LEIOMYOMA - pediagenosis
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Friday, November 23, 2018


Cutaneous leiomyomas are uncommon benign tumors of the arrector pili muscle of the skin. They can occur as a solitary tumor or as multiple lesions. Both types can be associated with underlying genetic defects. This occurs more commonly in multiple cutaneous leiomyomatosis, and one needs to look for systemic findings in affected patients. Other muscle sources of cutaneous leiomyoma formation include the smooth muscle of blood vessel walls and the dartos muscle. These rare forms of cutaneous leiomyomas are named angioleiomyomas and solitary genital leiomyomas, respectively. 


Clinical Findings: Leiomyomas manifest as dermal papules or nodules with a slight hyperpigmentation of the overlying epidermis. They can also have a reddish or brownish hue. The tumors are 1 to 2 cm in diameter. They occur equally in males and females and affect all races. They may occur anywhere on the skin, but the anterior chest and the genital region are two of the more common areas of involvement. They typically are tender, and they can be painful. Most leiomyomas become more painful and more sensitive over time. Cold temperatures have been shown to exacerbate the pain. The leiomyomas exhibit the pseudo-Darier’s sign. This sign is elicited by rubbing the leiomyoma; on manipulation, the lesion begins to twitch or fasciculate. It does not form an urticarial plaque as would be seen with a true Darier’s sign (e.g., in cutaneous mastocytosis). Malignant transformation is exceedingly rare.
Multiple cutaneous leiomyomas occur most commonly on the trunk and proximal extremities. They are the same size as their solitary counterparts, but they can become so numerous that they appear to coalesce into large plaques. In most patients, onset occurs in the third to fifth decades of life. There is a definite autosomal dominant inheritance pattern to multiple cutaneous leiomyomas. These patients have a genetic defect in the FH gene (also called MCUL1), which encodes the Krebs cycle protein fumarate hydratase. The fumarate hydratase protein has been found to have tumor suppressor functions. Many different types of mutations have been described, ranging from frameshift mutations to deletion of entire genes. This most likely explains the variety of phenotypes seen. The most concerning and life- threatening aspect of this mutation is the possibility of developing an aggressive and deadly form of papillary renal cell carcinoma. This tumor in patients with multiple cutaneous leiomyomas tends to be highly aggressive and metastasizes early. Early screening of the patient and genetic screening of family members may help decrease the risk of metastatic renal carcinoma. Patients should be evaluated routinely for kidney disease.
The term Reed syndrome is used to denote women with cutaneous leiomyomas and uterine leiomyomas.

Pathogenesis: Solitary leiomyomas not associated with the fumarate hydratase protein defect are believed to be caused by an abnormal proliferation of myocytes. The cause for this proliferation is unknown. Fumarate hydratase mutations result in a lack of tumor suppressor function. The role of this tumor suppressor protein in the production of multiple leiomyomas has yet to be determined.

Histology: The tumor is located within the dermis and is composed of interconnected fascicles of spindleshaped cells. The cells are arranged in a whorl-like pattern. The cells are uniform and bland appearing. Mitosis should be absent. The cells have been described as cigar shaped, meaning that they have a long, plump central region with blunt tip ends. The cell of origin is the myocyte. Immunohistochemical staining can be used to help differentiate difficult tumors. Leiomyomas stain with muscle markers such as smooth muscle actin. The overlying epidermis is usually normal.

Treatment: Surgical excision of the solitary form of leiomyoma is curative. Multiple cutaneous leiomyomatosis can be treated with a number of medications to help control the discomfort and pain. Use of α1-adrenergic receptor blockers has been reported most frequently. Doxazosin and phenoxybenzamine have both been successful. Calcium channel blockers such as nifedipine have also been successful anecdotally. Gabapentin and botulinum toxin have been reported to help. Surgical excision is warranted for any lesion that is painful and not responding to therapy. Patients with multiple cutaneous leiomyomas should be evaluated for the genetic defect in the fumarate hydratase protein and should have appropriate screening for kidney disease.

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