ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2022
Genomic evidence suggests that cutaneous neuroendocrine carcinomas can arise from squamous dysplastic precursors.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Merkel Cell Carcinoma With Divergent Differentiation-Or Something Else? A Triphasic Cutaneous Carcinoma With Lineage Plasticity.Journal of cutaneous pathology · 2026Review
- Vulvar small cell neuroendocrine carcinoma arising from differentiated vulvar intraepithelial neoplasia: evidence of a clonal relationship by mutation analysis.Virchows Archiv : an international journal of pathology · 2026Article
- RB1 inactivation in cutaneous carcinomas.Histopathology · 2026Review
- Primary cutaneous non neuroendocrine small cell carcinoma POU2F3 subtype: morphologic, immunohistochemical, transcriptomic and methylation analysis of two cases.Virchows Archiv : an international journal of pathology · 2026Article
- Diagnostic Utility and Clinicopathologic Associations of Histone H3 Lysine 27 Trimethylation (H3K27me3) Immunohistochemistry for Merkel Cell Carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- Merkel cell carcinoma of the parotid gland: a rare case report and literature review.International journal of surgery case reports · 2025Article
- Article
- The complex conundrum of Merkel cell carcinoma cellular ancestry.Cell death & disease · 2025Review
- Review
- Nicotinic Acetylcholine Receptor Expression in Merkel Cell Carcinoma Is Associated With Clinical and Histopathologic Parameters.Journal of cutaneous pathology · 2025Article
- Squamoid Eccrine Ductal Carcinoma Displays Ultraviolet Mutations and Intermediate Gene Expression Relative to Squamous Cell Carcinoma, Microcystic Adnexal Carcinoma, and Porocarcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Article
- Development of a Multiplex Immunofluorescence Assay for Tumor Microenvironment Studies of Human and Murine Merkel Cell Carcinoma.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- Review
- Merkel cell carcinoma: updates in tumor biology, emerging therapies, and preclinical models.Frontiers in oncology · 2024Review
- Merkel Cell Polyomavirus: Infection, Genome, Transcripts and Its Role in Development of Merkel Cell Carcinoma.Cancers · 2023Review
- RB1-deficient squamous cell carcinoma: the proposed source of combined Merkel cell carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study.Medicina (Kaunas, Lithuania) · 2022Article
- Review
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10 authors at 1 institution in 1 country.
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Abstract
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma without a known dysplastic precursor. In some cases, MCC is associated with SCCIS in the overlying epidermis; however, the MCC and SCCIS populations display strikingly different morphologies, and thus far a relationship between these components has not been demonstrated. To better understand the relationship between these distinct tumor cell populations, we evaluated 7 pairs of MCC-SCCIS for overlapping genomic alterations by cancer profiling panel. A subset was further characterized by transcriptional profiling and immunohistochemistry. In 6 of 7 MCC-SCCIS pairs there was highly significant mutational overlap including shared TP53 and/or RB1 mutations. In some cases, oncogenic events previously implicated in MCC (MYCL gain, MDM4 gain, HRAS mutation) were detected in both components. Although FBXW7 mutations were enriched in MCC, no gene mutation was unique to the MCC component across all cases. Transcriptome analysis identified 2736 differentially expressed genes between MCC and SCCIS. Genes upregulated in the MCC component included Polycomb repressive complex targets; downregulated transcripts included epidermal markers, and immune genes such as HLA-A. Immunohistochemical studies revealed increased expression of SOX2 in the MCC component, with diminished H3K27Me3, Rb, and HLA-A expression. In summary, MCC-SCCIS pairs demonstrate clonal relatedness. The shift to neuroendocrine phenotype is associated with loss of Rb protein expression, decrease in global H3K27Me3, and increased expression of Merkel cell genes such as SOX2. Our findings suggest an epidermal origin of MCC in this setting, and to our knowledge provide the first molecular evidence that intraepithelial squamous dysplasia may represent a direct precursor for small cell carcinoma.
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