Identification of pathological subtypes of early lung adenocarcinoma based on artificial intelligence parameters and CT signs

Objective: To explore the value of quantitative parameters of artificial intelligence and computed tomography (CT) signs in identifying pathological subtypes of lung adenocarcinoma appearing as ground-glass nodules (GGNs). Methods: CT images of 224 GGNs from 210 individuals were collected retrospectively and pathologically classified into atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) groups. Artificial intelligence was used to identify GGNs and to obtain quantitative parameters, and CT signs were recognized manually. The mixed predictive model based on logistic multivariate regression was evaluated. Results: Of the 224 GGNs, 55, 93, and 76 were AAH/AIS, MIA, IAC, respectively. In terms of artificial intelligence parameters, from AAH/AIS to MIA, and IAC, there was a gradual increase in two-dimensional mean diameter, three-dimensional mean diameter, mean CT value, maximum CT value, and volume of GGNs (all P < 0.0001). Except for the CT signs of the location, and the tumor-lung interface, there were significant differences among the three groups in the density type, shape, vacuole signs, air bronchogram, lobulation, spiculation, pleural indentation, and vascular convergence signs (all P < 0.05). The areas under the curve (AUC) of predictive model 1 for identifying the AAH/AIS and MIA and model 2 for identifying MIA and IAC were 0.779 and 0.918, respectively, which were greater than the quantitative parameters independently (all P < 0.05). Conclusion: Artificial intelligence parameters are valuable for identifying subtypes of early lung adenocarcinoma, and when combined with CT signs to improve its diagnostic efficacy.

Prognostic Significance of PD1, PD-L1 Expression , Pathological Subtypes and Metabolic Activity on 18F-FDG PET/CT in Refractory /Relapsing Pediatric Hodgkin Lymphoma

Background: Hodgkin Lymphoma (HL) is a unique disease entity both in its pathology and the young patient population that it primarily affects. Several meta-analyses have demonstrated that high PD-L1 expression levels are correlated with adverse clinical and pathologic features. Objectives: The aim of this study is to evaluate the correlation between the expression of PD-L1 and clinicopathological features, as well as the prognostic significance of PD-L1 expression with regard to interim PET response in relapsing / refractory pediatric HL. Methods: We measured the expression of PD-1/PD-L1 in the baseline diagnostic samples of children with relapsing/ refractory classical HL. The results were correlated with the pathological subtypes as well as the clinical outcome. Results: Of the 88 included patients, 77% had advanced stage HL. PD-1 expression was detected in 50% of cases, whereas PD-L1 (membranous) was expressed by tumor cells in 60% of the cases, and strongly expressed in 16% of cases. Notably, PD-L1 (cytoplasmic) was detected in 55% of the cases. There was a significant differences in the expression levels of PDL-1 between the different pathological subtypes (p = 0.006). OS of patients with PD-L1expression (Cytoplasmic) was 83% vs 91% in patients with absent expression (P=0.001). There was no prognostic significance of PD-L1 expression with regard to PET response (p=0.31). Conclusion: Although PD-L1 expressions did not show statistically significance with well-established prognostic factors, our preliminary data indicate that pathological subtypes and cytoplasmic expression of PD-L1 may have a prognostic implication on survival in pediatric HL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

HRCT features between lepidic-predominant type and other pathological subtypes in early-stage invasive pulmonary adenocarcinoma appearing as a ground-glass nodule

Background Different pathological subtypes of invasive pulmonary adenocarcinoma (IPA) have different surgical methods and heterogeneous prognosis. It is essential to clarify IPA subtypes before operation and high-resolution computed tomography (HRCT) plays a very important role in this regard. We aimed to investigate the HRCT features of lepidic-predominant type and other pathological subtypes of early-stage (T1N0M0) IPA appearing as a ground-glass nodule (GGN). Methods We performed a retrospective analysis on clinical data and HRCT features of 630 lesions in 589 patients with pathologically confirmed IPA (invasive foci > 5 mm) appearing as pure GGN (pGGN) and mixed GGN (mGGN) with consolidation-to-tumor ratio (CTR) ≤0.5 from January to December 2019. All GGNs were classified as lepidic-predominant adenocarcinoma (LPA) and nonlepidic-predominant adenocarcinoma (n-LPA) groups. Univariate analysis was performed to analyze the differences of clinical data and HRCT features between the LPA and n-LPA groups. Multivariate analysis was conducted to determine the variables to distinguish the LPA from n-LPA group independently. The diagnostic performance of different parameters was compared using receiver operating characteristic curves. Results In total, 367 GGNs in the LPA group and 263 GGNs in the n-LPA group were identified. In the univariate analysis, the CTR, mean CT values, and mean diameters as well as mixed GGN, deep lobulation, spiculation, vascular change, bronchial change, and tumor–lung interface were smaller in the LPA group than in the n-LPA group (P < 0.05). Logistic regression model was reconstructed including the mean CT value, CTR, deep lobulation, spiculation, vascular change, and bronchial change (P < 0.05). Area under the curve of the logistic regression model for differentiating LPA and n-LPA was 0.840 (76.4% sensitivity, 78.7% specificity), which was significantly higher than that of the mean CT value or CTR. Conclusions Deep lobulation, spiculation, vascular change, and bronchial change, CT value > − 472.5 HU and CTR > 27.4% may indicate nonlepidic predominant invasive pulmonary adenocarcinoma in GGNs.

Sex Hormone-Binding Globulin (SHBG) in Cerebrospinal Fluid Does Not Discriminate between the Main FTLD Pathological Subtypes but Correlates with Cognitive Decline in FTLD Tauopathies

Biomarkers to discriminate the main pathologies underlying frontotemporal lobar degeneration (FTLD-Tau, FTLD-TDP) are lacking. Our previous FTLD cerebrospinal fluid (CSF) proteome study revealed that sex hormone-binding globulin (SHBG) was specifically increased in FTLD-Tau patients. Here we investigated the potential of CSF SHBG as a novel biomarker discriminating the main FTLD pathological subtypes. SHBG was measured in CSF samples from patients with FTLD-Tau (n = 23), FTLD-TDP (n = 29) and controls (n = 33) using an automated electro-chemiluminescent immunoassay. Differences in CSF SHBG levels across groups, as well as its association with CSF YKL40, pTau181/total-Tau ratio and cognitive function were analyzed. CSF SHBG did not differ across groups, though a trend towards elevated levels in FTLD-Tau cases compared to FTLD-TDP and controls was observed. CSF SHBG levels were not associated with either CSF YKL40 or the p/tTau ratio. They, however, inversely correlated with the MMSE score (r = −0.307, p = 0.011), an association likely driven by the FTLD-Tau group (r FTLD-Tau = −0.38; r FTLD-TDP = −0.02). CSF SHBG is not a suitable biomarker to discriminate FTLD-Tau from FTLD-TDP.

CD158k and PD-1 expressions define heterogeneous subtypes of Sezary syndrome

Sezary syndrome (SS) is a rare leukemic form of cutaneous T-cell lymphoma. Diagnosis mainly depends on flow cytometry, but results are not specific enough to be unequivocal. The difficulty in defining a single marker that could characterize Sezary cells may be the consequence of different pathological subtypes. In this study, we used multivariate flow cytometry analyses. We chose to investigate the expression of classical CD3, CD4, CD7, and CD26 and the 2 new association of 2 markers CD158k and PD-1. We performed lymphocyte computational phenotypic analyses during diagnosis and follow-up of SS patients to define new SS classes and improve the sensitivity of the diagnosis and the follow-up flow cytometry method. Three classes of SS, defined by different immunophenotypic profiles, CD158k-positive SS, CD158k-negative PD-1-positive SS, CD158k and PD-1 double-negative SS, showed different CD8+ and B-cells environments. Such a study could help to diagnose and define biological markers of susceptibility/resistance to treatment including immunotherapy. -

Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions

Acral and mucosal melanomas are extremely rare in Caucasians; however, they are the predominant melanoma subtypes in Asians and other non-Caucasian populations. Acral and mucosal melanomas share many clinicopathological features, including aggressive phenotypes, similar genetic landscapes, and grim prognoses. In spite of advances in melanoma management, patients with acral and mucosal melanomas show limited benefit from current therapies. The rarity of these subtypes of melanoma is a significant factor contributing to the poor understanding of these pathological subtypes and the lack of effective interventions. Furthermore, the mechanisms contributing to disparities between different types of melanoma remain largely unclear. Herein, we comprehensively review current knowledge on the clinicopathological characteristics and mutational landscapes of acral and mucosal melanomas, as well as providing an overview of current therapies for patients with these aggressive melanoma subtypes, focusing on available immunotherapeutic interventions. We also discuss pathological differences between different melanoma subtypes and summarize current knowledge on melanoma disparities between Asians and Caucasians. Finally, we discuss emerging immunotherapeutic strategies for the treatment of acral and mucosal melanomas, focusing on combination therapies with immune checkpoint inhibitors. Unraveling the unique features of acral and mucosal melanomas is key for their early diagnosis and for the development of effective therapies.