Case Study Reports Multiple Giant Cell Collagenomas Associated With Cowden Syndrome

Giant cell collagenoma. Interface of the well-circumscribed, unencapsulated sclerotic spindle cell proliferation with normal collagen of dermis (H&E; ×40). Image courtesy of https://doi.org/10.1111/cup.14595

Storiform collagenoma, or sclerotic fibroma, characterized by a distinct histopathological pattern of collagen bundles, represents a relatively rare cutaneous tumor. It is often sporadic but can manifest in association with Cowden syndrome, particularly when occurring in multiples.

Giant cell collagenoma, a variant with similar histopathological features, is rarely linked to Cowden syndrome.¹

In a recent case report published in the Journal of Cutaneous Pathology,² authors Salusti-Simpson et al presented a case of multiple giant cell collagenomas in a patient with Cowden syndrome, considered rare in the scientific literature.

A 36-year-old female presented with 2 firm dome-shaped papules on her forehead, each measuring approximately 1 cm. Histopathological examination revealed a well-circumscribed spindle cell proliferation associated with prominent sclerotic dermal collagen. The collagen bundles exhibited a storiform pattern with intervening clefts, accompanied by an effaced epidermis.

One papule displayed a more cellular composition with multinucleate cells. Subsequently, the patient developed a similar lesion on the posterior scalp 7 years later, characterized by features of giant cell collagenoma with diffuse floret-like multinucleate giant cells.

The patient’s clinical history was further complicated by gait ataxia and fine motor control difficulties, leading to the discovery of a large left cerebellar mass consistent with Lhermitte–Duclos disease. Genetic testing confirmed a PTEN mutation and a diagnosis of Cowden syndrome, a condition associated with various benign and malignant lesions across multiple organs.

The cutaneous manifestations of Cowden syndrome include acral keratoses, trichilemmomas, and mucocutaneous neuromas, among others. Storiform collagenomas, particularly when multifocal, have been reported as a marker for Cowden syndrome. These papules typically present on the face, neck, and extremities, with histopathological features including a characteristic storiform pattern of collagen bundles and an effaced epidermis.

Giant cell collagenoma, sharing histopathological similarities with storiform collagenoma, is rarely associated with Cowden syndrome. Immunohistochemically, multinucleate cells within giant cell collagenomas are negative for various markers.

Differential diagnosis of such lesions includes dermatofibroma variants, multinucleate cell angiohistiocytoma, and pleomorphic lipoma, among others. However, in this case, the effaced epidermal rete ridge pattern, distinctive storiform collagen, and immunohistochemical profile favored a diagnosis of giant cell collagenoma.

This case underscores the importance of recognizing rare cutaneous manifestations in the context of syndromic diseases like Cowden syndrome, according to authors of the case report. The occurrence of multiple giant cell collagenomas in such patients suggests a possible association, warranting vigilant clinical surveillance and genetic testing.

Authors call for further research into the pathogenesis and clinical implications of giant cell collagenomas in the context of Cowden syndrome.

"Our hope is to add to the existing and limited literature on giant cell collagenoma and to report the association of multiple giant cell collagenomas with Cowden syndrome," according to Salusti-Simpson et al. "While giant cell collagenoma represents a rare variant of storiform collagenoma (sclerotic fibroma), it may be considered in the expanded list of cutaneous lesions associated with Cowden syndrome."

References

1. Requena L, Gutierrez J, Sanchez YE. Multiple sclerotic fibromas of the skin. A cutaneous marker of Cowden's disease. J Cutan Pathol. 1992; 19(4): 346-351. doi:10.1111/j.1600-0560.1992.tb01373.x
2. Salusti-Simpson M, Madrid M, Cook D. Giant cell collagenomas associated with Cowden syndrome: A case report. J Cutan Pathol. February 9, 2024. Accessed February 13, 2024. https://doi.org/10.1111/cup.14595