Digital dermatopathology implementation: Experience at a multisite academic institution.

BACKGROUND: Technology has revolutionized not only direct patient care but also diagnostic care processes. This study evaluates the transition from glass-slide microscopy to digital pathology (DP) at a multisite academic institution, using mixed methods to understand user perceptions of digitization and key productivity metrics of practice change. METHODS: Participants included dermatopathologists, pathology reporting specialists, and clinicians. Electronic surveys and individual or group interviews included questions related to technology comfort, trust in DP, and rationale for DP adoption. Case volumes and turnaround times were abstracted from the electronic health record from Qtr 4 2020 to Qtr 1 2023 (inclusive). Data were analyzed descriptively, while interviews were analyzed using methods of content analysis. RESULTS: Thirty-four staff completed surveys and 22 participated in an interview. Case volumes and diagnostic turnaround time did not differ across the institution during or after implementation timelines (p = 0.084; p = 0.133, respectively). 82.5% (28/34) of staff agreed that DP improved the sign-out experience, with accessibility, ergonomics, and annotation features described as key factors. Clinicians reported positive perspectives of DP impact on patient safety and interdisciplinary collaboration. CONCLUSIONS: Our study demonstrates that DP has a high acceptance rate, does not adversely impact productivity, and may improve patient safety and care collaboration.

Novel NONO::TFE3 fusion and ALK co-expression identified in a subset of cutaneous microcystic/reticular schwannoma.

Microcystic/reticular schwannoma (MRS) is a benign variant of schwannoma with a predilection for the gastrointestinal tract and skin. To date, genetic characterization of this tumor is limited. Prompted by the identification of TFE3::NONO fusion and ALK overexpression in an index case of MRS, a cohort of tumors was collected from institutional and consultation archives of two institutions. Next-generation sequencing (NGS), TFE3 fluorescence in situ hybridization (FISH), and TFE3 and ALK immunohistochemistry were performed, while clinicopathologic variables were documented. Eighteen MRS cases were identified (35 to 85 years) arising in the skin (n=8), gastrointestinal tract (n=5), adrenal gland (n=3), abdominal wall (n=1), and unknown site (n=1). Tumors showed a circumscribed to multinodular to plexiform low-power architecture with variable amounts of microcystic/reticular and solid schwannian components. Mitotic figures were scarce (0-1/10 HPFs), and atypia was absent. S100 protein and/or SOX10 immunoreactivity was noted in the microcystic/reticular and schwannian areas of all cases. NGS performed on two cutaneous tumors yielded NONO exon 12 fusion with TFE3 exon 4, and these lesions also showed HMB45 and ALK expression. Two additional cases showed ALK expression (1 weak), while a third was positive for TFE3, but these cases failed to show ALK or TFE3 rearrangement by FISH/NGS. There were no morphologic variables that correlated with the presence of NONO::TFE3. We identified a subset of microcystic/reticular schwannomas with NONO::TFE3 fusions and ALK co-expression, adding to the cohort of mesenchymal neoplasms that show ALK overexpression without rearrangement of the ALK gene.

Updates on the dermatopathology of pregnancy-associated skin conditions.

Pathologists provide valuable input in the dermatological care of pregnant patients in various contexts. This article provides dermatopathology updates on cutaneous changes associated with pregnancy, organized based on the following classification system: physiological skin changes in pregnancy, specific dermatoses of pregnancy, dermatoses modified in pregnancy, and skin neoplasms in pregnancy. Awareness of the impact of pregnancy on the skin by pathologists is important, as this is an opportunity to contribute to diagnostic precision in this patient population.

Utilization of skin biopsy for diagnosis in a case of Lafora disease.

Lafora disease is a rare inherited neurodegenerative disease with onset in adolescence. Patients present with progressive myoclonic seizures and cognitive decline. The disease is linked to mutations in either of the two genes encoding malin and laforin, and it is associated with the accumulation of polyglucosan inclusions (Lafora bodies [LBs]) in various tissues, such as brain, liver, muscle, and skin, with the skin being particularly accessible for biopsy. Histopathologic examination of affected tissue with demonstration of LBs, together with the presence of pathologic mutation in EPM2A or NHLRC1 genes, is sufficient for diagnosis of this neurologic disorder when clinically suspected. Here, we report the case of a 16-year-old female with progressive neurologic symptoms and homozygous mutation in the NHLRC1 gene encoding malin. The skin biopsy was instrumental in reaching the final diagnosis by showing LBs in sweat glands by histopathologic and electron microscopic examination.

Histopathology of autoimmune bullous dermatoses: what's new?

Autoimmune bullous dermatoses are characterized by the presence of tissue-bound and often circulating pathogenic autoantibodies targeting structural components of the skin and/or mucous membranes. The diagnostic workup for this heterogeneous group of disorders consists of a multi-step process, of which the light microscopic examination is a crucial component. This review is organized following a classification scheme that is based on two main histopathologic features, namely level of intraepithelial split and composition of the inflammatory infiltrate. Overall, we aim to place emphasis on the histopathologic clues that can assist pathologists in differential diagnosis and review the updates in the literature.

Impact of adding an IgG4 conjugate to routine direct immunofluorescence testing for subepithelial and intraepithelial autoimmune blistering disorders.

BACKGROUND: Certain autoimmune bullous dermatoses are mediated by autoantibodies of the IgG4 subclass. We determined the diagnostic impact of adding IgG4 to our conventional direct immunofluorescence (DIF) panel. METHODS: For all cases submitted to our referral laboratory for DIF over 1 month (n = 630), we performed IgG4 testing and collected consecutive biopsy specimens showing definite or indeterminate linear or cell-surface deposition of IgG, IgG4, and/or C3. On retrospective blinded review, we classified the pattern and whether the findings were definite, indeterminate, or negative. When present, substantial background staining was recorded. RESULTS: Seventy DIF specimens met the inclusion criteria. Of 22 (31.4%) specimens equivocal for linear or cell-surface deposition, 9 (40.9%) had definitive IgG4 findings, either linear (3 of 14 equivocal linear cases; 21.4%) or cell-surface (6 of 8 equivocal cell-surface cases; 75.0%). Background deposition was substantial in 14 cases (20.0%) for IgG but in none for C3 or IgG4. CONCLUSION: IgG4 allowed the classification of over 40% of DIF cases that were otherwise equivocal by IgG and C3. IgG4 staining showed lower levels of non-specific background staining than IgG or C3. IgG4 appears to contribute most value in cases with cell-surface deposition or with equivocal linear IgG deposition and negative C3 results.

A fatal case of malignant atrophic papulosis in a pediatric patient.

A 17-year-old Caucasian boy presented with progressive left-sided weakness, transient slurred speech, and skin lesions characterized by 3-5 mm, pink, asymptomatic papules with white atrophic centers on his central abdomen, back, and lower extremities. Skin biopsy confirmed the diagnosis of malignant atrophic papulosis, a rare vasculopathy that leads to the occlusion of small- and medium-sized arteries. He was treated with cyclophosphamide, eculizumab, treprostinil, pentoxifylline, heparin, and acetylsalicylic acid. Despite the aggressive immunosuppression, humanized monoclonal antibodies, and antiplatelet therapy, he died two months after presentation. We report this case to highlight diagnostic features, as well as to highlight the importance of early diagnosis and treatment.

An unusual pediatric case of atypical spitzoid neoplasm.

Spitzoid melanocytic lesions describe a spectrum of pediatric melanocytic proliferations ranging from benign Spitz nevi to malignant spitzoid melanomas typically arising within the first two decades of life. Atypical spitzoid neoplasm (ASN) is a poorly defined category within this spectrum that poses a unique diagnostic challenge due to histologic findings with insufficient atypical characteristics to make the diagnosis of melanoma. This report presents an exceptionally rare case of an ulcerative atypical spitzoid neoplasm mimicking an infantile hemangioma in a two-month-old girl treated with pulse dyed laser (PDL) and surgical excision. Our patient ultimately underwent five excisions over a 2-year period, with successful maintenance of function and dexterity of the affected fingers.

Cutaneous eccrine inflammation and necrosis: review of inflammatory disorders affecting the eccrine apparatus including new associations.

Despite being frequently overlooked during the examination of histopathological sections, eccrine sweat glands can offer clues for diagnosing various skin conditions. They provide important functions and can lead to several diseases when inflamed or injured. This review article provides information regarding eccrine physiology as well as well-established and novel entities that occur in association with eccrine gland pathology.

Primary Cutaneous Enteric Duplication Cyst: A Novel Entity.

ABSTRACT: Enteric duplication cysts (EDCs) are rare congenital malformations consisting of double-walled cystic or tubular structures lined by gastrointestinal type epithelium. EDCs share a common muscular wall and blood supply with the adjacent duplicated bowel with very rare exceptions. The majority of EDCs are intraabdominal with cases less commonly intrathoracic or thoracoabdominal. To the best of our knowledge, we present the first reported case of primary cutaneous EDC to occur outside the abdominal and thoracic cavities. A 17-year-old male without a significant medical or surgical history underwent excision of a cystic nodule on the left hip. On histopathology, a dermal to subcuticular cyst exhibited an epithelial lining with 2 distinct components including cuboidal to columnar mucinous cells (CK7+, CK20-, and CDX2-) and complex glandular colonic-type mucosa (CK7-, CK20+, and CDX2+). A thick muscular wall resembling muscularis mucosa and muscularis propria surrounded the cyst. Findings supported a primary cutaneous enteric duplication cyst of uncertain developmental etiology. The novel nature of this entity could represent a diagnostic challenge.

A rare case of childhood mucous membrane pemphigoid involving the oral and genital mucosa.

Mucous membrane pemphigoid (MMP) is a rare chronic immunobullous disease that involves the mucous membranes and may result in significant scarring and complications if diagnosis is delayed. MMP typically occurs in elderly patients, with very few cases reported in children. Here, we present a 12-year-old female patient with childhood-onset oral and genital MMP, clinically suspected to be lichen sclerosus, but eventually diagnosed as MMP after multiple supportive biopsies and confirmatory direct immunofluorescence. Although treatment was challenging, the combined use of systemic corticosteroids, dapsone, and mycophenolate mofetil was ultimately successful in achieving disease control.

Mixed Individual-Aggregate Data on All-Cause Mortality in Bullous Pemphigoid: A Meta-analysis.

Importance: The 1-year standardized mortality ratio (SMR) of bullous pemphigoid (BP) has been reported as 2.15 to 7.56 and lower in the US than in Europe. Objective: To estimate the worldwide 1-year SMR of BP. Data Sources: PubMed, Embase, Cochrane Library, Google Scholar, Lissa, and gray literature (eg, medRxiv) were screened for studies of BP published from inception to June 10, 2020, with review of reference lists. Study Selection: Retrospective and prospective studies reporting 1-year all-cause mortality rate in patients with BP and providing age statistics (eg, mean [SD]). Data Extraction and Synthesis: Two reviewers independently extracted the data. The 1-year SMR was computed in studies reporting 1-year mortality by combining information on age obtained from studies with aggregate data and individual data. Risk of representativity, misclassification, and attrition bias were assessed by a custom tool. Main Outcomes and Measures: The primary end point was the worldwide 1-year SMR. Secondary analysis included comparison of 1-year SMRs between continents in a meta-regression. Results: Three studies were performed in the US (n = 260), 1 in South America (n = 45), 16 in Asia (n = 1903), and 36 in Europe (n = 10 132) for a total of 56 unique studies and 12 340 unique patients included in the meta-analysis (mean [SD] age, 77.3 [12.7] years; 55.9% women). The mean (SD) patient age in the United States was 75.6 (13.7) years; in Asia, 73.8 (13.6) years; and in Europe, 78.1 (12.3) years. The worldwide 1-year SMR was estimated at 2.93 (95% CI, 2.59-3.28; I2 = 85.6%) for all 56 studies. The 1-year SMR in the US was 2.40 (95% CI, 0.89-3.90; I2 = 86.3%) for 3 studies; in Asia, 3.53 (95% CI, 2.85-4.20; I2 = 86.3%) for 16 studies; and in Europe, 2.77 (95% CI, 2.35-3.19; I2 = 86.3%) for 36 studies. After adjustment on the expected 1-year mortality rate, the European 1-year SMR did not differ significantly from the 1-year SMR in the United States (-0.48 vs Europe; 95% CI, -2.09 to 1.14; P = .56) and Asia (0.51 vs Europe; 95% CI, -0.56 to 1.58; P = .35). Risk of attrition bias was high (>10% censorship) in 16 studies (28.6%), low in 16 (28.6%), and unclear in 24 (42.9%). Only 4 studies (7.1%) had a sampling method guaranteeing the representativity of BP cases in a population. Conclusions and Relevance: Although heterogeneity was high and overall quality of follow-up was poor, this meta-analysis confirms the high mortality rate among patients with BP.

Heck's disease occurring after Epstein-Barr virus-associated smooth muscle tumors in an immunosuppressed child.

A 10-year-old Guatemalan girl with past medical history of Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) and combined immunodeficiency presented for evaluation of painful intraoral lesions. On examination, she was noted to have multiple, white to flesh-colored, soft, flat-topped papules, and plaques on the buccal and labial mucosa. Human papillomavirus type 13 was detected on PCR with PGMY primers of previously biopsied buccal tissue, confirming a diagnosis of Heck's disease (multifocal epithelial hyperplasia). We present an immunosuppressed, pediatric patient with two rare, virus-associated neoplastic disorders that have not been previously reported to occur in the same individual.