Agminated Pyogenic Granuloma: De Novo Presentations and Review of the Literature

Pyogenic granulomas (PG) are benign, vascular tumors that bleed frequently given their rich blood supply and friable surface. They can be found in patients of all ages but are most commonly seen in children (average age of onset 5.9 years old), young adults, and pregnant women.¹ While PGs are common they rarely occur as clusters, or as agminiated lesions, within a defined anatomical space. Pyogenic granulomas can occur in the setting of acquired vascular deformities, traumatic injury, or pregnancy.^1-3 However, they are most commonly associated with congenital lesions such as arteriovenous malformations or port-wine stains which are associated with increased blood flow and promotion of local angiogenesis.^4-6 We describe herein two cases of agminated PG without underlying congenital vascular malformations.

Case reports

Patient 1. An otherwise healthy four-year-old boy presented with a one-month history of a red, bleeding lesion on the neck. On exam, there was an isolated 6mm bright red papule located at the posterior neck (Figure 1). Excisional biopsy confirmed the diagnosis of PG. Six months later he presented with a 7mm red papule of the posterior neck base at the site of previous removal and was noted to have three to four scattered pinpoint to 1mm similar-appearing vascular papules on the adjacent skin. Shave removal with electrocautery was performed on the largest lesion and confirmed to be a recurrent PG. Treatment with one drop of timolol 0.5% solution twice a day was initiated for the smaller surrounding papules. Nine months later the patient again presented with recurrence though he denied episodes of bleeding. He had a 2cm pink to violaceous, blanching nodule on right posterior neck surrounded by scattered pinpoint to 3mm red papules. The largest lesion was treated with surgical excision, and pulsed-dye laser (PDL) therapy was used to treat the smaller, peripheral lesions.

Figure 1: Pyogenic granuloma. Singular 6mm red papule found at the posterior neck.

Patient 2. A healthy 10-year-old boy presented with clusters of mushroom-like, bleeding lesions on the lower right back. He had previously undergone surgical excision of the lesion from an outside hospital, confirming the diagnosis of pyogenic granuloma. He denied any preceding trauma or the presence of a birthmark in the affected area. On exam, he had a cluster of 1-2mm dull red papules in an area measuring approximately 4-6cm with a prominent 4mm exophytic papule (Figure 2). There was no background vascular stain. Patient was started on two drops of timolol 0.5% gel BID. At two months follow up, it appeared that the some of the smaller areas of erythema resolved with the larger 4mm exophytic papule progressing to a more dull red appearance. Given the clinical improvement, timolol drops were continued for three months with instruction to return if lesions progressed.

Figure 2: Agminated pyogenic granulomas. Clustering of 1-2mm red papules in an area of prior surgical excision for recurrent pyogenic granulomas, prior to treatment with 0.5% timolol solution.

Patient returned one year after initial visit with an enlarging lesion that had recurred after several months after discontinuing the topical timolol. He had developed a 5mm erythematous pedunculated papule of rubbery texture on the right mid-lower back with two to three smaller erythematous papules in close proximity. Shave excision confirmed recurrent PG. Three months later he again presented with a larger exophytic 1.3cm mushroom-like papule on the mid back. There were also now 10 to 12 intact pustules that extended from the area of the primary lesion to his upper back, left mid back, and right flank. These lesions were addressed with shave excision. Over the course of six months, patient returned twice with similar growths that were treated with shave excision. Given his numerous scars, some of which were hypertrophic, the decision was made to pursue pulsed dye laser therapy. This resulted in significant shrinkage of the lesions.

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Discussion

We present two cases of agminated PGs, each arising de novo without underlying congenital vascular anomalies and with recurrence despite non-surgical and surgical interventions. Both cases demonstrate characteristic exophytic vascular lesions, frequent bleeding, high rate of recurrence, and rapid growth. Both patients reported partial response to topical 0.5% timolol with shrinkage of the original lesions. However, both patients eventually required surgical and pulsed dye laser therapy.

Agminated PGs have been described within a setting of congenital vascular anomalies including congenital hemangioma and vascular stains.^4-5 Katta, et al. reports agminated PG arising in pregnancy in a 16-year-old female 4 months gestation with congenital port-wine stain.⁶ It has been reported that pregnancy and the hormonal changes associated with it predisposes to the growth of pyogenic granulomas as both estrogen and progesterone are angiogenic factors.6,7 Agminated PGs in the absence of other vascular anomalies or inducers of angiogenesis suggest alternative factors may contribute to the growth of these lesions. From a cell-signaling framework, key factors that have been implicated in the generation of PGs include the overexpression of VEGF, STAT3, and MAPK, all of which are involved in cellular proliferation and blood vessel growth.^8,9 Other prominent factors involved in pathogenesis include BRAF and KRAS, suggesting that PGs may be related to dysregulation of the Ras pathway.^10,11 Agminated PGs may occur in areas of mosaicism for these proangiogenic mutations and warrants future investigation into possible genetic influences.

Topical beta-antagonists have been reported to be a viable option for agminated PG in the setting of congenital vascular lesions.¹² It is thought that local vasoconstriction with subsequent reduction in blood supply, as well as inhibition of pro-angiogenic factors, leads to tumor shrinkage and resolution over time. Many authors have suggested that beta-antagonists such as timolol or propranolol can be utilized to address agminated PGs.^12-15 Topical imiquimod cream, an immunomodulating agent, is also effective in some cases. The mechanism of action is unclear but is thought to be related to its anti-tumor and proinflammatory effects; induction of TNF-a, IL-6, IFN-gamma, and anti-angiogenic factor expression all cause inhibition of vascular growth and increased apoptosis. Tritton, et al. report 10 children treated with topical 5% imiquimod cream, all of which had no recurrence with resolution sustained over an average of 9.6 months of follow up.¹⁶ Gencoglan et al similarly report two cases of pediatric PG treated with topical imiquimod, both of which had no recurrence at five and seven months follow up.¹⁷ There were no reports of adverse effects in either studies.

Other interventions for the management of PGs include surgical excision, shave excision with curettage, PDL therapy, and cryotherapy. Surgical excision appears to offer the lowest recurrence rates. Patrice, et al. report a 0% recurrence rate in children treated with surgical excision.¹⁸ In a more recent study, Gilbin, et al. demonstrate a 3.6 percent recurrence rate in those with PG addressed with surgical excision and closure.² The authors also identified shave excision and curettage as an option, despite a higher rate of recurrence at 10 percent. Despite their low rates of recurrence, consideration must be paid to complications such as infection and cosmetic defects. For patients who are unable or unwilling to tolerate surgical intervention, PDL therapy can be considered for smaller lesions. Tay, et al. demonstrate the effectiveness of PDL in 22 children with PGs of average diameter 4mm (range 2mm to 1cm).¹⁹ In 20/22 patients (91 percent), PDL was successful in eliminating the lesion, with five patients requiring one treatment, eight patients requiring two treatments, and six patients requiring three treatments. Cryotherapy with liquid nitrogen has also been reported to be successful in the management of PGs. Mirshams, et al. in a prospective observational study, treated 135 patients with liquid nitrogen.²⁰ The study reports complete resolution of PGs with a mean of 1.58 treatments resulting in minimal cosmetic deformities and no other side effects.

Conclusion

Pyogenic granulomas are benign vascular lesions that commonly present in the pediatric population. Agminated PGs are less common and typically arise in the setting of congenital vascular lesions but can appear de novo. Surgical excision is the gold standard for treatment, with the lowest recurrence rates. Pharmacotherapy with beta-antagonists and immunomodulators as well as treatment with pulsed dye laser can be considered as adjunctive therapies.

The authors have no relevant disclosures.

1. Pagliai KA, Cohen BA. Pyogenic granuloma in children. Pediatr Dermatol. 2004;21(1):10-3.

2. Giblin AV, Clover AJ, Athanassopoulos A, Budny PG. Pyogenic granuloma - the quest for optimum treatment: audit of treatment of 408 cases. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2007;60(9):1030-5.

3. Harris MN, Desai R, Chuang TY, Hood AF, Mirowski GW. Lobular capillary hemangiomas: An epidemiologic report, with emphasis on cutaneous lesions. Journal of the American Academy of Dermatology. 2000;42(6):1012-6.

4. Baselga E, Wassef M, Lopez S, Hoffman W, Cordisco M, Frieden IJ. Agminated, eruptive pyogenic granuloma-like lesions developing over congenital vascular stains. Pediatr Dermatol. 2012;29(2):186-90.

5. Barrick B, Lehman J, Tollefson M. Agminated pyogenic granuloma-like growth arising in a congenital hemangioma. JAMA Dermatol. 2014;150(7):781-3.

6. Katta R, Bickle K, Hwang L. Pyogenic granuloma arising in port-wine stain during pregnancy. The British journal of dermatology. 2001;144(3):644-5.

7. Sills ES, Zegarelli DJ, Hoschander MM, Strider WE. Clinical diagnosis and management of hormonally responsive oral pregnancy tumor (pyogenic granuloma). The Journal of reproductive medicine. 1996;41(7):467-70.

8. Arbiser JL, Weiss SW, Arbiser ZK, Bravo F, Govindajaran B, Caceres-Rios H, et al. Differential expression of active mitogen-activated protein kinase in cutaneous endothelial neoplasms: implications for biologic behavior and response to therapy. Journal of the American Academy of Dermatology. 2001;44(2):193-7.

9. Chen SY, Takeuchi S, Urabe K, Hayashida S, Kido M, Tomoeda H, et al. Overexpression of phosphorylated-ATF2 and STAT3 in cutaneous angiosarcoma and pyogenic granuloma. Journal of cutaneous pathology. 2008;35(8):722-30.

10. Lim YH, Douglas SR, Ko CJ, Antaya RJ, McNiff JM, Zhou J, et al. Somatic Activating RAS Mutations Cause Vascular Tumors Including Pyogenic Granuloma. The Journal of investigative dermatology. 2015;135(6):1698-700.

11. Groesser L, Peterhof E, Evert M, Landthaler M, Berneburg M, Hafner C. BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma. The Journal of investigative dermatology. 2016;136(2):481-6.

12. McGinness A, Gillam A, Yeh I, Mathes EF. Topical timolol: An effective treatment option for agminated pyogenic granuloma. Pediatric dermatology. 2018;35(5):e300-e3.

13. Wine Lee L, Goff KL, Lam JM, Low DW, Yan AC, Castelo-Soccio L. Treatment of pediatric pyogenic granulomas using beta-adrenergic receptor antagonists. Pediatric dermatology. 2014;31(2):203-7.

14. Ji Y, Chen S, Xu C, Li L, Xiang B. The use of propranolol in the treatment of infantile haemangiomas: an update on potential mechanisms of action. The British journal of dermatology. 2015;172(1):24-32.

15. Knopfel N, Escudero-Gongora MDM, Bauza A, Martin-Santiago A. Timolol for the treatment of pyogenic granuloma (PG) in children. Journal of the American Academy of Dermatology. 2016;75(3):e105-e6.

16. Tritton SM, Smith S, Wong LC, Zagarella S, Fischer G. Pyogenic granuloma in ten children treated with topical imiquimod. Pediatric dermatology. 2009;26(3):269-72.

17. Gencoglan G, Inanir I, Gunduz K. Pyogenic granuloma in two children successfully treated with imiquimod 5% cream. Pediatric dermatology. 2009;26(3):366-8.

18. Patrice SJ, Wiss K, Mulliken JB. Pyogenic granuloma (lobular capillary hemangioma): a clinicopathologic study of 178 cases. Pediatr Dermatol. 1991;8(4):267-76.

19. Tay YK, Weston WL, Morelli JG. Treatment of pyogenic granuloma in children with the flashlamp-pumped pulsed dye laser. Pediatrics. 1997;99(3):368-70.

20. Mirshams M, Daneshpazhooh M, Mirshekari A, Taheri A, Mansoori P, Hekmat S. Cryotherapy in the treatment of pyogenic granuloma. J Eur Acad Dermatol Venereol. 2006;20(7):788-90.