Diffuse dermal angiomatosis of the thigh as the presenting sign of critical limb ischemia.

Diffuse dermal angiomatosis (DDA) is a rare, benign disease that can serve as the precursor to critical limb ischemia. Pruritic, erythematous plaques form from a proliferation of endothelial cells in response to dermal hypoxia. We present the case of a 63-year-old female patient with DDA of the left medial thigh, followed by ischemia of her distal extremities. Revascularization of her left leg resulted in resolution of the DDA and healing of her ulcers. DDA can be an important clue to identify significant peripheral vascular disease.

Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.

Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Preferentially expressed antigen in melanoma expression in nonmelanoma skin cancers and melanocytes in surrounding skin.

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.

Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma.

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.

PAS and GMS utility in dermatopathology: Review of the current medical literature.

The American Society of Dermatopathology has established an Appropriate Use Criteria (AUC) Committee with the intention of establishing evidence-based recommendations regarding the appropriateness of various ancillary tests commonly utilized by dermatopathologists. Periodic acid Schiff (PAS) and Grocott (or Gomori) methenamine silver (GMS) stains represent some of the most commonly employed ancillary tests in dermatopathology. The utility of these tests was targeted for evaluation by the AUC. This literature review represents a comprehensive evaluation of available evidence for the utility of PAS and/or GMS staining of skin and nail biopsies. In concert with expert opinion, these data will be incorporated into future recommendations by the AUC for PAS and GMS staining in routine dermatopathology practice.

Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death.

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.

Muir-Torre syndrome appropriate use criteria: Effect of patient age on appropriate use scores.

BACKGROUND: Muir-Torre syndrome (MTS) is a rare inherited syndrome, with an increased risk of sebaceous and visceral malignancy. Prior reports suggest screening for mismatch repair (MMR) deficiency may be warranted in patients <50 years and when sebaceous neoplasms are located on a non-head and neck location. Previously, appropriate use criteria (AUC) were developed for clinical scenarios in patients >60 years concerning the use of MMR protein immunohistochemistry (MMRP-IHC). This analysis explores the appropriateness of testing in patients ≤60 years. METHODS: Panel raters from the AUC Task Force rated the use of MMRP-IHC testing for MTS for previously rated scenarios with the only difference being age. RESULTS: Results verify the previously developed AUC for the use of MMRP-IHC in neoplasms associated with MTS in patients >60 years. Results also show that in patients ≤60 years with a single sebaceous tumor on a non-head and neck site, MMRP-IHC testing should be considered. Testing can also be considered with a 2-antibody panel on periocular sebaceous carcinoma in younger patients. CONCLUSIONS: Our findings align with known evidence supporting the need to incorporate clinical parameters in identifying patients at risk for MTS, with age being a factor when considering MMRP-IHC testing.

Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology.

BACKGROUND: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy, and physician decision-making. OBJECTIVES: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology. METHODS: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience, and expert judgment, was used to develop AUC in dermatopathology. RESULTS: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate" and 52 (25%) "rarely appropriate" and 43 (20%) having "uncertain appropriateness." LIMITATIONS: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost. CONCLUSIONS: The ultimate decision to order specific tests rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-the AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.