Pyogenic Granuloma

A 35-year-old man presented with an asymptomatic lesion on his right upper chest that had been present for approximately 3 months. The lesion had bled on several occasions with minor trauma; he also had had a pimple there at one point that he had “played with.” The patient was otherwise healthy. He had not been exposed to anyone with a known infectious disease, and he was not on any medications.

Physical examination. A reddish, dome-shaped, nontender papule measuring 5 mm in diameter was present on the right upper chest. The mass had a smooth, glistening surface and clear border. The rest of the physical examination findings were unremarkable. Based on the clinical appearance, a diagnosis of pyogenic granuloma was made.

Outcome of the case. The man’s pyogenic granuloma was excised by his dermatologist under local anesthetic, and there was no recurrence of the lesion.

Discussion. Pyogenic granuloma, also known as lobular capillary hemangioma, is a common, acquired, benign vascular proliferation of the skin and mucous membranes.¹ The condition was first described in 1897 by Poncet and Dor, who reported on 4 patients with “vascular tumors” on the fingers.² The term pyogenic granuloma or granuloma pyogenicum, coined by Hartzell in 1904,³ is a misnomer in that the condition is neither pyogenic nor granulomatous.^3,4 In fact, it is a capillary hemangioma of lobular subtype that accounts for the proneness to bleeding with minor trauma. Although lobular capillary hemangioma is the preferred term, the term may lead to the condition being confused with infantile hemangioma.^3,4

Epidemiology. Although pyogenic granulomas can occur in patients of any age, they are more prevalent in children, adolescents, and pregnant women.⁵ Pyogenic granuloma accounts for 0.5% of all childhood skin nodules.⁶ In the pediatric age group, the mean age of onset is 6.7 years, with 42% of cases occurring by 5 years of age.⁵ In the adult population, the incidence peaks in the third decade of life.^4,5,7 Pyogenic granuloma, especially on the gingiva, occurs in approximately 2% to 5% of pregnancies, usually in the second or third trimester.^8,9 In this setting, pyogenic granuloma is often referred to as granuloma gravidarum, granuloma of pregnancy, epulis gravidarum, or pregnancy tumor.⁶ Cutaneous pyogenic granulomas usually have no gender predilection, whereas the oral mucosal ones have a female to male ratio of 2 to 1.⁵

Etiopathogenesis. The exact etiology is not known. Pyogenic granuloma is considered a reactive vascular response to a variety of stimuli such as physical trauma, burns, irritation, and increased levels of female sex hormones.^1,4,10,11 Approximately 7% of affected patients have a history of physical trauma preceding the lesion.^6,12 This is especially true of lesions in the oral cavity where physical trauma and poor oral hygiene are important predisposing factors.¹³ Female sex hormones may also play a role given that the condition occurs with increased frequency in pregnant women and in those who use oral contraceptive pills.^5,8,13 It is believed that trauma and female sex hormones enhance expression of angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), which leads to evolution of the pyogenic granuloma.^5,8 Recently, it has been shown that BRAF and RAS mutations play a role in the pathogenesis of pyogenic granuloma.^14,15 Medications such as isotretinoin, acitretin, cyclosporine, lamivudine, docetaxel, imatinib, afatinib, mitoxantrone, indinavir, and erythropoietin may also be contributing factors.^6,9,12,16,17 Infections such as those caused by herpes simplex virus type 1 and Epstein-Barr virus have also been incriminated.¹⁶

Histopathology. Histologically, the lesion appears as a lobular proliferation of capillaries, with each lobule containing a central feeder vessel surrounded by aggregates of capillaries.¹² The lobules are separated by a fibromyxoid stroma.⁵ In lesions undergoing regression, there may be extensive fibrosis.¹⁸

Clinical manifestations. Pyogenic granuloma typically develops as a small, pinhead-sized, erythematous papule on the skin or oral mucosal surface.¹ The papule usually enlarges quickly to a few millimeters and occasionally a few centimeters over weeks, and growth stabilizes over several months.^3,5,9 Clinically, pyogenic granuloma presents as a soft, dome-shaped papule/nodule or a sessile or pedunculated papule/nodule with a smooth, glistening, erosive, or friable surface.^4,6 The color initially is usually bright red or purple, to dusky red because of the high number of blood vessels. With time, the vascularity decreases, and the lesion tends to become more collagenized and pink.⁴ Characteristically, the lesion is asymptomatic and painless.^1,4,18 Due to its pronounced vascularity, pyogenic granuloma tends to bleed and ulcerate even with very minor trauma.^1,5 As such, patients often present with the “Band-Aid sign,” where the lesion is covered by an adhesive bandage before being removed to show the physician.⁴ The lesion is usually solitary, but multiple lesions may occur.^4,5 Rarely, multiple disseminated lesions have been reported.¹⁹

Cutaneous pyogenic granulomas are commonly located on the head and neck (62.5%), trunk (19.7%), and extremities (17.9%), especially the fingers.⁵ In the oral cavity, pyogenic granulomas are more frequent on the gingiva, followed by the lips, tongue, and buccal mucosa.^5,20 Lesions are slightly more common on the maxillary gingiva than the mandibular gingiva, anterior areas than posterior areas, and facial aspect of the gingiva than the lingual or palatal aspect.⁴ Nasal pyogenic granulomas generally arise from the nasal septum and/or turbinates on the roof of the nasal cavity, or in the maxillary sinus.^4,7 Pyogenic granulomas rarely occur in the gastrointestinal tract, trachea, urinary bladder, and central nervous system.¹⁸

Clinical variants such as satellite pyogenic granulomas, subcutaneous pyogenic granulomas, intravenous pyogenic granulomas, and disseminated pyogenic granulomas are rare.¹² Satellite pyogenic granulomas are most commonly seen in adolescents and young adults and are commonly seen on the trunk.²¹ Satellite lesions tend to occur 4 to 20 weeks after the primary lesion has been excised and to occur in very close proximity to the site of the original primary lesion.²¹ Satellitosis might be the result of release of angiogenic factors such as bFGF and VEGF by the primary lesion. Subcutaneous pyogenic granulomas occur predominantly in the female population.²² The lesion typically presents as a well-circumscribed subcutaneous nodule that usually does not bleed or ulcerate.²² Intravenous pyogenic granulomas occur mainly in middle-aged individuals.²³ The lesion is confined within the lumen of a vein; it typically presents as a soft, subcutaneous, slow-growing nodule that may be bluish, erythematous, or skin-colored.²³ Sites of predilection include the neck and upper extremities.²³ Disseminated pyogenic granulomas are generally seen after trauma such as burns and in patients with an accompanying systemic or skin disease.⁴

Diagnosis. The diagnosis is mainly clinical. Dermoscopy of the lesion reveals red homogenous areas (proliferating vessels) and a white scaly collarette (hyperplastic epithelium).²⁴ Dermoscopy increases the diagnostic accuracy and has been shown to be a very useful tool for the evaluation of pyogenic granuloma.²⁴ However, dermoscopy is not a substitute for histology; a biopsy or referral to a dermatologist is warranted if the diagnosis is in doubt (eg, to rule out amelanotic melanoma).²⁵

Differential diagnosis. Pyogenic granuloma must be differentiated from bacillary angiomatosis (disseminated vascular lesions in immunocompromised persons) and verruga peruana (crops of vascular nodules in immunocompetent individuals) caused by infection with Bartonella species.⁴ Other differential diagnoses include pedunculated cherry angioma, granulation tissue, infantile hemangioma, venous lake, epulis, glomus tumor, acquired digital fibrokeratoma, amelanotic melanoma, hyperplastic gingival inflammation, peripheral giant cell granuloma, peripheral ossifying fibroma, Spitz nevus, proliferating pilomatricoma, Kaposi sarcoma, and angiosarcoma.^{5,6,14,18,25,26}

Complications. Pyogenic granuloma can be unsightly and cosmetically disfiguring, especially if it occurs on the face.⁴ Other possible complications include hemorrhage, ulceration, and infection in an ulcerated lesion.⁶ Pyogenic granuloma has no malignant potential.

Management. Any offending agents such as medications should be discontinued or switched. Pyogenic granulomas developing during pregnancy tend to resolve on their own after delivery and usually require no treatment.^5,13 Spontaneous resolution of most other lesions are rare.²⁶ As such, they are often treated because of potential complications such as hemorrhage, ulceration, and infection.²⁶ A series of treatment modalities are available, including surgical excision, shave excision, laser surgery, electrodesiccation, curettage, liquid nitrogen cryotherapy, sclerotherapy, topical timolol, topical silver nitrate, and topical imiquimod.^9,15,25-28 Recurrences may occur and are largely attributed to inadequate removal or incomplete destruction of lesions. Surgical excision with linear closure allows histologic examination of the tissue.⁴ It also has the lowest rate of recurrence and is therefore the treatment of choice.^12,15 Surgical excision, however, may leave a scar.⁴ 

REFERENCES:

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