Association of germline variants in telomere maintenance genes (POT1, TERF2IP, ACD, and TERT) with spitzoid morphology in familial melanoma: A multi-center case seriesCapsule Summary

Background: Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation. Objective: To assess if familial melanoma cases associated with germline variants in TMG (POT1, ACD, TERF2IP, and TERT) commonly exhibit spitzoid morphology. Methods: In this case series, melanomas were classified as having spitzoid morphology if at least 3 of 4 dermatopathologists reported this finding in ≥25% of tumor cells. Logistic regression was used to calculate odds ratios (OR) of spitzoid morphology compared to familial melanomas from unmatched noncarriers that were previously reviewed by a National Cancer Institute dermatopathologist. Results: Spitzoid morphology was observed in 77% (23 of 30), 75% (3 of 4), 50% (2 of 4), and 50% (1 of 2) of melanomas from individuals with germline variants in POT1, TERF2IP, ACD, and TERT, respectively. Compared to noncarriers (n = 139 melanomas), POT1 carriers (OR = 225.1, 95% confidence interval: 51.7-980.5; P < .001) and individuals with TERF2IP, ACD, and TERT variants (OR = 82.4, 95% confidence interval: 21.3-494.6; P < .001) had increased odds of spitzoid morphology. Limitations: Findings may not be generalizable to nonfamilial melanoma cases. Conclusion: Spitzoid morphology in familial melanoma could suggest germline alteration of TMG

Ancient Skeletal Evidence for Leprosy in India (2000 B.C.)

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae that affects almost 250,000 people worldwide. The timing of first infection, geographic origin, and pattern of transmission of the disease are still under investigation. Comparative genomics research has suggested M. leprae evolved either in East Africa or South Asia during the Late Pleistocene before spreading to Europe and the rest of the World. The earliest widely accepted evidence for leprosy is in Asian texts dated to 600 B.C. METHODOLOGY/PRINCIPAL FINDINGS: We report an analysis of pathological conditions in skeletal remains from the second millennium B.C. in India. A middle aged adult male skeleton demonstrates pathological changes in the rhinomaxillary region, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton. The presence and patterning of lesions was subject to a process of differential diagnosis for leprosy including treponemal disease, leishmaniasis, tuberculosis, osteomyelitis, and non-specific infection. CONCLUSIONS/SIGNIFICANCE: Results indicate that lepromatous leprosy was present in India by 2000 B.C. This evidence represents the oldest documented skeletal evidence for the disease. Our results indicate that Vedic burial traditions in cases of leprosy were present in northwest India prior to the first millennium B.C. Our results also support translations of early Vedic scriptures as the first textual reference to leprosy. The presence of leprosy in skeletal material dated to the post-urban phase of the Indus Age suggests that if M. leprae evolved in Africa, the disease migrated to India before the Late Holocene, possibly during the third millennium B.C. at a time when there was substantial interaction among the Indus Civilization, Mesopotamia, and Egypt. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in India and Africa to confirm the African origin of the disease

The function and diagnostic potential of adipocyte-derived factors in the tumor microenvironment

Solid tumors resemble dysfunctional “organs” comprised of malignant cancer cells and heterogeneous components of the tumor microenvironment (TME). The TME includes extracellular matrix and non-cancer stromal cells (e.g., fibroblasts, immune cells, and vascular cells) that may support cancer progression. Adipocytes, despite being the most abundant cell type in certain tumor types (e.g., breast cancer), are often overlooked in the TME. It is now well established that the TME plays an important role in tumor growth and metastasis, and while multiple studies have contributed to our understanding of the TME, relatively little is known about how adipocytes, despite their role as major sources of paracrine and endocrine factors, influence tumor progression. In this chapter, we will briefly introduce the TME and its various components and then provide a comprehensive analysis of the roles of tumor-associated adipocytes and adipokines during solid tumor development. We will also highlight the potential diagnostic/prognostic value of adipose tissue and adipose-derived factors in cancer