OBJECTIVE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few.
METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared.
RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8).
CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.

OBJECTIVE: Patients with ovarian clear cell carcinoma (OCCC) often present with thrombosis. While cancer patients with concomitant thrombosis were generally reported to have worse prognoses than those without, the association between thrombosis and prognosis has not been elucidated in OCCC. This study aimed to determine how the co-occurrence of thrombosis affects OCCC prognoses.
METHODS: We retrospectively examined 115 patients with OCCC who were diagnosed and treated at the University of Tokyo Hospital between 2009 and 2019.
RESULTS: Of 115 patients with OCCC, thrombosis was present in 12.5% of 80 patients and in 42.8% of 35 patients who had OCCC stage I/II and stage III/IV, respectively. In stage I/II, the 5-year progression-free survival was 20.6% and 91.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 50.0% and 94.1%. Therefore, the outcomes were significantly poorer among patients with thrombosis (p < 0.0001 and p < 0.0001, respectively). In stage III/IV, the 5-year progression-free survival was 26.7% and 52.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 32.0% and 62.2%. Similarly, the outcomes were significantly poorer among patients with thrombosis (p = 0.0139 and p = 0.369, respectively).
CONCLUSIONS: We determined that thrombosis is more likely to develop in advanced OCCC stages than in early stages, and its co-occurrence is associated with a poor prognosis, regardless of disease stage.

UNASSIGNED: Postmenopausal bleeding (PMB) refers to any uterine bleeding in a menopausal women. In the early menopausal years, endometrial hyperplasia, polyps and submucosal fibroids are common etiologies of post menopausal bleeding. The most common cause of postmenopausal bleeding is endometrial atrophy, comprises of 60-80%, while endometrial hyperplasia and endometrial cancer contribute to only 11% of Post menopausal bleeding. The aim of study is to analyses histomorphological pattern of endometrium in patients presenting with post-menopausal bleeding in Jharkhand.
UNASSIGNED: 103 postmenopausal women presenting to tertiary center of Jharkhand in 2020-22 with bleeding were subjected to endometrial curettage for histopathology. Analysis is based on morphological criteria to assess endometrium. Endometrial histology is of four categories: Proliferative, Secretory, premalignant and carcinoma.
UNASSIGNED: The highest incidence of postmenopausal bleeding was noticed in age group of < 60 years and incidence of malignancy was higher after 57 years of age. The majority of patients had parity between 1 and 3 (78.6%). Malignant & premalignant lesions comprises about 22.3% among that 77.7% were due to benign causes. Among the benign causes of postmenopausal bleeding, proliferative endometrium was the commonest finding. Types of hyperplasia encountered were simple hyperplasia without atypia (6.8%), Complex hyperplasia without atypia (3.9%),Complex hyperplasia with atypia (4.8%) and Simple hyperplasia with atypia (4.8%). 21.4% of cases of postmenopausal bleeding were associated with atrophic endometrium. Secretory endometrium seen in 17.5% of women. Endometrial carcinoma accounted for 12.6% of cases of postmenopausal bleeding. Out of these 69.2% were of endometroid type of endometrial carcinoma, 15.3% were of papillary serous carcinoma and 15.3% had clear cell carcinoma. The mean age of patients with endometrium carcinoma was 62.3 years. All cases of endometrial carcinoma were associated with 1 or more risk factor like diabetes/hypertension/Nulligravida.
UNASSIGNED: Proliferative Endometrium was a major cause of postmenopausal bleeding. Among the malignant causes, endometrial adenocarcinoma of endometroid type was most frequent with a lower mean age at presentation than other high grade cancers like papillary serous carcinoma & clear cell carcinoma.

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.

Renal cell carcinoma (RCC) is the predominant solid lesion found in the kidney. Extra-renal RCC is a rare entity. We present the case of a 75-year-old male with an incidentally discovered mass in the right iliac fossa. The patient underwent active surveillance because a percutaneous biopsy revealed a mesenchymal neoplastic lesion of benign biological behavior. As the mass had high growth rates, a decision for open surgical exploration and excision was made. The pathology results indicated clear cell renal carcinoma, and negative results on 18F-FDG whole-body positron emission tomography-computed tomography (PET/CT) established the diagnosis of extra-renal clear cell RCC. Similar types of neoplasms are extremely rare and are estimated to have developed primarily in mesodermal embryonic remnants. Clinicians should be aware of this rare entity as its diagnosis is challenging and is based on pathology.

Renal cell carcinoma is a diverse group of diseases that can be distinguished by distinct histopathologic and genomic features. In this comprehensive review, we highlight recent advancements in our understanding of the genetic and microenvironmental hallmarks of kidney cancer. We begin with clear cell renal cell carcinoma (ccRCC), the most common subtype of this disease. We review the chromosomal and genetic alterations that drive initiation and progression of ccRCC, which has recently been shown to follow multiple highly conserved evolutionary trajectories that in turn impact disease progression and prognosis. We also review the diverse genetic events that define the many recently recognized rare subtypes within non-clear cell RCC. Finally, we discuss our evolving understanding of the ccRCC microenvironment, which has been revolutionized by recent bulk and single-cell transcriptomic analyses, suggesting potential biomarkers for guiding systemic therapy in the management of advanced ccRCC.

Non-small cell lung carcinoma with predominantly clear cell features is a rare histologic presentation of lung carcinoma. We have examined 31 cases of lung carcinomas showing extensive clear cell features. The patients were 10 women and 21 men aged 47-92 years (mean: 70 years). The tumors showed a predilection for the right upper and lower lobes and measured from 0.8 to 9.5 cm (mean: 4.2 cm). By immunohistochemistry, 9 cases were typed as adenocarcinoma, 19 cases as squamous cell carcinoma, and 3 showed a \"null\" phenotype with complete loss of markers for adenocarcinoma or squamous cell carcinoma. Most cases that typed as adenocarcinoma showed a solid growth pattern. A subset of the solid adenocarcinoma cases showed a distinctive \"pseudosquamous\" morphology. Next-generation sequencing was performed in 20 cases and showed a variety of molecular alterations. The most common abnormalities were found in the TP53 gene (9 cases), FGFR gene family (8 cases), KRAS (5 cases), AKT1 (5 cases), and BRAF (3 cases). Clinical follow-up was available in 21 patients; 16/21 patients died of their tumors from 6 months to 12 years after initial diagnosis (mean: 4.2 years, median: 1.5 years). Four patients were alive and well from 4 to 27 years (mean: 11.5 years, median: 7.5 years); all were pathologic stage 1 or 2. NSCLC with clear cell features can display aggressive behavior and needs to be distinguished from various other tumors of the lung that can show clear cell morphology. The identification of targetable molecular alterations in some of these tumors may be of value for therapeutic management.

The 5th edition of the World Health Organization (WHO) classification of tumors of the urinary tract and male genital organs introduced both general and specific changes in structure, classification, and nomenclature. This also applies to rarer tumors and tumor subtypes of the urinary system. Knowledge of these changes is relevant for routine histopathological work. This article provides an overview of the main new features of the rarer tumors and tumor subtypes of the urinary system in the new edition of the WHO classification.
UNASSIGNED: Mit der 5. Aufl. der WHO-Klassifikation der Tumoren der Harnwege und des männlichen Genitals wurden einige allgemeine und auch speziellen Neuerungen in Struktur, Klassifikation und Nomenklatur eingeführt. Dieses betrifft auch die selteneren Tumoren und Tumortypen des ableitenden Harnsystems. Die Kenntnis dieser Änderungen ist für den diagnostischen Alltag relevant. Dieser Artikel gibt einen Überblick über die wesentlichen Neuerungen der selteneren Tumoren und Tumortypen des ableitenden Harnsystems der neuen Auflage der WHO-Klassifikation.

A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient\'s tumour tissue. Notably, MTC-22 cells, and the patient\'s carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient\'s tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.

Endometriosis is a medical condition affecting at least up to 10% of women of reproductive age. This condition occurs when ectopic endometrial glands and stroma implant outside the uterus and there are several theories regarding the underlying origins of the disease. Endometriosis is one of the major causes of severe dysmenorrhoea, chronic pelvic pain and infertility. While endometriosis is generally a non-malignant condition, it rarely may transform into an invasive cancer, and increase the risk for epithelial ovarian cancer, notably endometrioid or clear cell ovarian cancer. Despite the increased risk, the mechanisms behind the development of endometriosis-associated ovarian cancer (EAOC) are not yet well understood. Recent investigations have delved into the intricate interplay between endometriosis and EAOC, exploring pathways involving oxidative stress, inflammation, hyperestrogenism, and the discovery of genetic mutations within endometriotic lesions that hint at a transition towards invasive carcinoma. Efforts have been made to identify intermediary lesions between endometriosis and EAOC, which may enable earlier detection of endometriosis at risk of malignant transformation or even prevention of the transformation altogether. However, given the rarity of this malignancy, there is still the risk of late or missed diagnosis, with the risk of inappropriate management being offered to the patient, and the higher risk of poor prognosis and increased morbidity and mortality. This scoping review aims to summarize existing data on EAOC, with a focus on endometrioid and clear cell histologic subtypes. It also provides insights into its identification, prognosis, and delineating management strategies, seeking to provide a holistic understanding of the complexities surrounding EAOC, facilitating further research and the development of more effective prevention and treatment approaches.