Ancillary immunohistochemistry testing for loss of p16 in melanoma: A systematic review and meta-analysis of diagnostic accuracy studies.

BACKGROUND: Ancillary immunohistochemistry testing for p16 loss has been proposed as a diagnostic tool for melanoma, but its accuracy remains uncertain. METHODS: A systematic review and meta-analysis were conducted on 26 studies involving 979 melanomas and 974 nevi. RESULTS: Through bivariate analysis of data across all cut-off values, the sensitivity and specificity were calculated to be 0.55 (95% confidence interval [CI]: 0.38, 0.70) and 0.85 (95% CI: 0.70, 0.94), respectively. Summary estimates of diagnostic accuracy fell below recommended thresholds for effective tests, but subgroup analysis suggested that p16 loss could aid in diagnosing ambiguous lesions as melanoma in certain scenarios. However, the presence of p16 expression in these contexts does not definitively rule out melanoma. The findings were limited by underpowered exploratory study designs at risk for bias in patient selection and test interpretation. CONCLUSIONS: While the use of p16 immunohistochemistry for detecting melanoma is not universally reliable, it may serve as a confirmatory test in differential diagnoses involving common, congenital, acral, Spitz, and deep penetrating nevi. Nevertheless, further studies are needed to validate its utility. Until then, the application of p16 immunohistochemistry in melanoma diagnosis should be regarded as experimental.

Trends in authorship in the Journal of Cutaneous Pathology, 1981-2020.

BACKGROUND: The increase in authors per scientific article in many different medical and scientific disciplines has raised concerns over ethical authorship. Trends in authorship in dermatopathology are unknown. METHODS: Cross-sectional study of a random sample of 200 articles from the Journal of Cutaneous Pathology (1981-2020). RESULTS: The number of authors per article increased by an estimated 96% between 1981 and 2020 (2.7-5.3), while the relative citation ratio decreased by an estimated 56% during the same period (1.19-0.52). Higher author counts were not associated with higher relative citation ratios (p = 0.2349) or analytic study designs (p = 0.2987). Higher relative citation ratios were associated with analytic study designs (p = 0.0374). CONCLUSIONS: There has been significant growth in authorship credit at the journal without a corresponding increase in research impact or study rigor. Remedial measures to stem authorship inflation and promote more impactful studies may be necessary.

Publications on the diagnostic accuracy of dermatopathology tests: A cross-sectional quality analysis.

BACKGROUND: Ancillary diagnostic tests are frequent in dermatopathology practice. Publications on their accuracy influence their utilization. The transparency and completeness of these publications are unknown. METHODS: We performed a cross-sectional study on diagnostic accuracy studies in dermatopathology published between 2020 and 2022 for compliance with Standards for Reporting of Diagnostic Accuracy Studies (STARD) and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). RESULTS: 14.67 ± 3.02 STARD items were reported in 62 publications (range, 9.5-23.5 out of the recommended total of 30). More items were reported in high-impact factor journals (16.01 vs. 13.32, p = 0.0002) and journals that endorsed STARD in their author instructions (17.22 vs. 14.11, p = 0.0039). Less than 10% of publications reported quantifiable hypotheses, sample size calculations, flow diagrams, or study registrations. The risk of bias by our analysis of QUADAS-2 criteria was high or uncertain for index test interpretation (36/62, 58%) and patient selection (44/62, 71%). CONCLUSIONS: Publications on dermatopathology tests are exploratory studies without prespecified hypotheses or study designs. They do not meet the criteria for transparent reporting. We suggest that medical journal leadership should consider updating their instructions with more explicit guidance on recommended manuscript elements.

PRAME immunohistochemistry for melanoma diagnosis: A STARD-compliant diagnostic accuracy study.

BACKGROUND: Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen that is frequently expressed in cutaneous melanoma and can be evaluated by immunohistochemistry. Earlier studies on PRAME utilized case-control study designs that may misestimate diagnostic accuracy and lack generalizability. METHODS: Using retrospective cohort selection, a cross-sectional study of diagnostic accuracy of PRAME was conducted according to standards for reporting diagnostic accuracy studies requirements. RESULTS: Mean PRAME positive fraction was higher in 42 malignant melanocytic lesions than 101 benign melanocytic lesions (0.71 ± 0.30 vs. 0.13 ± 0.20, p < 0.01). Receiver operating characteristic curve showed the test was effective (area under the curve = 0.90). Global PRAME 4+ scores (>75%) were associated with sensitivity of 0.63, specificity of 0.97, accuracy of 0.87, and excellent interrater concordance (Kappa = 0.83). Lower cutoffs for PRAME of 2+ (>25%) and 3+ (>50%) produced higher joint sensitivity/specificity (Youden index) than PRAME 4+, but lower accuracy. CONCLUSION: PRAME as it is used in clinical practice is an effective test for melanoma. PRAME is best used as an ordinal variable to calculate the posttest probability of melanoma. PRAME ≤25% (0/1+) favors nevus, PRAME 26%-75% (2/3+) is noncontributory, and PRAME >75% (4+) favors melanoma.

Gamma-Delta and CD20 Mycosis Fungoides: Two Cases Uncovered by Broad-Spectrum Immunostaining.

ABSTRACT: Mycosis fungoides (MF) expresses T-cell markers and the alpha-beta T-cell receptor (TCR) complex. Here, we describe a case of MF with dual expression of TCR delta and TCR beta and a case of MF expressing the B-cell marker CD20. Both anomalies were detected after we instituted a broad-spectrum immunostaining panel for cutaneous T-cell lymphomas. These findings suggest anomalous immunophenotypes may be more common in MF than previously appreciated. Histopathologists should be aware of unexpected malleability in the immunophenotype of MF to avoid confusion with other subtypes of cutaneous lymphoma. Further research into the prevalence and significance of CD20 and TCR-delta expression in MF is encouraged.

Giant Congenital Blue Nevus Presenting as Cutis Verticis Gyrata: A Case Report and Review of the Literature.

OBJECTIVES: Cerebriform intradermal nevus and giant congenital blue nevi are rarely reported melanocytic nevi with clinical and histopathologic similarities. Both are known to produce cutis verticis gyrata. We report a significantly large occipital scalp congenital blue nevus with secondary cutis verticis gyrata. The aim of this report is to increase clinical awareness of this entity, highlight histopathologic and mutational features of cerebriform intradermal nevi and giant congenital blue nevi, and stress the importance of clinicopathologic correlation for diagnosis. METHODS: Case report and review of the literature. RESULTS: A 20-year-old Asian male presented with a long-standing, large (20 cm × 30 cm), exophytic tumor at the occipital scalp and posterior neck. The skin overlying the lesion was arranged in thick folds resembling the surface of the brain, devoid of hair follicles, and discolored by salt-and-pepper pattern hyperpigmentation. After correlating the clinical and histopathologic findings, we diagnosed giant congenital blue nevus with secondary cutis verticis gyrata. Staged surgical excision was performed with subsequent treatment for hypertrophic scarring and occipital alopecia. CONCLUSIONS: Cerebriform intradermal nevus and giant congenital blue nevus have overlapping histologic and clinical features. Head and neck surgeons should be aware that nomenclature of these tumors is subjective and often imprecise. Diagnosis requires correlation of clinical findings, patient history, and histopathology. Surgical excision is advised due to rare malignant transformation potential.

Trichilemmal Cysts With Divergent Ductal Differentiation: A Series of 4 Cases.

ABSTRACT: Trichilemmal cysts are common clonal tumors with a predilection for the scalp. They are composed of an outer epithelial wall resembling the outer root sheath in the isthmus of the hair follicle and a central core of compact keratin. Sweat duct differentiation is exceptional with only one convincing case reported to date. Here, we sought to characterize the clinicopathological characteristics of sweat duct differentiation in trichilemmal cysts. We reviewed all cases of trichilemmal cyst diagnosed at our institution between 2008 and 2019. Ductal structures were found in 4 of 411 cases (0.97%). Subjects included 2 male and 2 female patients with a median age of 37.5 years (range 34-55). The ducts were lined by attenuated epithelial cells and immunoreactive for polyclonal carcinoembryonic antigen and cytokeratin 7. Ductal differentiation involved a median of 7.5% (range 1%-50%) of the cyst wall. All 4 cases were from the scalp and treated with local excision. No recurrence was identified with a median follow-up period of 1.5 years (range 1-12 years). In summary, sweat duct differentiation in trichilemmal cysts is rare but likely under recognized. Conceptually, we suggest it represents a type of divergent cellular differentiation within a clonal neoplasm rather than a retention cyst or hybrid cyst.

Compliance With Standards for STARD 2015 Reporting Recommendations in Pathology.

OBJECTIVES: Lack of experimental reproducibility has led to growing interest in guidelines to enhance completeness and transparency in research reporting. This retrospective survey sought to determine compliance with Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 statement in the recent pathology scientific literature. METHODS: Two raters independently scored 171 pathology diagnostic accuracy studies for compliance with 34 STARD items and subcomponents. Overall adherence was calculated as a proportion after excluding nonapplicable items. RESULTS: After excluding nonapplicable items, there was 50% overall adherence to STARD reporting recommendations. In total, 15.44 ±â€…3.59 items were reported per article (range, 4-28 out of maximum possible of 34). There was substantial heterogeneity in individual item reporting, with greater than 75% reporting in eight of 34 items and less than 25% reporting in 11 of 34 items. Less than 10% of articles reported hypotheses, subgroup analyses for confounding, sample size calculations, subject flow diagrams, study registrations, and links to full study protocols. Significantly more items were reported in articles from journals that endorsed STARD (16.14 vs 14.84, P = .0175). CONCLUSIONS: These findings demonstrate incomplete reporting of essential items in pathology diagnostic accuracy studies. More vigorous enforcement of reporting checklists might improve adherence to minimum reporting standards.

A smartphone application to improve the precision of biopsy site identification: A proof-of-concept study.

Dermatologists rely on skin biopsies to diagnose cutaneous tumors and rashes. Skin biopsy sites should be accurately identified with conventional anatomical site descriptors in the pathology request form. Reliance upon free-text entries to describe these biopsy sites is prone to user error and can cause medical misadventures such as wrong-site follow-up surgery. We sought to determine whether a smartphone application (RightSite) could improve the precision of biopsy site labeling. We conducted a prospective proof-of-concept study of 100 smartphone-assisted skin biopsy site identifiers with matched comparison to 100 historical controls. Student's t-test was used to identify significant differences in the precision of anatomic descriptors before and after adoption of the application. We found a 69% improvement in precision of anatomic site labeling with the RightSite smartphone application (P < 0.0001). These data show smartphone-assisted biopsy site labeling improves the precision of anatomic site descriptors. Integrating graphical user interfaces into the electronic health records system could improve health care by standardizing anatomic site nomenclature and site-specific descriptors.

Plasmacytoid dendritic cells in keratoacanthoma and squamous cell carcinoma: A blinded study of CD123 as a diagnostic marker.

BACKGROUND: Histopathologic distinction between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is challenging. We surmised that a discriminatory immunostain would be clinically meaningful. Previous investigators have found CD123-positive plasmacytoid dendritic cells (PDCs) are more prominent in KA than SCC. We sought to determine if CD123 immunostaining might have value as a diagnostic test for distinguishing KA from SCC. METHODS: We used blinded, semi-automated image analysis to compare CD123 expression in 66 KAs and 63 SCCs in a tissue microarray. RESULTS: PDCs were present in both KA and SCC. Mean PDC frequency was higher in KA than SCC (14.2 vs 11.2 mean cells/0.0945 square mm) but the difference was not statistically significant (P = 0.1240). There was no significant difference in mean PDC cluster frequency, mean intratumoral PDC frequency, or the percentage of PDCs as proportion of the total mononuclear inflammatory cell infiltrate between KA and SCC. CONCLUSION: CD123 immunostaining is not a clinically useful test for distinguishing KA from SCC.

Measuring Scholastic Production by Dermatopathologists Using the H-Index: A Cross-Sectional Study.

Academic advancement in dermatopathology requires evidence of scientific production. The H-index is a useful bibliometric for measuring scientific production because it weights both volume and impact of an individual's scholastic production. The H-index distribution among academic dermatopathologists is unknown. In this cross-sectional study of 299 dermatopathologists with academic appointments in North America, H-index, publication counts, and citation counts were retrieved from Thomas Reuters Web of Science. Analytic statistics were performed to identify best predictors of academic rank and cutoff points between academic ranks. The H-index was a superior predictor of overall academic rank than publication or citation counts. The median H-index for assistant, associate, and full professors was 4, 6, and 11, respectively. H-index cutoff scores of 8 and 10 favored associate and full professor rank, respectively. These data provide benchmarks for dermatopathologists to gauge their scientific productivity against that of their peers. Although advancement decisions will depend on a careful examination of the scope and impact of a candidate's work, assistant professors of dermatopathology with H-index scores of >7 and associate professors of dermatopathology with H-index scores of >9 may wish to consider application for promotion.