Clinical Morphological Features Research Articles

Higher density of CD4+ T cell infiltration predicts severe renal lesions and renal function decline in patients with diabetic nephropathy.

More evidence have shown that the combination of immune and inflammatory mechanism was critical in diabetic nephropathy (DN). However, the relationship between CD4+ T cells and the development of DN is still unclear. Therefore, this study will focus on this issue from the perspective of clinicopathology. From September 2019 to December 2022, a total of 112 adult patients with DN were enrolled in the study. According to the density of CD4+ T cell infiltration based on immunostaining, the patients were divided into high-CD4 group (56 patients) and low-CD4 group (56 patients). Another 25 diabetic patients with minimal change disease (non-diabetic nephropathy, NDN) was reviewed as control group in clinical and molecular analysis. The clinical parameters, morphological features, and molecular characteristics were compared. The predictive value of CD4+ T cells for DN prognosis was also investigated. DN patients in the high-CD4 group suffered from higher proteinuria and lower estimated glomerular filtration rate (eGFR) level than those in the low-CD4 group and NDN patients. Renal biopsy in the high-CD4 group presented with more severe glomerular lesions, higher density of interstitial inflammation, and more severe tubular atrophy/interstitial fibrosis than in the low-CD4 group. Multivariate logistic analysis indicated that the density of CD4+ T cell infiltration could independently predict the severity of tubular atrophy/interstitial fibrosis. In addition, more severe mitochondrial damage of renal tubular epithelial cells and a more obvious expression of Bcl6, IL-6, STAT3, and TGFβ1 were observed in DN patients of the high-CD4 group, indicating the possible mechanism of CD4+ T cells involving the progression of DN. Multivariate Cox regression analysis revealed that a higher intensity of interstitial CD4+ T cell deposition remained as an independent predictor of the double endpoint with doubling of baseline serum creatinine or end-stage renal disease. The high density of CD4+ T cell infiltration was associated with renal function decline and severity of renal lesions and predicted poor renal survival for DN patients.

A nomogram for predicting invasiveness of lung adenocarcinoma manifesting as ground-glass nodules based on follow-up CT imaging.

Different pathological stages of lung adenocarcinoma require different surgical strategies and have varying prognoses. Predicting their invasiveness is clinically important. This study aims to develop a nomogram to predict the invasiveness of lung adenocarcinoma manifesting as ground-glass nodules (GGNs) based on follow-up computed tomography (CT) imaging. We retrospectively collected data of 623 GGNs from 601 patients who underwent two follow-up chest CT scans and were confirmed as lung adenocarcinoma by postoperative pathology between June 2017 and August 2023. These patients were randomly divided into training and testing sets in a 7:3 ratio. Eighty-seven GGNs from 86 patients who underwent surgery between September 2023 and April 2024 were prospectively collected as a validation set. The volume, mean density, solid component volume (SV), percentage of solid component (PSC), and mass of GGNs were evaluated using the InferRead CT Lung software. Patients were classified into Group A (atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma) and Group B (invasive adenocarcinoma). Three predictive models were established: model 1 utilized clinical characteristics and morphological features on pre-surgical CT, model 2 incorporated clinical characteristics, morphological features and quantitative parameters on pre-surgical CT, and model 3 utilized all selected features on baseline and pre-surgical CT. Model 3 achieved a satisfying area under the curves values of 0.911, 0.893, and 0.932 in the training, testing, and validation sets, respectively, demonstrating superior predictive performance than model1 (0.855, 0.858, and 0.816) and model2 (0.895, 0.891, and 0.903). A nomogram was constructed based on model 3. Calibration curves showed a good fit, and decision curve analysis showed that the nomogram was clinically useful. The nomogram based on morphological features and quantitative parameters from follow-up CT images showed good discrimination and calibration abilities in predicting the invasiveness of lung adenocarcinoma manifesting as GGNs.

Clinical and hematological profile of patients with pancytopenia at a tertiary medical center in Ethiopia.

Pancytopenia is an important hematological problem encountered in routine clinical practice associated with a multitude of disease states. The possible causes of pancytopenia can be influenced by geography, socioeconomic conditions, and endemic illnesses. Information regarding the underlying clinical conditions and morphologic features of blood cells of pancytopenia is limited and varied across different regions. Thus, this study was designed to assess the peripheral morphologic features of blood cells and the underlying clinical causes of pancytopenia. A facility-based cross-sectional study was conducted at the Jimma Medical Center hematology laboratory from June 13 to November 13, 2022. A total of 3mL of whole blood was collected from each subject for complete blood count analysis and peripheral blood morphology examination. Data on sociodemographic and clinical conditions were collected from medical records using a checklist. The data were analyzed using Statistical Package for the Social Sciences version 26. A total of 163 patients with pancytopenia were identified within the 5 months. Hyper-reactive malarial splenomegaly was the most prevalent cause (29.4%), followed by megaloblastic anemia (20.2%), chronic liver disease (10.4%), and acute leukemia (8.6%). Anisocytosis was the predominant peripheral blood morphology finding (82.2%), along with microcytosis (49.7%), ovalocytosis (31.3%), and macrocytosis (30.7%). Severe anemia was observed in 57% of cases, whereas the majority (92%) exhibited moderate leukopenia. A significant proportion (42.3%) had a platelet count below 50,000/μL. Unlike previous studies conducted in other parts of the world, this study showed that hyperreactive malarial splenomegaly was the leading cause of pancytopenia. This emphasizes the necessity of considering this condition as a possible cause for pancytopenia, particularly in malaria-endemic areas. The findings of the hematological profiles and peripheral blood morphology strongly suggest that early identification and prompt management of patients with pancytopenia require collaboration between clinical and laboratory investigations.

Clinicopathological and molecular genetic features of neuromuscular choristoma-associated desmoid type fibromatosis

Objective: To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF). Methods: The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing. Results: The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve (n=4), brachial plexus (n=2) or multiple nerves (n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of β-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions: NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.

Risk factors of cerebral aneurysms rupture in an Indonesian population

ABSTRACT Background The demographic, clinical, and angiographic features of ruptured aneurysms compared to unruptured cerebral aneurysms in Indonesia are still limited. This study aims to determine risk factors for rupture according to clinical patterns and morphological features in the Indonesian population. Method We retrospectively reviewed all cerebral aneurysm registries at the largest comprehensive stroke center in Indonesia from January 2019 to January 2022. We compared demographic and vascular risk factors as well as angiographic features between patients with ruptured and unruptured aneurysms with univariate and multivariate analyses. Results Of 275 patients, 231 (84%) had ruptured cerebral aneurysms. We found a significant difference between the ruptured and unruptured groups in variables such as age, hypertension, dyslipidemia, smoking, location, and type of aneurysm. It was found that only the anterior circulation site (OR 4.91, 95% CI 1.47–16.48; p < 0.01) and saccular type (OR 5.45, 95% CI 1.42–20.93; p = 0.01) were significantly linked to ruptured aneurysms. Conclusion Our findings revealed that anterior location and saccular type were substantially linked with ruptured aneurysms in the Indonesian population.

An Imperative Role of Fetal Autopsy in Previable Fetuses - ADAM Complex Revisited

Abstract Objective To identify the occurrence of the amniotic deformity adhesions, mutilation (ADAM) complex and imperative role of fetal autopsy in diagnosing this condition. Methods A retrospective descriptive study spanning nine years, from January 2014 to January 2022, was conducted at the Department of Pathology within a tertiary care hospital in South India. The study focused on analyzing the clinical presentation, prenatal ultrasonogram, and morphological features of fetuses with the ADAM complex, limb body wall complex, or amniotic bands. Results Among the 438 fetuses assessed during the study period, five fetuses showed features of the ADAM complex (0.01%). The most frequent gestational age observed was 12–18 weeks and most fetuses were female. The common anomaly encountered was limb defects, followed by abdominal and cranial anomalies. Conclusion The diagnosis of the ADAM complex relies primarily on fetal autopsy to differentiate it from similar conditions like anencephaly or body-stalk anomalies. The pathologist plays a crucial role in understanding the complexities of the ADAM complex. Advanced antenatal imaging and therapies offer potential for prevention through improved counseling.

Unsupervised machine learning cluster analysis to identification EVAR patients clinical phenotypes based on radiomics.

This study used unsupervised machine learning (UML) cluster analysis to explore clinical phenotypes of endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA) patients based on radiomics. We retrospectively reviewed 1785 patients with infra-renal AAA who underwent elective EVAR procedures between January 2010 and December 2020. Pyradiomics was used to extract the radiomics features. Statistical analysis was applied to determine the radiomics features that related to severe adverse events (SAEs) after EVAR. The selected features were used for UML cluster analysis in training set and validation in test set. Comparison of basic characteristics and radiomics features of different clusters. The Kaplan-Meier analysis was conducted to generate the cumulative incidence of freedom from SAEs rate. A total of 1180 patients were enrolled. During the follow-up, 353 patients experienced EVAR-related SAEs. In total, 1223 radiomics features were extracted from each patient, of which 23 radiomics features were finally preserved to identify different clinical phenotypes. 944 patients were allocated to the training set. Three clusters were identified in training set, in which patients had identical clinical characteristics and morphological features, while varied considerably of selected radiomics features. This encouraging performance was further approved in the test set. In addition, each cluster was well differentiated from other clusters and Kaplan-Meier analysis showed significant differences of freedom from SAEs rate between different clusters both in the training (p = .0216) and test sets (p = .0253). Based on radiomics, UML cluster analysis can identify clinical phenotypes in EVAR patients with distinct long-term outcomes.

Comparison of MRI features among squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, usual-type endocervical adenocarcinoma and gastric adenocarcinoma of cervix

ObjectiveTo compare and explore the characteristics of squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC), usual-type endocervical adenocarcinoma (UEA) and gastric adenocarcinoma (GAC) of cervix. Materials and methodsA total of 728 cervical cancers (254 cases of AC, 252 cases of ASC, and 222 cases of SCC) confirmed by histopathology were retrospectively reviewed. Among AC, 119 UEA and 47 GAC were included. Clinical baseline data and tumor morphological features on MRI (including tumor location, shape, diameter and volume, margin, growth pattern, presence of fluid component or cyst, heterogenous and peritumoral enhancement) of all cases were collected and analyzed. The signal intensity (SI) of tumor and gluteus maximus muscle were measured and their ratios (SIR) were calculated based on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and contrast-enhanced T1WI at arterial and delay phases (A/DCE-T1WI). These clinical and MRI features were compared between SCC, AC and ASC, UEA and GAC, and the specific ones of each subtype were identified. ResultsThere was a significant difference in SCC-Ag, CA-199, CEA, ADC value, SIR-DWI, presence of intratumor cyst and peritumoral enhancement between AC and ASC; in patient age, menopausal status, International Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag, CA-125, CA-199, CEA, tumor shape, growth pattern, margin, presence of intratumor fluid component and cyst, tumor diameter and volume, ADC value, SIR-T1WI, SIR-T2WI, and SIR-DWI between SCC and AC, as well as SCC and ASC. Also, there was a significant difference in deep stromal invasion (DSI), peritumoral and heterogenous enhancement between SCC and AC, and in SIR-ACE-T1WI between SCC and ASC. There was a significant difference in reproductive history, menopausal status, FIGO stage, CA-199, DSI, lymph node metastasis (LNM), parametrial invasion (PMI), tumor location, shape, margin, growth pattern, presence of fluid component and cyst, tumor diameter and volume, SIR-T1WI, SIR-DWI, and heterogenous enhancement between GAC and UEA. ConclusionThe clinical and MRI features with significant differences among SCC, AC and ASC, and between UEA and GAC, can help to identify each subtype of cervical cancer.

PROGNOSTIC VALUE OF THE DENSITY OF TUMOR-INFILTRATING LYMPHOCYTES AND ITS ASSOCIATION WITH CLINICAL-MORPHOLOGICAL FEATURES OF COLON ADENOCARCINOMAS

Aim. To study the prognostic value of the density of tumor-infiltrating lymphocytes (TILs) and its association with other clinical-morphological parameters in colon adenocarcinomas (CAC). Materials and Methods. 236 CAC samples were examined. TILs density was estimated as the percentage of tumor stromal area occupied by TILs. By the index of TILs density, the patients were divided into 3 groups: TILs 0—9% (n = 88); TILs 10—39% (n = 106); TILs &gt; 40% (n = 42). Dependent on this index, their overall survival (OS) was analyzed. Results. Kaplan — Meier curves revealed a significant (p &lt; 0.001) difference in the OS for patients with different TILs infiltration intensities. Multivariate Cox’s proportional hazard regression model analysis has confirmed that patients with moderate TILs density (HR 0.57, 95% CI 0.34—0.96, p = 0.035) had better OS rates compared to low TILs density. TILs were associated with the stage (p &lt; 0.001), lymph node metastasis pN (p &lt; 0.001), distant metastasis M (p &lt; 0.001), and the patient’s outcome (p &lt; 0.001). Conclusion. TILs can be considered an additional prognostic tool during regular histological examination and are strongly associated with the most significant clinical-morphological features of CAC.

Characteristics and outcomes associated with sarcomere mutations in patients with hypertrophic cardiomyopathy: A systematic review and meta-analysis

BackgroundHypertrophic cardiomyopathy (HCM) is an inherited heart disease that can lead to sudden cardiac death. Impact of genetic testing for the prognosis and treatment of patients with HCM needs to be improved. We conducted a systematic review and meta-analysis to investigate the characteristics and outcomes associated with sarcomere genotypes in index patients with HCM. MethodsA systematic search was conducted in Medline, Embase, and Cochrane Library up to Dec 31, 2023. Data on clinical characteristics, morphological and imaging features, outcomes and interventions were collected from published studies and pooled using a random-effects meta-analysis. ResultsA total of 30 studies with 10,825 HCM index patients were included in the pooled analyses. The frequency of sarcomere genes in HCM patients was 41%. Sarcomere mutations were more frequent in women (p < 0.00001), and were associated with lower body mass index (26.1 ± 4.7 versus 27.5 ± 4.3; p = 0.003) and left ventricular ejection fraction (65.7% ± 10.1% vs. 67.1% ± 8.6%; p = 0.03), less apical hypertrophy (6.5% vs. 20.1%; p < 0.0001) and left ventricular outflow tract obstruction (29.1% vs. 33.2%; p = 0.03), greater left atrial volume index (43.6 ± 21.1 ml/m2 vs. 37.3 ± 13.0 ml/m2; p = 0.02). Higher risks of ventricular tachycardia (23.4% vs. 14.1%; p < 0.0001), syncope (18.3% vs. 10.9%; p = 0.01) and heart failure (17.3% vs. 14.6%; p = 0.002) were also associated with sarcomere mutations. ConclusionsSarcomere mutations are more frequent in women, and are associated with worse clinical characteristics and poor outcomes.

Differential cyclin-E1 expression in CIC-rearranged sarcoma

CIC-rearranged sarcoma (CRS) is a group of high-grade undifferentiated small round cell sarcomas examined as a separate entity in the current WHO classification; since it shows more aggressive clinical behavior and distinct morphological and molecular features compared to Ewing sarcoma (ES). As CCNE1 expression is associated with tumor growth in CIC::DUX4 sarcomas, we aimed to demonstrate the value of cyclin E1 expression in CRS. Cyclin E1 immunohistochemistry and break-apart FISH for EWSR1 and CIC gene rearrangements were performed on 3-mm tissue microarrays composed of 40 small round cell tumors. Five cases were classified as CRS, whereas 22 were ES and 13 were unclassified (EWSR1-/CIC-). Among all three diagnostic groups, we found cyclin E1 expression level to be higher in CRS (80 %) and unclassified groups (61.5 %) compared to ES (4.5 %, p < 0.001). In addition, high cyclin E1 expression levels were associated with higher mean age at diagnosis, presence of atypical histology and myxoid stroma, low CD99 expression, and presence of metastasis at diagnosis. The sensitivity and specificity of high cyclin E1 expression in detecting non-ES cases were 95.5 % and 66.7 %, respectively. However, the correlation between cyclin E1 expression level and survival was not statistically significant. This is the first study that shows cyclin E1 immunohistochemical expression in EWSR1-negative undifferentiated small cell sarcomas, particularly CRS.

Incidental carcinoma of the prostate in cystoprostatectomy specimens - is it always a toothless lion?

Incidental prostate carcinoma (iPC) is a subject of debate concerning its definition, incidence, biology, diagnosis, staging, and treatment. The present study aimed to assess the incidence and main clinical-morphological characteristics of iPC identified in radical cystoprostatectomy (RCP) specimens over a 5-year period. Using the database of the Urology and Pathology Departments, we identified all patients with bladder carcinomas (BCs) who underwent RCP within a 5-year frame time. We selected only those patients with synchronous BC and prostate carcinoma (PC). The following parameters were analyzed for these patients: age, type of bladder and prostate tumor, degree of differentiation, pathological stage, and other prognostic parameters. We identified 91 men with bladder tumors treated by RCP among whom 43, aged between 53 and 84 years (mean age: 69.2 years), presented synchronous PC. iPC was more prevalent in older individuals (>65 years: 30 patients, 69.8%), with only six out of the 43 (12.8%) patients with iPC being aged ≤60 years. All iPC cases were conventional adenocarcinoma. Well-differentiated prostate adenocarcinomas (grade group 1) predominated (65.1%). Among the 43 iPCs, 16 (37.2%) were clinically significant PCs. iPC is frequently identified in patients with BC when inclusion and evaluation of all or most of the prostate tissue are performed. Although more than half of iPCs were well-differentiated tumors confined to the prostate, a significant number of cases met the criteria of clinically significant PC. All men over the age of 50 who are candidates for RCP, should undergo evaluation through serum prostate specific antigen determination.

Potential Markers to Differentiate Uterine Leiomyosarcomas from Leiomyomas.

Uterine leiomyomas (ULM) are the most common benign tumors of the female genitalia, while uterine leiomyosarcomas (ULMS) are rare. The sarcoma is diffuse growth, prone to hematogenous metastasis, and has a poor prognosis. Due to their similar clinical symptoms and morphological features, it is sometimes difficult to distinguish them, and the final diagnosis depends on histological diagnosis. Misdiagnosis of ULM as ULMS will lead to more invasive and extensive surgery when it is not needed, while misdiagnosis of ULMS as ULM may lead to delayed treatment and poor prognosis. This review searched and studied the published articles on ULM and ULMS, and summarized the potential markers for the differential diagnosis of ULMS. These markers will facilitate differential diagnosis and personalized treatment, providing timely diagnosis and potentially better prognosis for patients.

Surgical treatment of littoral cell angioma of the spleen

Littoral cell angioma is a very rare benign splenic neoplasm with typical morphological features. It is difficult to differentiate this angioma from other benign or malignant splenic tumors. It is a unique vascular tumor followed by abdominal pain or detected incidentally during examination. Incidence of this tumor is small, as only few appropriate cases were described in the literature. We present successful surgical treatment of littoral cell angioma of the spleen. The issues of clinical course, diagnosis, therapeutic tactics, morphologic and histochemical features are discussed.

T-Cell Posttransplant Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: Case Series and Systemic Review.

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.

Clinical and morphological diagnostics of bening single focal lung lesions without necrotic changes

In recent decades, the problem of accidental detection by radiography or chest computer tomography of solitary focal formations smaller than 3 cm has become relevant. Although the primary task is to find out its benign or malignant nature as soon as possible, the clarification of the etiology of benign formations with non-neoplastic genesis retains an important clinical significance, in particular in cases of their infectious nature. The purpose of the study was to analyze the diagnostic significance of clinical and radiological data and morphological features of benign single focal lung lesions without necrotic changes, taking into account the final clinical diagnosis. The study group consisted of 42 patients with single benign focal lung lesions without necrosis. Among them there were 29 (69.0%) women and 13 (31.0%) men. Average age of the patients was (50.5±2.2) years. The total number of focal formations was 52. According to the number of focal formations, one patient was diagnosed with 1 formation in 34 cases, 2 formations in 6, and 3 formations in 2 cases. The dimensions of each of the formations did not exceed 30 mm. The most common diagnostic measures were direct biopsy at FBS, 10 (23.8%) cases; and transbronchial biopsy of lung under radiological control, 16 (38.1%) cases respectively. Among the operative interventions, lobe resection of the lung with a focus was mainly performed, in 16 (84.2%) cases. According to the results of the histological examination and taking into account the clinical and laboratory data, the following diagnoses were obtained, which corresponded to the final clinical diagnosis of the patients. A lung abscess was established in 4 (9.5%) cases; a chronic inflammatory process of a non-specific nature was diagnosed in 14 (33.3%) cases. Predominantly post-inflammatory changes and local pneumofibrosis were determined in 15 (35.7%) cases. Vascular malformation and pulmonary sarcoidosis were diagnosed once. In another 7 (16.7%) cases, the final clinical diagnosis was based on clinical and laboratory data and patient supervision - in 2 observations, the final diagnosis of chronic non-specific pulmonary disease was made; and in 5 cases, the nature of single focal pulmonary formations was not established. The most numerous subgroups were cases with a chronic nonspecific inflammatory process and with limited post-inflammatory changes (in total, they amounted to 69.0%), so the clinical and radiological indicators of these subgroups were analyzed more detail. Overall clinical data did not differ significantly between both subgroups. Females predominated in the group with post-inflammatory changes. The number of focal lesions in both lungs was equal; the upper lobes were more often affected. The average size of foci was significantly larger in patients with a chronic inflammatory process and was 22.2 mm compared to 16.3 mm in the subgroup with post-inflammatory changes (p&lt;0.05). Single foci with minimal destructive changes were observed only in the subgroup with a chronic inflammatory process. As a result of the research, such findings were obtained. Among benign single non-necrotized focal pulmonary lesions chronic non-specific inflammatory process and post-inflammatory fibrotic changes, including focal pneumofibrosis, predominate in etiology. In our study, they accounted for 69% of all cases. According to the main radiological indicators (localization, size, shape, characteristics of the internal contents) it is impossible correct determination of the benign nature of non-necrotized focal lung lesions in the vast majority of cases. Histological examination of tissue of focal lesions not only determines benign or malignant nature of the formations, but also, in the case of their benign nature, allows clarify their etiology in most cases (83.3%). Keywords: benign non-necrotized focal lung lesions, X-ray indicators, histological diagnostics.

Predicting the microvascular invasion and tumor grading of intrahepatic mass-forming cholangiocarcinoma based on magnetic resonance imaging radiomics and morphological features.

Preoperative diagnosis of microvascular invasion (MVI) and tumor grading of intrahepatic mass-forming cholangiocarcinoma (IMCC) using imaging findings can facilitate patient treatment decision-making. This study was conducted to establish and validate nomograms based on magnetic resonance imaging (MRI) radiomics and morphological features for predicting the MVI and tumor grading of IMCC before radical hepatectomy. A total of 235 patients with resected IMCC at the Chinese Academy of Medical Sciences and Peking Union Medical College were divided into a training set (n=167) and a validation set (n=68), retrospectively. Clinical data and MRI morphological features were recorded. Univariate and multivariate analyses were conducted to identify the significant features for the prediction of MVI and tumor grading. Radiomics features were extracted from T2-weighted imaging fat-suppressed and diffusion-weighted imaging (DWI). Radiomics signatures (rad_scores) were built based on the least absolute shrinkage and selection operator (LASSO) method. Then, the nomograms were constructed by combining the rad_scores and the significant clinical or MRI morphologic features. The predictive performances for MVI and tumor grading were evaluated by the area under the receiver operating characteristic curve (AUC), calibration, and clinical utility. Totals of 16 and 9 radiomics features were selected to build the rad_scores for the prediction of MVI and tumor grading for the training and validation set, respectively. The nomogram for the prediction of MVI comprised the morphologic features including number of tumors, tumor margin, and rad_score. For the prediction of tumor grading, the nomogram comprised the number of tumors, tumor necrosis, and rad_score. The best discriminations were observed in the training and validation sets for the MVI nomogram [AUCs of 0.874, 95% confidence interval (CI): (0.822-0.926) and 0.869 (0.783-0955)] and tumor grading nomogram [AUCs of 0.827 (0.763-0.891) and 0.848 (0.759-0.937)]. Decision curve analysis (DCA) further confirmed the clinical utilities of the nomograms. Nomograms based on MRI radiomics and morphological features can effectively predict the individualized risks of MVI and tumor grading for IMCC.

The clinical, imaging, pathological and genetic landscape of bottom-of-sulcus dysplasia.

Bottom-of-sulcus dysplasia (BOSD) is increasingly recognized as a cause of drug-resistant, surgically-remediable, focal epilepsy, often in seemingly MRI-negative patients. We describe the clinical manifestations, morphological features, localization patterns and genetics of BOSD, with the aims of improving management and understanding pathogenesis. We studied 85 patients with BOSD diagnosed between 2005-2022. Presenting seizure and EEG characteristics, clinical course, genetic findings and treatment response were obtained from medical records. MRI (3 T) and 18F-FDG-PET scans were reviewed systematically for BOSD morphology and metabolism. Histopathological analysis and tissue genetic testing were performed in 64 operated patients. BOSD locations were transposed to common imaging space to study anatomical location, functional network localization and relationship to normal MTOR gene expression. All patients presented with stereotyped focal seizures with rapidly escalating frequency, prompting hospitalization in 48%. Despite 42% patients having seizure remissions, usually with sodium channel blocking medications, most eventually became drug-resistant and underwent surgery (86% seizure-free). Prior developmental delay was uncommon but intellectual, language and executive dysfunction were present in 24%, 48% and 29% when assessed preoperatively, low intellect being associated with greater epilepsy duration. BOSDs were missed on initial MRI in 68%, being ultimately recognized following repeat MRI, 18F-FDG-PET or image postprocessing. MRI features were grey-white junction blurring (100%), cortical thickening (91%), transmantle band (62%), increased cortical T1 signal (46%) and increased subcortical FLAIR signal (26%). BOSD hypometabolism was present on 18F-FDG-PET in 99%. Additional areas of cortical malformation or grey matter heterotopia were present in eight patients. BOSDs predominated in frontal and pericentral cortex and related functional networks, mostly sparing temporal and occipital cortex, and limbic and visual networks. Genetic testing yielded pathogenic mTOR pathway variants in 63% patients, including somatic MTOR variants in 47% operated patients and germline DEPDC5 or NPRL3 variants in 73% patients with familial focal epilepsy. BOSDs tended to occur in regions where the healthy brain normally shows lower MTOR expression, suggesting these regions may be more vulnerable to upregulation of MTOR activity. Consistent with the existing literature, these results highlight (i) clinical features raising suspicion of BOSD; (ii) the role of somatic and germline mTOR pathway variants in patients with sporadic and familial focal epilepsy associated with BOSD; and (iii) the role of 18F-FDG-PET alongside high-field MRI in detecting subtle BOSD. The anatomical and functional distribution of BOSDs likely explain their seizure, EEG and cognitive manifestations and may relate to relative MTOR expression.

Using CT Radiomics and Machine Learning to Distinguish Radiotherapy vs. Immune Checkpoint Inhibitor-Induced Pneumonitis in Non-Small Cell Lung Cancer Patients

Both radiotherapy (RT) and immune checkpoint inhibitors (ICIs) may induce pneumonitis which is difficult to distinguish clinically. We tested the utility of computed tomography (CT) in identifying the cause of pneumonitis in patients with non-small cell lung cancer (NSCLC) who received RT, ICIs and RT combined with ICIs (RT+ICIs). In this study, we analyzed the clinical characteristics and CT morphology of 130 NSCLC patients who developed pneumonitis after receipt of ICIs only (n = 50), thoracic RT only (n = 50) (ICIs only + RT only, the training cohort, n = 100), and RT+ICIs (the test cohort, n = 30). CT radiomics features were extracted using 3D-Slicer software and selected using LASSO regression for training a random forest (RF) classifier and a linear discriminant analysis (LDA) classifier to discern pneumonitis etiology. Patients who received RT or ICIs only were defined as the training cohort since the cause of their pneumonitis was readily identifiable. Patients who received RT+ICIs were defined as the test cohort and the cause of their pneumonitis were determined by clinicians as the ground truth. In the study, the median time from the initiation of treatment to pneumonitis was 1.9 months in RT+ICIs patients, which was shorter than 2.5 months in RT only and 2.7 months in ICIs only patients. In addition, the patients in RT+ICIs group have more high grade (grade 3-4) pneumonitis compared to patients in ICIs only or RT only group (p<0.05). Pneumonitis after the combined therapy was not a simple superposition mode of RP and CIP, resulting in the distinct characteristics of both RT and ICIs-related pneumonitis. (1) Some cases resembled RP with sharp borders in the ipsilateral lung and others resembled the bilateral distribution of typical CIP, while some patients exhibit an intermediate morphology; (2) Some pneumonitis occurred in the areas of low and medium doses of radiation rather than the high-dose radiation areas similar to RP; (3) Some pneumonitis was initially limited to the ipsilateral lung that had received radiation and then developed in bilateral lungs. The RF classifier showed favorable discrimination between CIP and RP with an area under the receiver operating curve (AUC) of 0.859 (95% CI: 0.7884-0.9292) in the training cohort and 0.851 (95% CI: 0.6998-1) in the test cohort. The simplified LDA classifier consisting of 7 LASSO-selected features achieved an AUC of 0.881 (95% CI: 0.815-0.947) in the training cohort and 0.842 (95% CI: 0.686-0.997) in the test cohort. RT and ICIs-related pneumonitis exhibit distinct clinical characteristics and morphologic features on CT. CT radiomics-based classifiers could provide a noninvasive method to identify the predominant etiology in NSCLC patients who developed pneumonitis after thoracic RT and ICIs.

Baseline whole-lung CT features deriving from deep learning and radiomics: prediction of benign and malignant pulmonary ground-glass nodules.

To develop and validate the model for predicting benign and malignant ground-glass nodules (GGNs) based on the whole-lung baseline CT features deriving from deep learning and radiomics. This retrospective study included 385 GGNs from 3 hospitals, confirmed by pathology. We used 239 GGNs from Hospital 1 as the training and internal validation set; 115 and 31 GGNs from Hospital 2 and Hospital 3 as the external test sets 1 and 2, respectively. An additional 32 stable GGNs from Hospital 3 with more than five years of follow-up were used as the external test set 3. We evaluated clinical and morphological features of GGNs at baseline chest CT and extracted the whole-lung radiomics features simultaneously. Besides, baseline whole-lung CT image features are further assisted and extracted using the convolutional neural network. We used the back-propagation neural network to construct five prediction models based on different collocations of the features used for training. The area under the receiver operator characteristic curve (AUC) was used to compare the prediction performance among the five models. The Delong test was used to compare the differences in AUC between models pairwise. The model integrated clinical-morphological features, whole-lung radiomic features, and whole-lung image features (CMRI) performed best among the five models, and achieved the highest AUC in the internal validation set, external test set 1, and external test set 2, which were 0.886 (95% CI: 0.841-0.921), 0.830 (95%CI: 0.749-0.893) and 0.879 (95%CI: 0.712-0.968), respectively. In the above three sets, the differences in AUC between the CMRI model and other models were significant (allP< 0.05). Moreover, the accuracy of the CMRI model in the external test set 3 was 96.88%. The baseline whole-lung CT features were feasible to predict the benign and malignant of GGNs, which is helpful for more refined management ofGGNs.