BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification.
METHODS: In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34βE12, and P53, while they tested negative for CK35βH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion.
CONCLUSIONS: This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor.

The cellular origin of clear cell ovarian carcinoma (CCOC), a major histological subtype of ovarian carcinoma remains elusive. Here, we explored the candidate cellular origin and identify molecular subtypes using integrated genomic/epigenomic analysis. We performed whole exome-sequencing, microarray, and DNA methylation array in 78 CCOC samples according to the original diagnosis. The findings revealed that ARID1A and/or PIK3CA mutations were mutually exclusive with DNA repair related genes, including TP53, BRCA1, and ATM. Clustering of CCOC and other ovarian carcinomas (n = 270) with normal tissues from the fallopian tube, ovarian surface epithelium, endometrial epithelium, and pelvic peritoneum mesothelium (PPM) in a methylation array showed that major CCOC subtypes (with ARID1A and/or PIK3CA mutations) were associated with the PPM-lile cluster (n = 64). This cluster was sub-divided into three clusters: (1) mismatch repair (MMR) deficient with tumor mutational burden-high (n = 2), (2) alteration of ARID1A (n = 51), and (3) ARID1A wild-type (n = 11). The remaining samples (n = 14) were subdivided into (4) ovarian surface epithelium-like (n = 11) and (5) fallopian tube-like (considered as high-grade serous histotype; n = 3). Among these, subtypes (1-3) and others (4 and 5) were found to be associated with immunoreactive signatures and epithelial-mesenchymal transition, respectively. These results contribute to the stratification of CCOC into biological subtypes.

BACKGROUND: Hyalinizing clear cell carcinoma (HCCC) arising from a minor salivary gland is a rare malignant neoplasm. Most HCCC has been reported in the palate and tongue base, and only rarely in the nasopharynx. Here, we report a rare case of nasopharyngeal HCCC.
METHODS: A 44-year-old male who complained of otorrhea and aural fullness for 5 years was found to have a nasopharyngeal mass.
METHODS: HCCC by fluorescence in situ hybridization analysis.
METHODS: Surgical resection plus concurrent chemotherapy and radiation therapy were administered.
RESULTS: The patient recovered well with symptoms improved at postoperative follow-up.
CONCLUSIONS: HCCC should be included in the differential diagnosis of nasopharyngeal mass. Overall, the prognosis of HCCC is positive after tumor resection and adequate management.

BACKGROUND: Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium.
METHODS: This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrial hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subtotal hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutopic endometrium and adenomyoma. Ectopic endometrium in the myometrium combined with atypical hyperplasia and formation of endometrioid adenocarcinoma. Left parametrial lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. Combined with surgical founding and pathological characters of the left parametrial adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy.
CONCLUSIONS: We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis that may help inspire additional studies in the future. The patient underwent robot-assisted laparoscopic subtotal hysterectomy, bilateral adnexa resection, deep endometriosis lesion resection and bilateral ureteral stent placement. Following surgery, a chemotherapy regimen of Taxol and Carboplatin was administered.

Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted with 80 people with OCCC who underwent surgery followed by adjuvant chemotherapy. PR expression was assessed via immunohistochemical (IHC) staining and quantified using the H score. The platinum sensitivity and survival outcomes of patients with weak and strong PR expression were compared. Additionally, cisplatin viability and migration experiments were conducted with OCCC cell lines (ES-2 and TOV-21G) with varying PR isoform expressions. Among the 80 patients, 62 were classified as having platinum-sensitive disease, while 18 had platinum-resistant disease. The mean total PR H- score of platinum-sensitive tumors was significantly higher than that of platinum-resistant tumors (p = 0.002). Although no significant differences in progression-free and overall survival were observed between patients with high and low PR expression, those with high PR expression tended to have longer survival. While PR protein was only weakly detectable in ES-2 and TOV-21G cells, a transfection of the PR-A or PR-B gene resulted in a strong expression of PR-A or PR-B, which led to significantly reduced proliferation and migration in ES-2 and TOV-21G cells. Furthermore, overexpression of PR-A or PR-B enhanced cisplatin cytotoxicity in these cell lines. In conclusion, strong PR expression was associated with improved platinum sensitivity and survival outcomes, consistent with our experimental findings. The potential of PR as a tumor sensitizer to cisplatin in OCCC warrants further investigation.

BACKGROUND: Hyalinizing clear cell carcinoma (HCCC) of the salivary glands is a rare low-grade malignant tumor. This type of tumor is particularly uncommon in the sublingual glands.
METHODS: A 57-year-old female with a mass on the left side of the floor of the mouth that had been present for 2 months. The computed tomography scan of the neck revealed a nodular abnormal density shadow in the left sublingual area, measuring approximately 2.6 cm × 1.9 cm.
METHODS: Primary HCCC of the sublingual gland.
METHODS: The patient underwent surgical treatment and reconstruction using a left anterolateral femoral free flap, which showed immunohistochemical positivity for CK 5/6, CK 7, CK (AE1/AE3), and Ki-67 (<5%), but negative for SMA and S-100.
RESULTS: No recurrence was observed during the 12-month postoperative follow-up period.
CONCLUSIONS: The absence of characteristic clinical manifestations makes HCCC highly susceptible to misdiagnoses. This case presents a rare instance of HCCC in the sublingual gland, providing a reference for the clinical diagnosis and treatment of the disease.

BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignant tumor. The standard treatment for CCOC is surgical resection and adjuvant radiotherapy (RT). Radiotherapy is generally considered in inoperable cases. However, there are no reports on definitive RT for CCOC, and the role of RT in patients with inoperable CCOC remains unknown. Therefore, in this report, we present two cases of carbon-ion (C-ion) RT for CCOC.
METHODS: In case 1, a 73-year-old man with mandibular CCOC presented with recurrence in the inferior temporal fossa after two tumor resections. The tumor was considered inoperable, and C-ion RT (57.6 Gy in 16 fractions) was administered. The tumor remained controlled even after 20 months of C-ion RT; however, the patient died of other causes. In case 2, a 34-year-old man with maxillary CCOC presented with recurrence in the left sinonasal region after two tumor resections. The tumor was considered inoperable, and C-ion RT (64 Gy in 16 fractions) was administered. However, recurrence was observed in the irradiated field 19 months after the treatment. Subsequently, C-ion RT (64 Gy in 16 fractions) was repeated for the recurrent tumors. Seven years and 6 months after the initial irradiation, the tumor remains controlled, and the patient is alive without any unexpected serious adverse events.
CONCLUSIONS: C-ion RT may be an effective treatment option for patients with inoperable CCOC.

OBJECTIVE: Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations.
METHODS: Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells.
RESULTS: JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay.
CONCLUSIONS: Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.

BACKGROUND: Complete macroscopic resection is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high-grade serous ovarian carcinoma, and the benefit of complete macroscopic resection in other histotypes is poorly characterized. We sought to determine which histotypes derive the greatest benefit from complete macroscopic resection to better inform future decisions on radical cytoreductive efforts.
METHODS: We performed multivariable analysis of disease-specific survival across 2 independent patient cohorts to determine the magnitude of benefit associated with complete macroscopic resection within each histotype.
RESULTS: Across both cohorts (Scottish: n = 1622; Surveillance, Epidemiology, and End Results [SEER]: n = 18 947), complete macroscopic resection was associated with prolonged disease-specific survival; this was more marked in the Scottish cohort (multivariable hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.37 to 0.52 vs HR = 0.59, 95% CI = 0.57 to 0.62 in SEER). In both cohorts, clear cell ovarian carcinoma was among the histotypes to benefit most from complete macroscopic resection (multivariable HR = 0.23 and HR = 0.50 in Scottish and SEER cohorts, respectively); high-grade serous ovarian carcinoma patients demonstrated highly statistically significant and clinically meaningful survival benefit, but this was of lower magnitude than in clear cell ovarian carcinoma and endometrioid ovarian carcinoma across both cohorts. The benefit derived in low-grade serous ovarian carcinoma is also high (multivariable HR = 0.27 in Scottish cohort). Complete macroscopic resection was associated with prolonged survival in mucinous ovarian carcinoma patients in the SEER cohort (multivariable HR = 0.65), but the association failed to reach statistical significance in the Scottish cohort.
CONCLUSIONS: The overall ovarian cancer patient population demonstrates clinically significant survival benefit associated with complete macroscopic resection; however, the magnitude of benefit differs between histotypes.

BACKGROUND: Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti-PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC.
RESULTS: The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p < 0.001 and p = 0.003, separately). PD-L1 was expressed equally or more in the recurrent lesion compared with its matched primary lesion.
CONCLUSIONS: In conclusion, anti-PD-1/PD-L1 inhibitors are a promising therapeutic choice for OCCC. For evaluation of PD-L1 expression, CPS is more recommended than TPS. Evaluation of recurrent lesion was still suitable and predictive when the primary tumor tissue was not available. Distant metastatic lesions can serve as alternative samples for PD-L1 evaluation, while usage of lymphatic metastatic lesions is not recommended.