Storiform collagenoma as a clue for Cowden disease or PTEN hamartoma tumour syndrome

Cowden disease (CD) is a rare autosomal dominant disease with variable expression, affecting a number of systems in the form of multiple hamartomatous neoplasms of ectodermal, mesodermal, and endodermal origin¹ (multiple hamartoma neoplasia syndrome). CD usually presents in late adolescence and is caused by a germ mutation in the PTEN gene.² Classically, the mucocutaneous features of CD are tricholemmomas, oral fibromas, acral keratoses, palmar pits, and gingival and palatal papules. These mucocutaneous signs are important markers for systemic findings; in particular breast carcinoma (20%), which is often bilateral,³,⁴ thyroid carcinoma (8%) and endometrial carcinomas.² Various manifestations of the central nervous system (mental retardation,⁵ seizures, ganglinoneuromas), musculoskeletal system (craniomegaly, kyphoscoliosis and high arched palate) and gastrointestinal system (multiple hamartomatous polyps, adenocarcinomas arising in the polyps) are well documented. In addition, ovarian cysts and menstrual abnormalities are known to occur in the female genital tract.⁶

Bannayan–Ruvalcaba–Riley syndrome has many clinical features in common with CD, including mucocutaneous manifestations and an increased risk of gastrointestinal polyps and malignancy.⁷ Several other similar phenotypes caused by mutations in the PTEN gene have been described After studying 64 unrelated families with Cowden‐like features, Marsh et al proposed that these different entities lie within a spectrum; they referred to these conditions as the PTEN hamartoma tumour syndrome (PHTS).⁷,⁸,⁹

We report a case of an 18‐year‐old man of Fitzpatrick type 1 skin and freckles who developed a non‐tender, 10 mm erythematous nodule on his back over few months. The clinical differential diagnosis included an amelanotic melanoma, vascular tumour or a dermatofibroma. His past medical history included Pierre Robin syndrome (the triad of glossoptosis (downward displacement of the tongue), micrognathia (small jaw) and cleft palate), moderately severe learning difficulties and dyspraxia.

The nodule was excised. Microscopic examination (fig 1) showed a paucicellular (although a cellular variant has been reported¹⁰) well‐circumscribed dermal nodule composed chiefly of collagen bundles with a distinctive interweaving, storiform pattern with prominent elongated clefts between them, typical of a storiform collagenoma.¹¹ Tinctorial stains showed absence of elastic fibres (Orcein and EVG) within the lesion and reticulin fibres were seen prominently (Reticulin). Immunohistochemistry showed negative staining with CEA, EMA or keratin staining. Most of the cells within the nodule stained positively for vimentin, and factor XIIIa stain highlighted scattered dermal dendritic cells.¹¹ On the basis of similar fibrotic changes observed in dermatofibroma, it has been speculated that storiform collagenoma may have diverse origins. This issue has been resolved by showing that type 1 collagen synthesis indicates fibroblastic origin of storiform collagenoma.¹² Furthermore, storiform collagenoma is distinguished from dermatofibrom by an epidermis overlying amorphous, eosinophilic bundles in a laminated pattern extending into the deep dermis.¹³,¹⁴

Figure 1 Histopathological and immunohistochemical typical appearance of circumscribed storiform collagenoma (original magnification indicated in brackets).

Storiform collagenoma has been described in association with CD but can also arise sporadically.¹¹ It occurs most often in young and middle‐aged adults⁶ and usually presents as a slow growing solitary nodule up to 1 cm in diameter on the head and neck or upper extremities. Typical histopathological, histochemical and immunohistochemical appearances as described by Metcalf et al¹¹ were present in our patient.

The combination of a storiform collagenoma and mental retardation in our patient raised the possibility of CD/PHTS. Further clinical evaluation identified numerous shiny papules on the buccal mucosa and gingival, giving a deeply furrowed (“scrotal”) tongue (fig 2A) and a “cobblestone” appearance to the buccal mucosa (fig 2B). There were no facial or acral lesions and no skeletal abnormalities. There were no other cutaneous lesions. His younger brother and maternal aunt also had mild learning difficulties. Chromosomal analysis for mutation in the suspected PTEN gene on chromosome 10p23 is awaited to confirm the clinical diagnosis of storiform collagenoma in association with CD.

Figure 2 (A) Deeply furrowed (scrotal) tongue. (B) “Cobblestone” appearance of the buccal mucosa. Informed consent was obtained for publication of this figure.

In our case, the first presenting feature of CD was with a histologically diagnosed storiform collagenoma. Subsequent clinical examination raised the suspicion of CD.

Serious systemic complications of CD include carcinomas of the thyroid, breast and endometrium. Genetic counselling and appropriate screening of index cases and family members is advocated.

Multiple trichilemmomas have been classically regarded as the cutaneous hallmark of CD.¹⁵ We here emphasise that storiform collagenoma of the skin is another cutaneous clue of this entity, which may also be helpful in an early diagnosis. To the best of our knowledge, this is the first report in the English literature where a circumscribed storiform collagenoma has led to this important diagnosis, highlighting the importance of the awareness of cutaneous manifestations of systemic diseases.

In summary, a thorough systemic examination is of paramount importance in CD, which usually presents with cutaneous manifestations, as the patients and their relatives are at risk of developing serious medical conditions.

Finally, we report the first case where a circumscribed storiform collagenoma lead to the diagnosis of CD/PHTS; the patient and his relatives are receiving genetic counselling.

Acknowledgements

The authors thank Mr Roy Indrasenan for his great help during preparation of this manuscript.