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Abstract
A healthy 21-year-old woman was presented to our outpatient clinic with an asymptomatic swelling on her left arm. She reported the administration of two doses of BNT162b2 mRNA vaccination at the lesion site earlier. The pathology report confirmed the diagnosis of pilomatricoma. Previously, needlestick trauma and various immunisations have been attributed to the development of pilomatricoma. We present this case to emphasise the possible association between BNT162b2 mRNA vaccination and pilomatricoma development. The role of persistent inflammation is also discussed.
Keywords: Injection site reaction, Pilomatricoma, SARS-CoV-2 vaccination
Introduction 
Pilomatricoma (PM) (also known as pilomatrixoma or Malherbe's calcified epithelioma) is a benign neoplasm that originates from hair follicle matrix cells.[1] PMs are usually asymptomatic and often located on the head and neck region and upper extremities but can rarely occur on the chest, trunk or lower extremities.[2],[3],[4],[5],[6],[7],[8] There have been several cases of pilomatricoma documented after various immunisations. Here, we present a case of pilomatricoma that grew at the vaccination site after BNT162b2 mRNA vaccine (Pfizer-Bionthec).
Case A healthy 21-year-old woman was presented to our outpatient clinic with an asymptomatic swelling on her left arm. She had received two doses of BNT162b2 mRNA vaccination at the lesion site 1 year and 6 months before admission. Additionally, two to three weeks following the second dose of vaccine, she mentioned about an erythematous injection site reaction. Physical examination revealed a deeply palpable nodular lesion with overlying soft, erythematous skin in the deltoid region of the left shoulder [Figure 1]. An excisional biopsy was performed with a preliminary diagnosis of pilomatricoma and foreign-body granuloma. Histopathological investigation disclosed a tumoral lesion with centrally positioned large ghost cells with diffuse eosinophilic cytoplasm, multinucleated giant cells and calcification in the deep dermis and subcutaneous tissue, supporting the diagnosis of PM [Figure 2]. A Verhoeff–van Gieson stain showed normal elastic fibres (not shown). Following the total excision of the tumour, no recurrence was observed during a 10-month follow-up period.
Figure 1: Solid nodular lesion with overlying erythematous soft skin on the lateral side of upper left arm
Figure 2: (a-c) Pilomatricoma. (a) (H and EX100); solid islands of basaloid cells, which are the characteristic feature of the tumour (arrow), ghost cells (arrowhead) (b) (H and EX400) and multinucleated giant cells (asterisk) (c) (H and EX400) Discussion Following COVID-19 (coronavirus disease 2019) vaccination programmes, a number of adverse reactions have been documented. A wide spectrum of mucocutaneous adverse effects including local side effects (pain, erythema, swelling), exacerbation of pre-existing dermatosis, urticaria, morbilliform rash, pityriasis rosea-like eruption, purpura, herpes zoster, erythema multiforme, aphthae and telogen effluvium were observed.[9] We provide a case of pilomatricoma in this article, which could be considered a local side effect of COVID-19 vaccination.
Pilomatricomas can develop at any age, but regardless of gender, they often manifest in children and adolescents as a solitary tumour on the head or upper torso. Although the exact cause is unclear, it has been linked to trauma.[2],[5],[7] Reports of pilomatricoma with a history of preceding vaccine[2],[4],[5],[7],[10],[11],[12],[13] or drug injection[3],[14] are summarized in [Table 1]. Eight of these are associated with different vaccines and two with injectable drugs. There is a strong female predominance, and they are usually children and young adults. A recent publication also reported a case of PM with a history of BNT162b2 mRNA vaccination similar to ours.[9]
Table 1: Reported cases of pilomatricoma associated with vaccine or drug injectionCertain theories propose that injection site injury like trauma might cause pilomatricoma by preventing the apoptosis of damaged follicular epithelial cells.[4],[8] Tumour development may also be influenced by persistent inflammation, wound healing or the inoculated agent.[2],[4],[5],[7],[8] Previous reports have discussed ecchymotic reactions, persistent vaccine reactions after BCG vaccination and injection site reactions that proceed to severe erythema on the arm [Table 1]. Our patient also reported erythema at the injection site 2–3 weeks after the second dose of immunisation which can be described as a delayed-type localised hypersensitivity reaction possibly due to vaccine excipient.[15] Cases of PM with a history of injection site reactions, including ours, reinforce the idea that pilomatricoma development may be triggered by continuous inflammation.
Pilomatricoma usually appears as hard, bluish papules or nodules on the skin. But it can exhibit various clinical presentations, including ulcerating, perforating, keratotic, vascular, anetodermic and bullous types.[2] Histopathologically, it is typically observed as a well-defined nodular lesion composed of pink, basaloid epithelial cells that have lost their nuclei (ghost/shadow cells). Additional histological alterations, such as dilatation of lymphatics and loss of elastic fibres in the surrounding tissue, are anticipated in the uncommon subtypes of PM known as bullous PM and anetodermic PM.[4],[6],[8] Few cases of bullous pilomatricoma have been reported following vaccination.[4],[11],[12] However, the tumour in our patient did not show any changes related to these rare subtypes, despite having an imitative clinical appearance with its overlying soft skin.
Conclusion We presented a case of pilomatricoma possibly associated with SARS-CoV-2 mRNA vaccination. Certainly, we cannot totally exclude the coincidental occurrence. Given the previous similar reports, a true association is highly likely. However, the exact role of trauma and persistent inflammation still needs to be elucidated. Due to its infrequency, a diagnosis of pilomatricoma can be missed preoperatively. With the present case, we want to highlight that PM should be considered in the differential diagnosis of nodular lesions growing at the vaccination site. A history of injection site reaction may be a clue for the diagnosis of pilomatricoma.
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Conflicts of interest
There are no conflicts of interest.
References 
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