bims-necame 2025-07-27 papers

Issue of 2025–07–27
three papers selected by
Grigor Varuzhanyan, UCLA

Elife. 2025 Jul 22. pii: RP93170. [Epub ahead of print]13

Metastatic small cell lung cancer arises from TP53/RB1-deficient and MYC overproduction hESC-derived PNECs.

Huanhuan Joyce Chen, Eric E Gardner, Yajas Shah, Kui Zhang, Abhimanyu Thakur, Chen Zhang, Olivier Elemento, Harold Varmus.

We previously described our initial efforts to develop a model for small cell lung cancer (SCLC) derived from human embryonic stem cells (hESCs) that were differentiated to form pulmonary neuroendocrine cells (PNECs), a putative cell of origin for neuroendocrine-positive SCLC. Although reduced expression of the tumor suppressor genes TP53 and RB1 allowed the induced PNECs to form subcutaneous growths in immune-deficient mice, the tumors did not display the aggressive characteristics of SCLC seen in human patients. Here, we report that the additional, doxycycline-regulated expression of a transgene encoding wild-type or mutant MYC protein promotes rapid growth, invasion, and metastasis of these hESC-derived cells after injection into the renal capsule. Similar to others, we find that the addition of MYC encourages the formation of the SCLC-N subtype, marked by high levels of NEUROD1 RNA. Using paired primary and metastatic samples for RNA-sequencing, we observe that the subtype of SCLC does not change upon metastatic spread and that production of NEUROD1 is maintained. We also describe histological features of these malignant, SCLC-like tumors derived from hESCs and discuss potential uses of this model in efforts to control and better understand this recalcitrant neoplasm.

Keywords: SCLC; cancer biology; hESC; lung cancer; mouse

DOI: https://doi.org/10.7554/eLife.93170

Clin Radiol. 2025 Jun 21. pii: S0009-9260(25)00203-X. [Epub ahead of print]88 106998

Predictive value of multiparametric diagnostic model based on 2-[18F]-fluoro-D-glucose (2-[18F]-FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in differentiating between neuroblastoma and ganglioneuroblastoma.

S-Q Li, G-Y Wang, J Liu, Y Kan, W Wang, J-G Yang.

AIM: To evaluate the diagnostic performance of a multiparametric diagnostic model integrating intratumoral metabolic heterogeneity parameter and clinical parameters for differentiating neuroblastoma (NB) from ganglioneuroblastoma (GNB).
MATERIALS AND METHODS: This retrospective study included 107 patients (64 NB and 43 GNB) who underwent 2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]-FDG PET/CT). Baseline characteristics, clinical data, and metabolic parameters of the primary lesions, including peak standardised uptake value, maximum standardised uptake value, mean standardised uptake value, tumour metabolic volume, total lesion glycolysis, and the area under the curve of a cumulative standardised uptake value-volume histogram (AUC-CSH) index, were collected and analysed. Diagnostic performance of the model and predictors was assessed using area under the curve of the receiver operating characteristic curve, with integrated discriminatory improvement, net reclassification improvement, Delong test for performance improvement, and decision curve analysis for clinical utility evaluation.
RESULTS: Among the metabolic parameters, the AUC-CSH index demonstrated the highest diagnostic performance. Multivariate analysis identified the AUC-CSH index, age, and serum neuron-specific enolase level as independent predictors. The multiparametric model integrating these factors significantly outperformed individual metabolic parameters, and its clinical utility was validated by decision curve analysis.
CONCLUSION: A multiparametric diagnostic model integrating intratumoral metabolic heterogeneity parameter derived from 2-[18F]-FDG PET/CT with clinical parameters improves diagnostic performance for differentiating NB from GNB, offering potential for clinical application.

DOI: https://doi.org/10.1016/j.crad.2025.106998

BMC Womens Health. 2025 Jul 22. 25(1): 362

MRI and FDG PET/CT findings for small cell neuroendocrine carcinoma of the ovary: a case report and literature review.

Hiroki Matsutani, Go Nakai, Takashi Yamada, Yoshitaka Kurisu, Kazuhiro Yamamoto, Masahide Ohmichi, Keigo Osuga.

BACKGROUND: Ovarian small cell neuroendocrine carcinoma (OSCNEC) is rare and few cases have been reported, which makes preoperative diagnosis difficult. Moreover, no reports have yet described detailed imaging findings or findings of positron emission tomography with fluorine-18 fluorodeoxyglucose (18F-FDG-PET). Therefore, here we report a case of OSCNEC including detailed imaging findings and a literature review.
CASE PRESENTATION: A 74-year-old woman with clinical symptoms of abdominal distension was referred to our hospital because of a pelvic mass detected by ultrasonography at another hospital. Serum levels of cancer antigen 125 and neuron-specific enolase (NSE) were both elevated, at 203.0 U/mL (normal range 0-35.0 U/ml) and 47.6 ng/ml (normal range 0-16.3 ng/ml), respectively. Magnetic resonance imaging at 3.0 Tesla showed a multilocular cystic tumor 18 cm in diameter in the pelvic cavity. The tumor had irregular septa and included a solid component. The cystic component showed partially high intensity suggesting hemorrhage on fat-suppressed T1WI. The solid component showed high intensity on diffusion-weighted imaging and contrast enhancement on contrast-enhanced fat-suppressed T1WI. Irregular peritoneal thickening and nodules suggesting peritoneal dissemination were also detected. 18F-FDG-PET/computed tomography (PET/CT) revealed high FDG uptake (maximum standardized uptake value: 13.0) in the solid component. Para-aortic lymph node, spinal, iliac, and liver metastases were detected along with peritoneal dissemination. Intertrabecular bone metastases were also clinically detected on PET/CT. Abdominal bilateral salpingo-oophorectomy, partial omentectomy, and appendectomy performed for surgical staging revealed the ovarian tumor was primary OSCNEC with peritoneal dissemination because no lung tumor was identified on PET/CT, which ruled out a metastatic ovarian tumor from small cell lung cancer. The patient received radiation therapy for vertebral metastases without chemotherapy and died four months after the operation.
CONCLUSIONS: OSCNEC could be considered when elevated serum NSE at diagnosis and hematogenic spread such as bone or liver metastases are found in a patient with a primary malignant ovarian tumor without a lung tumor on imaging, although MR findings of OSCNEC were not specific enough to differentiate it from other ovarian cancers.

Keywords: MRI; Ovarian tumor; PET-CT; Small cell neuroendocrine carcinoma

DOI: https://doi.org/10.1186/s12905-025-03922-w