Benign metastasizing leiomyoma presenting with miliary pattern and fatal outcome: Case report with molecular analysis & review of the literature

Abstract

Benign metastasizing leiomyoma (BML) is a rare benign smooth muscle neoplasm that originates in the uterus and metastasizes to distant sites—most commonly the lungs. BMLs are often found incidentally in patients with a history of uterine leiomyoma(s) and tend to be indolent. Occasionally they may be symptomatic and rarely follow an aggressive clinical course. We report an unusual case of BML presenting in a 46-year-old woman as a miliary nodular pattern bilaterally in the lungs and progressive respiratory failure. Her past medical history was significant for uterine “leiomyomas” of at least 9 years' duration. Post mortem histologic evaluation of the uterine and lung lesions revealed benign smooth muscle neoplasms (leiomyomas and BMLs, respectively), and molecular analyses demonstrated identical clonal MED12 mutation, though with greater mutant allelic frequency in the uterus. We document a rare aggressive clinical course in a patient with BML, which presented as a miliary radiologic pattern mimicking an infectious etiology or interstitial lung disease.

Reasons to Reconsider Risk Associated With Power Morcellation of Uterine Fibroids

“…This is in accordance with previous studies demonstrating the presence of morphologically benign tumoral areas in a considerably high percentage of leiomyosarcomas (42,43), as well as common genetic alterations as outlined above and summarized by Mittal et al (42). In addition, patients apparently experiencing malignant transformation of leiomyomas, atypical leiomyomas, benign metastasizing leiomyomas or STUMP to leiomyosarcomas (33,(44)(45)(46)(47) have been described repeatedly. In contrast, evidence for the existence of a considerable percentage of STUMP or leiomyosarcomas with HMGA2 rearrangement is lacking.…”

“…Accordingly, they are often noted at distant sites several years after hysterectomy or myomectomy. Of note, the presence of UL-specific MED12 mutations has been described in apparent lung metastases in a patient suffering from benign metastasizing leiomyoma with fatal outcome (46), while other cases showed mutations different from those typically found in UL (77,78).…”

Cancer Genes Mutations in Benign Metastasizing Leiomyoma: A Case Report

“…Chromosomal level changes have been identified including 19q and 22q terminal deletions, loss of 1p and 13q material, and 6p21 rearrangement [16]. Point mutations have been identified in the BMP8B gene and MED12 genes [17,18]. We have identified five novel mutations in our BML patient: ARID2 (N1340K), BCL11B (amplification), NTRK1 (R6W), TCL1A (amplification), and XPO1 (rearrangement).…”

Benign metastasizing leiomyoma of the lung: diagnostic process and treatment based on three case reports and a review of the literature

“…On gross examination, BML presents as a well-demarcated solitary lesion or multiple tumors with a whorled cut surface resembling its uterine counterpart. Occasionally a miliary pattern of numerous nodules occupying large areas of the lung parenchyma and leading to the respiratory failure was observed [23]. Microscopically, the neoplasm is composed of spindle-shaped cells forming fascicles growing in a whorled pattern.…”

“…Cases with diffuse disease are more likely to bene t from a systemic approach. Observation, surgical resection, hysterectomy, and bilateral oophorectomy, administration of progestins and aromatase inhibitors, and luteinizing hormone-releasing hormone analogs have all been reported as potential treatment options [23,30].…”