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.

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.

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.

Skin wrinkling of the upper arms: a case of mid-dermal elastolysis.

Mid-dermal elastolysis is a rare acquired elastic tissue disorder with about 100 cases reported in the literature. It is characterized by localized patches of finely wrinkled skin on the shoulder and upper extremities and a band-like loss of elastic tissue in the mid-dermal layer on biopsy. Some patients may have symptoms of discomfort, erythema, and/or pruritis. Mid-dermal elastolysis is predominantly seen in young to middle-aged Caucasian females and extensive skin involvement may lead to cosmetic concerns. Furthermore, it is important to rule out other disorders of elastic fiber that are associated with systemic involvement. We present a case of MDE, discuss the differential diagnosis, and describe characteristic clinical features and histology findings of each condition.

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.

Histopathologic features of melanoma in difficult-to-diagnose lesions: A case-control study.

BACKGROUND: Dermatopathology is considered the gold standard for melanoma diagnosis, but a subset of cases is difficult to diagnose by histopathology. OBJECTIVE: The goals of this study were to measure the accuracy of histopathologic features in difficult-to-diagnose melanocytic tumors and the interobserver agreement of those features. METHODS: This is a case-control study of histopathologic features of melanoma in 100 difficult-to-diagnose melanocytic neoplasms (40 melanomas and 60 nevi). Slides were blindly evaluated by 5 dermatopathologists. Frequencies, predictive values, and interobserver agreement were calculated. Univariate and multivariate logistic regression analyses were performed to identify the most influential features in arriving at a diagnosis of melanoma. RESULTS: Asymmetry, single-cell melanocytosis, solar elastosis, pagetoid melanocytosis, and broad surface diameter were most influential in arriving at a diagnosis of melanoma. Asymmetry and single-cell melanocytosis were most predictive of melanoma. Fleiss kappa was <0.6 for interobserver agreement in 9/10 histopathologic features of melanoma. LIMITATIONS: This study is limited by the small sample size, selection bias, and binary classification of melanocytic lesions. CONCLUSION: Our results indicate histopathologic features of melanoma in difficult-to-diagnose lesions vary in accuracy and reproducibility.

Crystalline folliculitis revealed by non-aqueous staining technique.

Necrotizing infundibular crystalline folliculitis (NICF) is a rare superficial folliculitis characterized by expansive deposits of birefringent crystallized lipid. We report a case of NICF in a transplant patient presenting with folliculocentric acneiform papules across the lateral face and neck. Biopsy demonstrated intrafollicular crystalline deposits within an intact epidermis. Diagnostic crystals were identified using a non-aqueous histologic technique involving thick unstained sections. To our knowledge, this is the first report of NICF in a transplant patient. Our case suggests NICF is a follicular disorder and highlights a technique that may prevent loss of birefringent crystals and assist in facilitating accurate diagnosis.

Cutaneous Adenomyoepithelioma: Report of a Case and Review of the Literature.

Adenomyoepithelioma (AME) is a biphasic neoplasm of epithelial and myoepithelial cells. It is most commonly found in the breast, although rare cases have been reported from the lung, salivary glands, and skin. There are 5 well-documented cases of cutaneous AME in the literature. We report a new case of cutaneous AME. Our case was commingled with apocrine hidrocystoma. This is the first report of cutaneous AME in a male patient and the first to describe SOX10 immunostaining in cutaneous AME. We review the literature on cutaneous AME and note the greater than chance colocalization with other adnexal tumors. We speculate that AME may represent localized overgrowth of myoepithelial cells within a pre-existent sweat gland tumor. Histopathologists should be aware of the potential of SOX10-positive myoepithelial neoplasms to mimic nodular melanocytic proliferations.

Loss of CD30 Expression in Anaplastic Large Cell Lymphoma Following Brentuximab Therapy.

Monoclonal antibody therapy is a new innovation in cancer therapy. Binding of monoclonal antibodies to tumor cells facilitates their destruction by the immune system. Tumor cells with mutated target antigens may escape detection by monoclonal antibodies and exhibit a selective growth advantage. This phenomenon was first recognized in CD20-negative B-cell lymphomas in patients previously treated with the anti-CD20 monoclonal antibody rituximab. We report a cutaneous recurrence of systemic ALCL with an anomalous CD30-negative immunophenotype. The patient had been previously treated with the anti-CD30 monoclonal antibody brentuximab. To our knowledge, we present the first reported case of a cutaneous recurrence of systemic ALCL with an anomalous CD30-negative immunophenotype following chronic brentuximab therapy.

J Drugs Dermatol. 2016;15(7):894-895.

Economic Costs Avoided by Diagnosing Melanoma Six Months Earlier Justify >100 Benign Biopsies.

New melanoma drugs bring enormous benefits but do so at significant costs. Because melanoma grows deeper and deadlier over time, deeper lesions are costlier due to increased sentinel lymph node biopsy, chemotherapy, and disease-associated income loss. Prior studies have justified pigmented lesion biopsies on a "value per life" basis; by contrast we sought to assess how many biopsies are justified per melanoma found on a purely economic basis. We modeled how melanomas in the United States would behave if diagnosis were delayed by 6 months, eg, not biopsied, only observed until the next surveillance visit. Economic loss from delayed biopsy is the obverse of economic benefit of performing biopsy earlier. Growth rates were based on Liu et al. The results of this study can be applied to all patients presenting to dermatologists with pigmented skin lesions suspicious for melanoma. In-situ melanomas were excluded because no studies to date have modeled growth rates analogous to those for invasive melanoma. We assume conservatively that all melanomas not biopsied initially will be biopsied and treated 6 months later. Major modeled costs are (1) increased sentinel lymph node biopsy, (2) increased chemotherapy for metastatic lesions using increased 5-yr death as metastasis marker, and (3) income loss per melanoma death at $413,370 as previously published. Costs avoided by diagnosing melanoma earlier justify 170 biopsies per melanoma found. Efforts to penalize "unnecessary" biopsies may be economically counterproductive.

J Drugs Dermatol. 2016;15(5):527-532.

A chronic, bleeding, and painful nodule on the chest.

An 81-year-old man presented to the dermatology clinic with a painful lesion on his chest. The nodule would occasionally bleed and leak serous fluid for 10 years. Physical examination revealed an unspecified nodule with two superimposed nodules. A deep shave biopsy of the lesion was obtained and expressed a solid-cystic dermal neoplasm that was comprised of an admixture of cell types. Through the presenting clinical and histological features seen, a final diagnosis of nodular hidradenoma was made.

BAM! Utilizing the frequency of Benign, Atypical and Malignant diagnoses for quality improvement in the histopathologic diagnosis of melanocytic neoplasms.

BACKGROUND: Healthcare quality measures are metrics that quantify medical outcomes. There is a need for performance indicators in the diagnosis of melanocytic neoplasms. We sought to determine whether the atypical to malignant diagnosis ratio (AMR) and benign to malignant diagnosis ratio (BMR) could identify differences between practitioners within a group as well as individual diagnostic drift. METHODS: Diagnoses of melanocytic neoplasms from 2013 and 2014 by two dermatopathologists were prospectively subclassified as benign, atypical or malignant and reported on a monthly basis to the pathologists. Case diagnoses of melanocytic neoplasms from 2012 and 2009 were retrospectively subclassified as benign, atypical or malignant for comparison. RESULTS: A total of 33,169 cases were used in this study. Interpathologist AMR and BMR were significantly different. One pathologist demonstrated a significant increase in AMR over time. CONCLUSION: AMR and BMR metrics are potential performance indicators that can measure pathologist uncertainty, identify diagnostic drift and provide a surrogate measure of the relative risk level of laboratory patient populations. If applied to multiple laboratories, AMR and BMR metrics could help inform physicians' choice of dermatopathology laboratory and provide a method for comparative analysis between laboratories.

Pleomorphic spindle cell dermal neoplasm with dot-like keratin reactivity: keratin-positive AFX or carcinoma?

Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm of pleomorphic myofibroblast-like cells. Diagnosis requires exclusion of other undifferentiated spindle and pleomorphic cell neoplasms by immunohistochemistry. We report two patients with p63-non-reactive spindle cell neoplasms which resembled AFX but demonstrated anomalous dot-like immunolabeling with antibodies to high molecular weight keratin and keratin 5. One case recurred locally, suggesting such lesions may behave aggressively. Whether these lesions represent keratin-positive dermal sarcomas or poorly differentiated carcinomas is debatable. Regardless of exact classification, our experience suggests such cases should be managed as high-risk non-melanoma skin cancers.

Safe and efficacious use of intralesional steroids for the treatment of focally resistant mycosis fungoides.

Cutaneous T-cell lymphoma is a cancer of skin-homing T cells, of which mycosis fungoides (MF) is the most common variant. MF treatments range from topical steroids to systemic chemotherapy. Resistant cutaneous MF nodules can present a special challenge in that typical topical therapies may not penetrate thick lesions, and increasing systemic therapy brings added risk of side effects. We report successful use of intralesional steroids (ILS) for treatment-resistant MF, including tumor-stage plaques and nodules in 4 consecutive patients with focally resistant MF. ILS have been widely used to treat a broad range of cutaneous conditions such as alopecia areata and keloids. Side effects of ILS include hypopigmentation, atrophy, telangiectasias, lilac discoloration, acne, and striae. Rarely, and in circumstances involving unusually large doses, ILS may cause Cushing's syndrome, hypothalamus-pituitary-adrenal axis suppression, and reduced bone mineral density. The MF patients tolerated treatment well without any of the above side effects other than local hypopigmention in a single patient. These results point toward further exploration into ILS as a treatment for focally resistant MF.

Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis.

Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic cells. It usually manifests contemporaneously with the initial diagnosis of systemic leukemia, but may also precede or follow systemic leukemia. Most cases are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia cutis is very rare. We report a 59-year-old woman with a history of B-cell acute lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis. Lymphoglandular bodies were conspicuous on biopsy and may serve as a morphologic clue to lymphocytic differentiation while molecular and immunophenotypic studies are pending. The patient was successfully treated with local radiation therapy and oral ponatinib.