Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma

J Dtsch Dermatol Ges. 2024 Apr;22(4):513-519. doi: 10.1111/ddg.15379. Epub 2024 Mar 14.


Background and objectives: Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro-photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet-induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS-development.

Patients and methods: In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time-period of 7 years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus.

Results: Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients.

Conclusions: This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.

Keywords: Atypical fibroxanthoma; cutaneous sarcoma; hydrochlorothiazide; pleomorphic dermal sarcoma; spindle‐cell tumors.

MeSH terms

  • Carcinoma, Basal Cell* / chemically induced
  • Carcinoma, Basal Cell* / epidemiology
  • Carcinoma, Squamous Cell* / complications
  • Diabetes Mellitus*
  • Histiocytoma, Malignant Fibrous*
  • Humans
  • Hydrochlorothiazide / adverse effects
  • Retrospective Studies
  • Sarcoma* / epidemiology
  • Sarcoma* / pathology
  • Skin Neoplasms* / chemically induced
  • Skin Neoplasms* / complications
  • Skin Neoplasms* / epidemiology


  • Hydrochlorothiazide