Academic Journal
Dermal Interstitial Glycogenosis and Stromal Senescence-Associated Marker Expression in Fibrofolliculomas: Implications for Pathogenesis and mTOR-Targeted Therapy.
| Title: | Dermal Interstitial Glycogenosis and Stromal Senescence-Associated Marker Expression in Fibrofolliculomas: Implications for Pathogenesis and mTOR-Targeted Therapy. |
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| Authors: | Nazarian RM; Department of Dermatology, Boston University School of Medicine, Boston, MA., Miyagi Y; Molecular Pathology & Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan ; and., Nakatani Y; Department of Pathology, Yokosuka Kyosai Hospital, Yokosuka, Japan . |
| Source: | The American Journal of dermatopathology [Am J Dermatopathol] 2026 Aug 01; Vol. 48 (8), pp. 617-621. Date of Electronic Publication: 2026 Jun 02. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 7911005 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1533-0311 (Electronic) Linking ISSN: 01931091 NLM ISO Abbreviation: Am J Dermatopathol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hagerstown, MD : Lippincott Williams & Wilkins Original Publication: New York, Masson Publishing USA. |
| MeSH Terms: | Skin Neoplasms*/pathology , Skin Neoplasms*/drug therapy , Skin Neoplasms*/metabolism , Stromal Cells*/pathology , Cellular Senescence*, TOR Serine-Threonine Kinases/metabolism ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; Biomarkers, Tumor/analysis ; MTOR Inhibitors/therapeutic use ; Humans ; Female ; Male ; Middle Aged ; Adult ; Aged |
| Abstract: | Abstract: Fibrofolliculomas, benign adnexal tumors often associated with Birt-Hogg-Dubé syndrome, exhibit characteristic perifollicular epithelial and stromal proliferation. Although their clinicopathologic features are well established, the molecular and metabolic drivers of stromal remodeling remain poorly understood, particularly in sporadic cases. We investigate the presence of dermal interstitial glycogenosis (DIG) and stromal senescence in fibrofolliculomas, exploring potential mechanistic parallels with pulmonary interstitial glycogenosis and mammalian target of rapamycin (mTOR)-driven cutaneous lesions. Archival skin biopsy specimens diagnosed as fibrofolliculoma between 2015 and 2025 (n = 13) were analyzed using Periodic acid-Schiff ± diastase staining and immunohistochemistry for p53, GLB1 (β-galactosidase), CD68, and phospho-S6 and compared with age-matched, sex-matched, and site-matched controls (n = 3). Clinical data, including imaging and genetic testing, were reviewed in cases of fibrofolliculoma. All fibrofolliculomas exhibited diastase-sensitive Periodic acid-Schiff-positive stromal granules consistent with glycogen accumulation. Stromal cells demonstrated immunoreactivity for GLB1, p53, and phospho-S6 in the absence of CD68 expression, indicating nonhistiocytic stromal senescence and mTOR activation. Birt-Hogg-Dubé syndrome was suspected in 4 of 10 patients but unconfirmed; DIG and senescence markers were present regardless of clinical context. Glycogenosis and cellular senescence markers were absent in controls. These findings identify DIG and stromal senescence as conserved features of fibrofolliculomas, suggesting a metabolic-senescence axis driven by mTOR signaling, and provide a rationale for mTOR-targeted therapies, including topical rapamycin, in the treatment of fibrofolliculomas. (Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.) |
| Competing Interests: | The authors declare no conflicts of interest. |
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| Contributed Indexing: | Keywords: Birt–Hogg–Dubé syndrome; cellular senescence; fibrofolliculoma; glycogenosis; mammalian target of rapamycin; phospho-S6 |
| Substance Nomenclature: | EC 2.7.11.1 (TOR Serine-Threonine Kinases) EC 2.7.1.1 (MTOR protein, human) 0 (Biomarkers, Tumor) 0 (MTOR Inhibitors) |
| Entry Date(s): | Date Created: 20260626 Date Completed: 20260722 Latest Revision: 20260722 |
| Update Code: | 20260723 |
| DOI: | 10.1097/DAD.0000000000003336 |
| PMID: | 42357990 |
| Database: | MEDLINE |
| ISSN: | 1533-0311 |
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| DOI: | 10.1097/DAD.0000000000003336 |