CD30 Expression in Malignant Vascular Tumors and Its Diagnostic and Clinical Implications

Abstract

Angiosarcoma (AS) is a rare malignant vascular tumor while epithelioid hemangioendothelioma (EHE) is a vascular tumor of low grade malignancy. CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8). While expression of CD30 is most commonly associated with lymphoid malignancies or germ cell tumors, occasional angiosarcomas have been reported as CD30-positive. However, there is limited data to evaluate its role definitively in malignant vascular tumors. In this study, we evaluated 91 angiosarcomas (AS), 30 epithelioid hemangioendothelioma (EHE) from various sites, and 25 Kaposi sarcomas (KS). Overall, CD30 was expressed in 31/91 cases (34%) of AS, in 7/30 cases (30%) of EHE but in none of the KS. CD30 was expressed in a membranous staining pattern and positivity in tumor cells varied from focal to diffuse. The positive angiosarcomas included vasoformative more differentiated tumors and also solid, undifferentiated, lymphoma-like examples, one of which was classified as lymphoma prior to the era of immunohistochemistry. The CD30-expression was seen in >50% of tumor cells in a majority of angiosarcomas but only in 7% of EHEs. None of the 55 angiosarcomas studied were immunohistochemically positive for TIA-1 or granzyme B, antigens used as more specific markers for anaplastic large cell lymphoma. Compared with angiosarcoma, normal vascular endothelia of capillaries and muscular vessels showed variable positivity. Among hemangiomas, cavernous and spindle cell hemangiomas showed most frequent endothelial CD30-positivity, whereas in most other hemangiomas, CD30-positivity was scant. In conclusion, CD30 expression occurs in a significant subset of angiosarcomas and EHE and needs to be included in the differential diagnosis with other CD30-positive malignancies to avoid a diagnostic pitfall. It remains to be determined whether patients with strongly CD30-positive angiosarcomas could be candidates for targeted therapy using the recently introduced CD30 antibody drug conjugates.

Index report of cutaneous angiosarcomas with strong positivity for tyrosinase mimicking melanoma with further evaluation of melanocytic markers in a large angiosarcoma series

“…Synaptophysin positivity has been reported in 3 cases including 1 with co‐expression of chromogranin A . Interestingly, positivity for CD30 in a poorly differentiated angiosarcoma can raise the possibility of anaplastic large cell lymphoma . In a large study of 91 angiosarcomas, 34% were positive for CD30 .…”

Diagnostically Challenging Epithelioid Vascular Tumors

“…64 Similarly, in cases with immunoreactivity for CD30, anaplastic large-cell lymphoma is a differential consideration, but additional immunostains for vascular markers will allow recognition of epithelioid angiosarcoma. 65 Other epithelioid vascular tumors can be considered (see previously). As a rule, none of the other epithelioid vascular tumors have the degree of atypia seen in epithelioid angiosarcoma.…”

Unsustained response to brentuximab as single agent therapy in a patient with CD30 positive angiosarcoma

“…it is expressed on activated t-and B-cells and is a diagnostic marker of some lymphomas [Hodgkin's lymphoma, Anaplastic large cell lymphoma (AlCl), some B-cell lymphomas]. though not part of standard diagnostic immunohisotchemical analysis for sarcomas, high expression of CD30 has been reported in up to 30% of AS's [2,3,7,8], making this a potential diagnostic pitfall in AS's as well as opening up to potentially new treatment possibilities with targeted therapy using antibody drug conjugates.…”

“…it has shown response rates around 60% in patients with Hodgkin's lymphoma and AlCl and is now considered standard of care in relapse or refractory Hodgkins lymphoma and AlCl [10]. it was suggested therefore that brentuximab could be used to treat CD30 positive AS's [2] though this was never tested in a clinical trial.…”

“…they represent below 2% of all soft tissue sarcomas and present in a broad variety of anatomic locations [1,2]. Predisposing factors include lymphedema (Steward-treves syndrome) and radiation, and cutaneous post-irradiation AS has become a well known complication to breast conserving therapy [3,4].…”