Our patient is a 71-year-old woman with a past medical history of cerebral vasculitis, anti-cardiolipin syndrome, and previous bladder mass. She presented with a 0.5 centimeter painless, purple-colored lesion of the left upper eyelid initially self-identified two years prior. She had a history of amblyopia necessitating patching as a child for strabismus or muscle misalignment. Her eye exam demonstrated 20/25 vision in both eyes, intraocular lenses in both eyes after cataract surgery, dry findings of the cornea, and some mild left upper eyelid ptosis in conjunction with the lesion. The lesion was initially thought to be a benign hemangioma based upon shape, color, and external vascular features (Figure 1).

Figure 1: Left Eyelid Collagenoma Withabnormally Vascular Appearance (Blue Arrow) and Incidental Nevus (Green Arrow).

The patient underwent a simple excision of the lesion and subsequent tissue biopsy. There was minimal bleeding during the procedure, but the lesion was noted to have a rubbery texture. The lesion was also quite adherent to the eyelid tarsal plate. Her surgical course was uncomplicated, and she healed well from the procedure.

Histologic examination of the excised lesion revealed haphazard bundles of thickened, hyalinized collagen forming an unencapsulated circumscribed nodule in the dermis (Figures 2 and 3). Collagen bundles demonstrated some clefting, and the background spindle-shaped fibroblastic cells were overall sparse and bland in appearance (Figure 4). Immunohistochemical stains for smooth muscle markers including smooth muscle actin (SMA) and desmin were negative. Epithelial membrane antigen (EMA) was also negative. An immunohistochemical stain for CD34 showed patchy positivity in the spindled cells, supporting the diagnosis of collagenoma.

Figure 2: Collagenoma Characterized By an Unencapsulated Circumscribed Nodule in the Dermis (2x, H&E).

Figure 3: Collagenoma Characterized By Haphazard, Thickened and Hyalinized Bundles of Collagen (4x, H&E).

Collagenoma is a rare, benign soft tissue lesion in the spectrum of connective tissue nevus characterized by an abnormal increase in dermal collagen [1-3]. Collagenomas themselves are a part of a broader group of lesions called “connective tissue nevi'' (Table 1).

Table 1: Connective Tissue Nevi (CTN) Adapted From Arora, Harleen, et al.

*See Table 2 for disease and syndromic associations

**It has been suggested that fibrous connective tissue nevus could represent a monophasic fibrous hamartoma of infancy.

Clinically, collagenomas typically appear as firm, flesh-colored papules that range in size from 0.5-5.0 centimeters in greatest dimension and tend to occur on the trunk or upper extremities. 

Papular collagenomas can appear as a single isolated lesion, or less frequently, as agminated lesions with zosteriform, papulolinear, or “paving stone” patterns.

Figure 4: Collagenoma Characterized By Collagen Bundle Clefting with Background Spindle-Shaped Fibroblastic Cells (10x, H&E).

Additionally, collagenomas may have disease and syndromic associations (Table 2). Notable disease associations that involve multiple lesions include familial cutaneous collagenoma (also known as Buschke–Ollendorff syndrome) and eruptive collagenoma. Familial cutaneous collagenoma is a rare autosomal dominant disease that occurs due to mutation in the LEMD3 gene. It is thought to be hormonally driven, since the collagenomas in this disease have been observed to increase during pregnancy. Comparatively, eruptive collagenoma has a similar presentation on physical exam, but is more common than familial cutaneous collagenoma and tends to appear disproportionately in younger to middle aged Caucasian and Japanese males. Eruptive collagenoma has been found to be associated with multiple endocrine neoplasia type I (MEN I) syndrome [3,4]. Isolated and multiple collagenomas have also been reported to occur in relation to pseudo-Hurler syndrome and velocardiofacial syndrome (aka DiGeorge syndrome).

Table 2: Disease and Syndromic Associations of Collagenoma.

*Collagenoma can also be associated with cutis verticus gyrata, a clinical finding that can in turn be associated with Beare-Stevenson syndrome and Noonan’s syndrome.

Non-papular collagenoma variants that have important syndromic associations include the Shagreen patch and plantar cerebriform collagenomas. Shagreen patches typically appear as flesh-colored “orange peel” textured plaques on the lower back and are well known for their association with the tuberous sclerosis complex, due to mutations in TSC1 and TSC2 genes. The plantar cerebriform collagenoma appears as raised, undulating folds on the sole of the foot and is one of the criteria for a very rare genetic disease known as Proteus syndrome [5].

Additionally, collagenoma can be seen in conjunction with a condition called cutis verticis gyrata in which the scalp develops thickened furrows. Though not obligatorily, cutis verticis gyrata can subsequently be found in association with several syndromes and anomalies including, but not limited to Beare-Stevenson syndrome and Noonan’s syndrome.

Confusingly, collagenoma is not synonymous with an entity called “storiform collagenoma” also known as sclerotic fibroma. Instead of having the haphazard bundles of collagen seen in collagenoma, sclerotic fibromas have a more whorled, “pin-wheel” arrangement

Of collagen [6]. The distinction is not entirely trivial because unlike the previously discussed collagenomas, sclerotic fibromas can present as part of Cowden’s syndrome. 

Overall, our patient did not present with any additional clinical features that would necessitate further workup of disease and syndromic associations. Thus, this case most likely represents an instance of isolated sporadic collagenoma, albeit with a unique location on the upper eyelid and an abnormally vascular clinical appearance.

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3. Eichenfield LF, Frieden IJ, Esterly NB. Neonatal Dermatology E-Book. Elsevier Health Sciences. 2007.
4. Nelson AA, Ruben BS. Isolated plantar collagenoma not associated with Proteus syndrome. J Am Acad Dermatol. 2008; 58: 497-499.
5. Patterson JW. Weedon's Skin Pathology. Elsevier. 2014.
6. Stocchero GF. Storiform collagenoma: case report. Einstein (Sao Paulo, Brazil). 2015; 13.