Trichodysplasia spinulosa polyomavirus (TSPyV) is established as the causative agent of trichodysplasia spinulosa, a folliculocentric eruption usually affecting the face in immunocompromised patients. Beyond classic cases, TSPyV DNA or RNA has been reported in tonsils, blood, urine, cerebrospinal fluid, and respiratory specimens. A recent report identified TSPyV localized to endothelial cells within tumors from three patients after analysis of off-target next-generation sequencing reads and confirmed localization by in situ hybridization. Those findings, together with the fact that the three patients had received corticosteroids immediately before tumor resection, prompted investigation of whether TSPyV might also be present in endothelial cells in other cutaneous inflammatory conditions.
The authors evaluated 25 dermatologic biopsy specimens collected in California, representing a spectrum of inflammatory skin conditions. Diagnoses included:
One additional specimen of trichodysplasia spinulosa was included as a positive control. Clinical medication history showed that 13 of the 25 patients had received corticosteroid therapy before biopsy; of these, 10 received corticosteroids within 10 days of biopsy. Three patients had distant prior corticosteroid exposure at intervals of 108 days, 1,494 days, and 1,949 days from the time of biopsy.
The study used an in situ hybridization approach (RNAscope) with a custom probe targeting the full TSPyV genome to detect viral RNA in tissue. The assay was applied to tumor-associated and intratumoral endothelial cells within each dermatologic sample. To confirm RNA integrity and adequacy of fixation and processing across specimens, a peptidylprolyl isomerase B (PPIB) RNA probe was run as a positive control on all samples.
The trichodysplasia spinulosa positive control displayed expected TSPyV signal, confirming probe functionality and the ability of RNAscope to detect TSPyV in tissue.
PPIB staining was present in all 25 inflammatory skin biopsy specimens, supporting preserved RNA integrity in the cohort.
Despite these controls, no TSPyV signal was detected in endothelial cells in any of the 25 inflammatory dermatologic biopsy samples evaluated.
Representative photomicrographs (figure) illustrated positive staining in the trichodysplasia spinulosa control and absent TSPyV staining in a representative inflammatory dermatosis sample, with paired PPIB images confirming RNA preservation.
The absence of detectable endothelial TSPyV in this set of inflammatory skin biopsies suggests that endothelial infection by TSPyV is not common in the selected cutaneous inflammatory conditions. The authors note the contrast with an earlier report that identified TSPyV in endothelial cells in 3 cases identified from a larger specimen pool (3 cases among 252 specimens). They propose that the prevalence of endothelial TSPyV infection may be low and that detection could depend on clinical context, tissue type, or cohort size. The earlier series’ association with recent corticosteroid exposure in the three positive cases raises the possibility that timing or intensity of immunosuppression could influence detectability, but this study did not find evidence to support widespread endothelial involvement in the inflammatory conditions examined.
Cohort size: The investigation included only 25 inflammatory skin biopsies, limiting power to detect low-prevalence endothelial infection. The authors explicitly acknowledge that a smaller cohort could miss rare occurrences documented in larger series.
Case selection: Samples represented diverse inflammatory dermatoses rather than tumors or other tissue types where prior detection occurred; therefore, findings refine but do not exhaustively define the tissue spectrum of TSPyV.
Clinical context: Thirteen patients had prior corticosteroid exposure, but only ten had steroid administration within 10 days of biopsy. The study cannot determine whether specific timing, dose, or other immunosuppressive factors influence endothelial TSPyV localization.
Clinical implication: For routine evaluation of inflammatory cutaneous conditions similar to those sampled here, routine screening for endothelial TSPyV by RNAscope is unlikely to identify the virus, although clinicians and pathologists should remain alert to atypical presentations and to results from larger surveys or tumor-based investigations.
Evaluation and reporting of these cases were conducted under research protocols approved by the institutional review board of Stanford University, and patients provided informed consent for the research. The study methods, including use of a custom RNAscope probe and PPIB control, and the negative findings serve to narrow the contexts in which endothelial TSPyV has been documented and to inform future, larger-scale investigations.