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Background: Immunohistochemistry for preferentially expressed antigen in melanoma (PRAME) has been studied in melanocytic lesions but not nonmelanoma skin cancers (NMSCs). This study evaluated PRAME expression in NMSCs and dermoepidermal junction (DEJ) melanocytes in the surrounding skin., Methods: Ninety-nine NMSCs were studied: 23 Merkel cell carcinomas (MCCs), 25 well to poorly differentiated squamous cell carcinomas (SCCs), 14 basal cell carcinomas (BCCs), five basosquamous carcinomas, four sebaceous carcinomas, ten atypical fibroxanthomas, 11 dermatofibrosarcoma protuberans, and seven leiomyosarcomas. Staining quality was considered low or high intensity. Staining quantity was reported as negative 0%, 1% to 24%, 25% to 50%, and >50%. DEJ melanocyte PRAME expression was recorded., Results: Forty-eight percent of NMSCs showed PRAME expression, mostly low intensity in fewer than 25% of cells. High-intensity expression was noted in one poorly differentiated SCC, six BCCs, and seven MCCs. Only MCCs showed expression in greater than 25% of tumor cells. Focal DEJ melanocytes expressed high-intensity PRAME in 18% of cases, most commonly SCCs (11/23)., Conclusions: PRAME is negative or expressed with low intensity in a small percentage of NMSCs, with the exception of some MCC showing high-intensity and diffuse staining. Focal DEJ melanocytes showed high-intensity PRAME reactivity in the skin surrounding some NMSCs., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan-Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51-11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms.

Purpose: Biomarkers for disease-specific survival (DSS) in early-stage melanoma are needed to select patients for adjuvant immunotherapy and accelerate clinical trial design. We present a pathology-based computational method using a deep neural network architecture for DSS prediction., Experimental Design: The model was trained on 108 patients from four institutions and tested on 104 patients from Yale School of Medicine (YSM, New Haven, CT). A receiver operating characteristic (ROC) curve was generated on the basis of vote aggregation of individual image sequences, an optimized cutoff was selected, and the computational model was tested on a third independent population of 51 patients from Geisinger Health Systems (GHS)., Results: Area under the curve (AUC) in the YSM patients was 0.905 ( P < 0.0001). AUC in the GHS patients was 0.880 ( P < 0.0001). Using the cutoff selected in the YSM cohort, the computational model predicted DSS in the GHS cohort based on Kaplan-Meier (KM) analysis ( P < 0.0001)., Conclusions: The novel method presented is applicable to digital images, obviating the need for sample shipment and manipulation and representing a practical advance over current genetic and IHC-based methods., (©2019 American Association for Cancer Research.)

Introduction: Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors., Methods: Sixty-two stage II-III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers., Results: We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count., Conclusion: Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations.

Metastasis from malignant melanoma (MM) usually first presents in the draining lymph node basin and thus sentinel lymph node (SLN) biopsy is a staging tool used to predict risk of metastases and death in higher risk tumors and has become the standard of care. Differences in the processing and methods used in the histopathological examination of SLNs can affect the positivity rate for metastatic MM because isolated MM deposits may be small and variably distributed in the SLN. The examination of SLNs is not standardized. The authors surveyed institutions across the United States who process SLNs for MM to better characterize the current methods used and to suggest a standardized approach to improve the reliability of the SLN biopsy. A survey of 142 academic institutions in the United States regarding the methods used in the evaluation of the SLN biopsy for MM was conducted. Thirty-two institutions responded. Eighty-one percent of the institutions (26 of 32) had a protocol that they used for SLN examination. In regards to gross dissection, 28% of the responders (9 of 32) initially bivalve (cut the SLN in half), whereas 59% (19 of 32) use a bread loaf technique, cutting the SLN at even intervals without specifically commenting about orientation to the hilum. The number of levels initially cut from the SLN block varied from 1 to 8 levels per block. Thirty-nine percent of the respondents (12 of 31) routinely order immunohistochemistry before evaluation of the initial hematoxylin- and eosin-stained sections. Eighty percent of the respondents (24 of 30) report the maximum dimension of the metastatic tumor deposit. The response rate was low (22%), and most respondents did not indicate how many SLN accessions were performed at their institution each year. Histologic protocols for processing SLNs for MM vary among institutions. Different methods of handling SLNs result in varying sensitivities for detection of metastases. Data derived from these varied approaches to develop and determine prognostic and staging categories may be inconsistent. A standardized yet practical approach is needed to provide reliable information on which prognosis can be determined and therapeutic guidelines can be based. The hope is for dermatologists and those treating patients with MM to understand the intricacies and inconsistencies involved in performance and interpretation of this key staging tool.

This article is an up-to-date overview of the potential uses and limitations of immunohistochemistry (IHC) in melanocytic lesions. The information is intended to assist dermatopathologists and dermatologists who read slides to appropriately use IHC in this setting. In addition, dermatologists who do not review microscopic slides will better understand the rationale of the pathologist when reading and interpreting the pathology report., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The sentinel lymph node from a 72-year-old female with melanoma revealed a pigmented and spindled melanocytic proliferation in the capsule that extended into the trabeculae. Benign nodal nevi are uncommon but have been reported in lymph nodes of melanoma patients and less often in lymph nodes removed for other reasons. Nodal blue nevi are particularly rare. These melanocytic proliferations can be distinguished from metastatic melanoma by evaluation of the distribution in the node, morphologic characteristics and the assistance of immunohistochemistry., (Copyright © 2009 John Wiley & Sons A/S.)