{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T17:31:11Z","timestamp":1769707871479,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Basal cell carcinoma (BCC) is the most frequent malignancy in fair\u2010skinned populations. Although curable in most cases, approximately 4% of patients develop locally advanced or metastatic disease (advBCC) requiring systemic therapy. Hedgehog pathway inhibitors (HHIs; vismodegib\/sonidegib) constitute standard first\u2010line treatment, yet individual responses vary and no histopathological biomarker predicting therapeutic outcome exists. We conducted a retrospective, multicenter analysis of 70 BCCs encompassing clinically common and advanced stages. Routine hematoxylin and eosin and Alcian blue (AB; pH\u20092.5) staining was evaluated using a 17\u2010parameter, numerically encoded histopathology matrix spanning tumor morphology, stromal composition, and immune contexture. Data were mapped by unsupervised hierarchical clustering. Distinct AB staining patterns were observed: superficial and nodular BCCs typically exhibited an AB\u2010positive peritumoral border, whereas infiltrative and sclerosing subtypes displayed a diffuse AB\u2010positive desmoplastic stroma. The latter also correlated with advanced EADO clinical stages (correlation coefficients 0.46\u20130.48;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In a subset of 30 advBCCs obtained before or during HHI therapy, AB\u2010positive stroma was the only parameter independently associated with shorter progression\u2010free survival (multivariable hazard ratio\u2009=\u200923.8; 95% CI 4.02\u2013141.3;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Established clinical or histological features failed to associate with outcome. Our findings identify diffuse AB\u2010positive stroma as a readily detectable feature of histologically aggressive BCC and as a candidate biomarker associated with progression under HHI treatment. Because AB staining is routine, inexpensive, and easily standardized, this phenotype represents an immediately implementable readout for prospective validation and a potential link between extracellular\u2010matrix remodeling and therapy resistance in BCC.\n                  <\/jats:p>","DOI":"10.1002\/2056-4538.70074","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T16:41:48Z","timestamp":1768581708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alcian blue\u2010positive stromal phenotype in basal cell carcinoma is associated with progression on first\u2010line hedgehog inhibitors"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6246-8862","authenticated-orcid":false,"given":"Viola K","family":"DeTemple","sequence":"first","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Center Minden Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Stadler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Center Minden Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Bredemeier","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Center Minden Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungyoung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Center Minden Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Schaper\u2010Gerhardt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Center Minden Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mareike","family":"Alter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Center Minden Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yenny","family":"Angela","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Center Minden Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henner","family":"Stege","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital Mainz  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Leiter","sequence":"additional","affiliation":[{"name":"Division of Dermatooncology, Department of Dermatology University Medical Center  Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Ohletz","sequence":"additional","affiliation":[{"name":"Department of Dermatology Vivantes MVZ GmbH  Berlin\u2010Spandau Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Livingstone","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital Essen  Essen Germany"},{"name":"Skin Cancer Research German Cancer Consortium (DKTK), Partner Site Essen\/Duesseldorf  Duesseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imke","family":"von Wasielewski","sequence":"additional","affiliation":[{"name":"Skin Cancer Center Hannover, Department of Dermatology and Allergy Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica C","family":"Hassel","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Department of Dermatology 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