Adenoid cystic carcinoma (ACC) of the uterine cervix is a rare primary malignancy. A 60-year-old woman presented with a >1 year history of intermittent upper abdominal pain and discomfort, which had worsened over the preceding 4 days. Ten years earlier, the patient presented with irregular vaginal bleeding. Pelvic ultrasonography revealed a homogeneous myometrium, a clearly defined endometrium, and an indistinct echo pattern in the endocervical canal; no significant abnormalities were detected in either adnexa. Endometrial curettage and pathological biopsy confirmed ACC of the uterine cervix. The patient subsequently underwent total hysterectomy with bilateral oophorectomy, but declined postoperative adjuvant chemotherapy or radiotherapy. During the current admission, contrast-enhanced computed tomography of the entire abdomen revealed multiple, round, and slightly hypodense lesions in the right hepatic lobe, most of which were located near the liver margin and exhibited mild peripheral enhancement. Multiple soft tissue nodules of varying size were noted in the peritoneum and greater omentum, exhibiting heterogeneous and marked enhancement. Contrast-enhanced computed tomography of the head, neck, and chest revealed no significant abnormalities. Finally, fine-needle aspiration biopsy of the peritoneal nodule was performed, and metastasis of ACC of the uterine cervix was diagnosed. Palliative treatment was initiated; however, the patient died of multiple organ failure 1 month after treatment. This case indicates that ACC of the uterine cervix may develop distant metastasis as late as 10 years after initial diagnosis without adjuvant radiotherapy or chemotherapy. Clinicians should raise awareness of this disease, strengthen long-term follow-up, and perform timely imaging evaluations when symptoms occur.

Cervical cancer originates from precursor lesions in the cervix, where early diagnosis is essential to avoid progression to invasive carcinoma. Today, lesion detection relies mainly on colposcopy, a highly operator-dependent procedure with considerable variability in accuracy, particularly among less-experienced clinicians. In this study, we present a hyperspectral imaging-based approach for assisted colposcopy. We developed a custom hyperspectral colposcope covering 470-900 nm and conducted a 32-month clinical study including 116 patients and 245 hyperspectral images acquired during routine examinations. First, a dedicated algorithm automatically delineated the cervical region and segmented the tissue into ectocervix, endocervix and abnormal areas, achieving a macro-level DICE of 0.84. Subsequently, two approaches were studied for pixel-wise lesion classification: a binary model for high-grade squamous intraepithelial lesion and invasive carcinoma versus healthy tissue, which achieved a mean F1-score of 0.74 on an independent test set; and a multiclass model for grading according to the Bethesda system, which showed lower generalisation (F1-score = 0.26) due to limited spectral resolution and spectral overlap. Overall, the results show the potential of hyperspectral colposcopy for non-invasive detection and delimitation of cervical lesions.

Invasive stratified mucin-producing carcinoma (ISMC) of the uterine cervix can masquerade as non-keratinizing squamous cell carcinoma (SCC) on small biopsies because it often grows as solid nests with minimal gland formation and little or no keratinization, and may show patchy cytokeratin 5/6 (CK5/6) positivity. We report a 44-year-old woman whose outside cervical biopsy was interpreted as SCC. Repeat biopsy showed SCC-like solid nests without keratinization and patchy CK5/6 positivity, but p40 and p63 were negative and periodic acid-Schiff with diastase (D-PAS) demonstrated diastase-resistant intracytoplasmic mucin within tumor nests. Radical hysterectomy revealed a human papillomavirus (HPV)-associated endocervical adenocarcinoma with a predominant ISMC component, lymphovascular invasion, and nodal metastases. This case highlights a practical diagnostic pitfall and supports a minimal, reproducible workup for p16 block-positive, SCC-like biopsies: p40/p63 plus a mucin stain (D-PAS and/or Alcian blue), with PAX8 as needed. Funding: Japan Society for the Promotion of Science (JSPS) KAKENHI [25 K10294].

The tumorigenesis and progression of conventional cervical squamous cell carcinoma generally follow a well-defined cascade: from normal cervix uteri to high-grade cervical intraepithelial neoplasia (precancer), cervical carcinoma in situ, and ultimately invasive cervical carcinoma. However, biomarkers and targets that reflect tumor evolution during CSCC progression at different time points within the same patient remain lacking. We integrated single-cell RNA sequencing with spatial transcriptomics from a series of human cervix uteri tissues spanning the cascade of cervical premalignant lesions and malignant progression obtained from the same patients. We found that fibroblasts and endothelial cells decreased, whereas immune cells (mainly T cells and B cells) increased during CSCC development. Moreover, the immune response-related GNLY-fibroblasts and GNLY-endothelial cells were significantly enriched during the PCT of CSCC. Additionally, a panel of gene signatures (CLDN1, ISG15, PTGDS) with clinical significance for the precise diagnosis and personalized treatment strategies of PCT was identified. This gene panel may serve as an auxiliary diagnostic indicator in cervical biopsy specimens and help identify lesions associated with malignant progression. CLDN1 and ISG15 promote CSCC progression, whereas PTGDS suppresses it. Moreover, ISG15, synthesized by inflammatory cancer-associated fibroblasts (CAFs), enhances the stability of FGF1, thereby activating the FGF1/FGFR1/PI3K/AKT/mTOR signaling pathway. FGFR1 and PI3K/AKT/mTOR inhibitors were found to suppress CSCC cell proliferation in vitro and tumor growth in vivo. High ISG15 and CLDN1 expression correlated with poor survival in cervical cancer tissue microarrays and with reduced immunotherapy response in exploratory public datasets, pending validation in CSCC cohorts. Our study defines the ecosystem of PCT from cell subpopulations, the communicating gene networks, and key signal transductions involved in PCT of CSCC. These findings offer new insights into the spatiotemporal evolution of the human cervix in premalignant and malignant lesions, paving the way for improved CSCC diagnosis and therapy.

Cervical cancer (CC) remains a leading cause of cancer-related mortality among women, particularly in underdeveloped or developing countries lacking adequate screening programs. Despite being highly preventable through HPV vaccinations and screening tests, and highly treatable when detected early, CC continues to pose a significant health burden. MSX1, a transcription factor of the homeobox family, plays an important role in the development and differentiation of tissues, including the gynecological tract. Since MSX1 has been identified as both a tumor suppressor and an oncogene in tumorigenesis, but its function in CC remains elusive to date, the present study aims to elucidate the role of MSX1 in CC and its precancerous stages. Our results demonstrate that MSX1 acts as a tumor-promoting factor in CC. While normal squamous epithelium of the cervix is negative for MSX1, we observed de novo expression of MSX1 in precancerous lesions. We found that MSX1 expression enhances the clonogenic and migratory capacities of cervical cancer cell lines. Mechanistic insights revealed an MSX1-dependent induction of the epithelial-to-mesenchymal transition (EMT), a process highly correlated with cancer development and progression. CUT&RUN sequencing data identified enriched signaling of the cytoskeletal modulators RHO/RAC/CDC42 in MSX1-expressing cells, potentially mediated by MSX1. Additionally, FOS, a downstream effector of RHO, was found as a key factor contributing to CC aggressiveness. Interference with both RHO-signaling and FOS-mediated regulation completely reversed the aggressive phenotype of MSX1-expressing cells. In conclusion, our findings suggest that MSX1 plays a crucial role in cancer-related signaling pathways and may have implications for the development of therapeutic approaches in cervical cancer.