Venous Malformation-Like Kaposi Sarcoma: Revisiting a Known Variant

To the editor: Kaposi sarcoma (KS) is a vascular neoplasm of low-grade malignant potential associated with human herpesvirus 8 (HHV-8) infection. Traditionally considered of lymphatic endothelial origin, KS is classified into 4 epidemiologic forms: classic, endemic (African), iatrogenic, and epidemic (HIV-related). Histologically, KS progresses through 3 well-recognized stages (patch, plaque, and nodular) each with distinct microscopic features. However, in recent years, a broad histologic spectrum has been described, with variants that can mimic benign or malignant vascular proliferations and reactive dermatoses, thereby posing considerable diagnostic challenges.1 Among these, a rare presentation mimicking venous malformation has occasionally been described in the literature under the misleading term “cavernous hemangioma-like” KS.2–4 This terminology, although still sporadically used, does not conform to current vascular anomaly classifications and may contribute to diagnostic confusion.5 We report the case of a 58-year-old HIV-negative, immunocompetent southern European man with hypertension and type 2 diabetes. He initially presented with an asymptomatic bluish nodule on the left ear helix, which was excised and diagnosed as classic KS. Laboratory tests were unremarkable, with no mucosal or systemic involvement. One year later, he developed 3 new millimetric bluish nodules in the same area. These were again excised and submitted for histopathologic evaluation. On this occasion, the dermatopathologic features of the lesions had undergone significant alteration showing well-circumscribed dermal lesions with lobular (“cavernous-like”) architecture, composed of dilated, blood-filled vascular spaces lined by flattened endothelial cells. Some lobules exhibited fibrous septa, but there were no clearcut fascicles of spindle cells (Fig. 1). Adjacent areas showed immature vascular structures, erythrocyte extravasation, and focal hemosiderin deposits, suggestive of early stage KS. A discrete perivascular lymphoplasmacytic infiltrate was also present. Immunohistochemical analysis revealed a characteristic nuclear dot-like staining pattern for HHV-8 (LNA-1) in the endothelial lining of the lobular vascular spaces, which showed strong and diffuse expression of CD31 and D2-40 (Fig. 2). The dilated, cavernous vascular structures lacked a pericytic lining, as evidenced by the absence of smooth muscle actin immunoreactivity. These findings confirmed the diagnosis of KS in a rare histologic variant resembling a venous malformation. The patient was followed biannually for 10 years. During follow-up, local recurrences appeared on both ears. In addition, new lesions emerged at distant sites, specifically on the left forearm and right leg. They were treated with local excision or topical imiquimod. Notably, all the excised lesions exhibited similar histopathologic features, characterized by dilated cavernous vascular spaces and an identical immunohistochemical profile. The disease remained confined to the skin, with no evidence of systemic involvement or aggressive progression.FIGURE 1.: A, Clinical image showing 3 bluish nodules on the left ear helix. B–D, Hematoxylin and eosin staining (×40) of the excised lesions reveals well-circumscribed lobular (“cavernous-like”) vascular proliferations with dilated, blood-filled spaces resembling a venous malformation.FIGURE 2.: A, Detail of lobular vascular structures with congested lumina (hematoxylin and eosin, ×100). B, Immature vascular buds and lymphoplasmacytic infiltrate at the lesion periphery, consistent with early stage KS (hematoxylin and eosin, ×100). C, Immunohistochemical analysis revealed a diffuse and strong D2-40 expression in the endothelial lining of the lobular vascular spaces. D, Characteristic nuclear dot-like staining pattern for HHV-8 (LNA-1) in endothelial cells of the vascular structures.More than 10 histopathologic variants of KS have been described, most of which are clinically indistinguishable yet display significant microscopic differences.6,7 The so called cavernous hemangioma-like variant, while not newly recognized, is rarely reported and remains underappreciated. The earliest mention dates back to Templeton in 1988,8 who described nodular KS-containing cavernous vascular spaces resembling a “cavernous hemangioma.” Since then, lesions in which this morphology predominates have been documented in only 4 patients. In a retrospective analysis of 185 KS lesions, Onak et al3 identified this morphology in 2 cases, underscoring its rarity. To date, only other 2 similar cases have been published, all in patients who are HIV negative,2–4 except for 1 coinfected with HIV and hepatitis C. Histologically, these lesions consist mainly of dilated vascular structures with a lobular pattern. The vessels are congested, lined by flattened endothelium, and may show occasional intimal thickening. Endothelial atypia is usually absent, though some nuclei may protrude into the lumen. Peripheral features of early stage KS with immature vascular buds, erythrocyte extravasation, and hemosiderin, if present, are focal and subtle. Nuclear HHV-8 immunoreactivity remains a key diagnostic clue, along with positivity for lymphatic markers like D2-40 and absence of actin-positive pericytes. In 2023, Dr Ángel Fernández-Flores and colleagues cogently argued that the term “cavernous hemangioma-like” should be abandoned when referring to this variant of KS, because it perpetuates a historical misclassification of vascular malformations as neoplasms.5 This terminological inaccuracy—long embedded in the literature—has been progressively corrected reflecting a more rigorous distinction between vascular tumors and malformations. According to the International Society for the Study of Vascular Anomalies classification,9 the so called cavernous hemangioma is not a true tumor but a venous malformation. In the most recent World Health Organization classifications of skin and soft tissue tumors, the term has been removed or relegated to differential diagnosis tables, further supporting its obsolescence.1 Adopting the term “venous malformation-like KS” not only reflects current understanding but also reduces the risk of diagnostic error.5,10 In full agreement with this position, we contribute to the expanding body of evidence by reporting what we believe to be the fifth documented case of venous malformation-like KS, notable for its unique presentation involving both local and distant recurrences, all exhibiting a consistent histopathologic architecture mimicking venous malformations. The differential diagnosis of this KS pattern includes benign vascular lesions, particularly venous malformation, sinusoidal and spindle cell hemangiomas.3 Given the rarity of this variant and its histologic overlap with benign vascular entities, immunohistochemical staining for HHV-8 should be performed whenever KS is clinically suspected, particularly in elderly or immunocompromised individuals. In conclusion, venous malformation-like KS is a rare but important histologic variant. Its recognition requires awareness of its distinct morphology, familiarity with the broader histopathologic spectrum of KS, and use of targeted immunohistochemistry. Proper nomenclature and careful diagnostic workup are essential to avoid misclassification and ensure appropriate management.