Cutaneous cylindromas represent a benign adnexal neoplasm that is quite rare, describing a dual lineage proliferation of cells within the dermis. When these cell populations are cut in cross-section, they have a round morphology that is likened to cylinders, hence the name. Cylindromas are a slow-growing, usually small, benign entity, though there have been rare cases of malignant transformation and even metastases reported. They are usually located on the scalp or face and occur nine times more frequently in females as males. When multiple cutaneous cylindromas occur on the scalp, they can grow together and resemble a hat or turban, giving rise to the previously more common term “turban tumor.”
Cylindromas may occur in either a sporadic or familial fashion, and they are not thought to occur as the result of environmental factors. When they occur sporadically, it is usually as a solitary lesion. Sporadically occurring cylindromas, in contrast to familial inherited forms, will often exhibit expression of MYB-NFIB fusion transcripts. MYB is an oncogene that when fused with NFIB, a transcription factor gene, forms an oncoprotein which can encourage a neoplastic process. MYB, when activated or over-expressed, may also act as a driver to encourage dermal cylindromas, taking over the action that is usually performed by the MYB-NFIB fusion oncoprotein.
Familial cylindromatosis syndromes are associated with mutations in the CYLD tumor-suppressor gene, except for extremely rare exceptions. The CYLD gene was discovered in 2000 and implicated as the causal agent in the three inherited cylindromatosis syndromes. Of these syndromes, the Brooke-Spiegler Syndrome (BSS) is probably the most well known. Familial cylindromatosis (FC), and multiple familial trichoepitheliomas (MFT) are the other two inheritable cylindromatosis syndromes and also involve mutations in the CYLD gene. CYLD mutations are inherited in an autosomal dominant pattern but conform to the two-hit hypothesis, requiring a second mutation of the gene to occur randomly from DNA damage to effect a neoplastic change. Although the CYLD mutation is autosomal dominant, phenotypic expression of these mutations varies widely. There are over 100 mutations that have been identified in the CYLD gene, with more discovered all the time. The most common mutation is on chromosome 16q. It is not well understood which mutations will effect in specific phenotypic expression. Even within the same family, affected members will often exhibit differing phenotypes.
Cutaneous cylindromas are rare entities which affect females nine times more frequently than males and are more common in Caucasian populations. When they occur as solitary lesions, they are usually the sporadic type. Sporadic forms are more likely to occur in older patients. Multiple occurring lesions are more likely to be syndromic and will often manifest at an earlier age.
The pathogenesis of cylindromas is not yet well understood, and multiple theories exist on their origin. As the tumor develops exclusively in hair-covered areas, a follicular epithelium lineage is often defended. The cells within the cylindroma also have exhibited expression of follicular keratin. However, many experts maintain that this neoplasm's origins are of eccrine or apocrine differentiation. Cylindromas do not arise on palmar or plantar surfaces, which would contradict an eccrine lineage as there are many eccrine glands in these areas but no hair follicles or apocrine glands. The more differentiated cells that comprise cylindromas appear morphologically similar to secretory cells, which some may use to argue for the apocrine origin of these neoplasms.
Cylindromas are classically described as variably sized rounded islands of basaloid cells which are arranged together in a fashion reminiscent of a “jigsaw puzzle.” These islands are mostly contained within the dermis, but also often extend into the sub-cutis. These islands should not connect to the overlying epidermis. The islands are composed of two cell populations, with a palisading peripheral lining of smaller cells with more hyperchromatic nuclei and an inner population in the islands with larger, more differentiated pale cells and nuclei and small duct-like structures. These islands are surrounded by an interconnecting hyalinized sheath which looks like a thickened dense pink lining. Within these basaloid islands interspersed small round pink globules, or “hyaline droplets,” are often seen.
Solitary lesions, which are usually sporadic and not familial, present as slow growing, painless, round nodular lesions. They are sometimes pedunculated. Solitary lesions usually occur in older populations and do not usually grow larger than one centimeter. They are rarely painful or tender and may have a pinkish or tan coloring with a smooth surface. Small superficial blood vessels may be visualized.
Multiple cylindromas will usually occur in the setting of a familial syndrome and develop much earlier in life. When occurring in multiples, these lesions require excisions for treatment and re-excisions later in life as they often recur. Also, in syndromic patients, the cylindromas may exhibit accelerated growth and reach sizes over 20 centimeters in some cases. As they grow this large, they often will ulcerate and become painful.
Ninety percent of cylindromas occur in the head and neck region. They also can occur on the trunk and extremities, but the palms and soles are spared. A family history of multiple cylindromas should be helpful in aiding the diagnosis. Environmental factors have not been implicated in the development of these lesions.
Radiologic exams may be useful to identify the extent of the lesions as they have been known to involve underlying osseous structures, and some lesions are quite vascular. Both of these features are important to consider when planning treatment.
Genetic testing for mutations in the CYLD cylindromatosis gene and familial studies should be performed in patients in whom a cylindromatosis syndrome is suspected.
Treatment options include excision, laser ablation, and cryotherapy. Excision is the preferred treatment and is usually curative. Local recurrence has been documented. Large lesions should be imaged before planning treatment to determine vascularity and involvement of surrounding tissues, including underlying osseous structures. Pre-treatment embolization is vital in patients with large and multiple cylindromas to minimize intra-operative blood loss as they can be quite vascular lesions. Topical aspirin has been utilized to prevent recurrence after excision. Excision and histopathologic examination along with clinical correlation should lead to the correct diagnosis.
Trichoepitheliomas and spiradenomas appear similar and often occur simultaneously. Trichoepitheliomas are differentiated from cylindromas by the presence of horn cysts. Spiradenomas can prove exceedingly difficult in some cases to differentiate from cylindromas. Within a spiradenoma, there may be populations of basaloid cells that appear indistinguishable from a cylindroma. They will often appear more circumscribed and nodular than cylindromas. Spiradenomas are typically solitary lesions that often exhibit intermittent pain and are tender to palpation, as opposed to the majority of cylindromas which are painless. Thorough histopathologic examination of the entire lesion is vital in difficult cases to differentiate between cylindromas and spiradenomas.
Cylindromas may transform into the malignant cylindrocarcinoma in a rare number of cases. Malignant cylindromas are more frequently associated with Brooke-Spiegler Syndrome. The malignant form exhibits more rapid growth, atypical and asymmetrical architectural features, and invasive pattern of growth. Cytological features may include nuclear pleomorphism and crowding, loss of the characteristic jigsaw puzzle pattern, loss of intervening hyaline sheaths, loss of the biphasic cell population, and development of necrosis. Malignant cylindromas exhibit aggressive local infiltrative growth patterns and have been known to metastasize. Immunohistochemical stains do not help differentiate between benign or malignant lesions.