Langerhans cells in anaplastic Kaposi sarcoma with a paucivascular phenotype: a potential diagnostic pitfall

Anaplastic Kaposi sarcoma (AKS), a rare variant of Kaposi sarcoma, has a poorly recognized histomorphologic spectrum, including a paucivascular phenotype, that mimics a range of undifferentiated malignancies. This study, that highlights the hitherto undocumented phenomenon of S100-protein-positive Langerhans cells (SLCs) as a potential diagnostic pitfall in paucivascular AKS, involved review of nine such AKS that required diagnostic immunohistochemical (IHC) work-up. All biopsies had a predominant or exclusive spindle or epithelioid cell infiltrate. The first three tumors were diagnosed as malignant peripheral nerve sheath tumor (2) and metastatic melanoma (1), based on S100-protein immunopositivity. Biopsy of a co-existent pigmented sole lesion (patient 3) demonstrated nodular KS. Subsequent IHC investigation of these three tumors demonstrated an endothelial phenotype and HHV8 immunopositivity, confirming AKS. CD1a and langerin staining of the S100-protein-positive cells confirmed Langerhans cells as the cause of the diagnostic pitfall. Subsequently, six further paucivascular AKS with intratumoral SLCs were recognized on histomorphological and IHC appraisal. In conclusion, heightened awareness of the histomorphologic spectrum, appropriate IHC investigation, and informed appraisal thereof, are critical to the diagnosis of AKS with an undifferentiated phenotype, and the avoidance of IHC pitfalls, such as those caused by under-recognition and misinterpretation of bystander SLCs in AKS.