Faculty Bibliography

BACKGROUND: Complete removal of individual dysplastic nevi (DN) is often accomplished by a second surgical procedure after the initial biopsy. The choice to perform the second procedure is strongly influenced by histopathologic margin status of the initial biopsy specimen. OBJECTIVE: To evaluate the clinical and histopathologic outcomes of in toto biopsy of DN using a predetermined margin of normal skin. METHODS: We conducted a prospective study of a saucerization method using a defined 2-mm margin in patients undergoing biopsy of a pigmented skin lesion. RESULTS: We performed 151 biopsies in 138 patients. Overall, 137 of 151 lesions subjected to biopsy (90.7%) were melanocytic: 86 DN (57.0%), 40 nevi without atypia (26.5%), and 11 melanomas (7.3%). Of 78 DN, 68 (87.2%) were removed with clear histopathologic margins (8 DN were excluded because of inadequate processing). There was no clinical evidence of recurrence at any of the biopsy sites that were simply observed (i.e., not re-excised) over a median of 16.9 months. LIMITATIONS: There were few biopsies performed on the face. CONCLUSIONS: The complete histopathologic removal of nearly 9 of 10 DN using a peripheral margin of 2 mm of normal skin and a depth at the dermis and subcutaneous fat junction has the potential to decrease second procedures at DN biopsy sites, thereby decreasing patient morbidity and saving health care dollars.

Squamous cell carcinomas (SCCs) are heterogeneous tumors sustained by tumor-propagating cancer cells (TPCs). SCCs frequently resist chemotherapy through still unknown mechanisms. Here, we combine H2B-GFP-based pulse-chasing with cell-surface markers to distinguish quiescent from proliferative TPCs within SCCs. We find that quiescent TPCs resist DNA damage and exhibit increased tumorigenic potential in response to chemotherapy, whereas proliferative TPCs undergo apoptosis. Quiescence is regulated by TGF-beta/SMAD signaling, which directly regulates cell-cycle gene transcription to control a reversible G1 cell-cycle arrest, independent of p21CIP function. Indeed, genetic or pharmacological TGF-beta inhibition increases the susceptibility of TPCs to chemotherapy because it prevents entry into a quiescent state. These findings provide direct evidence that TPCs can reversibly enter a quiescent, chemoresistant state and thereby underscore the need for combinatorial approaches to improve treatment of chemotherapy-resistant SCCs.

For rapid pathological assessment of large surgical tissue excisions with cellular resolution, we present a line scanning, stage scanning confocal microscope (LSSSCM). LSSSCM uses no scanning mirrors. Laser light is focused with a single cylindrical lens to a line of diffraction-limited width directly into the (Z) sample focal plane, which is parallel to and near the flattened specimen surface. Semi-confocal optical sections are derived from the linear array distribution (Y) and a single mechanical drive that moves the sample parallel to the focal plane and perpendicular to the focused line (X). LSSSCM demonstrates cellular resolution in the conditions of high nuclear density within micronodular basal cell carcinoma.

The authors describe an isolated, yellowish papular lesion of the upper eyelid in a 63-year-old man. Following excision, histopathologic analysis showed the features of a benign hypopigmented cellular blue nevus, the first and only case involving the eyelid skin.

BACKGROUND: Little is known regarding the clinical practice of immunohistochemistry in the diagnosis of melanoma. We aimed to assess the incidence of immunostain usage by referring pathologists and dermatopathologists in melanoma cases sent for consultative review. As a secondary objective, associations between immunostain use and specific melanoma characteristics were also evaluated. METHODS: This is a retrospective review of consultation reports of referred melanomas at a tertiary academic center in New York, New York from 2001-2015. Univariate regression analysis was performed on melanomas with accompanying immunostains and on characteristics such as Breslow's depth, location, prognostic factors, and morphologic subtypes. Associations between immunostain usage and these characteristics were analyzed using Fisher's exact test. RESULTS: Immunostain use significantly increased over the study period (p<0.001) and was more likely to be associated with melanomas that were thicker (OR=2.5; 1.7-3.6); located on the head and neck (OR=1.6; 1.4-1.9) or acral sites (OR=1.5; 1.1-2.0); had ulceration (OR=2.1; 1.6-2.8), dermal mitoses (OR=1.3; 1.1-1.5), or perineural invasion (OR=3.6; 2.0-6.5); or were of desmoplastic (OR=7.4; 4.5-12), amelanotic (OR=7.1; 3.6-14), or nevoid subtypes (OR=4.0; 1.7-8.9). CONCLUSIONS: Immunostain use in the diagnosis of melanoma has increased significantly in the past 15 years for reasons that remain unclear.