This month’s news from across the specialty

October 1, 2025

In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.  

Pathologists and dermatopathologists frequently encounter poorly differentiated tumors that fail to reveal a defined lineage. In cutaneous specimens, these are most commonly classified as atypical fibroxanthoma and pleomorphic dermal sarcoma. Despite extensive immunohistochemical analysis, the cell of origin remains unknown. It has been proposed that these tumors do not represent a unique entity, but rather constitute poorly differentiated variants of other malignancies, such as malignant melanoma, squamous cell carcinoma, or mesenchymal tumors.

A recent Australian study (American Journal of Surgical Pathology. 2025. 49(7): 650–7) employed next-generation sequencing to evaluate tumors in this category. Among their cohort of 37 cases, seven (19%) harbored melanoma driver variants, including NRAS, KIT, and GNAQ mutations. These findings suggest that this subset of tumors represents poorly differentiated malignant melanomas. This molecular identification may have significant implications for clinical management, particularly in cases where metastases develop. Future molecular studies will likely provide additional insights into the clinical significance of these poorly differentiated neoplasms.

Avoid routine use of oral prophylactic antibiotics in dermatologic surgery on the lower extremities. Appropriate use of oral prophylactic antibiotics in dermatologic surgery is primarily guided by an advisory statement published in 2008 (10.1016/j.jaad.2008.04.031). Those guidelines recommend the use of oral prophylactic antibiotics for surgery on the lower extremities (LE), considered a ‘‘high-risk’’ surgical site due to a reported >5% risk of surgical site infection (SSI).

However, other reviews have shown a much lower risk of SSI after Mohs micrographic surgery (MMS) (10.1016/j.jaad.2008.03.042). The estimated >5% risk, for SSI on LE sites, was based on only two single-center retrospective studies; and there were no comparative studies available to suggest or demonstrate a decrease in that risk after use of prophylactic antibiotics.

Lambert Smith et al conducted a single-site retrospective review of patients undergoing MMS on a site below the knee (10.1097/DSS.0000000000004652). 45.5% of cases received oral prophylactic antibiotics (1g cefadroxil). The oral prophylaxis group had an SSI rate of 11.1%; patients not receiving oral prophylaxis had an SSI rate of 8.3% (p = 0.52). No other examined patient, tumor, or surgical variables were associated with an increased risk of SSI. These findings concur with a 2020 meta-analysis of MMS that found no difference in SSI after oral prophylactic antibiotic versus placebo (10.1097/DSS.0000000000001838).

This demonstrated lack of benefit suggests dermatologists should not routinely prescribe oral prophylactic antibiotics before surgery on the lower extremities. Unnecessary use of prophylactic antibiotics may contribute to antibiotic resistance, risk adverse effects for patients, and increase health care costs.

Pop quiz: In January 2024, a 73-year-old man in Central Oregon presented to the emergency department with an ulcer on his right wrist, present for four days, with surrounding cellulitis and lymphadenitis extending to the right axilla.

One day prior to noticing the ulcer, the man had cut his right index finger with a kitchen knife and went to urgent care, where the wound was irrigated and sutured.

After urgent care, the man returned home to care for his sick cat, which had been experiencing vomiting and a neck abscess that a veterinarian had drained and excised. The cat was prescribed an oral antibiotic.

What’s in your differential (for the man)? If you included plague, you nailed it!

Blood cultures done during the man’s hospital admission grew Yersinia pestis, according to a recent CDC report. He was treated with intravenous and then oral antibiotics and fully recovered, except for mild fatigue.

Unfortunately, the cat died and subsequent testing showed it also had Y. pestis infection.

Y. pestis can be transmitted by fleas or by ill animals, including pets. This case — only the 19th reported in Oregon in 90 years — occurred earlier in the calendar year than any prior case in the state. (With a national average of seven cases per year, most cases occur in New Mexico and Arizona.) Climate change and other factors might be contributing to geographically wider, and temporally longer, Y. pestis infections. Dermatologists would be wise to be newly vigilant for an old scourge.

A new study in Cell Reports offers fresh evidence that fibroblasts actively shape inflammatory environments in skin disease (Cell Rep. 2025 Aug 7;44(8):116114). Using single-cell RNA sequencing and multiplexed error-robust fluorescence in situ hybridization (MERFISH), the authors mapped the cellular dynamics of type 2 inflammation in mouse models of atopic dermatitis. They uncovered a basophil-fibroblast axis wherein basophils activate fibroblasts, which, in turn, recruits additional basophils, macrophages, dendritic cells, and T cells. These findings underscore that fibroblasts are not inert but are instead dynamic players that coordinate and amplify inflammation.

The authors identified that basophils play an early, central role in pushing fibroblasts into a pro-inflammatory state via IL-4 and oncostatin M (OSM). OSM appears to upregulate expression of the IL-4 receptor, further sensitizing fibroblasts to type 2 inflammation. Disrupting this axis by selectively deleting the IL-4 receptor in fibroblasts or pharmacologically inhibiting gp130 (a core component of the OSM receptor) significantly reduced skin inflammation. Simultaneously inhibiting IL-4 and OSM signaling synergistically suppressed inflammation, exceeding the effects of either pathway alone.

This work also reinforces what has long been suspected in an unrelated family of skin diseases: sclerosing dermatopathies. IL-4 signaling plays a central role in fibroblast activation and dermal fibrosis in systemic sclerosis, in which IL-4 and Th2 cells drive collagen production, extracellular matrix deposition, and tenascin expression in dermal fibroblasts. Th2 cytokines correlate with the clinical manifestations and severity of fibrosis in systemic sclerosis. This study now elegantly bridges molecular and mechanistic insights between the otherwise clinically unrelated diseases atopic dermatitis, morphea, and systemic sclerosis. It supports a broader view of fibroblasts as modulators of cutaneous immunity and identifies shared cytokine pathways that may be leveraged across inflammatory and fibrosing conditions. This study underscores the potential of targeting IL-4 signaling not just to treat atopic inflammation, but also to disrupt fibroinflammatory loops in sclerosing dermatopathies.

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