Computed tomography radiomics for the prediction of thymic epithelial tumor histology, TNM stage and myasthenia gravis

Objectives To evaluate CT-derived radiomics for machine learning-based classification of thymic epithelial tumor (TET) stage (TNM classification), histology (WHO classification) and the presence of myasthenia gravis (MG). Methods Patients with histologically confirmed TET in the years 2000–2018 were retrospectively included, excluding patients with incompatible imaging or other tumors. CT scans were reformatted uniformly, gray values were normalized and discretized. Tumors were segmented manually; 15 scans were re-segmented after 2 weeks by two readers. 1316 radiomic features were calculated (pyRadiomics). Features with low intra-/inter-reader agreement (ICC<0.75) were excluded. Repeated nested cross-validation was used for feature selection (Boruta algorithm), model training, and evaluation (out-of-fold predictions). Shapley additive explanation (SHAP) values were calculated to assess feature importance. Results 105 patients undergoing surgery for TET were identified. After applying exclusion criteria, 62 patients (28 female; mean age, 57±14 years; range, 22–82 years) with 34 low-risk TET (LRT; WHO types A/AB/B1), 28 high-risk TET (HRT; WHO B2/B3/C) in early stage (49, TNM stage I-II) or advanced stage (13, TNM III-IV) were included. 14(23%) of the patients had MG. 334(25%) features were excluded after intra-/inter-reader analysis. Discriminatory performance of the random forest classifiers was good for histology(AUC, 87.6%; 95% confidence interval, 76.3–94.3) and TNM stage(AUC, 83.8%; 95%CI, 66.9–93.4) but poor for the prediction of MG (AUC, 63.9%; 95%CI, 44.8–79.5). Conclusions CT-derived radiomic features may be a useful imaging biomarker for TET histology and TNM stage.

Oncogenic Activation of YAP Signaling Sensitizes Ferroptosis of Hepatocellular Carcinoma via ALOXE3-Mediated Lipid Peroxidation Accumulation

Ferroptosis, a form of programmed cell death process driven by iron-dependent lipid peroxidation, plays an important role in tumor suppression. Although previous study showed that intracellular Merlin-Hippo signaling suppresses ferroptosis of epithelial tumor cells through the inactivation of YAP signaling, it remains elusive if the proto-oncogenic transcriptional co-activator YAP could serve as a potential biomarker to predict cancer cell response to ferroptosis-inducing therapies. In this study, we show that both total YAP staining and nuclear YAP staining were more prevalent in HCC tissues than in nontumorous regions. Compared to low-density HCC cells, high-density cells showed decreased nuclear localization of YAP and conferred significant resistance to ferroptosis. Oncogenic activation of YAP signaling by overexpression of YAP(S127A) mutant sensitized ferroptosis of HCC cells cultured in confluent density or in the 3D tumor spheroid model. Furthermore, we validated the lipoxygenase ALOXE3 as a YAP-TEAD target gene that contributed to YAP-promoted ferroptosis. Overexpression of ALOXE3 effectively increased the vulnerability of HCC cells to ferroptotic cell death. In an orthotopic mouse model of HCC, genetic activation of YAP rendered HCC cells more susceptible to ferroptosis. Finally, an overall survival assay further revealed that both a high expression of YAP and a low expression of GPX4 were correlated with increased survival of HCC patients with sorafenib treatment, which had been proven to be an inducer for ferroptosis by inhibition of the xc-amino acid antiporter. Together, this study unveils the critical role of intracellular YAP signaling in dictating ferroptotic cell death; it also suggests that pathogenic alterations of YAP signaling can serve as biomarkers to predict cancer cell responsiveness to future ferroptosis-inducing therapies.

Aciniccell carcinoma of the salivary glands: clinical and histopathological study of 12 cases

Objective:Acinic cell carcinoma (CCA) is the third malignant epithelial tumor of the salivary glands in adults; low-grade tumor of malignancy, composed of neoplastic cells with serous acinar differentiation. The objective of this work was to analyze 12 cases of CCA according to their location, clinical characteristics, histological and immunohistochemical pattern and cell types, following the latest classification of the World Health Organization. Methods: The study included 12 cases of CCA from the files of salivary tumor biopsies of our work team, corresponding to the period 1997-2020. A numerical code was used to identify the samples, preserving the identity of the patients. Histological sections of the paraffin-embedded biopsies were evaluated with H/E, PAS and Toluidine blue and immunostained with the monoclonal antibodies pancytokeratin AE1 / AE3, Ki67, MUC-1 and mammaglobin. Results: The most frequent histologic pattern was the solid type as a single pattern or integrated with other patterns of lesser development, with almost exclusive location in the parotid gland and more frequent in women. Cells like normal acinar serocytes predominated in the solid growth pattern. The most frequent cell type in the microcystic patternwas the nonspecific glandular cell together with a lower proportion of acinar and intercalated duct-like cells. The papillary-cystic pattern was lined by nonspecific glandular cells. No clear cells found. With Ki67 a low cell proliferation was demonstrated in all the cases studied. Cell labeling for MUC-1 was grade 1 positive (less than 10% immunoreactive cells) and negative for mammaglobin.Conclusions: Patient follow-up is a priority because CCA tends to recur and metastasize and its behavior can become aggressive. We must deepen the study of its proliferative capacity as a treatment and prognosis tool, especially with immunohistochemistry and standardized molecular biology methods.

CLINICOPATHOLOGICAL STUDY OF OVARIAN NEOPLASMS – AN INSTITUTIONAL PERSPECTIVE

Objective: The objective of the study was to know the frequency and histomorphological patterns of ovarian neoplasms concerning age. Methods: A 2-year retrospective study was done in the pathology department, GITAM Institute of Medical Sciences and Research. Data were retrieved from laboratory records, H & E slides of ovarian biopsies of diagnosed neoplasms were screened. Results: During the study period, 70 ovarian neoplasms were reported. Ovarian tumors were categorized according to the WHO classification. In this study surface, epithelial tumors were most common at 87.14% followed by germ cell tumors at 11.42% and sex cord-stromal tumors at 1.42%. Serous cystadenoma was the most common benign surface epithelial tumor. Conclusion: Histopathology is the gold standard for diagnosing ovarian neoplasms. Newer diagnostic techniques such as immunohistochemistry and morphometric analysis help decide management and prognosis.

Endocrine Disorder in Patients With Craniopharyngioma

Craniopharyngioma is an intracranial congenital epithelial tumor growing along the pathway of the embryonic craniopharyngeal tube. The main clinical symptoms of patients with craniopharyngioma include high intracranial pressure, visual field defect, endocrine dysfunction, and hypothalamic dysfunction. At present, the preferred treatment remains the surgical treatment, but the recovery of endocrine and hypothalamic function following surgery is limited. In addition, endocrine disorders often emerge following surgery, which seriously reduces the quality of life of patients after operation. So far, research on craniopharyngioma focuses on ways to ameliorate endocrine dysfunction. This article reviews the latest research progress on pathogenesis, manifestation, significance, and treatment of endocrine disorders in patients with craniopharyngioma.

Biological Rationale and Clinical Evidence of Carbon Ion Radiation Therapy for Adenoid Cystic Carcinoma: A Narrative Review

Adenoid cystic carcinoma (ACC) is a rare, basaloid, epithelial tumor, arising mostly from salivary glands. Radiation therapy can be employed as a single modality for unresectable tumors, in an adjuvant setting after uncomplete resection, in case of high-risk pathological features, or for recurrent tumors. Due to ACC intrinsic radioresistance, high linear energy transfer (LET) radiotherapy techniques have been evaluated for ACC irradiation: while fast neutron therapy has now been abandoned due to toxicity concerns, charged particle beams such as protons and carbon ions are at present the beams used for hadron therapy. Carbon ion radiation therapy (CIRT) is currently increasingly used for ACC irradiation. The aim of this review is to describe the immunological, molecular and clinicopathological bases that support ACC treatment with CIRT, as well as to expose the current clinical evidence that reveal the advantages of using CIRT for treating ACC.

Craniopharyngioma in children: Report of three cases and review of the literature

Craniopharyngioma is a rare benign epithelial tumor, originating in the pituitary stem or pituitary gland and developing in the sellar and / or suprasellar region. Of embryonic origin, craniopharyngiomas are considered to develop from epithelial remains of Rathke's pouch. It affects children as well as adults. All ages combined, craniopharyngiomas represent between 3 to 4% of intracranial tumors worldwide, or 0.5 to 2 new cases per year and per million inhabitants. In children, they represent 10% of all intracranial tumors with a peak frequency between 7 and 13 years and a predominance of men. Although benign, this tumor remains a serious pathology because of the frequent visual, endocrine, neuro-intellectual sequelae and the risk of recurrence that it entails, involving the visual and vital functional.The management of this pathology is multidisciplinary and involves several modalities such as surgery, radiotherapy and medical treatment of hormonal deficits very often associated. We report in this article three cases of boys aged 9, 10 and 12; treated for symptomatic craniopharyngiomas with a favorable clinical and radiological outcome after partial surgical excision and adjuvant external radiotherapy. The aim of this article is to review the epidemiological, diagnostic, therapeutic and evolutionary aspects of these benign tumors of the sellar and / or suprasellar region, with an emphasis on the interest of radiotherapeutic treatment.

New Aspects of Sarcomas of Uterine Corpus—A Brief Narrative Review

Sarcomas of the uterine corpus are rare malignant neoplasms, which are further classified into mesenchymal tumors, and mixed (epithelial plus mesenchymal) tumors. The main issues concerning these neoplasms are the small number of clinical trials, insufficient data from evidence-based medicine, insignificant interest from the pharmaceutical industry, all of which close a vicious circle. The low frequency of these malignancies implies insufficient experience in the diagnosis, hence incomplete surgical and complex treatment. Additionally, the rarity of these sarcomas makes it very difficult to develop clinical practice guidelines. Preoperative diagnosis, neoadjuvant and adjuvant chemoradiation, target and hormone therapies still raise many controversies. Disagreements about the role and type of surgical treatment are also often observed in medical literature. There are still insufficient data about the role of pelvic lymph node dissection and fertility-sparing surgery. Pathologists’ experience is of paramount importance for an accurate diagnosis. Additionally, genetics examinations become part of diagnosis in some sarcomas of the uterine corpus. Some gene mutations observed in uterine sarcomas are associated with different outcomes. Therefore, a development of molecular classification of uterine sarcomas should be considered in the future. In this review, we focus on the epidemiology, pathogenesis, pathology, diagnosis and treatment of the following sarcomas of the uterine corpus: leiomyosarcoma, low- and high-grade endometrial stromal sarcomas, undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are excluded as they represent an epithelial tumor rather than a true sarcoma.