Dermatology

Tufted angioma (Angioblastoma of Nakagawa, progressive capillary hemangioma)

Are You Confident of the Diagnosis?

What you should be alert for in the history

Tufted angioma (TA) is a vascular tumor that is less common than entities such as infantile hemangioma (IH), port wine stains, and venous malformations; however, the diagnosis should be considered in the differential of slowly growing vascular tumors that present in early childhood. The most common locations are the upper chest, back, shoulders, and neck, although other locations are not unusual.

Characteristic findings on physical examination

The morphology of TA is varied, and may include poorly defined solitary nodules, infiltrating or thick plaques, or an area with nodularity or cobblestoning. Most often, the color is a dusky red to violaceous hue (Figure 1, Figure 2, Figure 3).

Figure 1.

Typical morphology of tufted angioma. (Courtesy of Ilona Frieden, MD)

Figure 2.

Tufted angioma. (Courtesy of Ilona Frieden, MD)

Figure 3.

Larger tufted angioma. (Courtesy of Ilona Frieden, MD)

Focal hyperhidrosis or hypertrichosis overlying the lesions can be an important clinical clue to diagnosing TA, with a lanugo-like appearance to the hairs (Figure 4). Many TAs also have an overlying vascular stain. This stain is often more dull red, red-brown, violaceous, or hyperpigmented than typical port-wine stains. There may be associated tenderness with palpation and even paroxysmal episodes of pain within the lesion.

Figure 4.

Tufted angioma with hypertrichosis. (Courtesy of Ilona Frieden, MD)

TA may be congenital or acquired later in life, but is most often present during infancy or early childhood. In one series, half of patients presented at younger than 5 years of age, and the remainder were younger than 10 . That being said, there are numerous individual case reports describing the onset of TA in adults.

Many TAs are initially noted as a bruise-like patch, but the evolution of the disease varies considerably. Some lesions remain stable in size over time. Most grow in an indolent fashion, extending their surface area slowly over time, but occasionally they expand rapidly, particularly in the setting of Kasabach-Merritt phenomenon (KMP) (Figure 5). Some TAs partially or even completely regress; however, there are currently no good clinical or histologic clues to predict the future behavior of a tufted angioma. Malignant transformation has not been reported.

Figure 5.

Tufted angioma with Kasabach-Merritt. (Courtesy of Ilona Frieden, MD)

Expected results of diagnostic studies

When a TA is suspected by exam and history, a skin biopsy is required to confirm the diagnosis (Figure 6).

Figure 6.

"Cannonball" clusters of glomeruloid capillary proliferations separated by dermis (H&E). (Courtesy of Ilona Frieden, MD)

Biopsy and histopathologic evaluation usually reveals a classic “cannonball” distribution of tightly packed vessels, scattered at various levels within the dermis and superficial subcutis. Often, these vessels form tufts, which are encircled by an empty crescent-shaped vessel surrounded by a fibrous dermis.

TA can mimic Kaposi’s sarcoma (KS) histologically, even demonstrating intracellular and extracellular hyaline bodies. However, TA manifests less nuclear atypia than KS, and mitotic activity is lower as well. KS lacks the classic “cannonballs” and characteristically shows a few plasma cells among the tumor cells. It also usually stains positively for human herpesvirus 8 (HHV-8), whereas TA does not.

IHs usually have a distinct architecture, with lobules of endothelial channels separated by fibrous bands. The cells in IH are GLUT-1 immunoreactive, in contrast to TA.

The high-power microscopic features of TA may be indistinguishable from kaposiform hemangioendothelioma (KHE), although immunostains for the endothelial markers CD34 and HHF-35 actin, as well as the lymphatic D2-40, may help separate the two diagnoses.

D2-40 seems to be markedly reactive in KHE lesions, whereas it is only partially positive in surrounding vessels and negative in the “cannonball”-like proliferative capillaries that classically occur in TA. Prox1 staining may be increased in the neoplastic spindle cells of TA and KHE. Its presence may reflect a more aggressive biologic behavior in terms of growth and local infiltration.

The histologic and clinical similarities between TA and KHE, as well as reports of their simultaneous presence within the same tumor, has led some to believe that these entities may actually represent one condition, with a spectrum of histologic findings based on anatomic location, depth of biopsy, or stages of evolution of the tumor. Cases of TA transforming into KHE and vice versa also support that these tumors lie closely within the same neoplastic spectrum.

In practice, the management of these tumors is somewhat similar, and their distinction is perhaps more academic than practical.

That said, the features of KHE are more likely to be mediastinal and retroperitoneal in location, with a higher propensity for the development of KMP, invasion of major vital organs, infiltrative growth, and local aggressiveness. In contrast, TA is usually confined to the skin as a solitary, noninfiltrative or locally invasive tumor. Therefore, the management of TA can usually be less aggressive in nature than KHE (as discussed further below and in the CDS Dermatology chapter specifically dedicated to KHE).

Laboratory tests that may be important in the workup of TA include a basic screen of coagulation factors; particularly complete blood count with platelets, D-dimers, and fibrinogen, but also prothrombin time (PT), partial thromboplastin time and international normalized ratio (INR).

The identification of an associated coagulopathy can support, but is not specific to, the diagnosis of TA. KHE, venous malformations, and other benign vascular proliferations can manifest a similar associated coagulopathy. The presence or absence of coagulopathy associated with TA has important implications for management. If one suspects KMP within the lesion, then these laboratory studies should be done prior to biopsy to assess bleeding risk in order to choose the appropriate biopsy venue (outpatient vs. operating room).

KMP is more of a concern in larger, rapidly expanding, or acutely symptomatic lesions. It may also be heralded by sudden change in texture, with increased fullness and firmness of the TA, or signs of coagulopathy such as nosebleeds, widespread bruising, bleeding gums, or petechiae on the skin.

For larger lesions, magnetic resonance imaging (MRI), with and without contrast, is the best study to delineate the size and extent of the tumor. This may be helpful to evaluate for encroachment into vital structures, and to plan surgical intervention.

MRI findings of TA clearly differ from those of common IH, which show well defined margins, a lobulated architecture, and uniform enhancement with flow voids. In contrast to IH but similar to KHE, TA characteristically involves a diffuse, enhancing, T2 hyper-intense lesion, with ill-defined margins and multiple tissue planes, with cutaneous thickening, subcutaneous stranding, and edema.

Gradient-echo images may demonstrate hemosiderin. Superficial feeding and draining vessels are less frequent and less prominent than with common hemangioma. Clinical correlation is often required to differentiate TA from various other slow-flow benign vascular proliferations such as venous malformation and mixed venous-lymphatic malformation radiographically (Figure 7).

Figure 7.

Tufted angioma showing characteristic high T2 signal and enhancement at the periphery within the subcutaneous fat of the thigh. (Courtesy Christopher Hess, MD, PhD)

Diagnosis confirmation

Other vascular proliferations can have a similar clinical presentation. The differential diagnosis includes IH, port wine stain, lymphatic malformation, hemangiopericytoma, myofibroma, and other benign vascular proliferations. KS and other malignant vascular tumors may resemble TA. Infantile fibrosarcoma and rhabdomyosarcoma can also present in early infancy as growths with a violaceous or highly vascular appearance, but are usually more exophytic.

The clinical course of the more common IH is somewhat different from TA. While both can be present at or soon after birth as a red macule or patch, the color of IH is usually much brighter red than TA, and often there is more of a telangiectatic component and/or some peripheral blanch that is usually not present in TA; however, some lesions may more difficult to clinically differentiate from IH, particularly when comparing very superficial TAs (which can be more red) and hemangiomas with less of a superficial component (which can have a subtle bluish hue).

With palpation, IH (with the exception of during the first few weeks of life) are often softer or more “doughy” feeling compared to TA, which is typically firmer with palpation. In contrast to TA, IH is rarely painful or tender unless ulcerated. TAs also may continue to slowly expand, even beyond 12-18 months, an age when most IH have completed their growth.

TA is most often a solitary lesion, whereas IHs, while often solitary, can occur in multiple locations on a single patient. IH never demonstrates associated KMP, although anemia and a mild thrombocytopenia and congestive heart failure have been reported in very large or multiple intrahepatic or visceral hemangiomas. However, it is prudent to re-evaluate a clinical diagnosis of IH and consider TA or KHE in the setting of a patient with a vascular tumor and rapidly dropping platelets (Figure 8).

Figure 8.

Infantile hemangioma on scalp. (Courtesy of Ilona Frieden, MD)

Two other hemangiomas, rapidly involuting congenital hemangiomas (RICH) and non-involuting congenital hemangiomas (NICH) are also considerations in differential diagnosis. Unlike TAs, which (if present congenitally) often enlarge after birth, both RICH and NICH are present at birth but do not increase in size postnatally. They usually occur on the head, neck, and extremities, and are less common on the trunk then TA (Figure 9).

Figure 9.

Typical NICH on extremity. (Courtesy of Ilona Frieden, MD)

RICH usually have a distinct appearance, presenting as a well-demarcated elevated soft-tissue tumor with radiating telangiectasias and a surrounding rim of pallor. Central eschar or depression may be present. NICH are usually flatter than RICH and present as a well-circumscribed, round to oval, slightly indurated or raised, soft-tissue mass with a blue-purple collar or with coarse superficial telangiectasia and rim of pallor.

Both NICH and RICH have high-flow components evident on Doppler interrogation, a finding not typically present in small- and medium-sized TA. IH, RICH, and NICH do not manifest associated coagulopathy, but a mild to moderate thrombocytopenia can occur occasionally. This is most likely related to shear forces within these high-flow lesions causing platelet destruction.

Spindle cell hemangiomas usually present on the extremities as vascular papules. They often arise in pre-existing vascular abnormalities such as the venous malformations present in Klippel-Trenaunay syndrome. They have also been found to be associated with Mafucci’s syndrome. Their histology is distinct, with cavernous vascular spaces that do not occur in TA.

Venous malformations are soft blue compressible nodules or plaques that may slowly expand with time. They usually do not grow as quickly in a radial fashion. Venous malformations can also manifest a low-grade localized intravascular coagulopathy, with elevated D-dimers and decreased fibrinogen; however, this usually only occurs in larger lesions and venous malformations do not exhibit true KMP.

The coagulopathy in these lesions results from stasis. With extensive venous malformations, localized intravascular clotting can lead to evidence of a systemic coagulopathy, but low platelet counts are rare and virtually never drop below 50,000-60,000 per cubic millimeter. D-dimers may be elevated and fibrinogen low in both conditions.

A rare, but interesting, entity that should be considered on the differential diagnosis of vascular malformations with an associated KMP-like coagulopathy and thrombocytopenia is multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT). In this disease, multifocal, red-brown to burgundy, flat plaques or indurated papules are usually present on the skin, sometimes with overlying scale; in other cases, small red and blue papules predominate.

The lesions have a unique histology, with dilated LYVE-1 (a lymphatic marker)-positive vessels that often contain characteristic endothelium-lined intra-luminal projections. Most cases describe hundreds of similar lesions, some with scar-like central areas and others with a central pallor. Usually, many lesions are present on the skin at birth, with subsequent progression in number over time, without regression.

In the cases described thus far, gastrointestinal (GI) bleeding in infancy is also characteristic. Patients with MLT often present with the cutaneous lesions, GI bleeding, and a coagulopathy that resembles KMP in its features, with moderate to severe fluctuating thrombocytopenia. This entity can easily be differentiated from TA by its multifocal nature (which is unusual in KHE), the characteristic GI involvement, and its unique histology.

Who is at Risk for Developing this Disease?

TA most often occurs during infancy or early childhood. There are rare reports of congenital and adult onset. There is no known sex or ethnic predominance. Most cases are sporadic, although familial cases have been rarely reported.

What is the Cause of the Disease?

Etiology

TA is a benign vascular tumor that is thought to originate from stem cells possessing the characteristics of both blood and lymphatic vessel lineages. Some have postulated that TAs represent the more endothelial differentiation of this progenitor cell, while KHE represents a more lymphatic differentiation.

Pathophysiology

The reasons for and mechanism of vascular proliferation are unclear. Some have postulated that high estrogen levels may promote proliferation of TA (because of cases arising in pregnancy). Others have interpreted the behavior of TA as more of a “reactive” process, akin to pyogenic granuloma, and consider it related to changes in vascular growth factor milieu caused by trauma or other triggers.

Systemic Implications and Complications

The clinical implications of TA vary widely, depending on anatomic location, size of the tumor, and biologic behavior. If there is a concern for the mass effect of the tumor causing functional issues or encroachment into vital structures, then MRI with and without contrast, is the best imaging technique to evaluate the extent and size of the lesion.

An associated coagulopathy may be present, ranging in severity from mild and low-grade to full-blown KMP. For this reason, patients with TA should have laboratory studies, including fibrinogen, D-dimer, and platelet count as well as PT, PTT, and INR. These can help can determine which of the following three clinical scenarios a patient with TA falls within.

1. TA without thrombocytopenia or coagulopathy

In this scenario, a TA is present, with no associated systemic abnormalities in coagulation factors or platelets.

2. TA without thrombocytopenia but with chronic low-grade coagulopathy (due to low-level chronic clotting within the tortuous vessels of the TA)

In this scenario, a TA is present, and mild low-level, chronic clotting occurs within the lesion. This will be reflected by an elevated D-dimer and a decrease in fibrinogen, sometimes with slightly low or low-normal platelet levels. This is presumably due to vascular sludging within the abnormal and tortuous endothelial-lined channels of the tumor. There is minimal platelet trapping and the TA does not always acutely change in appearance or firmness, but may become more tender, “lumpy,” or indurated than in patients without coagulopathy.

3. TA with associated KMP.

In this scenario, platelet trapping within the TA results in a severe consumptive coagulopathy, known as KMP. This rare condition was originally described by Kasabach and Merritt in 1941, and was thought to be a complication of IH; however, by the 1990s, it was recognized that KMP does not occur in IH, but rather in TA and KHE. The lesions of patients with KMP will often have marked enlargement, increased tenderness, increased intensity of violaceous color, and purpura extending beyond the apparent clinical borders of the tumor.

Multiple case series have shown that perhaps 90% of KMP are secondary to KHE, with most others related to TA. Therefore, this scenario is discussed more fully in the CDS Dermatology chapter devoted to KHE. The principles of management are the same for TA with KMP as they are for KHE with KMP.

Classification of the patient into one of the above categories will facilitate selection of the appropriate treatment and management strategy.

Treatment Options

Treatment options are summarized in Table I.

Table I.

Treatment options for TA.
Medical Therapy Surgical Therapy Physical Modalities
Aspirin, dipyridamole, or ticlodipine—for symptoms and prevention, coagulopathy/KMP
Systemic corticosteroids—successful in less then 10% tumors (to actually decrease tumor bulk) Surgical excision Embolization—sometimes combined with surgery
Vincristine Pulsed dye laser
Interferon alpha-2a—after the age of 1, less risk of spastic diplegia Argon laser
Topical or injected steroids—for symptoms only Radiotherapy—if risk outweighs benefit
Rapamycin (sirolimus), other anti-angiogenic, or chemotherapy Cryotherapy—usually not effective

Optimal Therapeutic Approach for this Disease

The rarity of TA makes the evidence on which to base treatment scarce and mostly anecdotal in nature. Often, the best intervention for a patient is no intervention at all, but treatment is quite dependent on the clinical situation. One must consider location, rapidity of growth, and coagulation study status when choosing the therapeutic approach.

1. TA without thrombocytopenia or coagulopathy

In smaller tumors, when there is no encroachment upon vital structures, no functional problems, and no systemic complications, a conservative approach may be appropriate. Watchful waiting will allow the clinician to determine if the TA will spontaneously regress on its own, which has been reported to occur in some instances.

If more aggressive treatment seems to be indicated, then systemic, surgical, or other physical modalities may be necessary. This would be analogous to the situation when an IH warrants aggressive therapy because it is causing ocular complications, airway complications, or disfigurement of a cosmetically sensitive area such as the central face.

For localized lesions, early excision is suggested to avoid expansion of the lesion and the need for future systemic therapy with agents that have shown variable efficacy and are not benign in their side effect profiles. Unfortunately, recurrences are not uncommon after excision.

Cryotherapy, electrocautery, and radiotherapy have been attempted in individual cases, with little success and high rates of recurrence. In the setting of aggressive growth or KMP, embolization of TA can sometimes be effective, particularly either pre-operatively or if the lesion is symptomatic, yet not amenable to surgical resection.

Pulsed dye laser has been used with variable results and most likely is more effective for a small superficial TA. In one reported case of a 7-year-old with TA , five treatments with a 585nm pulsed dye laser, using a 7mm spot size, 0.45 microsecond pulse width, and fluences increasing from 6.5-8 joules/cm2 resulted in noticeable lightening of the lesion, decrease in pain, and no recurrence for two years. Some atrophic scarring did result at these settings.

One article mentions successful lightening and resolution of TA in an adult after treatment with an argon tunable-dye laser after failure with pulsed dye laser; another details a good response to intense pulsed light. Other reports describe lesions treated with pulsed dye laser without success, likely due to deeper involvement that was not accessible to laser therapy.

Aspirin, typically in doses of 5 to 10mg/kg/day, has also been effective and can diminish pain, and in some cases soft-tissue swelling, in KHE, even in the absence of laboratory evidence of a coagulopathy (Figure 10). It may help prevent platelet trapping and KMP as well.

Figure 10.

TA after KMP treated and on aspirin. (Courtesy of Ilona Frieden, MD)

Adverse side effects such as hemorrhage, gastritis, and rare anaphylactic reactions must be considered. In pediatric patients, Reye’s syndrome is also a concern. This syndrome, involving mitochondrial dysfunction, leads to liver failure, encephalopathy, and death in 30-40% of cases.

It has usually been reported with higher dose (much greater than 5-10mg/kg/day) aspirin use in association with influenza or varicella. Consequently, children utilizing chronic aspirin therapy should have varicella vaccination prior to initiating therapy, a yearly flu shot, and close monitoring during a flu-like illness.

If these precautions are taken, we believe the risk of Reye’s is outweighed by the benefit to most patients in this setting; however, prospective trials evaluating the risks and benefits of aspirin in the treatment of KHE or other vascular malformations have not been conducted on a large enough scale to definitively answer this question.

Reports of efficacy with similar antiplatelet agents such as ticlodipine (10mg/kg/day) indicate that these responses are likely related to improvement in local platelet trapping rather than true decrease in lesion size. Multiple reports seem to indicate that sometimes KMP in KHE can be averted or even reversed using antiplatelet agents alone. Dipyridamole (1.5mg/kg/day) has also been shown in some series to be effective in bringing platelet levels up in the face of KMP.

Systemic corticosteroids have been used as a treatment for TA with some success. As with IH, the doses utilized range from 2 to 5mg/kg/day during the initiation phase of therapy. This treatment approach seems to be more successful in the setting of coagulopathy and/or platelet trapping and in KMP than in treating TAs without coagulopathy. Durable tumor size reduction occurs in less than 10% of lesions with steroids.

Vincristine has also been reported at the case report level as a therapy for TA. It has been used as monotherapy or in combination with steroids in life-threatening KMP. It can also be used in conjunction with excision to prevent recurrence and shrink remaining tumor burden. Typical dosing is 0.25mg/kg/weekly for many weeks, depending on response. Indwelling venous access is typically needed for administration of vincristine.

If systemic agents are required to shrink tumor, then vincristine is probably a better option than IFN-alpha-2a in children less than the age of 1 year because of the spastic diplegia issue discussed below.

Interferon alpha-2a (IFN-alpha-2a) at a dose of 1 million international units/m2 in children, and 1-3 million international units (MU) subcutaneously in adults, three times a week, has often been described as the first-line treatment of choice for systemic therapy if lesions are not amenable to local excision. The exact mechanism of this medication is unknown, but it seems to have anti-angiogenic properties that inhibit endothelial cell proliferation.

Interferon seems to stop proliferation in some cases, and has even led to tumor shrinkage in other reports, but there are also multiple case reports describing TA unresponsive to this therapy. Spastic diplegia and motor disturbances are a major risk of interferon therapy in children less then age one.

In one meta-analysis, 27 out of 441 children treated with interferon alpha developed neuromotor complications. All of these children were less than 1 year of age. Although minor motor disturbances usually correct after treatment is stopped, spastic diplegia often does not. Therefore, interferon should only be considered in this age group (<1 year old) if risk from the tumor is felt to outweigh risk of motor disturbance/spastic diplegia.

If utilized, baseline neurologic assessment and serial examinations are essential during interferon treatment. The side effects of interferon treatment can be uncomfortable in older patients. Adults often report flu-like symptoms, headache, abdominal pain, fatigue, nausea, and weakness. Interferon response does not seem to correlate with markers of vascular proliferation like urinary basic fibroblast growth factor levels.

The dosing, side effect profiles and practical aspects of utilizing systemic corticosteroids, vincristine, interferon alpha-2a, and other systemic agents are discussed in more detail in the CDS Dermatology chapter devoted to KHE, as they are more often necessary in this setting. The principles of management for very large extensive TA (or TA with KMP) are the same as for large extensive KHE (or KHE with KMP).

2. TA without thromboctypenia but with chronic low-grade coagulopathy

As discussed above, TA can often have a low-grade type of coagulation within the lesion rather than full-blown KMP. We feel that this can contribute to associated symptoms and even enlargement of the lesion. Theoretically, the remodeling associated with this coagulopathy may even contribute to angiogenesis and spread of the lesion. Clues to this include elevated D-dimers and decreased fibrinogen, with low normal or slightly decreased platelets.

When TA presents in this setting, aspirin can often be helpful in reversing the coagulopathy and normalizing the coagulation laboratory studies, and in decreasing symptoms and lesion size or firmness. This can be accomplished using 5-10mg/kg/day of aspirin on a chronic basis.

Although Reye’s syndrome is a concern in younger children (particularly in the setting of influenza or varicella), its rarity and the decrease in varicella incidence because of vaccination has made us more comfortable that benefit often outweighs risk for long-term use of aspirin therapy in the setting of vascular malformations. Of course, this calculation must be made on an individual basis for a given patient, dependent on their clinical situation.

Families should be instructed to stop therapy with aspirin if signs and symptoms of influenza, varicella, or (perhaps) any febrile illness occur; however, hypercoagulability can worsen in the setting of illness and dehydration, so the importance of hydration during illness should be emphasized. Ticlodipine 10mg/kg/day is another option if there is a contraindication to aspirin or additional therapy is required to control the coagulopathy. This therapy, like aspirin, interferes with platelet function.

3. TA with thrombocytopenia and a consumptive coagulopathy (true KMP):

The treatment of true KMP is complex and beyond the scope of this publication. Reference the KMP chapter of Decision Support in Medicine for discussion regarding treatment of the acute severe platelet trapping and consumptive coagulopathy involved in KMP.

Therapeutic approach is also discussed in more detail in the CDS Dermatology chapter devoted to KHE. This is because this situation is much more common in the setting of KHE. The principles of treatment discussed in the KHE chapter are very applicable to KMP in TA.

Patient Management

TAs usually appear in early childhood, most often in infancy. Most TAs expand slowly, in a radial fashion, for a period of months up to 10 years, and then stabilize. Some slowly diminish in size and others spontaneously regress. Therefore, clinical follow-up is of the utmost importance to characterize the trajectory of growth and changes in appearance of the lesion. Photographic documentation can be quite helpful in this respect.

If the lesion is not disfiguring, growing quickly, or causing complications, then watchful waiting may be an appropriate approach to management; however, it behooves the clinician to warn parents or patients that the time to regression is usually not a short one.

In one review of spontaneously regressing TA, the large majority of cases (86%) did not regress in less than 3 months. On the other hand, in cases of regression described in this review, almost all attained full regression in less than 2 years. Therefore, the authors (Ishikawa et al. 2005) recommend that an appropriate wait for spontaneous regression might be between 6 months and 2 years.

The lack of large-scale studies makes it difficult to predict the time course to regression or identify definitive characteristics, locations, or behavioral cues that might determine which TAs are more likely to regress spontaneously.

If the diagnosis is made of a lesion at an early stage, the size is small, and the lesion is in a cosmetically sensitive area; or, if the lesion is in an area that may lead to functional issues in the future, we would probably recommend a trial of pulsed diode or argon laser to try to eliminate or slow the growth of the lesion. If this fails or is unavailable, one might consider surgical excision, at an early time, to prevent having to perform larger procedures later, once full radial growth has occurred.

Embolization may be a good choice for shrinking larger tumors prior to other interventions; however, it is almost always necessary to combine embolization with other modalities for definitive treatment.

All patients with TA, particularly those with symptoms or larger lesions, deserve screening for coagulopathy, with coagulation studies to guide management.

Parents or patients should be particularly warned about the signs and symptoms of KMP in a TA. These include: rapid expansion of the lesion, acute increase or change in symptoms (particularly pain) in the lesion, sudden change in texture with increased fullness and firmness of the TA, and signs of coagulopathy such as nosebleeds, widespread bruising, bleeding gums, or petechiae on the skin (usually occurs when platelet levels fall below 10,000 per cubic millimeter). KMP is a medical emergency, and if these signs or symptoms occur, the patient should be evaluated immediately.

If the TA is not in a cosmetically sensitive area, does not seem to have potential for functional impairment (i.e. airway, eye involvement, or other), and the parents or patient feel comfortable, then watchful waiting with close follow-up is quite appropriate, with aspirin or ticlodipine for treatment of mild symptoms such as slow swelling or mild coagulopathy.

Topical or injected steroids (kenalog 10mg/ml) may also be effective for symptom control in this setting, but in our experience do not work as well as aspirin. The nonmalignant nature of the lesion and lack of progression to malignancy should be emphasized to parents or patients. The benign behavior of the lesion makes aggressive treatment unnecessary unless the clinician’s hand is forced by conditions.

Often, the management of TA is complex and multimodal. Therefore, if the resource is available, evaluation of the patient in a multispecialty vascular anomalies clinic is recommended. This will allow experts in medical or pediatric dermatology, lasers, interventional-radiology, plastic surgery, and other relevant specialties to confer and tailor the therapeutic plan to this diversely presenting vascular tumor.

Unusual Clinical Scenarios to Consider in Patient Management

Cases of eruptive TA have been reported in immunocompromised patients. In two of these cases, the lesions regressed spontaneously. One of these cases involved a patient with Crohn’s disease on azothioprine who resolved when switched to infliximab; another occurred in a liver transplant patient who was also immunosuppressed and had spontaneous resolution.

There have also been rare reports of multifocal presentations in infants. There have been a small number of cases of acquired TA associated with pregnancy, which have caused some to question the role of estrogen in the proliferation of these vascular lesions (analogous to pyogenic granulomas in pregnancy). Also, as happens with pyogenic granuloma, satellite lesions have been reported to appear after treatment with surgical excision, perhaps due to changes in cytokine milieu.

Other, even less common, presentations have been described. One patient had a TA assocated with non-regressing lipodystrophia centrifugalis abdominalis, an atrophy of the abdominal or chest wall in infants. The development of a TA within a pre-existing nevus flammeus and port wine stain have also been reported.

TA and KHE are on a spectrum, and there are reports of biopsies that show features of both. Most researchers in the field are coming to believe that these two entities exist on a spectrum and may even be different stages of evolution of the same histopathologic process. Some lesions have been known to transform from TA to KHE or vice versa. KMP has been associated with TAs and KHEs, further linking the two entities.

What is the Evidence?

Okada, E, Tamura, A, Ishikawa, O, Miyachi, Y. "Tufted angioma (angioblastoma): case report and review of 41 cases in the Japanese literature". Clin Exp Dermatol. vol. 25. 2000. pp. 627-30.

(One of the larger case series of this rare tumor. This article provides insight into the epidemiology, morphology, and clinical behavior of TA.)

Ishikawa, K, Hatano, Y, Ichikawa, H, Hashimoto, H, Fujiwara, S. "The spontaneous regression of tufted angioma. A case of regression after two recurrences and a review of 27 cases reported in the literature". Dermatology.. vol. 210. 2005. pp. 346-8.

(Summarizes the twenty-seven reported cases of TA with spontaneous regression. Major finding is that most of these cases showed regression within 6 months to 2 years.)

Mahendran, R, White, SI, Clark, AH, Sheehan-Dare, RA. "Response of childhood tufted angioma to the pulsed-dye laser". J Am Acad Dermatol.. vol. 47. 2002. pp. 620-2.

(There have also been reported cases of treatment failures with pulsed-dye laser and successes with tunable argon lasers and intense pulsed light.)

Suarez, SM, Pensler, JM, Paller, AS. "Response of deep tufted angioma to interferon alfa". J Am Acad Dermatol. vol. 33. 1995. pp. 124-6.

(The first report of success shrinking TA with interferon alfa. There have been multiple others since but also some reports of failure.)

Munn, SE, Jackson, JE, Jones, RR. "Tufted haemangioma responding to high-dose systemic steroids: a case report and review of the literature". Clin Exp Dermatol. vol. 19. 1994. pp. 511-4.

(Discusses treatment of TA with systemic steroids. As discussed above however, the rapid response may be more related to treatment of the platelet trapping syndrome [KMP] rather then actual tumor shrinkage.)

Ferrandiz-Pulido, C, Mollet, J, Sabado, C, Ferrer, B, Garcia-Patos, V. "Tufted angioma associated with Kasabach-Merritt phenomenon: a therapeutic challenge". Acta Derm Venereol. vol. 90. 2010. pp. 535-7.

(Provides insight into the usage of vincristine in combination with excision to prevent recurrence and treat and tumor left post-excision.)

Ramesh, R, De Silva, B, Atherton, DJ. "Congenital tufted angioma with persistent low-grade coagulopathy". Clin Exp Dermatol. vol. 34. 2009. pp. e766-8.

(One of the few articles to discuss that TA can be associated with a persistent low-grade coagulopathy, much in the same way that venous malformations can. This is in contrast to the acute consumptive coagulopathy found in KMP. In this report, the patient was just observed.

Léauté-Labrèze, C, Bioulac-Sage, P, Labbé, L, Méraud, JP, Taïeb, A. "Tufted angioma associated with platelet trapping syndrome: response to aspirin". Arch Dermatol. vol. 133. 1997. pp. 1077-9.

(Discussion of treatment of the above phenomena of low-grade coagulopathy in TA. In this case, the coagulopathy was treated with aspirin and ticlodipine, with resolution of symptoms.)

Osio, A, Fraitag, S, Hadj-Rabia, S, Bodemer, C, de Prost, Y, Hamel-Teillac, D. "Clinical spectrum of tufted angiomas in childhood: a report of 13 cases and a review of the literature". Arch Dermatol. vol. 146. 2010. pp. 758-63.

(A more recent review of the literature, with good discussion of the clinical heterogeneity of TA)

Arai, E, Kuramochi, A, Tsuchida, T, Tsuneyoshi, M, Kage, M, Fukunaga, M. "Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma". J Cutan Pathol. vol. 33. 2006. pp. 492-7.

(Discussion of histopathology of TA and KHE, and the usage of markers to differentiate the lesions)
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