PMC9890191_01
(A) Transvaginal ultrasound reveals a 3.9x2.3cm 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.
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The transvaginal ultrasound showed a 3.9x2.3cm solid pelvic mass with ascites (  Figure 1A  ;  Supplemental Figures S1A, B  ). The abdominal and pelvic enhanced CT, the pelvic magnetic resonance imaging (MRI), and the positron emission computed tomography (PET-CT) all revealed irregular, heterogeneous, and plump bilateral adnexal masses with diffusely thickened peritoneum, omentum, and mesangium, multiple soft-tissue nodules, slightly thickened intestinal wall, abdominal and pelvic effusion, and multiple enlarged lymph nodes (  Figures 1B-E  ;  Supplemental Figures S1C-F  ).
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.
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Imaging examination showed reduced abdominal and pelvic effusion, while abdominopelvic lesions were roughly the same as before (  Supplemental Figure S2  ). The tumor cells were uniform monotonous medium-sized round and oval with small-to-moderate eosinophilic cytoplasm, enlarged nuclei, high nuclear/cytoplasmic ratio, and uneven chromatin (  Figure 2A  ). Lymphatic vascular involvement and lymph node metastases were frequently observed (  Figure 2B  ). Solid sheets and nests of typically undifferentiated cells infiltrating surrounding normal omental tissue were present, with no abrupt keratinization (  Figure 2C  ). Comparing the two surgical specimens, there was no significant regression of tumor cells after neoadjuvant chemotherapy (  Figures 2C, D  ). Malignancy infiltration was found on the serosa of the uterus, while typical structures of the endometrium and myometrium remained, suggesting that it was not a primary uterine neoplasm (  Figure 2E  ). The lesions were mainly close to the ovarian hilus and surrounded by large blood vessels (  Figure 2F  ), so the possibility of secondary ovarian malignancy cannot be excluded. The Ki-67 labeling index was approximately 30%. There was no expression of CK pan (  Figure 2G  ), p40 (  Figure 2H  ), p63 (  Figure 2I  ), and other IHC markers (i.e., CD56, CK7, WT-1, TTF-1, Finally, we conducted NUT immunostaining (clone C52B1) and revealed diffusely positive expression in the nucleus of tumor cells (  Figure 2J  ). However, the FISH experiment found no disruption or translocation of the NUTM1 gene locus (  Figure 2K  ). We subsequently identified the gene fusion of MXI1 exon 5 (NM_130439.3) to NUTM1 exon 3 (NM_175741.3) via a targeted RNA-based NGS platform (DA8600, Daan Gene, Guangzhou, China) on tissue samples, which finally confirmed NUT carcinoma two months after cytoreductive surgery (  Figure 2L  ).
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.
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Upper GI endoscopy and colonoscopy were performed to distinguish gastrointestinal tumors, but no mucosal lesions were identified (  Supplemental Figure S3  ). She developed systemic symptoms and passed away four months and 18 days after cytoreductive surgery ( Figure 3 ).