Adding "Unlikely" as a Clinical Qualifier Is Unlikely to Be of Help: A Retrospective, Single-Center, Cross-Sectional Cohort Study.

ABSTRACT: Clinical correlation is essential to accurate and efficient diagnosis and differential diagnosis in dermatopathology. Poor-quality clinical information can lead to failures and delays in patient care. Some clinicians use the term "unlikely" when submitting a specimen. How frequently the "unlikely" clinical diagnosis correlates with the final pathologic diagnosis is unknown. We studied 203 dermatopathology reports from December 8, 2020, to July 1, 2021, that included the qualifier "unlikely" on the requisition sheet. Samples were stratified into either an inflammatory or neoplastic cohort based on final histopathologic diagnosis, with the neoplastic cohort being further stratified into pigmented and nonpigmented cohorts. Statistical analyses were conducted. The "unlikely" diagnosis in the clinical differential diagnosis and the final histologic diagnosis were the same in 7.9% of the 203 samples studied. This occurred in 8.5% of the inflammatory cohort and 7.6% of the neoplastic cohort. We concluded that the use of the qualifier "unlikely" is not helpful. We acknowledge the limitations of our study because of a small sample.

Diffuse neurofibroma with hypertrichosis in a toddler.

Diffuse neurofibroma is a rare type of neurofibroma uncommonly reported in infancy. It is a slow growing tumor originating in the peripheral nerve sheath. We present the case of a 17-month-old boy with diffuse neurofibroma of the scalp associated with hypertrichosis. His genetic and clinical workup for neurofibromatosis was negative.

Cutaneous VCL::ALK fusion ovoid-spindle cell neoplasm.

Cutaneous VCL::ALK fusion spindle (ovoid) cell tumor is unique. Recently emerged RAS::MAP tyrosine kinase fusion sarcomas more commonly involve subcutis, skeletal muscle and even bone. We share our experience with a novel cutaneous VCL::ALK spindle cell tumor. An 11-year-old male presented with a back pedunculated pink-red papule thought to be a pyogenic granuloma. Biopsy histopathology revealed an epithelial collarette with pedunculated tumor extending to deep dermis/subcutis interface. The combination of spindled and epithelioid cells, an ovoid myopericytoid appearance within myxoid to collagenous stroma, low to moderate MIB1 and focal S100 protein without SOX10 immunostaining, were suggestive of a novel RAS::MAPK tyrosine kinase fusion sarcoma that is well described. ALK immunostain being positive, a next-generation sequencing comprehensive fusion panel was performed to reveal a VCL::ALK fusion. While epithelioid fibrous histiocytoma shares this fusion and similar dermal location and collarette pedunculation, this and other entities were excluded by older patient age, deeper dermal involvement, ovoid-to-spindled morphology, central pericytoid vasculature, myxoid stroma, moderate cellularity with low to moderate MIB1 expression, superficial ulceration, and focal S100 protein expression. Complete excision was performed with favorable follow-up to date. This novel VCL::ALK fusion spindle (ovoid) cell tumor of the dermis is best considered as part of the recently emerged RAS::MAP tyrosine kinase fusion sarcomas.

Impact of trainee experience on shave biopsy specimen size.

BACKGROUND: Skin biopsies are crucial for the diagnosis of many cutaneous pathologies, yet specimen adequacy is essential for definitive diagnosis. Recent literature has noted a trend in decreasing biopsy size over time, which has created concern over implications regarding adequacy for diagnosis. METHODS: This study sought to evaluate if clinician training length or type of residency training impacted the average biopsy size and sample adequacy. Dermatopathology reports for shave biopsies between January 1, 2021, and June 30, 2021, at Penn State Health were queried through PathNet, the software application for pathology reports in this health system's electronic medical record system. Biopsy dimensions, volume, diagnosis, location, clinician training level, and descriptions of evaluation of deeper sections (recuts) and superficial sampling were recorded for each biopsy. Basic statistical calculations were performed to assess the mean and standard deviation for biopsy sizes per clinician group. RESULTS: Differences in biopsy size between training levels were statistically significant despite qualitatively similar biopsy locations and final diagnosis categories for each clinician training group. After evaluating measures for sample adequacy, our data showed significantly smaller biopsies; however, overall frequencies were minimal. Additionally, more inadequate specimens were noted for clinician groups with the least amount of dermatology experience. CONCLUSIONS: The results of this study identify a correlation with decreasing biopsy size amidst increased experience in dermatology training but find no evidence to support that this trend currently threatens sample adequacy.

Two cases of adenodermatofibroma.

Dermatofibromas (DF) are common skin lesions composed of a dermal proliferation of fibroblasts and histiocytes. Among the variants of DFs, adenodermatofibroma are characterized by a dense proliferation of fibroblasts and histiocytes admixed with entrapped dilated glandular structures. We report two additional cases of adenodermatofibromas, review the literature, theorize on the histopathogenesis of this variant, and suggest that there are different patterns among adenodermatofibromas, from primarily cystic to primarily glandular.

SOX10 Immunostaining in granulomatous dermatoses and benign reactive lymph nodes.

BACKGROUND: SOX10 immunostaining has been considered a highly sensitive and specific marker for melanoma. But there is evidence suggesting that SOX10 positive cells can be present in dermal scars. Therefore, we investigated whether non-melanocytic cell types present in chronic inflammatory processes or benign lymph nodes express SOX10. METHODS: We retrospectively selected 20 benign lymph nodes and 20 cutaneous granulomatous dermatoses. SOX10, CD68, and Melan-A immunohistochemistry was performed in all cases. RESULTS: Scattered SOX10 positivity was found in 85% of lymph nodes, specifically in subcapsular and medullary sinuses and in 85% of granulomatous dermatoses. In granulomatous dermatoses, the Melan-A stain did not label the scattered SOX10 positive cells and it was difficult to determine if CD68 was co-expressed on the SOX10 positive cells. In the lymph nodes, the SOX10 positive cells did not co-express Melan-A or CD68. CONCLUSIONS: We report SOX10 positive cells detected in granulomatous dermatoses and benign lymph nodes. In lymph nodes, SOX10 positive cells were exclusively in subcapsular and medullary sinuses. Therefore, SOX10 is an excellent stain for evaluation of metastatic melanoma with the caveat that positivity in subcapsular and medullary sinuses can be of non-melanocytic origin; the use of additional melanocytic markers is recommended in this situations.

Schweinfurthin natural products induce regression of murine melanoma and pair with anti-PD-1 therapy to facilitate durable tumor immunity.

Metastatic melanoma is a significant clinical problem with a 5-year survival rate of only 15-20%. Recent approval of new immunotherapies and targeted inhibitors have provided much needed options for these patients, in some cases promoting dramatic disease regressions. In particular, antibody-based therapies that block the PD-1/PD-L1 checkpoint inhibitory pathway have achieved an increased overall response rate in metastatic melanoma, yet durable response rates are reported only around 15%. To improve the overall and durable response rates for advanced-stage melanoma, combined targeted and immune-based therapies are under investigation. Here, we investigated how the natural products called schweinfurthins, which have selective anti-proliferative activity against many cancer types, impact anti-(α)PD-1-mediated immunotherapy of murine melanomas. Two different compounds efficiently reduced the growth of human and murine melanoma cells in vitro and induced plasma membrane surface localization of the ER-resident protein calreticulin in B16.F10 melanoma cells, an indicator of immunogenic cell death. In addition, both compounds improved αPD-1-mediated immunotherapy of established tumors in immunocompetent C57BL/6 mice either by delaying tumor progression or resulting in complete tumor regression. Improved immunotherapy was accomplished following only a 5-day course of schweinfurthin, which was associated with initial tumor regression even in the absence of αPD-1. Schweinfurthin-induced tumor regression required an intact immune system as tumors were unaffected in NOD scid gamma (NSG) mice. These results indicate that schweinfurthins improve αPD-1 therapy, leading to enhanced and durable anti-tumor immunity and support the translation of this novel approach to further improve response rates for metastatic melanoma.