14 Pathology of Acquired Vascular Neoplasms of the Head and Neck
Vascular-related neoplasms of the head and neck are rather common and include benign, intermediate, and malignant neoplasms. Most vascular-related neoplasms originate from vascular endothelial cells, although some neoplasms originate from lymphatic cells. Vascular-related neoplasms may occur in the soft tissues of the head and neck but may also localize to various mucosal sites of the head and neck. This chapter focuses on the pathologic features of select vascular-related neoplasms of the head and neck. In addition, some head and neck neoplasms have a prominent vascular component without originating from endothelial cells. Among such vascularized neoplasms that are discussed in this chapter are the paragangliomas and sinonasal-type hemangiopericytomas. Finally, some non-neoplastic lesions can simulate vascular-related neoplasms, potentially leading to an erroneous diagnosis. The nonneoplastic lesions simulating vascular-related neoplasms that are discussed in this chapter are bacillary angiomatosis and papillary endothelial hyperplasia.
14.2 Benign Vascular Neoplasms
Hemangiomas are benign tumors composed of blood vessels. They are one of the most common tumors of soft tissue and constitute the largest group of soft tissue tumors in children. 1 They occur in a wide variety of clinicopathologic settings, many of which have their own corresponding terminology, such as senile or cherry angioma, tufted angioma, and verrucous hemangioma. Hemangiomas as a group are most frequently encountered at superficial sites on the head and neck.
Lobular Capillary Hemangioma
Lobular capillary hemangioma (LCH) is a polypoid form of capillary hemangioma that occurs predominantly on the skin and mucous membranes. Other names for this lesion include pyogenic granuloma, granulation tissue-type hemangioma, pregnancy tumor, and granuloma gravidarum. Hemangiomas of the sinonasal tract tend to be mucosally based but also may arise from within the osseous components of this region (intraosseous hemangiomas). The cause of LCH is unclear, although hormonal factors are thought to play a role given the frequency of development during pregnancy, particularly on the gingiva, and subsequent regression after delivery. One mechanism that has been postulated involves the role of vascular endothelial growth factor (VEGF) in apoptosis of endothelial cells. A lack of VEGF after parturition may be responsible for the subsequent resolution of LCH; conversely, high levels of VEGF during pregnancy may promote tumorigenesis. 2 , 3
These lesions have a distinctive clinical and gross appearance; they are polypoid, erythematous, and, unless ulceration is present, have a smooth surface. They are usually less than 1.5 cm in diameter. In well-established or long-standing lesions, LCHs become friable with frequent bleeding and ulceration. On low power, the characteristic microscopic appearance of LCH is that of an exophytic, polypoid lesion attached to the skin or mucosa by a fibrous stalk. In some cases, the lesion is not distinctly polypoid, but a collarette of normal epithelium is present. The lesion is submucosal, appears circumscribed, and is composed of a lobular proliferation of small capillary-sized vessels organized around a slightly larger vessel with a well-developed muscular wall ( Fig. 14.1 a). The endothelial cells lining the vascular spaces are bland and lack significant nuclear pleomorphism or tufting of the endothelial cells ( Fig. 14.1 b). There may be increased mitotic activity, and examples with many mitoses have been referred to as “active” LCH. These lesions carry no additional risk of aggressive behavior or of transformation to an angiosarcoma. Very rarely, LCH shows an epithelioid morphology. Nuclear atypia and atypical mitotic figures are not present. In some cases, the central vascular component may have a dilated or “staghorn” shape ( Fig. 14.1 b), but intercommunication (ramifying vascular spaces) between vessels is not seen. The vascular proliferation is set within a fibromyxoid stroma, which may be markedly edematous, and is associated with an extensive inflammatory infiltrate. The infiltrate is composed of both acute and chronic inflammatory cells, which are more numerous toward the lesional surface.
Special stains for infectious organisms may reveal superficial bacterial or fungal colonization but are otherwise negative. Immunohistochemical stains are positive for CD31 and CD34. Immunohistochemical staining for human herpes virus 8 (HHV8) is negative.
The differential diagnosis includes angiosarcoma and occasionally sinonasal-type hemangiopericytoma (SNTHPC). In contrast to angiosarcoma, LCH lacks nuclear atypia, tufting of endothelial cells, intercommunicating or ramifying vascular spaces, atypical mitoses, and infiltrative growth. SNTHPC is characterized by a diffuse (not lobular) growth composed of a single cell type and with perivascular hyalinization.
Hemangioma, Capillary Type
Capillary-type hemangioma (CH) is a general term for benign vascular lesions characterized by a proliferation of small, capillary-sized blood vessels. Other names for CH include lobular hemangioma and senile or cherry angioma. Juvenile or infantile hemangioma is histologically a form of CH, but it has a very particular clinical setting and immunohistochemical staining pattern, including glucose transporter 1. Juvenile or infantile hemangioma is detailed elsewhere in this textbook (see Chapter 3). The pathogenesis for most capillary hemangiomas is unknown, but it seems that hormonal factors may play a role as these lesions are more commonly encountered in women, and may enlarge during pregnancy. This discussion is exclusive of juvenile or infantile hemangiomas.
Grossly, CH appears as a small reddish or blue lesion in the skin. Microscopic examination is characterized by a circumscribed proliferation of small vessels arranged in lobules around slightly larger blood vessels with a more developed muscular wall. The proliferation is usually in the dermis but may occur in deeper subcutaneous soft tissues. The endothelial cells lining these vascular spaces are bland and usually flattened. Anastomosing vascular spaces, nuclear atypia, and atypical mitotic forms are not present.
Immunohistochemical stains show positivity for vascular endothelial markers such as CD34, CD31, and FLI-1. HHV8 and GLUT-1 staining are negative.
The differential diagnosis includes more specific terms for various types of capillary proliferations, juvenile or infantile hemangioma, and, rarely, a morphologically low-grade angiosarcoma.
Hemangioma, Cavernous Type
Cavernous hemangioma (CVH) is a benign, but sometimes locally destructive, lesion composed of enlarged and dilated vascular spaces. Another term for these lesions includes sinusoidal hemangioma.
The cause is unknown, although they do occur in several syndromes, including blue rubber bleb nevus syndrome and Maffucci syndrome (dyschondroplasia with vascular hamartomas).
The gross appearance is dependent on the depth of the lesion. Superficially located tumors tend to appear blue, and the large dilated vascular spaces often impart a texture to the overlying skin. Deeper-seated lesions may not be visible from the skin. On cut section, CVH appears as a hemorrhagic multicystic mass or hematoma. Microscopically, these tumors are identified by the presence of large irregularly sized vascular channels that may be arranged haphazardly through the tissue. The vascular spaces can ramify through dermal collagen and may occasionally anastomose with each other. The vascular walls show some variation in thickness, but most have a thin, smooth muscle wall. Calcification and even bone formation may be seen. The endothelial cells lining these spaces are bland and flattened. Mitoses may be seen, but atypical forms and nuclear atypia are absent.
Immunohistochemical stains show positivity for vascular endothelial markers such as CD34, CD31, and FLI-1. HHV8 is negative.
The differential diagnosis includes other benign vascular lesions such as arteriovenous hemangioma. Rarely, angiosarcoma may enter the differential if local destruction is present.
14.2.2 Epithelioid Hemangioma
Epithelioid hemangioma (EH) is a benign vascular tumor composed of immature-appearing vessels, often associated with a prominent inflammatory infiltrate. This lesion was first described as angiolymphoid hyperplasia with eosinophilia, 4 and since then has been termed by various authors as histiocytoid hemangioma, inflammatory angiomatoid nodule, nodular angioblastic hyperplasia with eosinophilia, and lymphofolliculosis. 5 Kimura disease, which was once thought to be related to EH, is now understood to be an entirely separate entity. EH shares features with Kimura disease, but clinical differences and histologic differences allow for separation of these entities ( Table 14.1 ).
M = F or F > M
M > F
3rd to 5th decade
2nd to 3rd decade
Head and neck site
Absent to rare
More superficial; situated in subcutaneous, dermis
More deeply situated extending to the subcutaneous fat, fascia, and skeletal muscle
Nodular vascular proliferation lined by plump-appearing (epithelioid) endothelial cells with pleomorphic changes and hyperchromatic nuclei and accompanied by a prominent inflammatory cell infiltrate with variably admixture of lymphocytes, histiocytes, plasma cells, and eosinophils
Vascular component is sparse with minimal epithelioid endothelial changes; lymphoid proliferation predominates, but prominent eosinophilic cell infiltrate, including eosinophilic microabscesses, may be seen; associated fibrosis is present
Abbreviations: ALHE, nagiolymphoid hyperplasia with eosinophilia; F, female; M, male.
The cause of EH is unknown, and there is some controversy as to whether it is a benign neoplasm or a reactive condition, 5 but there is well-documented evidence of very occasional recurrence and rare metastasis. 5 , 6
Gross examination of EH reveals a small (usually < 5 cm) lesion with a nonspecific nodular appearance, sometimes suggestive of a hematoma or a lymph node. An EH may be a circumscribed dermal or subcutaneous lesion, or it may occur in the deeper soft tissues. The microscopic appearance is distinctive and characterized on low power by nodules of capillary-sized vessels surrounded by prominent lymphoid aggregates. This proliferation is usually well defined and demarcated from the surrounding tissues, and it may surround or involve a medium- sized “parent” vessel. On higher power, the small capillary-sized vessels are lined by prominent plump epithelioid endothelial cells that protrude in the lumina with a “hobnail” appearance ( Fig. 14.2 ).
The vascular lumina may not be well defined, but the epithelioid endothelial cells are present in a single layer along the vascular spaces, which have an intact smooth muscle layer. The plump epithelioid cells have a relatively high nuclear-to-cytoplasmic ratio, with a single nucleus with open chromatin and often a prominent nucleolus. The cytoplasm is eosinophilic to amphophilic and sometimes contains vacuoles, which some authors refer to as primitive vascular luminal formation. In deep-seated (noncutaneous) lesions, the vascular proliferation may extend through the muscular wall of an involved medium sized artery and involve the lumen with an appearance similar to papillary endothelial hyperplasia. This appearance is not noted in superficial or cutaneous examples of EH. A marked inflammatory infiltrate is present in the vast majority of cases; eosinophils are often prominent, as the early descriptions of this lesion suggest, but lymphocytes mast cells and plasma cells are also present and may predominate. Lymphocyte aggregates, sometimes with germinal centers, may also be present and are thought to represent a host response to long-standing lesions.
Immunohistochemical stains are positive for CD31 in the endothelial component; CD34 is variably positive. Cytokeratin stains may also be positive in the endothelial cells. The smooth muscle or myopericytic, which are present around the small vessels, are positive for smooth muscle actin. The lymphocytic infiltrate may be positive for large activated CD30 cells. 7
The differential diagnosis includes epithelioid hemangioendothelioma, epithelioid angiosarcoma, and cutaneous lymphoma.
14.3 Nasopharyngeal Angiofibroma
Nasopharyngeal angiofibroma is a benign, although locally destructive, vascular and fibrous tumor that occurs almost exclusively in males. Other names used for this entity include juvenile angiofibroma, juvenile nasopharyngeal angiofibroma, angiofibroma, and fibroma. Evidence suggests that this tumor does not originate from the nasopharynx but rather from a fibrovascular nidus in the posterolateral wall of the nasal cavity near the sphenopalatine foramen, secondarily extending into the nasopharynx and other adjacent or contiguous anatomic sites. 8 The site of occurrence is usually the posterolateral portion of the roof of the nasal cavity in the area of the sphenopalatine foramen. The cause of tumor development is not understood, but hormonal factors seem to play some role as they arise most often in adolescent males 9 and express androgen receptors, 10 and there is some evidence that anti-androgen therapy may help reduce the tumor volume preoperatively. 11 , 12 There is also evidence of an association with familial adenomatous polyposis and nasopharyngeal angiofibroma. 13
Grossly, nasopharyngeal angiofibromas are lobulated submucosal masses and range from sessile to polypoid. The overlying mucosa is smooth and may or may not be ulcerated. On cut section, the tumors are firm and tan-gray, often with a vaguely spongy consistency. Microscopically, these lesions are unencapsulated and poorly circumscribed. On low power, a prominent vascular component consisting of variably sized and irregularly shaped (“staghorn”) vascular spaces is apparent ( Fig. 14.3 a). These vascular spaces may be dilated or compressed and are lined by a single layer of bland endothelial cells ( Fig. 14.3 b). The vessel walls have an identifiable muscular wall, but this smooth muscle layer is eccentric, irregular, and may be incomplete; elastic fibers are not identified within the vessel walls. The stromal component is composed of bland stellate to spindled cells with plump ovoid nuclei, which are set within a collagenous stroma and often radiate out from the vascular spaces. The stroma is composed of delicate or thick collagen bundles, often oriented in parallel to each other, and can also exhibit focal myxoid change ( Fig. 14.3 b). Multinucleated or pleomorphic stromal cells may be present, but mitoses are rare. In long-standing lesions, the overall appearance may be more fibrous than vascular. Mast cells are commonly noted, but other types of inflammatory cells are not present, except near areas of mucosal ulceration.
14.3.2 Special Stains
Immunohistochemical staining shows that the endothelial cells are positive for vascular endothelial markers such as CD31 and CD34, and the intratumoral vessels are focally positive for smooth muscle markers, such as smooth muscle actin. The spindled to stellate stromal cells are positive for vimentin, β-catenin (nuclear), androgen receptor (nuclear), and testosterone receptor.
14.3.3 Differential Diagnosis
The differential diagnosis includes inflammatory nasal polyp, lobular capillary hemangioma, schwannoma, antrochoanal polyp, and fibromatosis.
14.4 Lymphatic Malformation (Lymphangioma)
A lymphatic malformation or lymphangioma is a benign lesion of lymphatic spaces. There is some debate as to whether these tumors represent neoplasms, 14 hamartomatas, or simply lymphangectasias resulting from congenital malformation or acquired damage to lymphatic channels. These lesions have traditionally been divided into three clinicopathologic categories: cystic (also referred to as cystic hygroma), capillary lymphangioma (lymphangioma simplex), and cavernous lymphangioma, which may actually represent the same process occurring at different anatomic sites. 15 In the head and neck, cystic lymphatic lesions are most commonly encountered in the neck, and cavernous lesions are most commonly encountered in and around the mouth, particularly the dorsal tongue. 16 There is significant histologic overlap between these categories, and overall they are not diagnostically useful. 17
Grossly, lymphatic malformations are soft and compressible. If they are subcutaneous, the overlying skin may exhibit thinning or atrophic changes, or it may have a bluish hue. On cut section, they appear unicystic to multicystic and contain clear to whitish thin fluid. Microscopic examination of cystic and cavernous lesions is characterized by variously sized, thin-walled channels lined by a bland, flattened epithelium. Larger vessels might have an eccentric muscular wall ( Fig. 14.4 ). The lumina may or may not contain proteinaceous material. The stroma may be loose and edematous or fibrous; stromal mast cells and hemosiderin deposition are commonly encountered, as are lymphocytic aggregates. Electron microscopy confirms the absence of a basement membrane or pericytes around the thin-walled lymphatic spaces, although they may be seen associated with the larger-caliber vessels. 18