Case report: NUT carcinoma with MXI1::NUTM1 fusion characterized by abdominopelvic lesions and ovarian masses in a middle-aged female

Abstract

Background: Nuclear protein of the testis (NUT) carcinoma is a rare subset of poorly differentiated, highly aggressive malignancy defined by NUTM1 gene rearrangements. Only three NUT cases of probable ovarian origin have been reported.

Case presentation: We report a case of NUT carcinoma in a 53-year-old female who presented with extensive abdominopelvic lesions and bilateral ovarian masses suggestive of advanced ovarian cancer. This patient was admitted to our hospital due to abdominal pain and distension for over two months. Imaging examinations suggested a possible malignancy of bilateral adnexal origin. This patient first underwent diagnostic laparoscopy. After receiving neoadjuvant chemotherapy, she underwent cytoreductive surgery. Surgical pathology showed infiltration of monotonous round tumor cells with no apparent differentiation characteristics. Immunohistochemistry (IHC) revealed nuclear expression of the NUT protein. And MXI1::NUTM1 fusion was identified by next-generation sequencing (NGS). Herein, we introduce an unusual NUT carcinoma and describe the clinical, imaging, and pathological features. In addition, we briefly reviewed the published literature and discussed the possibility of primary gynecological NUT carcinoma.

Conclusions: Identifying a NUT carcinoma arising from the abdominopelvic cavity is essential, and we underscore the need for NUT testing in undifferentiated malignant neoplasms that appear in this clinical setting. Although it is unclear from which origin this tumor arose, proper classification is essential for treatment planning.

Keywords: NUT carcinoma; NUT rearrangement; case report; ovarian neoplasms; undifferentiated pelvic neoplasms.

Figure 1

(A) Transvaginal ultrasound reveals a 3.9×2.3cm irregular hypoechoic mass in the right abdominal cavity with blood flow signals closely related to the peritoneum. (B) Pelvic MRI shows a suspicious mass in the right adnexal area and thickening of the omentum with pelvic effusion. (C) Abdominal and pelvic enhanced CT reveals plump bilateral adnexal masses, diffusely thickened peritoneum, omentum, and mesangium, slightly thickened intestinal wall, and abdominal and pelvic effusion. PET-CT displays plump bilateral adnexal areas, poorly demarcated from surrounding tissue, showing signs of hypermetabolism with (D) the SUVmax2.2 on the right and (E) the SUVmax3.1 on the left.

Figure 2

Microscopic findings. (A) Uniform monotonous medium-sized round and oval tumor cells with moderate eosinophilic cytoplasm, enlarged nuclei, high nuclear/cytoplasmic ratio, and uneven chromatin (hematoxylin and eosin (HE)). (B) Tumor cells infiltrate the pelvic lymph nodes (HE, yellow arrow). (C) A section of the omental biopsy specimen with the omental tissue at the upper right (HE, green arrow) and the tumor cells at the lower left (HE, yellow arrow). (D) A section of the omental specimen from cytoreductive surgery with no significant regression of tumor cells after chemotherapy (HE, omental tissue: green arrow, tumor cells: yellow arrow). (E) Tumor cells (HE, yellow arrow) infiltrate the serosa of the uterus (HE, azure arrow). (F) The tumor mass is close to the ovarian hilus (HE, yellow arrow), surrounded by large blood vessels (HE, orange arrow), with most of the typical stricture of ovarian cortical and corpus albicans preserved (HE, sapphire arrow). (G) Negative CK pan IHC staining. (H) Negative p40 IHC staining. (I) Negative p63 IHC staining. (J) Strong and diffuse nuclear reactivity for NUT in the tumor cells (NUT IHC staining). (K) Negative NUT FISH test. No significant red-green signal separation was observed. (L) NGS identified an MXI1::NUTM1 fusion consisting of MXI1 exon 5 and NUTM1 exon 3 obtained for the tumor specimens of the patient.

Figure 3

Time diagram from Jan 2022 to Sep 2022 of the patient: on Jan 14, 2022, abdominopelvic lesions and ovarian masses were identified by imaging examination; on Jan 18, 2022, diagnostic laparoscopy was performed. Pathological findings of the omentum and peritoneum biopsies suggested a poorly differentiated carcinoma. On Jan 20, 2022, the patient began the first course of neoadjuvant chemotherapy with Paclitaxel-albumin, Carboplatin, and Bevacizumab; on Feb 10, 2022, the patient received the second course of neoadjuvant chemotherapy; on Mar 4, 2022, the patient received the third course of neoadjuvant chemotherapy; on Apr 12, 2022, cytoreductive surgery was performed; on Jun 9, 2022, NUT carcinoma was confirmed by morphology, immunohistochemistry, and genetic alterations. On Jun 18, 2022, imaging examinations revealed a progressed malignancy burden. The patient refused antitumor therapy and passed away on Aug 30, 2022.