The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs).

Interobserver agreement in the histopathological classification of desmoplastic melanomas.

Desmoplastic melanoma is a subtype of melanoma characterised by amelanotic fusiform melanocytes dispersed in a collagenous stroma. Cell-poor and fibrous stroma-rich 'pure' variants have been distinguished from 'mixed' variants with areas of higher cell density and/or less desmoplastic stroma. This distinction is relevant because patients whose tumours display a pure phenotype have a lower risk for regional lymph node metastasis and distant recurrence.

Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement.

Importance: A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.

Objective: To revise the MPATH-Dx version 1.

Next-generation sequencing improves agreement and accuracy in the diagnosis of Spitz and spitzoid melanocytic lesions.

Background: Spitzoid melanocytic neoplasms can be challenging to diagnose on histopathology alone. Next-generation sequencing (NGS) offers promise as a valuable aid in the diagnosis. Recently, one study reported increased inter-rater agreement in the diagnosis of spitzoid melanocytic neoplasms among 20 expert melanoma pathologists after incorporating NGS data.

Next-Generation Sequencing Reveals a New Class of Melanocytic Neoplasms With Hybrid Genomic Features of PEM Including Protein Kinase R 1 Alpha Gene Inactivation and Spitz Tumor-Defining Protein Kinase Fusions.

Background: Pigmented epithelioid melanocytoma (PEM) is a subtype of melanocytic tumor with frequent involvement of the sentinel lymph node but rare distant metastasis. Rendering a diagnosis and prognosis based on histology can be challenging. Recent genomic studies identified 2 molecular variants of PEM.

Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms.

Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features.

Blue Nevi and Related Tumors.

The major entities related to blue nevus are common blue nevus, cellular blue nevus, atypical blue nevus, and malignant blue nevus. These lesions share presence of dermal pigmented dendritic melanocytes derived from embryonal precursors to melanocytes, Schwann cells, and glial cells migrating to the skin from the ventral neural crest. Genetically, blue nevi harbor mutations in G-protein-coupled receptor subunits GNAQ and GNA11.

Genomic Analysis of Pigmented Epithelioid Melanocytomas Reveals Recurrent Alterations in PRKAR1A, and PRKCA Genes.

Pigmented epithelioid melanocytoma (PEM) is a rare cutaneous melanocytic tumor first described as epithelioid blue nevus in patients with the Carney Complex (CC). PEM was among the first established examples of an intermediate class of melanocytic tumors, including atypical Spitz tumors, with frequent metastasis to lymph nodes but only rare extranodal spread. Sporadic and CC-associated PEM are essentially histologically indistinguishable.

Successful multimodality treatment of recalcitrant necrobiotic xanthogranuloma using electron beam radiation and intravenous immunoglobulin.

Necrobiotic xanthogranuloma (NXG) is a rare dermatosis with a poorly understood pathophysiology. Studies comparing treatments for such lesions are limited. We present the case of a patient with a 30-year history of NXG refractory to several individual therapeutic interventions [excision, intravenous immunoglobulin (IVIg), systemic chemotherapies and immunosuppressants, cryotherapy and laser therapy], who ultimately responded to a combination of treatment with electron beam radiation therapy (EBRT) in conjunction with IVIg.

Metastatic atypical fibroxanthoma: a series of 11 cases including with minimal and no subcutaneous involvement.

Atypical fibroxanthoma (AFX) is a dermal mesenchymal neoplasm arising in sun-damaged skin, primarily of the head and neck region of older men. Conservative excision cures most. However, varying degrees of subcutaneous involvement can lead to a more aggressive course and rare metastases.

Soluble adenylyl cyclase antibody (R21) as a diagnostic adjunct in the evaluation of lentigo maligna margins during slow Mohs surgery.

Margin-controlled staged excision (slow Mohs) has emerged as a preferred method for the treatment of lentigo maligna (LM). The interpretation of margins for LM is one of the most challenging tasks faced by a dermatopathologist. R21 is a mouse monoclonal antibody against soluble adenylyl cyclase (sAC), overexpressed in the nuclei of LM but not in native melanocytes.

Expression of soluble adenylyl cyclase in lentigo maligna: use of immunohistochemistry with anti-soluble adenylyl cyclase antibody (R21) in diagnosis of lentigo maligna and assessment of margins.

Context: Soluble adenylyl cyclase (sAC) is an enzyme that generates cyclic adenosine monophosphate, a signaling molecule involved in regulating melanocyte functions. R21, a mouse monoclonal antibody against sAC, shows a striking pan-nuclear staining in lentigo maligna, indicating possible utility for diagnosis and margin assessment.

Objective: To evaluate R21 in the diagnosis and evaluation of margins in lentigo maligna.

Correlation between histologic assessment and fluorescence in situ hybridization using MelanoSITE in evaluation of histologically ambiguous melanocytic lesions.

Context: The 4-probe, multicolor, fluorescence in situ hybridization (FISH) panel targeting chromosomes 6 and 11 has shown promising sensitivity and specificity in distinguishing between benign nevi and malignant melanoma. Only a few studies have assessed the potential utility of FISH in classification of histologically ambiguous melanocytic lesions. In the United States, this assay is exclusively licensed to NeoGenomics Laboratories (Irvine, California), which provides the technical component and has developed an innovative service (MelanoSITE) allowing pathologists to interpret FISH results using a dedicated Web portal.

Syringotropic melanoma: a variant of melanoma with prominent involvement of eccrine apparatus and risk of deep dermal invasion.

We report 7 cases which can be regarded as a syringotropic melanoma-a unique presentation of melanoma defined as melanoma spreading within the eccrine apparatus into the reticular dermis and/or subcutaneous tissue deeper than any (if present) associated invasive melanoma. Six patients were females, and 1 was a male. Their ages ranged from 32 to 85 years old (average 63).

Update on fluorescence in situ hybridization in melanoma: state of the art.

Context: Recent advances in understanding the molecular basis of melanoma have resulted in development of fluorescence in situ hybridization (FISH) protocols designed to detect genetic abnormalities discriminating melanoma from nevi. The most extensively studied is a 4-probe multicolor FISH probe panel targeting chromosomes 6 and 11. Validation studies showed promising sensitivity and specificity for distinguishing benign nevi and malignant melanoma by FISH.

Sebaceous gland loss and inflammation in scarring alopecia: a potential role in pathogenesis.

Background: Primary scarring alopecia (SA) comprises a group of disorders with poorly defined origins. Improving diagnostic and therapeutic capabilities requires a better understanding of their pathogenesis.

Objectives: We sought to assess the frequency of sebaceous gland loss in SA and to identify the role of sebaceous gland and sebaceous gland duct inflammation in the pathogenesis of SA.

Blue nevi and related tumors.

Blue nevi and related lesions are characterized by the proliferation of dermal dendritic melanocytes. Although they share certain common clinical and histologic features, they encompass a spectrum of lesions ranging from benign melanocytic hamartomas and common blue nevi to borderline malignant pigmented epithelioid melanocytoma and aggressive malignant blue nevi. This article succinctly describes the common dermal dendritic proliferations and updates readers on newly classified entities and variants.

A comprehensive analysis of a web-based dermatopathology second opinion consultation practice.

Context: Sharing cases and seeking second opinion consultations is an important part of everyday pathology practice. Internet-based communications and upcoming digital slide technologies have the potential to decrease barriers and open access to the best expertise. We recently developed a dedicated Web-based process for communication with outside practices seeking second opinion consultations.

Blue nevi and variants: an update.

Context: Blue nevi are a subset of melanocytic proliferations containing cells reminiscent of the embryonal neural crest-derived dendritic melanocytic precursors. They are common specimens in a general pathology practice, but some of their rare variants may pose diagnostic difficulty. Recent molecular studies provide new insights into genetics of blue nevi.