Squamous Cell Carcinoma in Situ Achieves Tumor Clearance in More Mohs Stages Than Invasive Squamous Cell Carcinoma.

BACKGROUND: Squamous cell carcinoma in situ (SCCIS) has more subclinical lateral extension than invasive squamous cell carcinomas (SCC). OBJECTIVE: To determine whether it takes a greater number of Mohs stages for clearance of SCCIS compared with SCC and whether the difference in final defect size and clinical size is larger in SCCIS than SCC. METHODS: All Mohs micrographic surgery cases of SCCIS and SCC performed between January 2011 and December 2021 were identified. Number of Mohs stages were recorded and difference in final defect size and initial clinical size were calculated for SCCIS and SCC. RESULTS: 4,363 cases were included, 1,066 SCCIS and 3,297 invasive SCC. The initial clinical size, final defect size, and the size difference were similar between SCCIS and SCC groups. However, SCCIS underwent more Mohs stages to achieve tumor clearance than invasive SCCs (1.5 ± 0.7 vs 1.4 ± 0.7 respectively, p < .001). In fact, 71% of SCCs were cleared after 1 Mohs stage compared with 61.1% of SCCIS. CONCLUSION: These findings support that SCCIS has more subclinical lateral extension and therefore is appropriate for Mohs surgery.

Disruptive lysosomal-metabolic signaling and neurodevelopmental deficits that precede Purkinje cell loss in a mouse model of Niemann-Pick Type-C disease.

Purkinje cell (PC) loss occurs at an early age in patients and animal models of Niemann-Pick Type C (NPC), a lysosomal storage disease caused by mutations in the Npc1 or Npc2 genes. Although degeneration of PCs occurs early in NPC, little is known about how NPC1 deficiency affects the postnatal development of PCs. Using the Npc1nmf164 mouse model, we found that NPC1 deficiency significantly affected the postnatal development of PC dendrites and synapses. The developing dendrites of Npc1nmf164 PCs were significantly deficient in mitochondria and lysosomes. Furthermore, anabolic (mTORC1) and catabolic (TFEB) signaling pathways were not only perturbed but simultaneously activated in NPC1-deficient PCs, suggesting a loss of metabolic balance. We also found that mice with conditional heterozygous deletion of the Phosphatase and Tensin Homolog Deleted on Chromosome 10 gene (Pten-cHet), an inhibitor of mTORC1, showed similar early dendritic alterations in PCs to those found in Npc1-deficient mice. However, in contrast to Npc1nmf164 mice, Pten-cHet mice exhibited the overactivation of the mTORC1 pathway but with a strong inhibition of TFEB signaling, along with no dendritic mitochondrial reductions by the end of their postnatal development. Our data suggest that disruption of the lysosomal-metabolic signaling in PCs causes dendritic and synaptic developmental deficits that precede and promote their early degeneration in NPC.