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Biology
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Molecular Insights into Malignant Cutaneous Adnexal Neoplasms
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Molecular Insights into Malignant Cutaneous Adnexal Neoplasms

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cancer Biology".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 2572

Editors

Dr. Albert Alhatem

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Geisel School of Medicine, Lebanon, NH 03756, USA
Interests: carcinogenesis; metabolic reprogramming; pathology; cutaneous adnexal neoplasms; molecular mechanisms; skin cancer
Dr. Rosalynn M. Nazarian

E-Mail Website
Guest Editor
Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
Interests: calciphylaxis; cutaneous fibrosis; inflammatory dermatoses; wound repair; adverse drug reactions

Special Issue Information

Dear Colleagues,

Malignant cutaneous adnexal neoplasms are rare but clinically significant tumors arising from hair follicles, sebaceous glands, apocrine glands, and eccrine glands. Despite their histologic diversity and aggressive potential, the molecular mechanisms underlying their pathogenesis remain poorly understood compared with more common skin cancers. Recent advances in genomic and transcriptomic profiling have begun to uncover recurrent genetic drivers, including TP53 mutations, PI3K/AKT/mTOR signaling alterations, mismatch repair deficiencies, and aberrations in Hedgehog and Wnt/β-catenin pathways. These findings not only provide insights into tumor initiation and progression but also highlight potential targets for precision medicine.

Given their rarity, malignant adnexal tumors serve as a valuable model to study lineage-specific tumorigenesis, differentiation pathways, and tumor microenvironmental influences. This Special Issue aims to gather contributions focused on the molecular and cellular biology of malignant adnexal neoplasms, including mechanistic studies, molecular classification efforts, and integrative analyses linking genetics, epigenetics, and tumor–stroma interactions. Reviews that synthesize current knowledge and identify future research priorities are also welcome. By bringing together cutting-edge research, this collection seeks to advance our understanding of malignant adnexal neoplasms and shed light on their unique role in skin tumor biology.

We look forward to receiving your contributions.

Dr. Albert Alhatem
Dr. Rosalynn M. Nazarian
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • malignant adnexal neoplasms
  • sebaceous carcinoma
  • hidradenocarcinoma
  • malignant spiradenoma
  • trichoblastic carcinoma
  • molecular mechanisms
  • signal transduction pathways
  • tumor microenvironment
  • epigenetics
  • genomic profiling

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Published Papers (1 paper)

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Review

16 pages, 1763 KB  
Review
When the Skin Tells a Bigger Story: Distinguishing Cutaneous Metastases from Primary Adnexal Carcinomas in Dermatopathology
by Elsayed Ibrahim and Phyu P. Aung
Biology 2026, 15(14), 1108; https://doi.org/10.3390/biology15141108 - 9 Jul 2026
Viewed by 219
Abstract
Cutaneous metastases are an uncommon but clinically significant manifestation of internal malignancy, occurring in approximately 0.7–10.4% of patients with cancer. In some cases, they represent the first clinical manifestation of an otherwise occult malignancy, making accurate diagnosis critical for timely patient management. Distinguishing [...] Read more.
Cutaneous metastases are an uncommon but clinically significant manifestation of internal malignancy, occurring in approximately 0.7–10.4% of patients with cancer. In some cases, they represent the first clinical manifestation of an otherwise occult malignancy, making accurate diagnosis critical for timely patient management. Distinguishing cutaneous metastases from primary cutaneous neoplasms, particularly malignant adnexal tumors, remains one of the most challenging problems in dermatopathology because of their substantial clinical, histopathologic, and immunophenotypic overlap. This review summarizes the epidemiology and biology of cutaneous metastasis and the clinical presentation of cutaneous metastases and emphasizes the central role of clinicopathologic correlation in diagnosis. Histologic features such as a purely dermal or subcutaneous location, intravascular tumor emboli, and a “bottom-heavy” growth pattern favor metastasis, whereas the presence of an in situ component or transition from a benign precursor lesion strongly supports a primary cutaneous neoplasm. We review the diagnostic utility of optimized immunohistochemical panels, highlighting the complementary roles of p63, cytokeratin 15, calretinin, and D2-40 (podoplanin) in establishing primary adnexal lineage, together with emerging markers including SOX10, androgen receptor, TRPS1, adipophilin, INSM1, SATB2, and BerEP4 for diagnostically challenging cases. We also discuss recent advances in molecular biology and comprehensive genomic profiling, including recurrent gene fusions (e.g., MYB::NFIB, CRTC1::MAML2, and YAP1 fusions) and characteristic mutational signatures that provide increasingly robust diagnostic evidence of tumor lineage. Finally, we provide a comprehensive, practical diagnostic algorithm for differentiating primary cutaneous adnexal carcinomas from cutaneous metastases of adenocarcinomas. By integrating traditional histopathologic techniques with modern immunohistochemical and molecular techniques, pathologists and clinicians can successfully navigate this complex differential diagnosis and thereby facilitate appropriate patient management and therapeutic intervention. Full article
(This article belongs to the Special Issue Molecular Insights into Malignant Cutaneous Adnexal Neoplasms)
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