Characterizing Granuloma Annulare in 73 Pediatric Patients.

Background: Granuloma annulare (GA) is a common, benign, idiopathic inflammatory dermatosis. Aside from case reports and small studies, there are limited data about the characteristics of GA in children. Objective: This study aimed to better characterize the epidemiologic and clinical features, triggering factors, disease associations, and outcomes of GA in the pediatric population. Methods: We conducted a retrospective study of 73 pediatric patients diagnosed with GA at the University of Rochester Medical Center over a 7-year period. Results: The most common subtype was localized GA (71.2%, n = 52), followed by subcutaneous (also known as "deep GA"; 16.4%, n = 12) and generalized (12.3%, n = 9) subtypes. Over 90% of patients had idiopathic GA, with the remaining patients reporting viral infection or trauma as triggers. Half of the patients studied had comorbid conditions, most frequently atopic dermatitis (17.8%, n = 13), obesity (9.59%, n = 7), asthma (6.85%, n = 5), and allergic rhinitis (6.85%, n = 5). The median duration of the disease was 11.00 months (interquartile range (IQR) 15.75 months); generalized GA had the shortest duration (median 10.00 months, IQR 15.50 months), while subcutaneous GA had the longest duration (median 12.00 months and IQR 29.00 months). Although recurrence rates for subcutaneous and generalized GA were high at 45.5% and 33.3%, respectively, most patients achieved clearance or improvement with treatment. Conclusion: Most cases of GA in our study were idiopathic, with no clear differences between GA subtypes and associated comorbidities. Topical steroids were the most prescribed treatment with mixed efficacy.

A case of severe nivolumab-induced lichen planus pemphigoides in a child with metastatic spitzoid melanoma.

Dermatologic reactions are among the most common adverse events of antiprogrammed cell death-1 (anti-PD-1) monoclonal antibodies agents and include maculopapular rash, psoriasiform rash, lichenoid eruptions, autoimmune bullous disorders, and vitiligo. Here, we present a case of a 12-year-old African American male with metastatic spitzoid melanoma treated with nivolumab who developed a mild lichenoid eruption that progressed to a severe case of lichen planus pemphigoides (LPP). Management was complex given the patient's age and history and included hospitalization for intravenous steroids, an intensive topical steroid regimen, methotrexate, and discontinuation of nivolumab. This case illustrates a rare but dramatic progression from a mild LP-like eruption to severe bullous lichenoid eruption, most consistent with LPP, as well as the diagnostic and treatment challenges in the setting of a pediatric patient on nivolumab.

Painful Purulent Nodules Caused by Mycobacterium at Site of Lipodissolve Injections.

ABSTRACT: "Lipodissolve" (LD) is a non-FDA-approved solution of phosphatidylcholine in deoxycholate that was developed around 2004. A study of its safety reported minor and uncommon side effects including pain, tender nodules, pigmentary alterations, and ulceration at the site of injection. We present a 53-year-old woman who received LD injections bilaterally to her proximal arms. One week later, she developed painful nodules at each injection site. She was treated with a 10-day course of trimethoprim/sulfamethoxazole without improvement. An incisional biopsy was performed and showed deep dermal suppurative inflammation with numerous neutrophils and granulomas. Stains for bacteria, fungus, and acid-fast organisms were negative. Cultures for acid-fast bacilli grew Mycobacterium abscessus, sensitive to amikacin and clarithromycin. The patient was subsequently treated with intravenous amikacin, azithromycin, and bedaquiline with symptom resolution. Investigation revealed 3 similar infections linked to LD injections originating from the same physician's office. The most common organism implicated in injection infections is Staphylococcus aureus. Infections at injection sites caused by atypical mycobacteria have been reported to occur after tattooing, other types of injections, and implants. Of atypical mycobacteria, M. abscessus accounts for the greatest number of postinjection or iatrogenic infections. Common antitubercular drugs are not effective for treating atypical mycobacteria, making species identification and sensitivity testing imperative for treatment. This case highlights an unusual infection caused by cosmetic injections of LD, previously reported to be associated with minimal side effects, and the importance of examination for acid-fast bacilli and follow-up with culture, even in the absence of organisms identified on stained sections.

Characterization of the CpG Island Hypermethylated Phenotype Subclass in Primary Melanomas.

Cutaneous melanoma can be lethal even if detected at an early stage. Epigenetic profiling may facilitate the identification of aggressive primary melanomas with unfavorable outcomes. We performed clustering of whole-genome methylation data to identify subclasses that were then assessed for survival, clinical features, methylation patterns, and biological pathways. Among 89 cutaneous primary invasive melanomas, we identified three methylation subclasses exhibiting low methylation, intermediate methylation, or hypermethylation of CpG islands, known as the CpG island methylator phenotype (CIMP). CIMP melanomas occurred as early as tumor stage 1b and, compared with low-methylation melanomas, were associated with age at diagnosis ≥65 years, lentigo maligna melanoma histologic subtype, presence of ulceration, higher American Joint Committee on Cancer stage and tumor stage, and lower tumor-infiltrating lymphocyte grade (all P < 0.05). Patients with CIMP melanomas had worse melanoma-specific survival (hazard ratio = 11.84; confidence interval = 4.65‒30.20) than those with low-methylation melanomas, adjusted for age, sex, American Joint Committee on Cancer stage, and tumor-infiltrating lymphocyte grade. Genes hypermethylated in CIMP compared with those in low-methylation melanomas included PTEN, VDR, PD-L1, TET2, and gene sets related to development/differentiation, the extracellular matrix, and immunity. CIMP melanomas exhibited hypermethylation of genes important in melanoma progression and tumor immunity, and although present in some early melanomas, CIMP was associated with worse survival independent of known prognostic factors.

A Young Boy With Hemophagocytic Lymphohistiocytosis Presenting With Vaccine-Related Granulomatous Dermatitis: A Case Report and Literature Review.

ABSTRACT: Cutaneous eruptions associated with hemophagocytic lymphohistiocytosis (HLH) have been reported in 6%-63% of patients. Clinical findings of these skin lesions vary widely and include maculopapular rashes, ulcers, and violaceous nodules. Corresponding histologic findings are also variable and are considered nonspecific. We report the case of a 4-year-old boy who initially developed a widespread popular-pustular rash 2 weeks after his 12-month measles, mumps, and rubella vaccinations. These resolved with scarring then recurred following his 24-month vaccinations. Multiple skin biopsies were negative for infectious organisms and showed a granulomatous infiltrate with perforation and necrobiosis. The differential diagnosis included perforating granuloma annulare, infection, or rheumatoid nodules. At the age of 4, he developed fever, hepatosplenomegaly, pancytopenia and other laboratory abnormalities, requiring hospitalization. A number of studies were performed including biopsies of bone marrow and liver. Molecular testing revealed 2 mutations in UNC13D known to be associated with familial HLH. His prior cutaneous lesions were likely caused by immune dysregulation exacerbated by immunizations because of underlying familial HLH. This case illustrates the importance of recognizing an unusual cutaneous manifestation of a rare disease to arrive at an earlier diagnosis in a pediatric patient. Although cutaneous eruptions usually develop concurrently with other systemic symptoms of HLH, preceding unusual skin lesions may be the first indication of this rare disease.

Concordance of Squamous Cell Carcinoma Histologic Grading Among Dermatopathologists and Mohs Surgeons.

BACKGROUND: Current staging systems for cutaneous squamous cell carcinoma (cSCC) incorporate histologic grade. There are no universally agreed on criteria to define differentiation for cSCC. OBJECTIVE: To determine the interrater and intrarater reliability among dermatopathologists and Mohs surgeons in grading histological differentiation for cSCC. METHODS AND MATERIALS: One hundred thirty-one archived slides were selected. Three dermatopathologists and 3 Mohs surgeons graded the tumors in a blinded manner (Round 1). In an attempt to improve concordance, all 6 participants were then asked to regrade the tumors based on a devised quantitative grading scale (Round 2). RESULTS: For Round 1, overall κ was 0.56 corresponding to a weak agreement. κ for well, moderate, and poorly differentiated tumors was 0.68, 0.39, and 0.59, respectively, corresponding to moderate, minimal, and weak concordance. For Round 2 of the study, overall κ was 0.60, with κ = 0.75, 0.46, and 0.61 for well, moderate, and poorly differentiated tumors, respectively. Overall intrarater reliability was 0.70 (κ = 0.70, 0.77, 0.68, 0.71, 0.56, and 0.75), corresponding to a moderate concordance. CONCLUSION: Overall concordance for cSCC histologic grading is weak to moderate among the experimental group. Substantial differences in concordance exist among histological degrees of differentiation, with lowest agreement in moderately differentiated tumors.

Picomets: Assessing single and few cell metastases in melanoma sentinel lymph node biopsies.

BACKGROUND: Lymph node involvement is a significant prognostic factor for melanoma. Both number of positive nodes and disease burden within a lymph node affects survival. However, the significance of few tumor cells within a single node and subsequent optimal management remains without consensus. We investigated the implications of minimal nodal disease on clinical outcomes. METHODS: We reviewed 752 patients who underwent lymph node sampling at time of primary melanoma resection at our institution over 15 years. We deemed patients who had 1 node with 1 to 4 atypical cells staining positive for either Melan-A or Sox-10 as having "picomets." We examined the initial clinicopathological features, subsequent management, and outcomes. RESULTS: Thirty-three patients (4%) met criteria for having picomets. The most common number of positively staining atypical cells was 1 (n = 13). Nodal staging at initial pathology review varied, and overall stage ranged from IA to IIIC. Four patients underwent further therapy, none of whom had recurrent disease. Of the 29 patients undergoing observation/surveillance only, 5 had disease recurrence (17%). CONCLUSION: Although patients with picomets had better outcomes than historical stage matched cohorts, a small subset had recurrent disease. Staging patients with picomets as "N0" may not reflect the true negative prognostic significance of picomets. A larger population of patients meeting picomets criteria is needed to draw further conclusions.

A Rare Case of Porocarcinoma and Trichoblastoma Arising in a Nevus Sebaceus of Jadassohn.

Nevus sebaceus of Jadassohn, or "organoid nevus," is a common, benign hamartoma of the skin consisting of epithelial and adnexal components. Its natural history and association with neoplastic growths is well documented. The majority of concomitant neoplasms are benign-trichoblastoma and syringocystadenoma papilliferum are most frequently discovered-but malignant tumors have been described. We present the case of a 58-year-old male with a congenital nevus sebaceus of Jadassohn on his left parietal scalp that had been enlarging, changing color, and bleeding over the prior year. Clinical exam and histology disclosed the presence of a trichoblastoma and porocarcinoma arising within the nevus sebaceus. Porocarcinoma is a rare, intermediately aggressive, malignant eccrine gland tumor that is frequently metastasized at presentation. Otolaryngology performed wide local resection with sentinel lymph node biopsy. This case highlights the diversity of tumors associated with nevus sebaceus of Jadassohn, potential for malignant expansion, and necessity for close monitoring and maintaining a low threshold for biopsy in evolving lesions.

Pyoderma gangrenosum associated with levamisole-adulterated cocaine in a c-ANCA positive patient.

Pyoderma gangrenosum (PG) is an inflammatory, ulcerative condition that is characterized by painful ulcers that commonly present on the lower extremities. Up to half of PG cases are associated with underlying systemic disease, including inflammatory bowel disease, various autoimmune conditions, and malignancy. Another well-known association is the manifestation of PG with recreational cocaine use, especially cocaine contaminated with the adulterant agent levamisole. Once utilized for its immunomodulatory capabilities, levamisole was withdrawn from the market in 2002. It has since been repurposed to potentiate the amphetamine-like effects and duration of cocaine and has reduced preparation cost. We present a 52-year-old woman with chronic maxillary sinusitis and cocaine use disorder presenting with a two-week history of painful ulcers on bilateral lower extremities, each with a purulent base and undermined, violaceous borders. Urine toxicology was positive for cocaine and serologic studies were positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and lupus anticoagulant. Underlying conditions, especially that of granulomatosis with polyangiitis, were considered and ultimately ruled out. The patient's lesions exhibited a marked response with a short course of oral corticosteroids, typical of PG associated with levamisole. This case highlights the crucial role that drug abstinence plays in the prevention of recurrence.

Degos Disease (Malignant Atrophic Papulosis) With Granular IgM on Direct Immunofluorescence.

Degos disease is a rare vasculopathy characterized by skin papules with central porcelain white atrophy and a surrounding telangiectatic rim. Etiology of this condition is unknown. There are benign and systemic forms of the disease, and the latter may lead to fatality. Connective tissue diseases with Degos-like features have been described, and many authors speculate that Degos is not a specific entity but, rather, a distinctive pattern of disease that is the common endpoint of a variety of vascular insults. We describe the case of a 45-year-old female who presented with numerous red papules with sclerotic white centers and minimal systemic symptoms. Laboratory workup was notable for a negative autoimmune panel and hypercoagulation panel. Histopathology revealed epidermal atrophy, abundant dermal mucin, a perivascular lymphocytic infiltrate, interface inflammation, papillary dermal hemorrhage, and several small thrombi in the mid-to-superficial vessels. Direct immunofluorescence (DIF) showed strong granular immunoglobulin M (IgM) deposition at the dermal-epidermal junction. Based on the pathognomonic skin findings, persistently negative antinuclear antibody, lack of systemic signs of systemic lupus erythematosus, and characteristic hematoxylin and eosin findings, a diagnosis of Degos disease was rendered. In the fewer than 200 published cases of Degos disease, DIF findings have been conflicting and often negative. The DIF pattern of granular IgM is classically found in lupus erythematosus. To our knowledge, this is the first case of Degos disease reporting deposition of strong granular IgM on DIF. This case serves as additional evidence of the considerable clinical and histologic overlap between Degos disease and lupus erythematosus.

Autologous Stem Cell Rescue recipient with neutrophil tissue delivery detected prior to blood engraftment: a case report.

Neutrophil recovery after autologous hematopoietic cell transplantation (auto-HCT) is affirmed with achievement of an Absolute Neutrophil Count (ANC) of ≥500/uL. There is growing evidence that neutrophils may be observed despite undetectable peripheral ANC counts following autologous hematopoietic cell transplant and are preferentially delivered to sites of inflammation. We report an interesting case that confirms neutrophil tissue delivery to the skin two days prior to evidence of blood engraftment after an auto-HCT.

Putting the Pieces Into Place: A Case of Systemic Polyarteritis Nodosa.

This is a case of systemic polyarteritis nodosa (PAN) in a 43-year-old male who initially presented to the hospital with a puzzling collection of signs and symptoms, including fever, arthralgias, myalgias, abdominal pain, dark urine, and rash. His illness evolved over the course of four weeks, and skin biopsy helped to clinch the diagnosis and lead to appropriate treatment. It is important to consider systemic PAN in the work-up of patients with subtle skin findings in the context of seemingly unrelated constitutional, abdominal, genitourinary, cardiac, and neurological signs and symptoms.

Primary Syphilis Presenting As a Chronic Lip Ulcer.

Syphilis is usually a sexually transmitted infection caused by the spirochete Treponema pallidum. Primary syphilis classically presents as a painless, ulcerated lesion on the genitals. However, the primary lesion is not restricted to this site and appears wherever the spirochete enters through the skin. The symptomatology and appearance of the primary lesion can also vary.  We present a case of a 59-year-old man with a primary syphilitic chancre of the lower lip. The patient was referred to the dermatology clinic by their primary care provider after the ulceration failed to heal with antibiotic therapy. A biopsy of the lesion was taken at this time; the diagnosis of syphilis was then made by histologic examination and immunohistochemical staining. Subsequent serologic tests were also positive. Upon prompting, the patient did report a history of sexually transmitted disease but not of syphilis specifically. The patient was treated with penicillin, and there was clinical improvement of the lesion at the follow-up visit.

Identification of a Robust Methylation Classifier for Cutaneous Melanoma Diagnosis.

Early diagnosis improves melanoma survival, yet the histopathological diagnosis of cutaneous primary melanoma can be challenging, even for expert dermatopathologists. Analysis of epigenetic alterations, such as DNA methylation, that occur in melanoma can aid in its early diagnosis. Using a genome-wide methylation screening, we assessed CpG methylation in a diverse set of 89 primary invasive melanomas, 73 nevi, and 41 melanocytic proliferations of uncertain malignant potential, classified based on interobserver review by dermatopathologists. Melanomas and nevi were split into training and validation sets. Predictive modeling in the training set using ElasticNet identified a 40-CpG classifier distinguishing 60 melanomas from 48 nevi. High diagnostic accuracy (area under the receiver operator characteristic curve = 0.996, sensitivity = 96.6%, and specificity = 100.0%) was independently confirmed in the validation set (29 melanomas, 25 nevi) and other published sample sets. The 40-CpG melanoma classifier included homeobox transcription factors and genes with roles in stem cell pluripotency or the nervous system. Application of the 40-CpG melanoma classifier to the diagnostically uncertain samples assigned melanoma or nevus status, potentially offering a diagnostic tool to assist dermatopathologists. In summary, the robust, accurate 40-CpG melanoma classifier offers a promising assay for improving primary melanoma diagnosis.

Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis.

Telomerase reverse transcriptase (TERT) promoter mutations are commonly found in malignant melanomas but rare in melanocytic nevi. To assess its potential diagnostic utility for the distinction of melanoma from nevus, we determined the TERT promoter mutation status of 86 primary melanomas, 72 melanocytic nevi, and 40 diagnostically problematic melanocytic proliferations. Of the 86 melanomas, 67 (77.9%) were TERT-positive, defined as harboring a hotspot TERT promoter mutation at positions -124C>T, -124_125CC>TT, -138_139CC>TT, or -146C>T. Of the 72 nevi, only 1 (1.4%) was TERT-positive. Of the 40 diagnostically uncertain melanocytic proliferations, 2 (5.0%) were TERT-positive. TERT positivity as a test for melanoma versus nevus had an accuracy of 87.3% [95% confidence interval (CI), 81.1-92.1], a sensitivity of 77.9% (95% CI, 68.9-85.4), a specificity of 98.6% (95% CI, 95.8-100), a positive predictive value of 98.5% (95% CI, 95.6-100), and a negative predictive value of 78.9% (95% CI, 72.6-85.4). Our results indicate that hotspot TERT promoter mutation status may be a useful ancillary parameter for the diagnosis of melanoma. In particular, the high specificity of these mutations for melanoma indicates the presence of a TERT promoter mutation in a melanocytic neoplasm associated with diagnostic controversy, or uncertainty should increase concern for a melanoma.