Smoothelin, a new marker for smooth muscle hamartoma

ARTICLE

ejd.2012.1744

Auteur(s) : María Jose Espiñeira-Carmona¹, José Aneiros-Fernández², María-Sierra Girón Prieto³, Victor Carriel⁴, María Antonia Fernandez¹, Augustín Buendía-Eisman⁵, Antonio Campos⁴, Miguel Alaminos Mingorance⁴, Salvador Arias-Santiago^1,4,5 salvadorarias@hotmail.es

¹ Dermatology Unit,

² Pathology Unit, San Cecilio University Hospital, Av Dr. Oloriz 16, Granada 18012, Spain

³ Metropolitan District, Granada, Spain

⁴ Histology Department, School of Medicine, Granada, Spain

⁵ Dermatology Unit, Baza General Hospital, Baza, Spain

Smoothelin is a cytoskeleton protein of differentiated smooth muscle cells with contractile capacity, distinguishing it from other smooth muscle proteins, such as smooth muscle actin (SMA). Smoothelin has two tissue-specific isoforms: the short 59-kDa isoform (A), found in smooth muscle cells of the organs; and the long 110-kDa isoform (B), in smooth muscle cells of vascular structures [1, 2]. Smoothelin has not been studied in cutaneous pathology; however, it could behave as a specific marker for the diagnosis of congenital smooth muscle hamartoma.

A 9-year-old healthy girl was referred for a localized pigmented lesion in the submandibular region, present at birth. Physical examination revealed a 6 × 4 cm plaque of uniform brown color with well defined borders and increased hair growth on the surface (figure 1A- B). The dermatoscopic examination showed areas of homogenous brown pigment with hypopigmented dots without pigmented network. Histological examination (figures 1C-F) showed variably-oriented small bundles of smooth muscle in superficial and middle portions of the reticular dermis, separated by bands of normal collagen. The epidermis was middle hyperplastic with acanthosis, papillomatosis and basal layer hyperpigmentation. Immunohistochemistry was performed with smooth muscle actin (clone 1A4, Master Diagnostica, Granada, Spain) and smoothelin (clone R4A, Master Diagnostica, Granada, Spain); both were positive, smoothelin was more specific for the detection of smooth muscle fibers in the hamartoma (figures 1C-F).

Smooth muscle hamartoma (SMH) is a rare hyperplasia of piloerector skin muscles within the reticular dermis [3]. It has a more frequent congenital variant (CSMH) and an acquired variant (ASMH). The most common presentation of CSMH is a slightly hyperpigmented plaque, usually located on the trunk, especially in the lumbosacral area and proximal extremities [4]. The friction of the plaque can cause transient piloerection or induration, known as the pseudo-Darier sign [5].

Clinical diagnosis is difficult, although it should be suspected in any congenital lesion with hypertrichosis, especially on the lower back [3]. In congenital localized forms the clinical differential diagnosis includes dysraphism of the spine and connective or elastic tissue hamartoma. Pigmented forms should be distinguished from melanocytic nevi and café au lait spots. For ASMH, Becker nevus, especially in case of hypertrichosis and onset in adolescence, should be considered.

Histological examination is essential for the diagnosis and it is characterized by markedly increased bundles of smooth muscle fibers in the reticular and deep dermis, not necessarily attached to hair follicles. Histochemical study with Masson trichrome and immunohistochemical stains with specific smooth muscle actin or desmin are used to confirm the nature of the smooth muscle proliferation.

However, these histological findings are not specific, since smooth muscle hyperplasia can be found in Becker's nevus. Several authors consider SMH and Becker's nevus as part of a spectrum of hamartomatous lesions showing increased smooth muscle cells with hypertrichosis and hyperpigmentation. On the one hand SMH, with mesenchymal predominance and, on the other, Becker nevus with epidermal predominance. Other authors consider them as independent entities [6].

Here, we highlight the use of smoothelin for the diagnosis of SMH. The hair erector muscle and vessel walls of deep vascular plexus are smoothelin-positive, so this expression can be applied in the diagnosis of benign and malignant muscle tumors of the skin, such as smooth muscle hamartoma.

In conclusion, although smoothelin presents a more specific immunohistochemical marker for the diagnosis of smooth muscle hamartoma than smooth muscle actin, improving its ability to detect subtle lesions and distinguish other structures that are positive for smooth muscle actin, such as myofibroblasts or superficial vessels, several cases of smooth muscle tumors need to be comparatively studied for the expression of both smoothelin and SMA.

Disclosure

No funding sources. No conflict of interest.

References

1. Aneiros-Fernández J, Husein-ElAhmed H, Arias-Santiago S, et al. Expression of smoothelin and smooth muscle actin in the skin. Histol Histopathol 2011;26:673-8.

2. Van der Loop FT, Schaart G, Timmer ED, Ramaekers FC, van Eys GJ. Smoothelin, a novel cytoskeletal protein specific for smooth muscle cells. J Cell Biol 1996 ;134:401-11.

3. Haydeh G, Massoud A, Pedram N. Multiple smooth muscle hamartoma: case report and review of the literature. Indian J Dermatol 2009;54:68-71.

4. Zvulunov A, Rotem A, Merlob P, Metzker A. Congenital smooth muscle hamartoma. Prevalence, clinical findings, and follow-up in 15 patients. Am J Dis Child 1990;144:782.

5. Monteagudo B, Ramírez-Santos A, Cabanillas M, Suárez-Amor O, Pérez-Valcárcel J. Smooth muscle hamartoma associated with acquired Blaschkoid nevus spilus. Actas Dermosifiliogr 2010;101:734-6.

6. Darling TN, Kamino H, Murray JC. Acquired cutaneous smooth muscle hamartoma. J Am Acad Dermatol 1993;28:844-5.