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Biology
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Cutaneous Neoplasms with Uncertain Biological Potential
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Cutaneous Neoplasms with Uncertain Biological Potential

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (30 October 2021) | Viewed by 24031

Special Issue Editors

Dr. George Jour

E-Mail Website
Guest Editor
New York University Grossman School of Medicine, New York, NY 10016, USA
Interests: bone and soft tissue tumors; molecular testing in hematological and solid cutaneous neoplasms
Dr. Randie H. Kim

E-Mail Website
Guest Editor
The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, NY 10016, USA
Interests: melanoma; artificial intelligence; deep learning; infectious dermatology; big data
Dr. Rami Al-Rohil

E-Mail Website
Guest Editor
The Duke University School of Medicine, Durham, NC 27710, USA
Interests: melanocytic neoplasms; molecular testing in dermatopathology; soft tissue tumors of the skin

Special Issue Information

The last decade witnessed an increasing number of novel challenging entities in the field of cutaneous neoplasms. While some of have been classified into benign or malignant categories, others remain poorly classified and characterized and thus are referred to as "cutaneous neoplasms of uncertain biological potential". These cases, while not representing the most common in daily dermatopathologist, represent a diagnostic and prognostic conundrum for both the dermatopathologists and treating clinicians. The advent of cutting edge molecular technologies propelled accurate classification of many of these entities and shedding the light on genomic and epigenetic events of pinnacle importance for treatment and prognosis. In this issue, we aim to shed the light on these Borderline entities and discuss the challenges they present at a diagnostic and prognostic level alluding to the different novel ancillary techniques available to better classify them. The integration of different ancillary methods along with the conventional hematoxylin eosin is instrumental to our ability to accurately classify knowledge of the links among the genome, the epigenome, the environment, and phenotypes. Such an overview will both stimulate the emergence of expert opinion on what strategies to adopt in the future to promote the development of innovative diagnostic, prognostic, and therapeutic modalities for these grey-zone entities.

Dr. George Jour
Dr. Randie H. Kim
Dr. Rami Al-Rohil
Guest Editors

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Keywords

  • Intermediate potential
  • cutaneous neoplasm
  • melanoma
  • lymphoma
  • soft tissue tumors

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Published Papers (5 papers)

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Research

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15 pages, 2192 KiB  
Communication
NRAS Mutations May Be Involved in the Pathogenesis of Cutaneous Rosai Dorfman Disease: A Pilot Study
by Kuan-Jou Wu, Shu-Hao Li, Jia-Bin Liao, Chien-Chun Chiou, Chieh-Shan Wu and Chien-Chin Chen
Biology 2021, 10(5), 396; https://doi.org/10.3390/biology10050396 - 2 May 2021
Cited by 11 | Viewed by 3734
Abstract
Background: Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in histiocytic proliferative disorders, it [...] Read more.
Background: Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in histiocytic proliferative disorders, it provides a novel perspective on the pathomechanism of cutaneous RDD. We aim to investigate the genomic mutations in MAPK/ERK pathway in cutaneous RDD. Methods: We retrospectively recruited all cases of cutaneous RDD from two hospitals in Taiwan from January 2010 to March 2020 with the clinicopathologic features, immunohistochemistry, and treatment. Mutations of neuroblastoma RAS viral oncogene homolog (NRAS), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in MAPK/ERK pathway were investigated by the highly sensitive polymerase chain reaction with Sanger sequencing. Results: Seven patients with cutaneous RDD were recruited with nine biopsy specimens. The median age was 46 years (range: 17–62 years). Four of seven patients (57.1%) received tumor excision, while the other three chose oral and/or topical or intralesional steroids. NRAS mutation was detected in 4 of 7 cases (4/7; 51.7%), and NRAS A146T was the most common mutant point (n = 4/7), followed by NRAS G13S (n = 2/7). There is no KRAS or BRAF mutation detected. Conclusions: We report the NRAS mutation is common in cutaneous RDD, and NRAS A146T was the most frequent mutation in this cohort. Mutations in the NRAS gene can activate the RAS/MAPK signaling and have been reported to be associated with various cancers. It indicates that NRAS mutation in MAPK/ERK pathway may involve the pathogenesis of cutaneous RDD. Full article
(This article belongs to the Special Issue Cutaneous Neoplasms with Uncertain Biological Potential)
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Review

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13 pages, 6833 KiB  
Review
Conventional and Atypical Deep Penetrating Nevus, Deep Penetrating Nevus-like Melanoma, and Related Variants
by Pavandeep Gill and Phyu P. Aung
Biology 2022, 11(3), 460; https://doi.org/10.3390/biology11030460 - 17 Mar 2022
Cited by 4 | Viewed by 8694
Abstract
Deep penetrating nevus (DPN) is an uncommon acquired melanocytic lesion with a distinct histopathological appearance that typically behaves in an indolent manner. The lesion is characterized by a symmetrical proliferation of epithelioid to spindled melanocytes associated with abundant melanophages and wedge-shaped extension to [...] Read more.
Deep penetrating nevus (DPN) is an uncommon acquired melanocytic lesion with a distinct histopathological appearance that typically behaves in an indolent manner. The lesion is characterized by a symmetrical proliferation of epithelioid to spindled melanocytes associated with abundant melanophages and wedge-shaped extension to the deep reticular dermis and subcutis. Pronounced cytologic atypia and mitotic figures are usually absent, which helps distinguish DPN from melanoma with a deep penetrating growth pattern. Recently, the concept of atypical DPN has been proposed for lesions that demonstrate borderline histomorphologic features and may be associated with lymph node deposits but lack the copy number aberrations typical of melanoma by either fluorescence in situ hybridization or comparative genomic hybridization. While most of these lesions have a favorable clinical course, rare lesions may progress to melanoma. In this review, we summarize the current literature on atypical DPNs with uncertain behavior/metastatic potential and outline the characteristics that distinguish these lesions from conventional DPN and melanoma with DPN-like features. Full article
(This article belongs to the Special Issue Cutaneous Neoplasms with Uncertain Biological Potential)
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12 pages, 38823 KiB  
Review
Pigmented Epithelioid Melanocytomas and Their Mimics; Focus on Their Novel Molecular Findings
by Erol C. Bayraktar and George Jour
Biology 2021, 10(12), 1290; https://doi.org/10.3390/biology10121290 - 8 Dec 2021
Cited by 4 | Viewed by 4206
Abstract
Pigmented epithelioid melanocytoma (PEM) is a unique tumor with significantly pigmented appearance and indolent behavior; however, it can demonstrate cytological atypia and metastasize to local lymph nodes. Clinical and histomorphological overlap between PEM and its lower or higher-grade mimics can make it difficult [...] Read more.
Pigmented epithelioid melanocytoma (PEM) is a unique tumor with significantly pigmented appearance and indolent behavior; however, it can demonstrate cytological atypia and metastasize to local lymph nodes. Clinical and histomorphological overlap between PEM and its lower or higher-grade mimics can make it difficult to distinguish in certain cases. Genomic, transcriptomic and epigenetic data indicate that PEMs are molecularly distinct entities from other melanocytic neoplasms and melanomas. In addition, methylation studies are emerging as a tool that can be useful in difficult cases. In this review, we focus on the clinical, histopathologic and recent insights in the molecular features of pigmented epithelioid melanocytic melanocytomas and their mimics. We also present a challenging case that was resolved using methylation analysis providing a proof of concept for using epigenetic studies for similar challenging cases. Full article
(This article belongs to the Special Issue Cutaneous Neoplasms with Uncertain Biological Potential)
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10 pages, 7874 KiB  
Review
Cutaneous Melanocytic Tumor with CRTC1::TRIM11 Fusion: Review of the Literature of a Potentially Novel Entity
by Ourania Parra and Konstantinos Linos
Biology 2021, 10(12), 1286; https://doi.org/10.3390/biology10121286 - 7 Dec 2021
Cited by 4 | Viewed by 3687
Abstract
“Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion” (CMTCT) is a recently described entity belonging to the family of superficial tumors displaying melanocytic differentiation. Thirteen cases have been reported so far, on the head and neck, extremities, and trunk of adults of all ages (12 [...] Read more.
“Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion” (CMTCT) is a recently described entity belonging to the family of superficial tumors displaying melanocytic differentiation. Thirteen cases have been reported so far, on the head and neck, extremities, and trunk of adults of all ages (12 cases) and one in an 11-year-old child. Histopathologically, it is a nodular or multilobulated tumor composed of spindle and epithelioid cells arranged in nests, fascicles, or bundles that are surrounded by thin collagenous septa. By immunohistochemistry, the tumor shows variable immunoreactivity for S100-protein, SOX10, and MITF, as well as specific melanocytic markers such as MelanA and HMB-45. The neoplasm’s biologic behavior remains uncertain since the reported cases are limited and the follow-up is short (median 12 months). However, local recurrence and synchronous distant metastasis after 13 years of initial resection has been described in one case. Herein, we present a comprehensive literature review of CMTCT hoping to raise awareness among the dermatopathologists of this potentially novel entity. Full article
(This article belongs to the Special Issue Cutaneous Neoplasms with Uncertain Biological Potential)
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18 pages, 15869 KiB  
Review
Cutaneous Vascular Neoplasms of Uncertain Biological Behavior
by Kasey J. McCollum and Rami N. Al-Rohil
Biology 2021, 10(11), 1160; https://doi.org/10.3390/biology10111160 - 9 Nov 2021
Cited by 5 | Viewed by 2321
Abstract
Neoplasms of uncertain biological behavior present physicians with a genuine conundrum in practice. Cutaneous vascular neoplasms within this category are exceedingly rare, possessing significant gaps and uncertainty in many facets of clinical practice. Firstly, lesions were selected for review based on their categorization [...] Read more.
Neoplasms of uncertain biological behavior present physicians with a genuine conundrum in practice. Cutaneous vascular neoplasms within this category are exceedingly rare, possessing significant gaps and uncertainty in many facets of clinical practice. Firstly, lesions were selected for review based on their categorization as indeterminate behavior, indicating the potential for local recurrence and rarely metastasize. After identification of the target lesions, a comprehensive review of the literature using national databases produced several landmark studies and case series regarding these neoplasms. Limiting the review to only cutaneous limited tumors narrowed the pool of studies; however, quite a large sum of papers remained. Examination of each paper yielded beneficial results on diagnosing, effective treatments, follow-up findings, and prognosis for each indeterminate lesion discussed. Overall, the literature search combined the molecular, histologic, immunohistochemical, surgical strategies to develop an up-to-date and comprehensive framework to guide physicians when encountering such lesions. The tumors reviewed include: kaposiform hemangioendothelioma, endovascular papillary angioendothelioma, pseudomyogenic hemangioendothelioma, retiform hemangioendothelioma, epithelioid hemangioendothelioma, and composite hemangioendothelioma. Full article
(This article belongs to the Special Issue Cutaneous Neoplasms with Uncertain Biological Potential)
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