{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:04:32Z","timestamp":1779789872309,"version":"3.53.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) presenting with disseminated cutaneous involvement represents an aggressive disease subset with poor response to conventional chemotherapy and dismal prognosis. The tissue-specific molecular mechanisms driving cutaneous aggression remain poorly characterized at single-cell resolution. Here we report a 67-year-old male PTCL-NOS patient with hypertension and coronary artery disease history, presenting with generalized cutaneous nodules and rapid progression despite multi-line chemotherapy. Single-cell RNA sequencing (scRNA-seq) performed on paired skin lesions and peripheral blood at diagnosis revealed striking microenvironmental dichotomy: skin-resident malignant T cells exhibited hyperproliferative phenotypes (high CDC20B, HIST1H3B, MKI67+), activation of NF-\u03baB and IL-17 signaling, and extensive crosstalk with endothelial cells; conversely, blood-derived lymphoma cells displayed immune evasion signatures and metabolic stress markers. Copy number variation analysis confirmed clonal expansion across both compartments with distinct tissue-specific transcriptional programs. Despite CHOP, CHOEP, DA-EPOCH, and AC-CHOP (azacitidine plus chidamide) regimens, the patient experienced primary refractory disease and died 6 months from diagnosis following COVID-19 superinfection. To our knowledge, this is the first case reporting single-cell transcriptomic comparison of skin versus blood compartments in PTCL-NOS, revealing how cutaneous microenvironment sculpts aggressive malignant phenotypes and providing potential targets for compartment-specific therapy.<\/jats:p>","DOI":"10.3389\/fonc.2026.1827539","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:24:37Z","timestamp":1779787477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Cutaneous niche-restricted malignant phenotypes in PTCL-NOS revealed by single-cell sequencing"],"prefix":"10.3389","volume":"16","author":[{"given":"Shucheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Shandong First Medical University","place":["Jinan, China"]},{"name":"China Foundation for Youth Entrepreneurship and Employment-Incaier Public Welfare Fund","place":["Beijing, China"]},{"name":"Shandong Key Laboratory of Digital Diagnosis and Treatment of Thoracic Oncology, Shandong Engineering Research Center of Intelligent Surgery, Shandong Data Open Innovative Application Laboratory, The First Affiliated Hospital of Shandong First Medical University& Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Shandong First Medical University","place":["Jinan, China"]},{"name":"China Foundation for Youth Entrepreneurship and Employment-Incaier Public Welfare Fund","place":["Beijing, China"]},{"name":"Shandong Key Laboratory of Digital Diagnosis and Treatment of Thoracic Oncology, Shandong Engineering Research Center of Intelligent Surgery, Shandong Data Open Innovative Application Laboratory, The 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