Based on the morphologic appearance and immunophenotype, this tumor was diagnosed as a leiomyoma.
Leiomyomas are the most common tumor of the female genital tract, occurring in up to 40% of women over the age of 40, although the true incidence is still unclear and varies by population (Sparic et al., 2016). In adolescents, however, these tumors are quite rare, with only case reports and no definitive incidence (Grapsa et al., 2006, Khorrami and Rackow, 2011, Naiditch et al., 2011, Wright and Laufer, 2011, Kayadibi et al., 2014).
A subset of leiomyomas will show identifiable clonal molecular phenotypes. Because of the large size and atypical presentation of this case, molecular analysis of the tumor was performed. This revealed a complex karyotype, with likely balanced translocations between the long arms of chromosomes 2, 3, and 12. The breakpoint at 12q14 has been previously described in leiomyomas (Eggert et al., 2012), and has been found in intravenous leiomyomatosis (Ordulu et al., 2016), a condition in which benign leiomyomas spread intravascularly and begin to grow in the venous system. There is no clinical or imaging evidence of this occurring in this patient.
The leading differential diagnoses in this case were rhabdomyosarcoma, perivascular epithelioid cell tumor (PEComa), leiomyosarcoma, or endometrial stromal sarcoma. Rhabdomyosarcoma is a rare tumor, but one of the more common malignant uterine tumors in pediatric populations (Garrett et al., 2013). The remainder of the differential diagnoses, like the majority of gynecologic malignancies, are extremely rare or unreported in the pediatric population (Lammers and Fowler, 1998). Of the subtypes of rhabdomyosarcoma, embryonal would be most common in the uterine fundus in this age range. No rhabdomyoblasts were identified; however, this does not rule out the spindle cell form of this tumor, which could have a similar morphology to the patient's tumor. Rhabdomyosarcomas stain positive for MyoD1 and myogenin, both of which were negative in this case, making this diagnosis significantly less likely. The morphology was not classic for PEComa, and the tumor was negative for MelanA and HMB45. The tumor did not show increased mitotic rate or nuclear atypia normally seen in leiomyosarcoma, although the whole tumor was not sampled due to this being an excisional biopsy. Whether or not leiomyosarcoma can arise from a leiomyoma, or must arise de novo, is currently under investigation, but if it does occur the incidence is extremely low even in adult patients (Mittal et al., 2009, Yanai et al., 2010). Endometrial stromal sarcoma was also unlikely given the radiologic appearance (tumor displacing, not expanding, the endometrial canal), as well as the inconsistent histologic appearance and immunophenotype.
In conclusion, while rarely observed, leiomyomas can occur in pediatric populations, and when they do, they can often lead to significant clinical concern. Careful histologic analysis can lead to the correct diagnosis, which importantly allows consideration of treatment options that spare reproductive ability.
Contributed by Daniel Marker, MD, PhD and Jennifer Picarsic, MD