clinical image were evaluated. They were classified according to their microscopic grade (high vs low), predominant cell size (small vs medium/large), and cellular lineage (B cell vs T cell). Clinical images were described according to tumor location, number, swelling, ulcer, necrosis, telangiectasia, predominant color, and lobulation. Lymphomas affecting the palate were compared with salivary gland tumors (SGTs) affecting this location. RESULTS: Data from 107 cases were included. High-grade subtypes (80.4%), with medium/large-sized cells (52.3%), and diagnosed as diffuse large B cell lymphomas (29%) predominated. High-grade lymphomas often presented as painful, ulcerative, and osteolytic diseases (P < .05). Tumors predominantly composed of medium/large-sized cells were associated with painful lesions, ulcerated, with necrosis and bone destruction (P < .05). When only palate tumors were considered, multiple and bilateral lesions, the presence of pain, ulceration, and necrosis were significantly more associated with a diagnosis of lymphoma than SGT (P < .001). CONCLUSION: High-grade oral lymphomas are more associated with destructive presentation than low-grade subtypes, and bilateral lesions in the palate are more associated with a lymphoma diagnosis than SGT.

Shall we exclude parapsoriasis from the medical vocabulary?

Since the first description of parapsoriasis more than 100 years ago, parapsoriasis has been a questionable condition and occasionally considered a precursor of cutaneous lymphoma. The name "parapsoriasis" is related to a heterogenous group of diseases that show a distinct clinical presentation; however, the histopathological criteria are not strongly specific. Pathologists do not consider parapsoriasis as a possible histopathological diagnosis, but dermatologists use the term as clinical hypothesis. We aim to provide an historical review of parapsoriasis focusing on histopathological criteria, considering its possible relation with cutaneous skin lymphoma, based on articles from PubMed and standard dermatopathological books. Parapsoriasis does not have well-defined histopathological criteria, so its use should be avoided. Being aware of parapsoriasis complexity, a consensus meeting can help to create a guideline regarding this topic.

Primary sclerosing cholangitis associated with severe ulcerative colitis in a young man.

Primary sclerosing cholangitis, a chronic progressive cholestatic liver disease, is the most serious hepatobiliary complication of ulcerative colitis (UC). The authors present the case of a severe and intractable form of UC associated with primary sclerosing cholangitis, in which the diagnosis of this hepatobiliary complication was made during the postmortem examination. A 19-year-old man, with an 8-month diagnosis of UC, was non-responsive to any therapeutic approach. He presented at the emergency care unit severely ill and with cachexia, and subsequently died of septic shock. The postmortem examination confirmed the clinical diagnosis of severe UC and disclosed the presence of primary sclerosing cholangitis. Although laboratory tests have shown a typical cholestatic profile with elevated alkaline phosphatase and gamma-glutamyl transferase levels, hepatic dysfunction was related to sepsis. This report highlights how challenging the diagnosis of primary sclerosing cholangitis can be and shows the value of the postmortem examination to add important information to a medical diagnosis.