Uterine cellular leiomyomata with chromosome 1p deletions represent a distinct entity

Abstract

OBJECTIVE This study aims to determine whether 1p deletion defines a subset of cellular leiomyomata (CL), a hypercellular variant of uterine leiomyomata (UL) that may have delayed malignant potential, and correlate this genetic change with clinical and pathologic characteristics including those present in uterine sarcomas. STUDY DESIGN Available CL cases at Mayo Clinic (n=101) and variant cases reported by Giuntoli et al. (n=16) were identified. Each case with sufficient tissue that met histologic criteria for CL when reviewed by a single pathologist underwent interphase FISH to determine the presence of 1p deletion. Clinical characteristics of women with confirmed CL were compared on the basis of 1p deletion status using univariate analysis. RESULTS Of the Mayo cohort of histologically confirmed CL, 23% had deletion of 1p. Women with this subset of CL when compared to those without 1p deletion were more likely to be postmenopausal (P=0.049) and their uteri tended to be heavier (P=0.039) with a larger dominant leiomyoma (P=0.030). The pathological features associated with 1p deletion were high cellularity (P=0.036) and hyaline necrosis (P=0.047), which remained significant after inclusion of the CL cases from the Giuntoli et al. series. CONCLUSION Deletion of 1p occurs in approximately one-quarter of CL. This genetic alteration is potentially associated with clinicopathologic features present in uterine sarcomas, suggesting a distinct clinical entity that may have malignant potential. Our findings are particularly pertinent considering the increased preference for uterine-sparing options in leiomyoma treatment, suggesting assessment of 1p deletion status in CL may influence clinical surveillance decisions.

Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers

“…Deletions of 1p have been associated with distinct histopathological features and possible malignant progression of leiomyomas (11,16). Interestingly, we identified NPHP4 as the most commonly deleted gene on chromosome 1p.…”

“…Leiomyomas frequently harbor recurrent deletions affecting 7q22, 22q, and 1p, suggesting that these regions contain tumor suppressor genes (8)(9)(10)(11). High-throughput sequencing studies have rarely detected second hit mutations within these regions, however (3,4,13), suggesting that the target genes may act in a haploinsufficient manner.…”

“…Leiomyomas also may harbor recurrent deletions and rearrangements of 7q22, 22q, and 1p (8)(9)(10)(11). These deletions co-occur with other genetic alterations and may be secondary driver events, often present only in a subpopulation of tumor cells (4,7,8,(11)(12)(13).…”

Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMP): Review of Pathophysiology, Classification, Diagnosis, Treatment, and Surveillance

“…New evidence of increased mitotic index and chromosome 1p deletions may lead treating physicians to a more aggressive and more intense follow up as these have been shown to have more malignant potential and likely increased recurrence rate [16,42]. Recommendations include the following: if a patient has been diagnosed with STUMP after tissue sample from biopsy or hysteroscopy, the surgeon should perform a hysterectomy on the patient (regardless of vaginal, abdominal, or laparoscopic).…”

“…Mehine et al and Hodge et al confirmed a malignant behavior in myometrial cells containing the chromosome 1p deletion. Further identification and classification of chromosomal mutations and signaling pathways will aide in correct diagnosis and management [11,16,17].…”