Embryonal Rhabdomyosarcoma of the Ovary and Fallopian Tube

Abstract

DICER1 mutations (somatic or germline) are associated with a variety of uncommon neoplasms including cervical and genitourinary embryonal rhabdomyosarcoma (ERMS). We report a primary ovarian and 2 primary fallopian tube ERMS occurring in 60-, 13-, and 14-year-olds, respectively. The 3 neoplasms exhibited a similar morphologic appearance being polypoid and containing edematous hypocellular areas and hypercellular foci composed of small cells with scant cytoplasm exhibiting rhabdomyoblastic differentiation (desmin, myogenin, myoD1 positive). There was cellular cartilage in all cases and extensive foci of anaplasia, eosinophilic globules, and bone/osteoid in 1 case each. All 3 neoplasms exhibited DICER1 mutations; in 1 of the tubal cases, the patient had a germline mutation and in the other 2 cases, the DICER1 mutations were somatic. Accompanying DICER1 “second hits” were identified in all cases. In 2 of the neoplasms, SALL4-positive glandular structures were present which we speculate may represent an unusual primitive “metaplastic” phenomenon. Our study adds to the literature on ERMS at unusual sites associated with DICER1 mutations. ERMS arising at such sites, especially when they contain cartilage or bone/osteoid, are especially likely to be associated with DICER1 mutations. Pathologists should be aware of this as these may be the sentinel neoplasms in patients with DICER1 syndrome and confirming a germline mutation can facilitate the screening of the individual and affected family members for other neoplasms which occur in this syndrome.

Clinicopathologic and molecular analysis of embryonal rhabdomyosarcoma of the genitourinary tract: evidence for a distinct DICER1-associated subgroup

“…In contrast, most cases of molecularly analyzed ERMS of the uterine corpus and cervix harbor DICER1 mutations [ 7 ]. In addition, few cases of ERMS arising in the broad ligament, the ovary, and the fallopian tube are also DICER1 mutation-positive [ 18 , 20 ]. In combination with published evidence, our results suggest that ERMS of the inner female genital tract—maybe with the exception of most tumors arising in the vagina—are associated with DICER1 mutations, in contrast to other ERMS arising in the urinary tract which is usually DICER1 -wt.…”

“…While clinical information on DICER1-associated ERMS has rarely been published to date, potentially aggressive behavior of these tumors is exemplified by one of our patients who died of disease 3 years after initial diagnosis. Further, McCluggage et al recently reported a DICER1 -mut ERMS of the ovary, which relapsed only 3 months after surgery [ 20 ]. Given the above, further investigations of the clinical behavior of DICER1 -mut ERMS are clearly needed.…”

“…Recent studies have shown recurrent germline and somatic DICER1 mutations to occur in a majority of uterine ERMS [ 7 , 16 , 17 ]. At the same time, only rare cases of extrauterine DICER1-associated ERMS, mostly located in the genitourinary tract, have been reported [ 16 , 18 – 20 ]. In addition, molecular studies of larger cohorts of ERMS have failed to identify significant numbers of DICER1 alterations, considering that most analyzed cases were located outside of the genitourinary tract [ 21 – 23 ].…”

Malignant teratoid tumor of the thyroid gland: an aggressive primitive multiphenotypic malignancy showing organotypical elements and frequent DICER1 alterations—is the term “thyroblastoma” more appropriate?

“…Notably, many of these DICER1associated neoplasms have some site dependent morphological resemblance to the developmental stages in organogenesis, resulting into a teratoid or blastomatous appearance in many of them. Foci of cartilage are another common feature of several DICER1-associated lesions and represent a strong histological clue to suspicion of the disorder [29]. Indeed, the presence of cartilage in these DICER1-related teratoid thyroid neoplasms might have enhanced misinterpretation of malignant thyroid teratoma as being related to genuine germ cell tumors.…”

<p>Coexistence of Low-Grade Fetal Adenocarcinoma and Adenocarcinoma in situ of the Lung Harboring Different Genetic Mutations: A Case Report and Review of Literature</p>

“…Several studies have reported that DICER1-associated malignancies, especially with blastomaoid components, show SALL4 expression. 10,11 However, owing to the limited data available, this interpretation needs further supportive evidence.…”