Uterine Tumors With Neuroectodermal Differentiation

Abstract

Uterine tumors with neuroectodermal differentiation, frequently referred to as primitive neuroectodermal tumors (PNETs), are uncommon. The clinicopathologic features of 17 such cases reviewed at the M.D. Anderson Cancer Center (MDACC) are presented along with a review of the literature. All of the pathology material was reviewed at MDACC, and in all cases, immunohistochemistry contributed to the diagnosis. In 12 cases, in situ hybridization techniques were used to determine whether a rearrangement of the EWSR1 gene, required for a diagnosis of peripheral PNET, was present. Clinical information was obtained from a patient chart review. Ages ranged from 31 to 81 years (median 58). Clinical presentations included vaginal bleeding (9), back pain (1), presumed fibroids (2), pelvic mass (1), incidental finding at hysterectomy (1), and unknown (3). Twelve patients had surgery or imaging to determine stage: I (2), II (0), III (6), and IV (4). Five patients had biopsy only. Ten tumors had only neuroectodermal components. In 7 tumors, the neuroectodermal component was admixed with an additional component including unclassified sarcoma (2 cases), rhabdomyosarcoma, endometrioid carcinoma, adenosarcoma and malignant mixed Mullerian tumor (2 cases). Follow-up, available for 13 patients, ranged from 2 to 41 months with 7 patients dead of disease 2 to 26 months after diagnosis. Six patients are alive with no evidence of disease after follow-up ranging from 6 to 41 months. Four patients were lost to follow-up. Results for the most commonly used immunohistochemistry studies include cytokeratin, 13/15 tumors negative (2 focally positive); synaptophysin, 15/16 tumors positive; neurofilament, 10/11 tumors positive; and CD99, 7/9 tumors positive (2 tumors had nonspecific cytoplasmic staining). None of the 12 tumors tested had a detectable rearrangement in the EWSR1 gene. Uterine tumors with neuroectodermal differentiation, similar to more common endometrial malignancies, tend to occur in postmenopausal women and frequently present with vaginal bleeding. An immunohistochemistry panel including cytokeratin, neurofilament, synaptophysin, and CD99 can highlight neuroectodermal differentiation and identify tumors for which molecular testing should be considered. Tumors without a rearrangement of the EWSR1 gene should be descriptively characterized as uterine tumors with neuroectodermal differentiation or alternatively central type PNETs rather than PNET, not otherwise specified to avoid confusion with peripheral PNET.

Primitive neuroectodermal tumor of the uterus

“…The survival rate of our case was similar to previous ones published on the literature regarding patients diagnosed with Stage IV with the same features (Euscher et al, 2008). The two year survival of younger patients and postmenopausal patients has been reported as 75% and 32%, respectively (Odunsi et al, 2004).…”

“…Also none of the 12 cases tested for typical EWSR1 rearrangement were positive. However, five cases of typical gene rearrangement are described in the literature (Euscher et al, 2008, Blattner et al, 2007). …”

“…To date, over 64 cases of primary uterine PNET have been reported in the literature (Ng, 2002, Dizon et al, 2013, Novo et al, 2015), the largest being a seventeen-patient case series by Euscher et al (2008).…”

Primitive Neuroectodermal Tumors of the Female Genital Tract

“…Gynecologic PNETs have been reported in the ovary (1–7), broad ligament (1, 8), uterine corpus (1, 9–18), uterine cervix (1, 19–25), vagina (26–32), and vulva (1, 26, 31, 33–39); to date, none have been reported to have arisen in the fallopian tube. PNETs of the ovary and uterus are frequently associated with another tumor type (2, 4–6, 10, 11, 18), although many, including those arising elsewhere, occur in pure form (1, 3, 4, 7, 9, 10, 13–17, 19–37, 39–41). Together, they represent a peculiar group of rare neoplasms that show varying degrees of neuroectodermal differentiation and remain poorly understood when compared to their bone and soft tissue counterparts (42) and tumors that until recently were classified as PNETs of the CNS (43).…”

“…PNETs arising in the female genital tract that lack EWSR1 rearrangements and show readily recognizable neuroectodermal differentiation morphologically reminiscent of CNS tumors are likely histogenetically separate from Ewing sarcoma/peripheral PNETs (4, 10, 13). However, distinction of central PNETs from Ewing sarcoma/peripheral PNETs remains a significant challenge due to overlapping histologic and immunophenotypic features seen in both types and because the literature contains the term Ewing sarcoma/peripheral PNET that has been used loosely and is largely limited to descriptive case reports and small case series in which the status of EWSR1 rearrangement is not known.…”