Introduction

Trichoadenoma is a rare benign tumor derived from the infundibular part of the pilosebaceous unit. Nikolowski [1] described the first case in 1958 as “organoid folicular hamartoma”. Clinically, it appears as a solitary tumor. It involves adults without sex predilection [2] and is most commonly presented on the face (57.5%) and the buttocks (24.2%) and may involve eyelid, shoulder [2], lip [3], vulva [4], penis [5]. Only three cases reported are located on the eyelid, and the present case represents the fourth found in the eyelid reported in the literature.

The clinical appearance of trichoadenoma can be misleading and suggest a diagnosis of basal cell carcinoma, epidermal cyst, or seborrheic keratosis.

Histologically, it is characterized by numerous horny cysts lined with stratified squamous epithelium that resembles the external root lamia of the hair follicle.

The aim of this report is to review the literature and collect the cases reported to date about trichoadenoma and detail the clinical and histologic features of a trichoadenoma of the eyelid, a rare location of this lesion. Table 1 lists the published cases, ordered by year of publication, and the location of the lesion and the previous clinical diagnosis are also presented.

Case report

A 45-year-old woman was referred to Ophthalmology Department for evaluation of a pigmented lesion on her left eyelid.

Four lesions in the inner third of the upper eyelid as a group of nodules stuffed with black material mimicking comedos (Fig. 1A) were founded on a slit-lamp exam.

Figure 1. A. Multiple nodular comedo-mimicking lesions on upper eyelid. B. Keratin cysts surrounded by mature squamous cells (H&E, ×4). C. White arrows shows hair shafts among cystic keratin, an unusual finding in these tumors (H&E, ×10). D. White arrow showing detailed hair shaft (H&E, x15)

The lesions were surgically removed under local anesthesia and sent for histopathological examination.

Histological exam revealed the existence of several cystic formations lined by squamous epithelium that resembled a follicular infundibulum. They were occupied by abundant keratotic material in which hair structures were recognized. In some cysts, there were projections from the epithelium towards the periphery that resembled abortive follicular bulbs and was surrounded by a lymphocytic inflammatory cyst at the dermal level (Fig. 1B).

Discussion

Trichoadenoma generally occurs as a solitary, nodular lesion that clinically resembles basal cell carcinoma, epidermal cysts, or seborrheic keratosis, and differential diagnosis of these lesions is needed. The lesions are usually isolated, asymptomatic, and slow-growing, with a size of less than 1.5 cm. The evolution of trichoadenoma is benign, and surgical excision is the preferred treatment.

This is the second reported case of comedo-like trichoadenoma on the upper eyelid to the best of the authors’ knowledge. There are only three reports of trichoadenoma affecting the eyelids [6–8].

The lesion reported by Shields et al. [6] was suspected to be a basal cell carcinoma affecting the lower eyelid. The lesion published by Lever was thought to be a sebaceous cell carcinoma that involved the lower eyelid [7], and Cheng reported a case mimicking comedo affecting the upper eyelid [8], as in the reported case.

Microscopic examination is necessary to make the diagnosis of trichoadenoma. The tumor is composed of keratin-filled cysts surrounded by mature squamous cells similar to the follicular infundibulum. Stromal fibroblastic inductions are evident around these cysts, sometimes associated with solid outgrowths of epithelium. The differential diagnosis with other cystic cutaneous neoplasms is based on the absence of basaloid cells (cystic basal cell carcinoma, seborrheic keratosis, or trichoepithelioma) and the absence of stromal induction in the case of epidermal cysts [9]. Interestingly, in our case, several hair shafts were identified among the cystic keratin, which is unusual in these tumors (Fig. 1C–D).

Table 1 lists over 70 cases of trichoadenoma reported to date, and most of them are single cases. Shimanovich [2] in 2010 reported 19 cases, and Huet [10] in 2020 — 12 cases, and these are the largest case series. Another case series found in the literature was: Rahbari [11] in 1978 (8 cases), Nikolowski [12] in 1978 (4 cases), Hey [13] in 1987 (2 cases), Jaqueti [14] in 1989 (2 cases) and Reibold [15] in 1998 (7 cases). The histogenesis of trichoadenoma remains unclear. In terms of morphological differentiation, trichoadenoma is less mature than trichofolliculoma and more differentiated than trichoepithelioma. Trichoadenoma is characterized by a prominent cyst formation and resembles some features of trichoepithelioma. Both lesions retain Merkel cells as an element of differential diagnosis [2] regarding basal cell carcinoma. Regarding follicular neoplasms, trichofolliculoma is characterized by numerous secondary hair follicles radiating from primary central dilated hair follicles and a well-organized fibrovascular stroma. Immunohistochemical studies have shown cytokeratin (CK) 20 positive in trichoadenoma and trichoepithelioma as a specific marker for epithelial neuroendocrine cells of Merkel. In 2005 [16], Kurokawa reported a case with the immunohistochemical study of cytokeratins and found that CK10 and CK15 were present in trichoadenoma. CK10 may be found in most horn cysts with keratohyalin granules and CK15 in the outermost cells in horn cysts and the basaloid epithelium, suggesting that trichoadenoma differentiates towards the follicular infundibulum and follicular hair bulge of the outer root sheath.

Trichoadenoma is an underdiagnosed tumor, mainly due to its resemblance to common periocular lesions such as actinic keratosis, seborrheic keratoses, or epidermal cysts. These lesions are not routinely sent to the histopathological exam. Most of the histopathologically diagnosed cases of trichoadenoma are due to clinical suspicion of basal cell carcinoma and its referral to histopathological analysis.

Conclusions

Despite the studies focused on the immunohistochemical analysis of the lesions, the histopathological diagnosis continues to be the one that provides the most cost-benefit balance. We suggest referring all excised periocular lesions for a correct histopathological diagnosis, even those suspected of macroscopically benign or common lesions.