Vascular papules
 - Clinical Advisor

Vascular papules


Slideshow

  • Case #1

    Infantile hemangioma_0713 Derm Look 1

    Case #1

  • Case #2

    Pyogenic Granuloma_0713 Derm Look 2

    Case #2

CASE #1

A white infant, aged 2 months, was seen in the dermatology clinic for two seemingly asymptomatic scalp lesions. When the infant’s mother first noticed the lesions at approximately age 2 weeks, she thought they were scratch marks. However, over the past six weeks, the lesions had thickened and were continuing to enlarge. The infant was born one month premature but was otherwise healthy. On physical examination, two erythematous vascular papules were noted on the scalp. The remainder of the exam was within normal limits.


CASE #2


A white man, aged 28 years, presented with a tender lesion that had been present for one month on the upper area of his right neck. The man recalled having a mosquito bite in that area that had never healed and that grew rapidly to its present state. More recently, he felt as though the growth had stabilized. He had stopped shaving that area because minor trauma resulted in significant bleeding. Medical history and review of systems was otherwise negative. On physical examination, a 9-mm, erythematous, and sessile papule was noted on the right upper neck. 




HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Hyperkeratotic papules with nail changes and Multiple cutaneous and GI vascular lesions.

CASE #1
: Infantile hemangiomaInfantile hemangioma, a benign endothelial-cell neoplasm, is the most common soft-tissue tumor occurring in the neonatal period. Despite early efforts to distinguish between the various vascular tumors, the term hemangioma was frequently used as a generic term...

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CASE #1
: Infantile hemangioma

Infantile hemangioma, a benign endothelial-cell neoplasm, is the most common soft-tissue tumor occurring in the neonatal period. Despite early efforts to distinguish between the various vascular tumors, the term hemangioma was frequently used as a generic term to encompass all vascular anomalies. In 1982, Mulliken and Glowacki were the first to recommend that vascular birthmarks be classified according to their biological and clinical behavior.1

Today, vascular birthmarks are divided into two broad categories: vascular tumors and vascular malformations. Vascular tumors, which include infantile hemangiomas, usually appear in the neonatal period, and their clinical course is marked by an early proliferative phase lasting several months followed by slow spontaneous resolution over several years. Vascular malformations are thought to represent errors in vascular morphogenesis. These malformations also usually appear during the neonatal period but, unlike infantile hemangiomas, do not proliferate rapidly or resolve spontaneously. 


Infantile hemangiomas are thought to arise sporadically and appear more commonly in females, with a 2.5:1 female-to-male ratio.2 Other risk factors include white race, low birth weight, premature infants, multiple gestations, advanced maternal age, and chorionic villus sampling. 


Infantile hemangiomas are thought to represent localized areas of abnormal angiogenesis; however, the exact pathogenesis is largely unknown. Some hypothesize that a somatic mutation occurs in a normal microvasculature endothelial cell or that hemangiomas arise from immature endothelial progenitor cells. Another theory asserts that such extrinsic factors as fibroblasts, mesenchymal cells, adipocytes, mast cells, and monocytes cause endothelial cells to undergo aberrant proliferation.

Still others believe that hemangioma cells are of placental origin, because infantile hemangiomas share an immunohistochemical phenotype with placental endothelium. One such marker is erythrocyte-type glucose transporter protein-1 (GLUT-1), which is expressed by infantile hemangiomas during all stages of their development but is not expressed by other vascular tumors or malformations. Most likely, several mechanisms under the control of multiple genes, in addition to local effects, play a role in the initiation, proliferation, and involution of hemangiomas. 


Hemangiomas can occur anywhere on the skin, including mucosal surfaces. They are described as being superficial (50% to 60% of cases), deep (15% of cases), or mixed (25% to 35% of cases).3 In superficial hemangiomas, the abnormality lies within the superficial dermis. Superficial hemangiomas are bright-red in color during the proliferative phase and have been referred to as as strawberry hemangiomas.

Deep hemangiomas lie within the deep dermis and/or subcutis. Clinically, deep hemangiomas are blue-purple masses with minimal or no overlying skin changes. Mixed hemangiomas have both superficial and deep components and can further be classified as being either focal or segmental. Segmental lesions are often described as “plaquelike” or “diffuse” and appear to arise from a broad area or developmental unit. 


The natural history of a hemangioma follows three phases: proliferation, involution, and involuted. Most hemangiomas begin as telangiectasias surrounded by a border of pallor, faint erythematous macules, or blue bruiselike patches. Superficial hemangiomas classically proliferate for several months and clinically become warmer, firmer, and raised.

Deep lesions may proliferate for up to one year. Involution usually begins around the first year of life and continues for several years. The first signs of involution within a superficial hemangioma are often a color change from deep red to gray-purple and a flattening of the surface. 


Although most hemangiomas are small and require no intervention, some may become problematic. Ulceration is the most common complication, occurring in approximately 10% of all infantile hemangiomas.4 The lip, neck, and anogenital regions that are affected with large, mixed, and segmental hemangiomas are most at risk for ulceration. Large hemangiomas may distort normal tissues, interfere with the function of certain structures (e.g., periocular, nasal tip, lip, ear, anogenital), or lead to significant cosmetic impairment.

Segmental lesions have a higher incidence of such associated systemic anomalies as PHACES syndrome (Posterior fossa malformations, Hemangiomas, Arterial lesions, Cardiac abnormalities, Eye abnormalities, Sternal abnormalities), laryngeal involvement, spinal dysraphism, and GI and genitourinary anomalies. Multiple hemangiomas may signify a risk for visceral hemangiomatosis.


Histology depends on the developmental stage of the hemangioma. Proliferating tumors are characterized by collections of endothelial cells, pericytes, and vascular lumens. Once involution is complete, the lesion is predominately composed of fibrofatty tissue and a few vessels where the tumor lobules used to reside. As discussed earlier, GLUT-1
is expressed during all stages of infantile hemangioma development but is absent in other vascular tumors and malformations. 


Early superficial hemangiomas may be misdiagnosed as capillary malformations, telangiectasias, or trauma. Deep hemangiomas may mimic venous, lymphatic, or combined venous-lymphatic malformations. Other soft-tissue tumors should also be considered in the differential diagnosis. Pyogenic granulomas may mimic hemangiomas, but these lesions usually arise after the first few months of life. 


Small hemangiomas are often managed without active intervention. Timolol maleate (Blocadren) 0.5% gel-forming solution, a topical nonselective beta-blocker, has recently been reported as an effective treatment for superficial hemangiomas.5 Complicated hemangiomas usually require systemic treatment with propranolol (Inderal, InnoPran, Pronol), corticosteroids, interferon α (Intron A, Roferon-A), or vinca alkaloids. 


Studies have shown that 30% of untreated hemangiomas will involute by age 3 years, 50% by age 5 years, 70% by age 7 years, and 90% by age 9 years.2 Following involution, some hemangiomas may appear normal, while others may leave behind atrophic, fibrofatty, or telangiectatic residua. Once involuted, laser therapy or surgical excision may be undertaken for cosmetic improvement if desired. 


Because the lesions in this case were asymptomatic and posed no cosmetic concern (any residua would be hidden by the infant’s hair) the parents decided not to treat.


Case #2: Pyogenic granuloma

In 1897, Poncet and Dor believed that Botryomyces infection was the cause of pyogenic granuloma. Although they were the first to describe the disease, it was not until 1904 that Hartzell named it granuloma pyogenicum.6 Hartzell and others were under the impression that the lesions were a granulation tissue-type response to an infectious agent.

The exact pathogenesis is still unknown; however, there is no evidence to suggest a pyogenic agent as the cause, nor is the histologic appearance granulomatous. Immunohistochemical studies have demonstrated a clear endothelial-cell predominance with positive staining of endothelial cells for such vascular markers as CD31 and pericytes for smooth-muscle actin.


Pyogenic granulomas occur equally in males and females. The condition afflicts people of all ages but is more commonly seen in children and young adults. Racial predilection and familial predisposition are not contributing factors. 


The exact etiology of pyogenic granuloma is unknown. Some believe that pyogenic granulomas are a benign neoplasm, while others believe that they may represent reactive neovascularization. In about one-third of cases, a history of pre-existing injury or irritation can be elicited, which supports the theory of reactive neovascularization. It has been suggested that abnormal blood flow may be the culprit because pyogenic granulomas occasionally erupt within pre-existing port-wine stains.

Certain medications, including systemic retinoids, indinavir (Crixivan), and anti-epidermal growth factor receptor antibodies, may predispose patients to the development of pyogenic granulomas or pyogenic granuloma-like lesions. 


Patients will report a history of a bright-red sessile or pedunculated papule that has been growing rapidly over the course of several weeks to months. Once its final size is reached (rarely >2 cm), the growth of the lesion will stabilize, and the liesion will persist indefinitely until destroyed. One study found the most common site of involvement to be the gingiva, followed by the fingers, lips, face, and tongue.7 The lesions are very friable and will frequently ulcerate and bleed, even with minor trauma. Interestingly, pregnant women are more at risk of developing gingival lesions (epulis of pregnancy). 


Histologically, a well-circumscribed and exophytic mass of angiomatous tissue is appreciated protruding above the normal skin. A collarette of acanthotic epidermis usually constricts the lesion at its base, and ulcerations are commonly seen on the surface. Dilated and congested capillaries are often grouped into discrete lobules by dense fibrous bands; hence, the alias lobular capillary hemangioma. The capillaries are lined by flattened and slightly plump endothelial cells that are surrounded by an edematous fibromyxoid interstitial stroma. Occasional mast cells, lymphocytes, and plasma cells may also be seen. Mitotic activity and cytologic atypia are variable. 


Pyogenic granulomas are often diagnosed clinically. However, amelanotic melanoma should be considered in the differential diagnosis. In the setting of an immunosuppressed patient, Kaposi sarcoma or bacillary angiomatosis should also be considered. If suspected clinically, Kaposi sarcoma can be confirmed histologically by the expression of the latency-associated nuclear antigen or polymerase chain reaction detection of human herpesvirus-8.8

Bartonella henselae and Bartonella quintana, the etiologic agents of bacillary angiomatosis, are best observed with either a Warthin-Starry silver stain or a Grocott methenamine silver stain. Although infantile hemangiomas are also included in the differential diagnosis, these tend to arise within the first couple weeks of life, while pyogenic granulomas most commonly develop in childhood and young adulthood.

Histologically, thick intervening bands of dense fibrous tissue are appreciated in pyogenic granulomas but are not seen in infantile hemangiomas. Immunohistochemical analysis is also helpful when differentiating between the two disorders because placenta-associated vascular proteins such as GLUT-1, Lewis Y antigen, FcγRII, and merosin are present in infantile hemangiomas and absent from pyogenic granulomas. 


If left untreated, most pyogenic granulomas will remain indefinitely. However, those that occur during pregnancy may resolve following parturition. Eliminate any provoking factors that exist (e.g., a medication). For most lesions, shave excision followed by electrosurgery is curative. Electrodesiccation and curettage, alone or in combination, is another treatment option and may be performed following the shave excision. Full-thickness excision of the lesion with suture repair may result in less postoperative bleeding and a lower recurrence rate (2.94%).9

Other treatment options include topical imiquimod (Aldara, Zyclara) cream, alitretinoin (Panretin) gel, injectable sclerosing agents, topical phenol, and silver nitrate cauterization. Good results have also been achieved with such laser systems as carbon dioxide, argon, pulsed-dye, and neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers.10,11

Occasionally, multiple satellite lesions develop within the general vicinity of the treated primary lesion. These satellite lesions have been successfully treated with intralesional and systemic corticosteroids.12,13 Regardless of the treatment modality, patients should be advised that pyogenic granulomas can recur. 


The patient in this case was offered a shave excision followed by curettage and electrodesiccation to the base. The lesion has not recurred.

Kerri Robins, MD, is a resident in the Department of Dermatology at Baylor College of Medicine in Houston.


References


  1. Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69:412-422.

  2. Moroz B. Long-term follow-up of hemangiomas in children. In: Williams HB (ed.). Symposium on Vascular Malformations and Melanocytic Lesions. 
St. Louis, Mo.: C.V. Mosby; 1983:162-171.

  3. Esterly NB. Cutaneous hemangiomas, vascular stains and malformations, and associated syndromes. Curr Probl Pediatr. 1996 Jan;26(1):3-39.

  4. Chamlin SL, Haggstrom AN, Drolet BA, et al. Multicenter prospective study of ulcerated hemangiomas. J Pediatr. 2007;151:684-689.

  5. Chakkittakandiyil A, Phillips R, Frieden IJ, et al. Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study. Pediatr Dermatol. 2012;29:28-31.

  6. Hartzell MB. Granuloma pyogenicum (botryomycosis of French authors). J Cutan Dis. 1904;22:520-523.
  7. Kerr DA. Granuloma pyogenicum. Oral Surg Oral Med Oral Pathol. 1951;4:158.

  8. Hammock L, Reisenauer A, Wang W, et al. Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in HIV-positive patients. Mod Pathol. 2005;18:463-468.

  9. Lee J, Sinno H, Tahiri Y, Gilardino MS. Treatment options for cutaneous pyogenic granulomas: a review. J Plast Reconstr Aesthet Surg. 2011;64:1216-1220.

  10. Tay YK, Weston WL, Morelli JG. Treatment of pyogenic granuloma in children with the flashlamp-pumped pulsed dye laser. Pediatrics. 1997;99:368-370. 

  11. Hammes S, Kaiser K, Pohl L, et al. Pyogenic granuloma: treatment with the 1,064-nm long-pulsed neodymium-doped yttrium aluminum garnet laser in 20 patients. Dermatol Surg. 2012;38:918-923.

  12. Parisi E, Glick PH, Glick M. Recurrent intraoral pyogenic granuloma with satellitosis treated with corticosteroids. Oral Dis. 2006;12:70-72. 

  13. Tursen U, Demirkan F, Ikizoglu G. Giant recurrent pyogenic granuloma on the face with satellitosis responsive to systemic steroids. Clin Exp Dermatol. 2004;29:40-41.


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