Multiple Cutaneous Leiomyomas

Correct Answer: C. Piloleiomyomas

Leiomyomas are tumors composed of smooth muscle. The smooth muscle can be found in the skin in erector pili muscles and are associated with hair follicles, arterioles, or in the genitalia (eg, dartos or vaginal smooth muscle). Tumors of the erector pili muscle are known as piloleiomyomas.^1-4

The patient’s skin biopsy revealed fascicles of spindled cells with eosinophilic and fibrillary cytoplasm. Additionally, the nuclei have blunted ends and lack prominent nucleoli. The fascicles of spindle cells with vacuolated cytoplasm are characteristic of leiomyoma. Smooth muscle actin and desmin stains can be used to decorate neoplastic cells if the diagnosis is uncertain upon microscopic examination of routine hematoxylin and eosin-stained sections, but these are often not needed. If the tumor is infiltrative or if there are atypical mitotic figures or marked pleomorphism, then a leiomyosarcoma should be considered.⁵ Because the typical and characteristic features of a leiomyoma were identified with routine hematoxylin and eosin-stained sections, no additional studies were needed in this case to establish a confident diagnosis of piloleiomyoma.

Contact dermatitis is associated with itching and scaling but is not associated with an increased number of spindle cells in the dermis. Although contact dermatitis may be associated with clustered, erythematous, skin-colored lesions, these lesions are not fixed and firm like in cases of piloleiomyomas, such as in our patient. A biopsy of contact dermatitis typically reveals spongiosis and eosinophils are often conspicuous within the inflammatory infiltrate.⁵ Scale crust and vesicle formation is often encountered in contact dermatitis but are not identified with piloleiomyomas.   

Herpes simplex infection is also associated with clustered lesions, but those lesions are blisters or vesicles. Lesions often flare episodically in the same area, but do not remain fixed. A biopsy of herpes simplex infection-associated lesions reveals multinucleated giant cells, as well as reticular degeneration and ballooning of the epidermis.⁵ Some nuclei can exhibit a steel grey color.  These viral cytopathic effects are not encountered with piloleiomyomas.  

Mastocytosis (also known as mast cell disease or urticaria pigmentosa) is associated with itchy lesions that may appear skin colored or erythematous. A biopsy of lesions in individuals with mastocytosis reveals large numbers of mast cells accompanied with eosinophils but not fascicles of spindled muscle cells. Mast cells have granules that appear purple with a Giemsa stain and stain with immunohistochemical makers for CD117. Mast cell disease lesions may occasionally hive upon stroking. This finding is known as Darier sign and describes urticarial wheal and flare formation after lesions are stroked. Leiomyomata have been associated with Pseudo-Darier sign, which describes transitory piloerection with induration from muscle tensing when a lesion is firmly rubbed.¹ The biopsy findings of bundles of muscle cells in our case excluded a diagnosis of mastocytosis.

Treatment and management. Our patient sought symptomatic relief of select tender lesions. The lesions were excised without incident by simple fusiform excision. 

Outcome and follow-up. She continues to follow-up regularly for her psoriasis and has not had additional symptomatic piloleiomyomas to date. Our patient was referred for genetic testing and counseling for potential genetic causes of piloleiomyoma.

Discussion. Leiomyomas may be associated with pain when located in pressure or contact points, or when exposure to cold temperatures causes muscle contraction. Brisk muscle contraction is associated with symptoms such as episodic aching or shooting pain. Calcium channel blockers such as nifedipine can mitigate muscle contraction and lesson symptoms.^1,4 We have used nifedipine 10 mg three times daily with positive results. Bothersome cutaneous lesions can be treated with simple surgical excision.  

When an individual develops multiple cutaneous leiomyomas, Reed syndrome, an autosomal dominant genetic disorder, should be considered.  Not all patients with cutaneous leiomyomas have Reed syndrome, but when multiple piloleiomyomas are noted, underlying autosomal dominant hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome should be considered. Women with HLRCC may develop uterine leiomyomas and have an increased risk of leiomyosarcoma. Accurate and timely diagnosis of HLRCC is important because of the risk of associated renal carcinoma in 15-30% of patients with HLRCC syndrome.^1-3

Germline genetic testing for the causative abnormality in the fumarate hydratase gene can be performed upon a blood sample. HLRCC is associated with inactivating mutations in the fumarate hydratase gene, which predispose the individual to tumor development through a buildup of succinate and fumarate.³ HLRCC should be suspected in any individual with multiple cutaneous leiomyomas (with at least one leiomyoma confirmed by biopsy) or with a single leiomyoma in the setting of a family history of HLRCC. Women are often diagnosed earlier than men because uterine leiomyomata (also known as uterine fibroids) are often detected. Regular screening studies of the kidneys are warranted for individuals with HLRCC.⁴ About 1 in 6 patients with HLRCC develops renal cancer, often when in their early 40s years of age. Multiple leiomyomas may occur in Alport syndrome, which is associated with lenticonus, sensorineural hearing loss and progressive loss of kidney function, as well as with neurofibromatosis type 1. 

If our patient is confirmed to have HLRCC, yearly surveillance magnetic resonance imaging (MRI) of the kidneys would be warranted, along with regular gynecological examinations and imaging studies looking for uterine fibroids. Genetic counseling is important to alert affected individuals to the autosomal dominant nature of this disorder.

Conclusion. Leiomyomas may be bothersome for patients but can be effectively treated with simple surgical excision. Genetic testing should be done in individuals with multiple cutaneous leiomyomas to screen for HLRCC syndrome, as HLRCC syndrome is associated with tumor development and additional screening in these individuals is needed.