Table 1.
Clinical and histologic features of vascular lesions included in the differential diagnosis of epithelioid hemangioma
| Vascular lesion | Key clinical features | Key histologic features | Cytogenetics | Immunohistochemistry |
|---|---|---|---|---|
| Capillary hemangioma | Usually observed within the first few weeks of life; Rarely seen in adult patients; typically solitary red or purplish raised nodule on eyelid, of variable size; course is rapid growth followed by slow regression | Proliferation of capillary vessels and perivascular pericytes; often has considerable mitotic activity in proliferative phase; progressively replaced by connective tissue | Nonspecific or none reported | Positive for factor VIII, CD31; Juvenile hemangioma stains positive for GLUT-1 |
| Cavernous hemangioma | Well-circumscribed, slow-growing; presents as proptosis in adults; usually located in the retrobulbar region | Large, blood-filled, endothelial-lined vascular spaces. The walls may have adventitial fibrosis | Nonspecific or none reported | Positive for factor VIII, CD31 |
| EH: includes typical, cellular and ALHE variants | Rare vascular tumor; nodules, or erythematous subcutaneous papules, usually in the head/neck region of young females but can also involve organs and other soft tissue locations | Well circumscribed lesion composed of vessels lined by plump endothelial cells that protrude into the lumen in a“tombstone fashion”; vascular component features capillaries, arterioles, and venules; inflammation is usually lymphoplasmacytic with numerous eosinophils; Frequently demonstrates atypia and intracytoplasmic vacuoles | See below | Positive for factor VIII, CD31 |
| Typical EH | Usually located in bone and soft tissue sites | Epithelioid cells have eosinophilic cytoplasm, scattered vacuoles, vesicular nuclei, and prominent nucleoli; often a background inflammatory infiltrate which includes eosinophils | FOS gene rearrangements are common | |
| Cellular EH | Usually located in bone and soft tissue sites | Increased cellularity, solid growth pattern, moderate mitotic activity, and a mild inflammatory background | FOS gene rearrangements are common | |
| ALHE variant of EH | Usually located in the head/neck and extremities; often seen in the setting of prior trauma, with this history and the histopathology suggesting a reactive process, unlike the neoplastic appearance of other EH variants | Vascular“blow out” pattern associated with damaged medium-sized vessels and extensive inflammation, often with prominent lymphoid follicles | FOS gene rearrangements are uncommon | |
| KD | Subcutaneous nodules in the head and neck, most often in young, Asian males; probable allergic or autoimmune response; frequently associated with lymphadenopathy and peripheral blood eosinophilia | Proliferation of capillaries without endothelial cell atypia; occurs with lymphoid follicles, a marked eosinophilic infiltrate, and dense fibrosis | Nonspecific or none reported | Positive for factor VIII, CD31 |
| EHE | Rare, malignant vascular tumor, often with a relatively indolent course; most commonly occurs in the liver, lung, or veins of the extremities, but may be found at other sites especially in bones and skin; occurs over a broad age-range, with a slight female predilection | Strands or cords of epithelioid cells with abundant glassy eosinophilic cytoplasm and prominent cytoplasmic vacuolation, embedded in a chrondromyxoid or hyalinized stroma; Most EHE lack well-formed vascular channels, and display more significant cytologic atypia than EH, but less than EA | WWTR1-CAMTA1 fusion, or less commonly YAP1-TFE3 fusion | Positive for factor VIII, CD31; variable staining for SMA, CK |
| AVM | Non-neoplastic vascular lesion characterized by AV shunts; angiography demonstrates high flow angioma with feeder vessels; may see pulsating exophthalmos with a bruit, hemorrhage, or thrombosis | Large numbers of veins and arteries of different size; areas resembling a cavernous or capillary hemangioma are frequent, as are thromboses and calcification; can be combined with lymphatic vessels | Nonspecific or none reported | Positive for factor VIII, CD31; elastin stain may help distinguish between arteries and veins |
| KS | Low-grade vascular malignancy associated with HHV8 infection; clinical forms include: classical (elderly), endemic (African), iatrogenic (immunosuppresion), and AIDs-related; can present as a patch, plaque or nodule, which is classically solid, red-violet, slightly elevated, and involves eyelid skin or margin and extends to conjunctiva; Often multifocal | Proliferation of spindle-shaped cells, slit-like vascular channels, fibroblasts, inflammatory cells, and extravasated RBCs; minimal to no pleomorphism; HHV8 is a specific marker for KS | DNA fragments of HHV8 have been found in 90% of confirmed KS cases | Positive for factor VIII, CD31, and HHV8 |
| EA | Rare, highly malignant neoplasm of endothelial cell origin; most common in elderly white males; my begin as ill-defined red plaque that resembles a bruise/sty; borders may extend beyond margin of visible lesion; can metastasize, usually with hematogenous spread | Sheets of large, mild to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli; often with infiltrative growth and irregular anastomosing vascular channels; prominent cytologic atypia and frequent mitoses are common | varied cytogenetic abnormalities | positive for factor VIII, CD31, Vimentin, Fli-1; variable staining for CK, CD34, and EMA (in cutaneous lesions) |
EH, epithelioid hemangioma; KD, Kimura's Disease; EHE, epithelioid hemangioendothelioma; AVM, arteriovenous malformation; KS, Kaposi Sarcoma; EA, epithelioid angiosarcoma;