Vascular lesions of the head and neck: an update on classification and imaging review

Hemangiomas come in two forms infantile or congenital. Infantile hemangiomas are glucose transporter protein-1 (GLUT1) positive while congenital hemangiomas are not. Interestingly, GLUT-1 expression has been linked to poor prognosis in many neoplastic processes [5‐7]. This over expression is thought to be due to increased need for glucose mediated by hypoxia. It is hypothesized that in utero episodes of hypoxia may lead to upregulation of GLUT-1 and angiogenic cytokines contributing to hemangioma formation [8, 9].

In addition to this genetic difference, they have several unique features that can help differentiate them. Infantile hemangiomas are usually diagnosed in the first year of life. They follow a pattern of rapid growth in the first few months followed by slower growth and involution phases that are slower and more variable. These lesions can be contrasted with congenital hemangiomas, which by definition are present at birth, and become symptomatic as they increase in size or in response to hormonal changes, infection and trauma.

Infantile hemangiomas can be hyper or hypoechoic on ultrasound but demonstrate hypervascularity on color flow Doppler. These are best imaged on T1, T2, and post-contrast sequences when using MRI. Proliferating hemangiomas are iso to intermediate T1 and relatively hyperintense on T2 (however, not as hyperintense as cerebral spinal fluid), with enhancement after contrast administration. A serpiginous vessel with a prominent flow void denotes an arterial feeder, this along with lack of perilesional edema are important supporting findings. Dynamic contrast-enhanced imaging will demonstrate gradual, intense enhancement of the lesion, followed by gradual washout. In the involuting phase; these lesions demonstrate fibro-fatty infiltration with T1 hyper intense foci and decreasing contrast enhancement (Figs. 1 and 2).

These are further broken down based on their distribution into focal (single localized lesion, which is the most common), multifocal (several lesions), segmental (diffuse plaque like), and indeterminate [10]. In addition to the location, depth is used to characterize these lesions. The most common are superficial lesions limited to the skin. These are commonly dubbed “strawberry” lesions. Deep lesions occur under the skin and often appear bluish on gross examination. There are also mixed lesions with superficial and deep components. The last major subtype is reticular, abortive, minimal growth; these present as reticular or telangiectatic patches. They do not proliferate as readily and often involute faster than the other subtypes [11]. These hemangiomas are associated with posterior fossa malformations, arterial anomalies, cardiac abnormalities, and eye anomalies (PHACE syndrome).

It is important to contrast these lesions to Kaposiform hemangioendothelioma (KHE), which can also have a rapidly expanding phase, but is more infiltrative often crossing multiple soft tissue planes and often involving of the overlying skin. Most hemangiomas are clinically observed, but treatment maybe indicated if there is involvement of the airway, visual system, permanent disfigurement, or large lesions that may result in cardiac symptomatology. The mainstay of treatment is beta-blockers, namely propranolol [2].

Congenital hemangiomas are similar to infantile hemangiomas in regards to their US and MRI findings. They are diagnosed retrospectively by their natural progression into rapidly involuting congenital hemangiomas (RICH), partially involuting congenital hemangiomas (PICH) and non-involuting capillary hemangioma (NICH) subtypes. RICH involute during the first year of life, in contrast to PICH and NICH. These lesions are associated with GNAQ/GNA11 genetic changes [10, 12]. Similar to infantile hemangiomas, most of these can be observed unless there is a complicating factor; the mainstay of treatment is beta blockers, but excision, laser therapy, or sclerosants can be used for residual lesions.

Tufted angioma is a rare vascular tumor that presents with red or violet plaques. Histologically, it is characterized by capillary vessels forming oval or rounded “tufts.” These develop usually within the first 5 years of life and can extend into many layers beyond the dermis. There is differing data on the location of these lesions but they tend to occur in the trunk and extremities in children. In adults, lesions are more likely to present in the head and neck, specifically the oral mucosa [13, 14]. It is important to biopsy these lesions to exclude a malignant neoplasm namely Kaposi sarcoma or angiosarcoma. Once pathological diagnosis is obtained, these lesions are usually observed; some of these lesions have known to regress. Treatment is usually symptomatic or cosmetic [15, 16]. Imaging is rarely performed on these lesions. Similar to KHE, these lesions have also been associated with GNA14.

Spindle cell hemangioma can present as a red–brown nodule ranging from a few millimeter to a few centimeter in diameter. They can present as a solitary lesion or cluster of several lesions. These lesions can be painful and have been associated with lymphedema, Mafucci syndrome, and Klippel–Trenaunay syndrome. These are mostly superficial lesions limited to the dermal and subcutaneous tissues. On MRI, they have low T1 signal and lobulated high T2 signal, often with phleboliths due to abnormal venous vessels. The most common treatment is surgical excision. While imaging is of limited utility, in select cases it can be helpful prior to treatment to characterize extent and when extensive reconstruction is expected [17, 18].

Epithelioid hemangiomas, previously named angiolymphoid hyperplasia with eosinophilia, are slow growing vascular lesions that present as one or more nodules in the soft tissues. It can also occur within osseous structures. It is most common in patients in their third through sixth decade of life with a mean age of onset in the early 30s. These lesions most commonly occur in the head and neck, most commonly in the periauricular region [19, 20]. These usually present as small erythematous dermal nodules in the head and neck, bleed easily and can itch [21]. Scarce literature is found on imaging characteristics of epithelioid hemangiomas, most reported as case reports. Soft tissue lesions have been described as well-circumscribed periorbital masses or as diffuse thickening and/or enlargement of the lacrimal gland [22]. Osseous lesions tend to present as well-defined expanding lytic lesions with thinned or destroyed cortex. MRI lesions have been described in literature as T1 hypointense, intermediate signal intensity on T2 with variable enhancement [23] (Fig. 3). Imaging plays a key role in determining extent especially when extensive reconstruction is expected as these lesions have been shown to involve the orbit, airway, and external auditory canal [24, 25].

Pyogenic granulomas, also known as lobular capillary hemangiomas, are relatively common and commonly present as a angiomatous pedunculated polyp or papule. These lesions commonly occur on the forehead and check, but can also occur on the mucosal surface including the conjunctiva and oral mucosa. These lesions most often occur secondary to prior trauma, infection, burns, and even pregnancy [26‐28]. These lesions are usually first found on clinical examination often presenting as enlarging lesions over the course of a few weeks often with bleeding and ulceration. The underlying pathogenesis of these lesions is still unclear; historically, these were thought to be reactive hyperplasia. However, recent genetic studies showing mutations in BRAF, RAS, and GNA14 suggest that this is truly a benign neoplastic process. Sonographic evaluation usually demonstrates hypoechoic nodules in the region of interest with marked internal vascularity [29]. On MRI, these lesions present as T1 iso-intense to muscle with variable T2 signal. As expected, these lesions demonstrate avid enhancement [30]. Imaging can be used to guide biopsy and excision in more extensive cases.

Kaposiform hemangioendotheliomas are the most common aggressive vascular tumors, but still rare with a reported incidence between .07 and .091 per 100,000 children, presenting usually within the first year. It is an enlarging cutaneous lesion often associated with thrombocytopenia and pain. The majority of these lesions occur in the extremities, but about one-fifth occur in the head and neck region. On imaging, it is an ill-defined region of soft tissue thickening that crosses multiple planes. On T2-weighted imaging, the lesions demonstrate a hyperintense mass with an ill-defined margin that crosses multiple soft tissue planes. Additionally, there can be stranding of the subcutaneous fat, hemosiderin deposits, and destructive changes in the adjacent bone [31] (Fig. 4). This lesion is associated with GNA14, thought to act via a MAPK upregulation [32]. It is usually treated with propranolol and corticosteroids along with chemotherapeutic agents, classically vincristine. More recently, there has been good clinical success with mTOR inhibitors such as everolimus and sirolimus [33‐35].

In addition to these, there are several other less common hemangioendotheliomas. These mainly affect adults. Overall, these commonly present as a solitary or several nodules in the skin, but can be seen elsewhere. They generally have a low metastatic potential, but can and often recur locally. Retiform hemangioendothelioma is a rare tumor with few cases and only one noted on the face. It has been shown to present as a dermal or subcutaneous nodule with slow growth over the course of months to several years. It is most common among young and middle-aged adults [36, 37]. These are similar to pseudomyogenic hemangioendothelioma [38]. Polymorphous hemangioendothelioma are extremely rare and characterized by varying patterns in different tumor areas. This is similar to composite hemangioendothelioma, which are actually composites of other types of hemangiomas. This variant can also include parts that resemble angiosarcoma [39].

Papillary intralymphatic angioendothelioma (PILA), also known as Dabska Tumor, is a rare locally aggressive tumor that involves the skin and subcutaneous tissues, with few case reports reporting lesions in the bone and other organs. It rarely metastasizes. On imaging, it has been shown to demonstrate aggressive features with isointense T1, heterogeneously increased T2 signal, and variable enhancement that can invade adjacent structures and demonstrate infiltrative characteristics [40, 41].

Lastly, there is Kaposi sarcoma (KS), a mesenchymal tumor that arises from lymphatic endothelial cells first described in 1872 [42]. KS garnered attention in literature and worldwide in the 1980s for its association with acquired immune deficiency syndrome (AIDS) [43]. Kaposi sarcoma herpesvirus/human herpes virus 8 (KSHV/HHV8) was identified in 1994 and plays a key role in the pathogenesis of KS, particularly in the setting of immune dysregulation [44, 45].

KS is divided into four variants: classic, endemic, iatrogenic (most commonly post-transplant), and AIDs related. Classic and endemic KS have a more indolent course and typically do not require imaging evaluation. Iatrogenic and AIDS-related KS are much more aggressive and often present with disseminated disease [43]. There has been significant decrease in AIDS-related cases since the introduction of highly active antiretroviral therapy (HAART) [46].

Conversely, due to increase number of transplants, biologic treatment, and long-term immunosuppression, the iatrogenic variant has been increasing in incidence [47, 48]. Patients typically present with multiple characteristic purple macules and papules, which can coalesce to form large plaques and tumors on the skin and can involve multiple organs. Cutaneous involvement is the most common presentation in head and neck KS seen in 66% of cases, 56% involve the mucosa, most commonly intraoral and laryngeal-pharyngeal mucosa, with the remainder presenting with isolated lymphadenopathy without papules. KS can be multifocal, which helps to differentiate it from other lesions [45, 49, 50]. CT and MR characteristics of KS are multiple nodular or polypoid lesions in the skin or mucosa. These lesions can vary in size and can infiltrate deep tissue however do not typically ulcerate. They most commonly demonstrate avid, enhancement on post-contrast imaging, however, can present as subtle asymmetries in the valleculae and pyriforum sinus [51]. In cases that present as isolated lymphadenopathy, it is important to have a good clinical history to help early diagnosis.

Angiosarcoma is a rare aggressive soft tissue malignancy arising from endothelial cells. Overall survival is approximately 6 to 16 months as these tumors have a propensity to recur and metastasize [52]. Angiosarcoma can occur at any age with the reported median age between 60 and 71 years [53]. There is a male predilection for soft tissue angiosarcomas; however, the incidence of deep soft tissue and parenchymal tumors is the same in men and women [52, 54]. Approximately 50% of angiosarcomas occur in the head and neck soft tissue, particularly the scalp; 10% occur in the deep soft tissue including the peritoneum, retroperitoneum, and mediastinum; and the remainder present in parenchymal organs including breast, bone, and liver. Lung and bone are the most common site for metastasis through hematogenous spread. The two most common risk factors are chronic lymphedema and radiation therapy [55]. Patients often present with skin lesions such as an enlarging bruise, a discolored nodule, or persistent ulceration. In the early stages, these lesions can be misdiagnosed for benign entities caused by cellulitis, infection, or skin injuries [56]. Typical imaging characteristics include intermediate T1 signal intensity and high T2 heterogeneity with avid enhancement. Flow voids or high-flow serpentine loss of signal on T1 and T2 imaging in a soft tissue mass is characteristic of the lesions [57]. On contrast-enhanced CT, lesions are typically irregular, enhancing soft-tissue masses with possible invasion of adjacent osseous and parenchymal structures [56] (Fig. 5).

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor first described in 1975 as an aggressive bronchoalveolar cell carcinoma [58]. Later named EHE by Weiss and Enzinger in 1982 for its similar features between a hemangioma and angiosarcoma [58]. EHE is exceedingly rare and accounts for 1% of all vascular malignancies; it is often misdiagnosed at presentation. Most commonly it affects the lungs, liver, or bones, although can present in the head and neck area, mediastinum, among many other sites. EHE is often incidentally diagnosed and over 50–76% of patients are asymptomatic. Typically, the lesion presents in patients between the age of 30 and 50 years [59, 60]. There is limited literature describing imaging characteristics of EHE involving the head and neck, but aggressive features can suggest the diagnosis (Fig. 6).

The lesions discussed above are not inclusive of all vascular malignant vascular tumors; there are others, which are exceedingly rare and mostly differentiated on pathology.