Pseudoepitheliomatous hyperplasia (PEH) is a benign proliferative pseudoneoplastic response to trauma, wounds, burns, radiation therapy, cryotherapy, pharmaceutical agents, and cutaneous malignancies.¹,²,³,⁴,⁵,⁶,⁷,⁸,⁹ It can simulate basal cell carcinoma clinically and squamous cell carcinoma (SCC) histopathologically, which often complicates the initial diagnosis and management.⁴ One case of PEH was reported to be associated with a cutaneous horn.¹⁰

PEH can be secondary or idiopathic.³,⁵ Secondary PEH is by far the most common form, associated with a known etiology such as infectious agents, insect bites, some drugs, or cutaneous malignancies. It also has been reported after Mohs micrographic surgery¹¹ and following diode laser therapy.¹³ In primary PEH on the other hand, there is no clinical or histopathological evidence for a definite etiology.¹⁴ These lesions have been described under various names such as verrugoma, molluscum sebaceum, and self-healing squamous cell epithelioma.¹⁴

Clinically, the most important associations of PEH are with malignant cutaneous tumors such as SCC, basal cell carcinoma, melanoma, cutaneous lymphoma, pulmonary adenocarcinoma, and metastatic breast cancer.¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹ This makes initial biopsy or excision necessary to uncover the underlying pathology.

Besides its cutaneous manifestations, PEH can involve the conjunctival epithelium,²²,²³,²⁴,²⁵ where it can be associated with vernal keratoconjunctivitis,²²,²⁵ possibly resulting from chronic inflammation exacerbated by mechanical trauma to the limbal epithelium.²³ It also has been described as a complication of cultivated limbal epithelium transplantation.²³

PEH is frequently associated with tattoo dye. The development of PEH in response to red tattoo pigment was first reported by Sulzberger in 1937.²⁶ In 1959, Goldberg²⁷ further defined this condition as multiple verrucous papules within an area of red ink. The verrucous growth pattern is often mistaken for SCC, which is important clinically since cases of SCC have also been reported arising in tattoos.²⁸,²⁹,³⁰,³¹,³² Although most reported tattoo-related PEH cases were associated with the use of either red or purple dye,³³,³⁴,³⁵,³⁶ occasional cases also have been seen in black, green, and blue tattoos.³⁰,³⁷ While PEH has not been described associated with blepharopigmentation, granulomatous reactions have been reported.³⁸,³⁹,⁴⁰

The interval between tattooing and the onset of PEH varies from several days to several years. Upon transfer of the pigment into the dermis, pigment granules are ingested by skin phagocytes and a transient inflammatory period, characterized by a foreign body reaction and fibrous tissue formation, begins and lasts about 2 weeks.⁴¹ Later, the pigment becomes encapsulated in dense layers of connective tissue located in the papillary dermis either within fibroblasts or between collagen bundles.⁴¹