Tufted Angioma 

Updated: Apr 26, 2017
Author: Alexandra R Vaughn; Chief Editor: Dirk M Elston, MD 

Overview

Background

Tufted angiomas are rare vascular tumors characterized by tightly packed capillaries (“tufts”) in discrete lobules scattered through the dermis and, sometimes, subcutaneous tissue. Although adult-onset cases have been described, tufted angiomas occur far more frequently in infants and children. Tufted angiomas usually have a benign course, with only rare reports of aggressive behavior or local invasion.[1] However, tufted angiomas seldom self-involute.[2]

Pathophysiology

The pathogenesis of tufted angiomas is not well understood. Vascular markers (CD31 and CD34), vascular endothelial growth factor receptor-3 (VEGFR-3), and lymphatic markers (D2-40 and PROX1) on the neoplastic cells suggest they may be derived from the endothelial cells of lymphatic vessels.[3, 4]

Epidemiology

Frequency:

Tufted angiomas are rare, and the true incidence is unknown. As of 2015, only 158 cases are described in the English-language literature.[5]

Race:

No racial predilection is recognized for tufted angioma.

Sex:

The prevalence of tufted angioma is equal in males and females.

Age:

Approximately 50% of cases of tufted angiomas present at birth, while most other cases develop within the first year of life.[6] Although rare, there are reports of onset later in childhood and even in adulthood.

Less than 10% of tufted angiomas develop in individuals older than 50 years, and tumors in persons older than 60-80 years are rare.[2, 7] One 81-year-old patient with a tufted angioma of 2 years' duration is reported in the French-language literature, and a case has been described in an 84-year-old man in Japan.[8, 9]

One case report describes a 69-year-old man who was found to have an intracranial tufted angioma, suggesting potential for aggressive behavior and invasion into the brain.[1] Another case describes a 40-year-old man with a 2-year history of a lesion on his lower eyelid, which was confirmed on histology to be a tufted angioma.[10]

Prognosis

Tufted angiomas may spontaneously regress or may regress after treatment, but they do not completely resolve.[6, 11, 12] In fact, in a study of patients 10 years after diagnosis and treatment of tufted angioma, presence of tumor was still evident on repeat biopsy.[13] Pain and tenderness are common associated symptoms, and hyperhidrosis is a frequent finding that occurs in 30% of patients.[14]

The growth pattern of tufted angioma tends to be slow and progressive (ie, occurring over 5 months to 10 years). However, an occasional tufted angioma undergoes a rapid expansion phase that leads to localized swelling and a decreased range of motion of the structures in the affected area. One report described a patient with a painful tufted angioma on the lateral neck and jaw. The tumor also had deep extension into the underlying fascia and muscle, a rare finding.[15]

Residual lesions after treatment of tufted angioma usually looks like one of three patterns: (1) discoloration resembling a port-wine stain with superimposed papules, (2) an indurated area with telangiectasias, or (3) a fibrotic infiltrate within the subcutaneous tissue. Long-term symptoms can include chronic pain and swelling.

Kasabach-Merritt syndrome occurs in association with tufted angioma in approximately 10% of patients. Fortunately, most of these patients have a favorable response to treatment without further sequelae. However, there is a mortality rate of up to 24% in patients with Kasabach-Merritt syndrome.[16] Death in these cases results from bleeding, sepsis, invasion of a vital structure, or organ failure.[17]

Patient Education

Tufted angioma is a benign tumor, with very rare reports of deaths directly or indirectly attributable to complications. However, pain and tenderness are common associated symptoms, and hyperhidrosis is a frequent finding that occurs in 30% of patients.[14]

The growth pattern of tufted angioma tends to be slow and progressive (ie, occurring over 5 months to 10 years). However, an occasional tufted angioma undergoes a rapid expansion phase that leads to localized swelling and a decreased range of motion of the structures in the affected area.

Kasabach-Merritt syndrome, characterized by severely low platelets and coagulopathy, has been reported to occur in 10% of patients with a diagnosis of tufted angioma. Fortunately, most of these patients have a favorable response to treatment.

 

Presentation

History

Most tufted angiomas develop by the time the patient is aged 1 year, although a number of juvenile and adult cases have been reported. Tufted angiomas typically manifest as firm, dark-red, reddish-brown, or violet plaques and/or nodules with poorly defined borders. Their size is variable, ranging from less than 1 cm to over 10 cm in diameter.[18]

At birth, the lesions are usually barely evident as slight-pink or brown discoloration with an ill-defined border. Over 1-10 years, the area thickens into a red or violet plaque or patch that can form nodules and papules. Eventually, the tumors tend to stabilize and remain that size indefinitely. Some cases have reported partial or total regression of the tumor during childhood.[19, 20]

Most reported tumors occur on the trunk, arms, and legs, while tumors of the face and scalp are rare.[18] Involvement of the feet and oral mucosa is observed, but only in rare cases.[21, 22] Hypertrichosis with lanugo hairs and hyperhidrosis is often observed overlying the tumor.[18]

Generally, the lesion is described as solitary. However, multifocal or disseminated presentations are reported. In immunosuppressed patients, a rare eruptive form of tufted angiomas has been described.[23] Approximately 10% of patients with tufted angiomas develop the life-threatening Kasabach-Merritt syndrome.

Many tufted angiomas are associated with painful episodes as they increase in size.

Physical Examination

A tufted angioma appears as a purplish-red to red-brown patch or plaque that predominantly appears on the upper thorax; neck; shoulders; and, less commonly, on the face, scalp, and proximal extremities.[24, 25]

The diameter of the patch or plaque generally ranges from less than 1 cm to over 10 cm. The tufted angioma may be solitary (most common) or multifocal (rare), and it can be round to polycyclic in more extensive cases (see the image below). The border is always ill defined.

This lesion is a tufted angioma in a 1-year-old gi This lesion is a tufted angioma in a 1-year-old girl. Present since birth, this bluish-red hemangioma-like plaque on the patient's right upper leg slowly enlarged and became tender during the month prior to presentation. The child was otherwise well. A skin biopsy specimen revealed dilated congested capillaries in the lower dermis and subcutis. Clusters of capillaries with hyperplastic endothelial cells were also scattered in the mid and upper parts of the dermis. The epidermis revealed a slight basket-weave orthokeratosis, with minimal acanthosis, and papillomatosis. The patient was treated conservatively with only observation. The lesion remained stable and did not progress since presentation. Courtesy of National Skin Centre, Singapore.

On palpation, tufted angiomas often have a rubbery consistency, and they may be painful.

Ulceration is rare; this finding may be predicted from its slow rate of growth.

Hyperhidrosis of the skin overlying the area of the tufted angioma is reported. Histologically, hyperhidrosis corresponds with areas of abundant eccrine glands.[7]

Peripheral extension occurs, and lesions of tufted angioma are described as having a thick, indurated border and a central depression, with an appearance similar to that of a doughnut.[14] Tufted angioma lesions may also appear as deep-red or purple patches with scattered round-to-oval, dark-red nodules on their surface.

Causes

No causes of tufted angioma have been established. Trauma does not appear to be a predisposing factor.

Several authors have noted the development of tufted angioma within port-wine stains or in the context of these stains.[26, 27, 28]

Some authors have postulated that high hormonal levels during pregnancy and puberty may induce the development of tufted angiomas.[29, 30] However, these etiologies are not supported in current medical literature as causes of tufted angiomas.

Complications

In approximately 10% of cases, tufted angiomas are associated with a serious life-threatening platelet-trapping syndrome, called Kasabach-Merritt syndrome (KMS). Suspect Kasabach-Merritt syndrome in patients with tufted angioma in whom ecchymotic patches, thrombocytopenia, and/or blood-clotting abnormalities develop. In this setting, rapid enlargement of the lesion accompanied by pain and ecchymosis is the presenting sign of KMS.[31] Along with these signs, the patient has severe thrombocytopenia (3,000-60,000/µL, low fibrinogen levels (16</ref> Responses to a variety of appropriate treatment modalities are noted in patients with Kasabach-Merritt syndrome and tufted angioma.[31, 32]

 

DDx

Diagnostic Considerations

A proper diagnosis of tufted angioma requires careful clinical and histological examination. Laboratory evaluation is required for the diagnosis of Kasabach-Merritt syndrome (KMS).

Also consider the following information with regard to differential diagnoses:

  • Arteriovenous malformations: Often present at birth, these lesions are usually blue, soft, and compressible vascular masses. Doppler ultrasound and MRI are helpful for differentiating venous malformations and tufted angiomas. [33]
  • Congenital hemangioma: These include rapidly involuting congenital hemangiomas and noninvoluting congenital hemangiomas; they may involve thrombocytopenia and coagulopathy.
  • Dermatologic manifestations of Kaposi sarcoma: This is an extremely rare tumor reported in children in Africa. The human herpesvirus 8 (HHV-8) is detected in all Kaposi sarcoma variants.
  • Infantile hemangioma: Also known as strawberry angioma, it commonly occurs in the head and neck area, is not associated with coagulopathy, and has strong expression of GLUT-1 on immunochemistry.
  • Infantile hemangiopericytoma: This is a rare soft-tissue tumor presenting in the first year of life as a multilobulated mass in the subcutaneous tissue. [34] Bleeding and coagulopathy may mimic Kasabach-Merritt syndrome.
  • Infantile sarcoma: This rare malignant tumor can present at birth or within the first few years of life as a firm, fixed tumor in deep tissue. [35]
  • Kaposiform hemangioendothelioma: This tumor shares many clinical and histological features with tufted angiomas, but it is locally aggressive involving the soft tissues and even internal organs. Additionally, over 70% of patients with kaposiform hemangioendothelioma go on to develop Kasabach-Merritt syndrome.

 

Differential Diagnoses

 

Workup

Approach Considerations

A diagnosis of tufted angiomas is classically suspected in an infant or young child presenting with a red or violet vascular lesion with ill-defined borders present on the trunk or extremities. Hypertrichosis and/or excessive sweating overlaying the lesion further supports a diagnosis of tufted angioma.

Upon suspicion of tufted angioma, a biopsy specimen to obtain histological confirmation should be obtained whenever possible. However, there are times when a biopsy carries more risk than benefit and is deferred, such as when the lesion is highly vascular and/or the patient also presents with thrombocytopenia and coagulopathy. When a risky biopsy is pursued, there should be careful planning and communication between the surgeon, anesthesiologist, hematologist, and pathologist to ensure preparation with platelets, fresh frozen plasma, and other supportive measures if needed intraoperatively and postoperatively.

Laboratory Studies

No specific laboratory study is useful in the diagnosis or treatment of tufted angioma. However, upon diagnosis, laboratory workup of tufted angioma should include a complete blood cell (CBC) count, fibrinogen, D-dimer, prothrombin time (PT), and activated partial thromboplastin time (aPTT). Further evaluation with kidney and liver function tests should also be ordered in severely ill patients. Urinary levels of basic fibroblast growth factor are of no value in the diagnosis of this condition, unlike juvenile capillary angioma.

If the patient has coexistent Kasabach-Merritt syndrome, laboratory tests reveal severe thrombocytopenia, low fibrinogen, and elevated d-Dimer.

Imaging Studies

MRI studies have been proven useful in the examination of patients with deep and/or extensive tufted angiomas. MRI has been successful in evaluating the depth of invasion and extent of growth of tufted angiomas that extend deep into the muscle and fascia, as well as in documenting the response to treatment.[14]

Procedures

Other than biopsy for diagnosis and the surgical and laser treatments described, no other procedures are indicated for tufted angioma.

Histologic Findings

Tufted angiomas have a specific histologic pattern. They are characterized by the lobular arrangement of densely cellular capillaries (tufts), often referred to as a “cannonball” pattern, that are scattered throughout the dermis.[36] The vascular tufts consist of tightly packed hypertrophic endothelial cells with scanty cytoplasm and nuclei that are round, ovoid, or fusiform. Mitoses are rarely seen.

Immunohistochemistry usually reveals positive D2-40 and POX1 staining, while GLUT1 (a marker for infantile hemangiomas) is always negative.

Occasionally, hemosiderin deposits may be observed within the endothelial cells. Capillary spaces are narrow and elongated, and they are more noticeable in the periphery of the lobules, where they have a characteristic half-moon cleft shape.[37]

The capillary lobules are present throughout the dermis and subcutaneous tissue; the epidermis is uninvolved in most cases. Rare cases with fascial and muscular involvement are reported.[14] The surrounding pilosebaceous units of the dermis are unaffected, although hypertrophy of neighboring eccrine sweat glands is reported. No edema or inflammation surrounds the vascular lobules.

 

Treatment

Approach Considerations

The treatment for tufted angioma is multimodal and individualized, depending on the extent of tumor invasion, tumor size, presence of symptoms, and presence or absence of Kasabach-Merritt syndrome. Treatment generally consists of one or multiple approaches, including surgical excision, pulsed-dye laser (for superficial tumors), and several medications and chemotherapy agents. The efficacy of one treatment approach over another has not been established in large randomized clinical trials, and current available evidence is based on anecdotal clinical experience, case reports, and small case series.

For patients with small tufted angiomas who are asymptomatic, observation only can be considered. There have been a few reports of patients whose tufted angiomas spontaneously regressed in infancy and childhood.[6, 38, 39]

Medical Care

For patients without Kasabach-Merritt syndrome who are symptomatic and who opt not to have surgical excision or who are not surgical candidates, pharmacological management with aspirin 5 mg/kg/day is first-line treatment.[40]

In patients with unresectable tumors owing to size, location, or surgical risks, pharmacotherapy can be used to decrease the tumor size. Although no single agent or combination of agents has been proven better than another, several chemotherapy agents haven been used, including vincristine, sirolimus (an mTOR inhibitor), interferon-alfa, and systemic corticosteroids. Systemic corticosteroids are often used as first-line therapy to stabilize the platelet count and then slowly tapered.[41] Vincristine administered via a central line is usually given in conjunction with corticosteroids.[42] Sirolimus is an oral chemotherapy agent that is still under investigation for the treatment of infantile vascular tumors.[43] It has been effectively used to treat several cases of tufted angioma, demonstrating it to be a possible promising treatment with good preliminary results. According to a 2016 meta-analysis of 15 clinical studies of various therapies used to treat tufted angioma, results suggest vincristine may be most effective relative to other agents.[44]

 

Hemostasis Support

For patients with coexistent Kasabach-Merritt syndrome, the coagulopathy must be carefully managed with hemostasis support. In these patients, hemorrhage is rare but can occur in disseminated intravascular coagulation (DIC) and multiorgan failure. Despite severely low platelet counts in these patients, platelets should only be given prior to surgery and in patients with active bleeding; platelets administration can rapidly increase the size of and pain associated with the tumor, leading to increased platelet trapping. In patients with low fibrinogen levels, cryoprecipitate should be given if one of the following four conditions is present: (1) active bleeding, (2) in preparation for surgery, (3) platelet count less than 10,000/µL, or (3) a fibrinogen level less than 1 g/L. Recombinant human factor VIIa can be given in cases of active bleeding.[45] Fresh frozen plasma may be required in infants with DIC. Packed red blood cells should be given for symptomatic anemia.

Surgical Care

Complete surgical excision, if chosen, allows permanent removal of small or localized tufted angiomas, although local recurrence of some surgically excised tumors is observed.[46] Surgical excision can be tried as second-line therapy after failure of medical management.[47]

Cryosurgery, radiation therapy, and embolization are successful to varying degrees in tufted angioma patients.[48] Use of the pulsed-dye laser has had variable results in both children and adults with tufted angioma.[11]

Consultations

If Kasabach-Merritt syndrome is suspected in a child, consultation with a hematologist/oncologist and a dermatologist may be indicated.

Prevention

Because the cause of tufted angioma is poorly understood, no specific method of prevention or deterrence is recommended.

Long-Term Monitoring

In patients who opt not to undergo medical or surgical management, tumors should be carefully monitored for size expansion and the development of Kasabach-Merritt syndrome.

 

Guidelines

Guidelines Summary

For patients without Kasabach-Merritt syndrome with small tumors, surgical excision is first-line management. For nonresectable tumors, patients should be given 5 mg/kg/day of aspirin as the treatment of choice. In patients who are asymptomatic, careful observation for regression is an option.

For patients with Kasabach-Merritt syndrome, surgical excision is the treatment of choice if the tumor is small and localized. However, large or nonresectable tumors should be treated with intravenous vincristine plus systemic corticosteroids or oral sirolimus. Hemostasis support with platelet infusion, fresh frozen plasma, recombinant human factor VIIa, and cryoprecipitate should only be administered to patients who are actively bleeding or being prepared for surgery.

 

Medication

Medication Summary

The use of no one specific drug is indicated in the treatment of patients with tufted angioma. However, anecdotal cases that benefited from several agents are reported; see the list below:

  • Systemic corticosteroids have been successfully used in patients with tufted angioma, and, according to a meta-analysis of 11 studies using systemic corticosteroids, there was a 27% response rate. [44]
  • In a pooled analysis of ten studies, there was a 72% response rate to intravenous vincristine. [44]
  • Oral sirolimus for tufted angioma has been investigated in two separate studies, with approximately 57% of 37 participants showing good response. [12, 43]
  • Topical steroids decreased painful episodes in one patient. [49]
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) also are useful in the treatment of painful episodes. [48]
  • Interferon-alfa therapy significantly improved a rapidly growing and locally invasive tufted angioma in one pediatric patient. [14]