Agminated presentation of fusion-driven melanocytic neoplasms.

BACKGROUND: The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms. METHODS: We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed. RESULTS: Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis. CONCLUSIONS: We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation.

Poroid adnexal skin tumors with YAP1 fusions exhibit similar histopathologic features: A series of six YAP1-rearranged adnexal skin tumors.

BACKGROUND: Adnexal skin tumors are diagnostically challenging with few known molecular signatures. Recently, however, YAP1-MAML2 and YAP1-NUTM1 fusions were identified in poroid adnexal skin tumors. METHODS: Herein, we subjected eight poroid adnexal skin tumors (three poromas and five porocarcinomas) to fusion gene analysis by whole transcriptome sequencing and next-generation DNA sequencing analysis. RESULTS: YAP1 fusions were identified in six cases. YAP1-NUTM1 fusions were identified in two poromas and three porocarcinomas. A single case of porocarcinoma harbored a YAP1-MAML2 fusion. Two cases were negative for gene fusion. All cases that harbored YAP1-NUTM1 fusions showed nuclear protein in testis (NUT) expression by immunohistochemistry, with NUT being negative in the YAP1-MAML2-positive case. In this case series, we provide a detailed histopathologic description of six YAP1-fused poroid skin tumors, which we show harbor reproducible histopathologic features, to include broad, bulbous tumor tongues with admixtures of basaloid, poroid cells punctuated by squamatized cuticles and ductules, with uniform tumor nuclei featuring frequent grooves and pseudonuclear inclusions. CONCLUSIONS: Awareness of the characteristic histopathologic features of YAP1-fused poroid adnexal skin tumor is a step toward a more reproducible classification of adnexal skin tumors as well as a step toward targeted therapy for metastatic and/or unresectable examples of this poroid group of neoplasms.

Negative predictive value of biopsy margins of dysplastic nevi: A single-institution retrospective review.

BACKGROUND: Biopsies of dysplastic nevi processed by bread-loafing allow for limited margin assessment; however, reported biopsy margins often influence management. OBJECTIVE: To evaluate the negative predictive value of biopsy margins of dysplastic nevi. METHODS: A retrospective search of a single academic institution's pathology database was conducted to identify all biopsy specimens of dysplastic nevi between January 1, 2015, and December 31, 2017. Biopsy specimen margin assessments were compared with excision pathology reports to calculate negative predictive value and to assess the frequency of residual nevus on excision after positive biopsy margins. RESULTS: A total of 1245 dysplastic nevi from 934 patients were identified. Clear biopsy margins had a negative predictive value for the absence of residual nevus on excision of 87.3% for dysplastic nevi of moderate atypia or greater. Residual nevus was identified on excision in 29.41% of cases of dysplastic nevi of moderate atypia or greater when initial biopsy margins were positive. LIMITATIONS: This was a retrospective, single-institution study. The calculations likely overestimate the true negative predictive value of biopsy margins because of processing of excision specimens by bread-loafing. CONCLUSIONS: This study provides additional evidence that reported biopsy margins are not representative of true margin status.

Chronic granulomatous dermatitis induced by talimogene laherparepvec therapy of melanoma metastases.

Talimogene laherparepvec (TVEC) is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing granulocyte macrophage-colony stimulating factor (GM-CSF) and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB-IV M1a melanoma. However, clinical response assessment can be problematic due to immune-related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients. Over 5 months, TVEC injections were administrated in a median of 20 tumors per patient for 9 median doses prior to biopsy of persistent, indurated nodules. Granulomatous dermatitis with melanophages and melanin pigment incontinence was observed in all samples without evidence of melanoma cells in 4 patients. The fifth patient was rendered melanoma-free by resection of the 1 nodule out of 4 with persistent tumor. Repetitive administration of TVEC or other oncolytic viral immunotherapies mimicking unresolved infection can produce granulomatous inflammation confounding assessment of the degree of tumor response and need for additional TVEC therapy. Tumor biopsies are encouraged after 4 to 6 months of TVEC administration to differentiate melanoma from granulomatous inflammation. Patients with confirmed granulomatous dermatitis replace continued with remained in remission after treatment discontinuation. Inflammatory nodules typically regress spontaneously.

Injection Site Necrosis and Ulceration Following Vaccination in an Adult Patient.

Local adverse reactions to vaccination are typically mild and often quickly resolve. Vaccine adjuvants such as aluminum salts in combination with improper vaccination technique may result in severe local adverse reactions. As far as we know, there is only one prior case of frankly necrotic rapidly progressing vaccine site necrosis, which occurred in a pediatric patient.1 To our knowledge, this is the first adult case of vaccine site necrosis to be reported. The presumed etiology has been aluminum salt adjuvants and improper vaccination technique. Here we present an adult case of a severe local reaction to a vaccine resulting in necrosis of the epidermis and dermis with central ulceration. Skin appendages were also involved, with necrosis of eccrine coils and hair follicles. This necrotic ulceration was likely due to robust inflammatory response to aluminum salt subcutaneous injection. Correct vaccine placement, needle size, and needle length may reduce adverse local skin reactions.

J Drugs Dermatol. 2018;17(3):364-367.

Pediatric ocular lichen planus and lichen planopilaris: One new case and a review of the literature.

When lichen planus involves the scalp, it is known as lichen planopilaris, and when it involves the eye, it is known as ocular lichen planus; both are rare. Early detection and targeted therapy are crucial in preventing hair loss and scarring conjunctivitis. Little is known regarding appropriate treatment for lichen planopilaris. The objective of this case study is to present a new case of pediatric ocular lichen planus and lichen planopilaris and to identify all reported cases of pediatric lichen planopilaris, highlighting disease involvement, treatment, and response to treatment.

Two Cases and a Review of Graft-Versus-Host Disease and the Role of Hepatitis C Treatment in Liver Transplant Patients.

Graft-versus-host disease (GvHD) is a rare but fatal complication after solid organ transplantation arising in 1% to 2% of cases. We report 2 cases of GvHD after orthotopic liver transplantation. Both patients had a history of hepatitis C virus (HCV) infection prior to transplantation. Both cases presented between 1 and 4 months after transplantation with rash, pancytopenia, and/or diarrhea. Our second case also developed oral and ocular manifestations after liver transplantation, which are more commonly described after stem cell transplantation. Diagnosis in both cases was made by clinical presentation in conjunction with histopathology and flow cytometry. Both patients were treated by increasing immunosuppression with tacrolimus and high-dose steroids. Response to treatment differed based on the degree of pancytopenia. Our case report is distinguished by several factors such as the context of GvHD presentation and the role of HCV treatment. Diagnosis of GvHD is difficult and often delayed due to nonspecific presentation that overlaps with other conditions. Furthermore, the relation between HCV treatment and potential initiation of GvHD in solid organ transplant patients is unclear.

Perforating disorder secondary to leflunomide and review of the literature of medications associated with perforating disorder.

The perforating dermatoses are a group of disorders characterized by transepidermal elimination of a material from the upper dermis. The most widely accepted classification consists of four primary perforating disorders that are defined by the type of material eliminated and the type of epidermal disruption. Pathogenesis of the perforating dermatoses is poorly understood, but some appear to have a genetic component. There are also acquired forms, which have been associated with underlying systemic diseases and the use of certain drugs. In this report, we describe a perforating disorder that occurred secondary to leflunomide therapy. To our knowledge, this is the first case in which this has been reported. We also review the recent literature on medications associated with perforating disorders.

Successful treatment with IVIg therapy of diabetes-associated scleredema severe progressive case and review of the literature.

Scleredema is a deposition disorder which presents as diffuse, symmetric, non-pitting skin induration from dermal deposits of glycosaminoglycans ("mucins"). It classically affects the upper back and posterior neck, often causing skin tightness and decreased range of motion. In most patients the clinical course is chronic and treatment options are limited. We report a case of a patient diagnosed with scleredema associated with longstanding insulin dependent diabetes who was treated successfully with IVIg. Additionally, we have reviewed the literature reporting other patients with scleredema treated with IVIg.

Follicular center helper T-cell (TFH) marker positive mycosis fungoides/Sezary syndrome.

We identified 11 patients with CD10(+) cutaneous T-cell lymphoma by flow cytometry. All cases were CD4(+) and CD8(-). Three patients had extensive lymphadenopathy, systemic symptoms and an aggressive clinical course consistent with angioimmunoblastic T-cell lymphoma or peripheral T-cell lymphoma. However, 8 of the 11 patients had a prolonged disease course with gross morphology, histology and tumor cell phenotype indistinguishable from mycosis fungoides or Sezary syndrome. Immunohistochemical studies confirmed CD10 expression in seven of the eight cases and revealed the lymphoma cells were Bcl-6(+), PD-1(+), and EBV(-). Two had significant expression of CXCL-13(+). The findings indicate that lymphoma cells from mycosis fungoides or Sezary syndrome may express follicular center helper T-cell markers CD10, Bcl-6, and PD-1 and occasionally CXCL-13. The expression of these markers in some cases of mycosis fungoides/Sezary syndrome suggests follicular center helper T-cell differentiation and may lead to confusion in distinguishing mycosis fungoides/Sezary syndrome from other follicular center helper T-cell marker positive T-cell lymphomas with cutaneous manifestations.

Neutrophilic dermatosis revisited: an initial presentation of lupus?

BACKGROUND: We report 7 patients with a distinct and unusual eruption consisting of a neutrophilic dermatosis in conjunction with lupus erythematosus (LE). The significance of these findings and their relevance to LE are discussed. OBJECTIVE: We aimed to evaluate the significance of eruptive neutrophilic dermatosis in conjunction with LE. METHODS: Seven original cases were collected during 10 years at a tertiary referral center, and were reviewed by a single board-certified dermatopathologist. All patient demographics were tabulated and analyzed. Eleven articles reporting 15 similar cases were obtained from a literature review. RESULTS: Of a total of 7 adult patients, 14% (1 of 7) had a history of LE, whereas 86% (6 of 7) exhibited synchronous initial presentation of neutrophilic dermatosis with LE. Of note, 100% (7 of 7) of the patients exhibited cutaneous lesions on sun-exposed sites. LIMITATIONS: Only 7 of 400,000 cases showed this phenomenon, giving rise to the idea this may be just by chance. CONCLUSIONS: Our data and literature review suggest the existence of a neutrophilic dermatosis distinct from conventional Sweet syndrome that may herald conventional signs and symptoms or represent an initial presentation of cutaneous LE. This neutrophilic dermatosis may share a similar pathogenic mechanism related to ultraviolet exposure.

Drug-induced Grover's disease: a case report and review of the literature.

BACKGROUND: Grover's disease (GD) is a relatively rare transient dermatosis that can be idiopathic or acquired. Acquired GD may occur secondary to internal triggers such as medications and malignancies and external factors such as friction. OBJECTIVE: The purpose of this report is to describe the clinical and histological presentation of drug-induced Grover's disease (DIGD) and discuss potential pathogenic mechanisms. METHODS: A systemic review of the literature was performed to identify medications implicated in DIGD. RESULTS: We identified 13 reports of patients with DIGD. Most patients presented with a papular or papulovesicular morphology involving the trunk and extremities. Pruritus was the most common symptom. The majority of the offending agents were cancer therapeutics. Discontinuation of the culprit medication was sufficient for rash clearance and symptom resolution in most cases. CONCLUSION: The overlap in morphology and associated symptoms in DIGD and GD makes the diagnosis of DIGD challenging and has potentially led to underdiagnosis. However, in cases of more extensive involvement and treatment recalcitrance, a drug-induced eruption should be considered.