AI Deployment on GBM Diagnosis: A Novel Approach to Analyze Histopathological Images Using Image Feature-Based Analysis.

BACKGROUND: Glioblastoma (GBM) is one of the most common malignant primary brain tumors, which accounts for 60-70% of all gliomas. Conventional diagnosis and the decision of post-operation treatment plan for glioblastoma is mainly based on the feature-based qualitative analysis of hematoxylin and eosin-stained (H&E) histopathological slides by both an experienced medical technologist and a pathologist. The recent development of digital whole slide scanners makes AI-based histopathological image analysis feasible and helps to diagnose cancer by accurately counting cell types and/or quantitative analysis. However, the technology available for digital slide image analysis is still very limited. This study aimed to build an image feature-based computer model using histopathology whole slide images to differentiate patients with glioblastoma (GBM) from healthy control (HC). METHOD: Two independent cohorts of patients were used. The first cohort was composed of 262 GBM patients of the Cancer Genome Atlas Glioblastoma Multiform Collection (TCGA-GBM) dataset from the cancer imaging archive (TCIA) database. The second cohort was composed of 60 GBM patients collected from a local hospital. Also, a group of 60 participants with no known brain disease were collected. All the H&E slides were collected. Thirty-three image features (22 GLCM and 11 GLRLM) were retrieved from the tumor volume delineated by medical technologist on H&E slides. Five machine-learning algorithms including decision-tree (DT), extreme-boost (EB), support vector machine (SVM), random forest (RF), and linear model (LM) were used to build five models using the image features extracted from the first cohort of patients. Models built were deployed using the selected key image features for GBM diagnosis from the second cohort (local patients) as model testing, to identify and verify key image features for GBM diagnosis. RESULTS: All five machine learning algorithms demonstrated excellent performance in GBM diagnosis and achieved an overall accuracy of 100% in the training and validation stage. A total of 12 GLCM and 3 GLRLM image features were identified and they showed a significant difference between the normal and the GBM image. However, only the SVM model maintained its excellent performance in the deployment of the models using the independent local cohort, with an accuracy of 93.5%, sensitivity of 86.95%, and specificity of 99.73%. CONCLUSION: In this study, we have identified 12 GLCM and 3 GLRLM image features which can aid the GBM diagnosis. Among the five models built, the SVM model proposed in this study demonstrated excellent accuracy with very good sensitivity and specificity. It could potentially be used for GBM diagnosis and future clinical application.

Schneiderian papillomas and carcinomas: a retrospective study with special reference to p53 and p16 tumor suppressor gene expression and association with HPV.

Schneiderian papillomas are uncommon benign tumors of the sinonasal area. They are prone to local aggressiveness and recurrence, and some undergo malignant progression. We analyzed specimens obtained from 67 Chinese patients who had presented to the ENT department of a regional hospital with biopsy-proven schneiderian papilloma. Seven of these patients had either synchronous or metachronous carcinoma, 1 of whom had pure carcinoma in situ. For each case, we documented the morphology, immunohistochemical expression of tumor suppressor genes p53 and p16, and any association with human papillomavirus (HPV) infection as detected by either polymerase chain reaction or in situ hybridization techniques. We found that severe dysplasia and p53 positivity were strongly associated with malignant progression. Association with HPV was demonstrated in 22 of the 67 patients (33%); the association was strongest among patients with exophytic papillomas and carcinomas. The effect of HPV in papilloma oncogenesis probably begins during the early phase, while other factors are responsible for progression to carcinoma. We conclude that p53-positive, dysplastic schneiderian papillomas warrant aggressive surgical treatment.

Hypermethylation of SOX2 gene in hydatidiform mole and choriocarcinoma.

This study investigated the expression and methylation profiles of SOX2, a stem cell-related transcription factor, in placentas and gestational trophoblastic disease. The methylation status of SOX2 promoter region in 55 hydatidiform moles, 4 choriocarcinoma, 23 first trimester, and 15 term placentas was evaluated by methylation-specific polymerase chain reaction. The methylated allele was found in 4.4% (1/23) of first trimester placentas, 26.7% (4/15) term placentas, and 56.4% (31/55) of hydatidiform moles and all choriocarcinoma samples and cell lines. A significant reduction in SOX2 messenger RNA expression was found in the hydatidiform moles (P = .027) when compared with that in the placentas. SOX2 messenger RNA expression was significantly correlated with SOX2 hypermethylation (P < .001). SOX2 expression was restored in choriocarcinoma cell lines following treatment to 5-Aza-2(')-deoxycytidine and/or Trichostatin A, demethylation and histone deacetylase inhibitors, respectively, and the response was synergistic. Epigenetic mechanisms may play important role on the transcriptional regulation of SOX2 and contribute to pathogenesis of gestational trophoblastic disease.

Significance of atypical repair in liquid-based gynecologic cytology: a follow-up study with molecular analysis for human papillomavirus.

BACKGROUND: "Atypical repair" is a controversial topic in gynecologic cytology. Although some cases do represent reparative change of dysplastic epithelium, the overall significance of identifying atypical reparative cells, especially in liquid-based cytology specimens, has not been investigated thoroughly. METHODS: All the liquid-based cytology cases with the diagnostic connotation of atypical repair were retrieved from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a 4.5-year period from early 1998 to mid 2002. The clinical data and follow-up cytology/surgical biopsy findings were analyzed to explain the atypical cytologic change. Retrospective molecular analysis for human papillomavirus (HPV) using polymerase chain reaction and restriction fragment length polymorphism was also carried out on the liquid-based cytology samples. RESULTS: During the study period, the authors identified 21 patients with a cytologic diagnosis of atypical repair, for which follow-up information was available. The liquid-based cytology samples revealed scattered atypical squamoid cells demonstrating reparative change, including the presence of prominent nucleoli. In addition to typical repair, these cells showed more obvious nuclear pleomorphism, anisonucleosis, irregularities of nuclear outline, slight coarsening of the chromatin, and focal loss of nuclear polarity. Of the 21 patients, 4 did not have a significant history of cervical/vaginal pathology before or after the cytologic examination, whereas the 17 remaining patients had squamous intraepithelial lesions (SIL; n = 9), genital prolapse (n = 3), endocervical polyps (n = 2), SIL/cervical carcinoma with local radiotherapy (n = 2), or uterine malignancy with cervical extension (n = 1). These associations could not be delineated solely on the basis of morphologic assessment of the liquid-based cytology preparations. However, HPV DNA was detected frequently in cases of atypical repair associated with subsequent development of SIL (positive predictive value = 71.4%; negative predictive value = 77.8%). CONCLUSIONS: The presence of atypical reparative cells in liquid-based cytology is associated with a variety of conditions ranging from reactive to neoplastic conditions. Close follow-up with clinical correlation and further investigations (if indicated) are necessary for this group of high-risk patients. Reflex molecular analysis for HPV performed on liquid-based cytology samples is also helpful in predicting the possible association with an underlying SIL.

Warty (condylomatous) carcinoma of the cervix. A review of 3 cases with emphasis on thin-layer cytology and molecular analysis for HPV.

OBJECTIVE: To describe the thin-layer cytology (if available) and histologic findings of warty (condylomatous) carcinoma of the cervix, with molecular analysis for HPV screening. STUDY DESIGN: The authors reviewed the clinical features, thin-layer cytology (if available) and histologic findings of all cases of warty carcinoma of the cervix encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period January 1998-April 2002. Molecular techniques for HPV screening using polymerase chain reaction were carried out on thin-layer cytology specimens or paraffin-embedded tumor tissue. RESULTS: Three cases of warty carcinoma of the cervix were encountered during the study period. Thin-layer preparations (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) were available for 2 of them, and both were of moderate cellularity. There were small, cohesive clusters and syncytial sheets of tumor cells with vague papillary configurations. Dispersed squamous carcinoma cells and necrotic tumor debris (diathesis) were focally present in the background. The tumor cells were polygonal to elongated and contained oval nuclei, coarse chromatin and sometimes distinct nucleoli. Dyskeratotic tumor cells with bizarre shapes were also noted. Characteristically, there were also many koilocytes demonstrating extreme nuclear atypia and increased nuclear/cytoplasm ratio. These koilocytic cells possessed pleomorphic nuclei, distinct nucleoli and perinuclear cytoplasmic halos. Histologic examination of the tumor biopsies showed classic features of warty carcinoma, with papillary architecture, obvious koilocytic cytopathic change and focal stromal invasion. Molecular analysis confirmed the presence of HPV DNA in all the samples. CONCLUSION: Although koilocytes are rarely found in cervical cytology specimens of conventional squamous cell carcinoma, they are characteristically observed in warty carcinoma. A correct cytologic diagnosis is possible if one pays attention to the extreme koilocytic atypia, focal papillary configurations and otherwise classic features of squamous cell carcinoma. Abundance of koilocytes does not necessarily rule out invasive malignancy.

Thin-layer cytology findings of small cell carcinoma of the lower female genital tract. Review of three cases with molecular analysis.

OBJECTIVE: To describe the thin-layer cytology findings of small cell carcinoma of the low female genital tract, with histologic correlation and human papillomavirus (HPV) genotyping. STUDY DESIGN: The authors reviewed the clinical findings, thin-layer cytology and histologic features of small cell carcinoma of the lower female genital tract (cervix or vagina) occurring in three postmenopausal Chinese women at Pamela Youde Nethersole Eastern Hospital, Hong Kong, over a four-year period, from January 1998 to December 2001. Molecular techniques for HPV screening and genotyping using the polymerase chain reaction and restriction fragment length polymorphism were employed on the cytologic specimens. RESULTS: The thin-layer preparations were of moderate to high cellularity. There were loose aggregates of or isolated small round cells with a high nuclear/cytoplasmic ratio, thin but irregular nuclear membrane, hyperchromatic nuclei, inconspicuous nucleoli and scanty cytoplasm. Tumor cell cannibalism was commonly found. Small groups of tumor cells with nuclear molding were noted. There was also obvious tumor diathesis in the background. The necrotic debris was admixed with isolated small round cells, apoptotic bodies and nuclear dust. Associated koilocytosis or squamous intraepithelial lesions were not seen. Histologic examination of the tumor biopsies showed classic features of small cell carcinoma associated with squashing artifacts and vascularized stroma. Molecular analysis revealed the presence of HPV DNA (either type 18 or 16) in all the three liquid-based cytology samples. CONCLUSION: While the cytomorphologic features of small cell carcinoma of the cervix or vagina in thin-layer preparations are slightly different from those in conventional smears, due mainly to the absence of smearing effect, recognition of the subtle but characteristic appearance can enhance the accuracy of the cytologic diagnosis. The association between HPV and primary small cell carcinoma of the lower female genital tract was confirmed by this study.

Transitional cell metaplasia of the uterine cervix is related to human papillomavirus: molecular analysis in seven patients with cytohistologic correlation.

BACKGROUND: Transitional cell metaplasia of the uterine cervix is an under-recognized entity in cervical pathology. The underlying etiology and biologic significance remains uncertain. The thin-layer cytology findings and association with human papillomavirus (HPV) have not been studied thoroughly. METHODS: The authors retrospectively reviewed the clinical findings, thin-layer cytology and histologic features of pure transitional cell metaplasia of the uterine cervix occurring in seven perimenopausal or postmenopausal Chinese women at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the period from January, 1998 to April, 2001. Molecular techniques for HPV screening and genotyping using polymerase chain reaction and restriction fragment length polymorphism analysis were employed in the thin-layer cytology specimens and paraffin block material. RESULTS: In all seven patients, transitional cell metaplasia represented an incidental histologic finding. It occurred in the ectocervix, transformation zone, endocervix, or vagina. Histologically, it resembled urothelium of the urinary bladder and was comprised of multilayers of mitotically inactive, immature epithelial cells with vertically aligned oval nuclei, fine chromatin, indistinct nucleoli, and conspicuous longitudinal nuclear grooves. The superficial cells were oriented more horizontally and contained pale-staining cytoplasm similar to umbrella cells. Features consistent with transitional cell metaplasia were identified in two of seven preoperative thin-layer preparations. Cytologically, the affected parabasal cells recapitulated the features that were seen in histologic sections. In addition to the bland nuclear morphology and longitudinal nuclear grooves, the cell borders appeared distinct, and the appearance of a perinuclear cytoplasmic halo was common. Sometimes, the metaplastic cells assumed a spindle shape and appeared as cohesive, streaming cell clusters. Molecular study successfully demonstrated the presence of HPV in all seven patients, mostly in the liquid-based cytology samples. In general, the viral DNA load was relatively low; and, for samples in which HPV genotyping was feasible, HPV type 58 was the prevalent genotype. CONCLUSIONS: The current study demonstrates that transitional cell metaplasia of the uterine cervix is related to HPV. It also carries a distinctive cytologic appearance in thin-layer preparations. Based on the limited follow-up data from a small number of reported patients, transitional cell metaplasia seems to run an indolent clinical course. However, its peculiar association with HPV and its possible correlation, both morphologic and histogenetic, with cervical intraepithelial neoplasia need further investigation.