Answer C

Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a common benign tumor consisting of vasculature overgrowth.11-13 The term pyogenic granuloma was first used by Hartzell in 1904, and these lesions were originally thought to be a granulomatous reaction to an infectious insult, although the name is now considered to be a misnomer, as pyogenic granulomas are neither pyogenic nor granulomatous.12-14 Study of additional PGs revealed that the skin lesions consist of concentrated lobules of capillaries, leading to a more accurate name of “lobular capillary hemangioma.”12,15

Conflicting data exist on the epidemiology of PGs. One report shows a slight female predominance with a male:female ratio of 1:1.2, yet other studies report a slight male predominance.12,13 Mucosal PGs are twice as common in female persons than in male persons.13 The mean age of occurrence is 30 to 40 years.13 Female individuals tend to develop PGs later, between 40 and 50 years of age, whereas male individuals tend to develop the lesions younger, usually before the age of 30 years.12,13 There is no known racial or geographic pattern of distribution for this condition.

The etiology of PGs is unclear, although studies have implicated an excess of proangiogenic factors and deficit of antiangiogenic factors, leading to rapid development of poorly formed capillaries.12 In one retrospective study, a reported association between trauma (14%) and irritation (8%) at the site of the lesion before its development was reported13; however, in the same study, an unknown etiology was reported in the vast majority of patients (78%).13


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Women tend to develop PGs during childbearing years, which implies a relationship between hormonal changes and PG development.16 Women can develop PGs intraorally during pregnancy, most commonly on the gingiva, during the second or third trimester; it is hypothesized that this is because of an exaggerated inflammatory response of the gingiva during pregnancy.12,16

Other potential causes of PG include medications such as systemic and topical retinoids; antiretrovirals (eg, indinavir); pyrimidine analogs; taxanes; epidermal growth factor receptor (EGFR) inhibitors; tyrosine kinase inhibitors; BRAF inhibitors; and immunosuppressants, such as tumor necrosis factor (TNF)-α antagonists and mechanistic target of rapamycin (mTOR) inhibitors.12 Patients treated with cyclosporine and tacrolimus after hematopoietic stem cell transplant have developed intraoral PGs.12 Pyogenic granuloma formation has also been reported within other vascular malformations, either spontaneously or after treatment of the lesions with laser or cryotherapy.12

Pyogenic granulomas are solitary lesions found on cutaneous or mucosal surfaces. They start as small, red papules that grow rapidly over weeks to months, eventually stabilizing in size. Mature lesions range from several millimeters in small lesions to several centimeters in larger lesions. Pyogenic granulomas are red to purple in color and are friable, often bleeding profusely with minor trauma. Mature lesions are pedunculated with a collarette of scale at the base of the lesion.12,13 Cutaneous PGs are most commonly found on the upper extremities, trunk, and head whereas mucosal PGs are most commonly seen on the lips, gingiva, and tongue.16

Histopathology shows a well-circumscribed, polypoid mass with atrophic epidermis that can potentially erode or ulcerate. The papillary and upper reticular dermis contain lobules of capillaries embedded in a fibromyxoid stroma. The stroma contains an inflammatory infiltrate of lymphocytes, neutrophils, plasma cells, or mast cells.12,15 Atypical lesions may require immunohistochemistry staining. Pyogenic granulomas stain positive for the vascular markers cluster of differentiation (CD)31, CD34, and factor VIII antigen. Unlike infantile hemangiomas, PGs stain negative for glucose transporter 1 (GLUT1).12,17

Differential diagnosis for PG includes several malignant skin lesions. These diseases include but are not limited to, amelanotic melanoma, squamous cell carcinoma, basal cell carcinoma, and angiosarcoma.12 In immunosuppressed patients, bacillary angiomatosis and Kaposi sarcoma also may be considered.12 Additional differential diagnoses include warts, hemangiomas, irritated nevi, granulation tissue from trauma, Spitz nevus, and glomus tumor.12

Diagnosis of PG is dependent on history, clinical findings, and, if needed, dermatoscopy and histopathology. In particular, questions regarding previous trauma, pregnancy status, and medications are important to investigate potential causes of the lesion. Histology can be used to confirm the diagnosis and rule out malignant lesions (see Table 1).12

Patients with PGs generally seek treatment for frequent ulceration and bleeding. Complete excision is used for lesions in nonvisible areas and recurrent lesions and has the lowest recurrence rate. Cosmetically sensitive areas are sometimes more amenable to shave removal or curettage followed by electrocautery, although recurrence is more common with this treatment.12 Additional treatment options include cryotherapy and laser therapy. Topical and intralesional medications have been reported, such as topical imiquimod and timolol, although they are generally not recommended. Recurrence of PGs has been reported at approximately 7.7%.12,13 Pyogenic granulomas caused by pregnancy and medications tend to recur more frequently. Complete surgical excision is typically needed for recurrent lesions.12,13

Our patient was suspected to have PG according to clinical history and examination. The lesion was removed via shave removal followed by electrocautery and the lesion has not recurred. Histopathologic findings confirmed the diagnosis of PG.

Dina Zamil, BS, and Shangyi Fu, BS, are medical students at Baylor College of Medicine in Houston, Texas; Tara L. Braun, MD, is a resident in the department of dermatology at Baylor College of Medicine.

References

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12. Sarwal P, Lapumnuaypol K. Pyogenic granuloma. In: StatPearls. Bethesda, MD: StatPearls Publishing LLC; 2021. Accessed November 17, 2021. https://www.ncbi.nlm.nih.gov/books/NBK556077/

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14. Patrice SJ, Wiss K, Mulliken JB. Pyogenic granuloma (lobular capillary hemangioma): a clinicopathologic study of 178 cases. Pediatr Dermatol. 1991;8(4):267-276. doi:10.1111/j.1525-1470.1991.tb00931.x

15. Mills SE, Cooper PH, Fechner RE. Lobular capillary hemangioma: the underlying lesion of pyogenic granuloma. A study of 73 cases from the oral and nasal mucous membranes. Am J Surg Pathol. 1980;4(5):470-479.

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18. Ghodsi SZ, Raziei M, Taheri A, Karami M, Mansoori P, Farnaghi F. Comparison of cryotherapy and curettage for the treatment of pyogenic granuloma: a randomized trial. Br J Dermatol. 2006;154(4):671-675. doi:10.1111/j.1365-2133.2005.06923.x