Pathology & Oncology Research最新文献

Objective: Recently, several non-conventional variants of IBD-associated dysplasia have been described; however, their prevalence in Central-Eastern Europe is unknown. We aimed to perform a retrospective pilot study by re-evaluating several IBD-associated adenocarcinoma cases to survey the incidence of adjacent non-conventional dysplasia and validate that recent North American findings may apply to a European population.

Methods: Retrospectively, 28 randomly chosen cases of IBD-associated adenocarcinomas diagnosed between 2010 and 2022 were re-evaluated. The patient's sex, age (at the diagnosis of IBD and neoplasia), type of IBD, type of specimen [biopsy (n = 8)/surgical specimen (n = 20)], histological type, grade, localisation, stage, disease-free (DFS) and overall survival (OS) were obtained. Statistical analyses were carried out by using Mann-Whitney (continuous variables), Fisher's exact (categorical variables), Kaplan-Meier (DFS/OS curves), and logrank test (survival curves).

Results: Exclusively, conventional dysplasia was observed in 11, and non-conventional dysplasia in 8 patients. Combined conventional and non-conventional dysplasia was detected in 9 patients. Non-conventional dysplasia showing a combination of multiple subtypes was noted in 10 cases. Altogether, 25 non-conventional dysplastic foci were identified, which were diagnosed as hypermucinous (n = 9), goblet cell-deficient (n = 6), serrated not otherwise specified (NOS) (n = 6), and traditional serrated adenoma-like (n = 4). The majority of non-conventional dysplasias were associated with ulcerative colitis (n = 12). Mucinous adenocarcinoma was exclusively associated with non-conventional dysplasia, while medullary carcinoma was only with conventional dysplasias (p = 0.014 and 0.041).

Conclusion: Based on our results, non-conventional dysplasia is common (60%) adjacent to IBD-associated adenocarcinomas in a Central-Eastern European population and may be detected in biopsies. As multiple recent publications reported evidence of a worse prognosis and more common flat morphology compared to conventional dysplasias, their recognition is of great importance, and stricter follow-up with random biopsy samples may be considered.

[This retracts the article DOI: 10.3389/pore.2021.588084.].

Invasive micropapillary carcinoma of the breast is characterized by clusters of cells presenting with inverted polarity. Although the apico-basal polarity is a fundamental property of the epithelium, the biological alterations leading to the inside-out pattern observed in invasive micropapillary carcinoma (IMPC) remain mostly unknown. The regulation of tight junctions in polarity formation and maintenance is acknowledged. By using immunohistochemistry, we have analysed claudin-1, -3, -4, and -7 tight junction proteins expression and their prognostic value on IMPCs and compared them to invasive breast carcinomas of no special type (IBC-NST) tumors. Our cohort consisted of 37 IMPCs, 36 IBC-NST and 9 mixed IMPC/IBC-NST tumors. Two scoring systems were used to quantify protein expression: a 4-tier scoring system and the H-score method. Distant metastasis free survival (DMFS) intervals and overal survival (OS) data were used for prognosis evaluation. The analysed samples were characterized mainly by low or no claudin-1 expression whereas claudins-3, -4 and -7 showed variable positivity. We have found no significant differences in claudin-3 and -4 protein expression between IMPC and IBC-NST groups with either scoring methods, however high claudin-7 expression was found in significantly more IMPCs than IBC-NST tumors according to the H-score system (p = 0.02). The 4-tier scoring method revealed association of claudin-7 expression with molecular tumor subtypes (p = 0.001). IMPC and IBC-NST tumors did not show difference in DMFS (p = 0.70). In the analysis of pure IMPC and IBC-NST tumors, positive/high claudin-4 protein expression was significantly associated with shorter DMFS (p = 0.02/p = 0.008, respectively according to the two scoring methods). Claudin-3 and claudin-7 expression showed no association with DMFS or OS. Changes in epithelial polarity seem not to be related to claudin-1, -3, and -4 expression. Increased claudin-4 expression may have a role in breast cancer progression.

Pancreatic adenocarcinoma is one of the deadliest forms of cancer with no effective therapeutic options. A KRAS mutation can be found in up to 90% of all pancreatic tumors, making it a promising therapeutic target. The introduction of new KRAS inhibitors has been a milestone in the history of KRAS mutant tumors; however, therapeutic resistance limits their efficacy. Thus, new therapeutic options, including combination therapies, are urgently needed. Recently, we have shown that KRAS G12C inhibitors in combination with farnesyl-transferase inhibitors exert synergistic antitumor effects. Here, we provide evidence for the feasibility of this combinational approach to break down resistance in KRAS G12D mutant pancreatic cancer. Although we have shown that the 3D environment dramatically sensitizes cells to MRTX1133 treatment, the synergistic effect of this drug combination is present in both 2D and 3D in the PANC1 pancreatic adenocarcinoma model, which showed high resistance to MRTX1133 in 2D. The effects of the combination treatment show an association with the inhibition of farnesylated regulatory proteins, including HRAS and RHEB, along with the expression level of KRAS. Our study warrants further investigation for the potential applicability of KRAS G12D inhibitors in combination with farnesyl-transferase inhibitors for the treatment of KRAS mutant pancreatic adenocarcinoma.

Background: Peripherally inserted central catheters (PICC) are increasingly used in clinical practice, which also leads to an increased incidence of PICC-related thrombosis. Local thrombus formation could be prevented by limb ischemic preconditioning (IPC). This study aimed to determine whether IPC can prevent deep vein thrombosis in patients with PICC.

Methods: A total of 600 breast cancer patients receiving PICC were randomized into two groups between July 2016 and July 2018 at the Department of Radiation Oncology. In the preconditioning group, 5 min of ischemic preconditioning was performed three times before PICC, whereas no preconditioning was performed in the sham group. The coagulation function levels, the PICC-related complications, the length of hospital stay, the cost of hospitalization, and the satisfaction of patients were compared.

Results: The coagulation function levels of patients in the preconditioning group were more normal than in patients from the sham group. In total, 56/300 patients in the sham group had presence of PICC-related thrombosis, with only 23/300 in the IPC group, with no significant difference in other complications between the two groups. However, a longer hospital stay was observed in the sham group compared to the IPC group. Moreover, the cost of hospitalization was also reduced in the IPC group, which also improved the satisfaction of patients.

Conclusion: Limb ischemic preconditioning may attenuate the severity of vein thrombosis in patients with PICC, which contributes to reducing the incidence of PICC-related thrombosis in clinical practice.

[This retracts the article DOI: 10.1007/s12253-012-9519-7.].

Sebaceous carcinoma (SC) is a rare aggressive malignant tumor that originates in the adnexal epithelium of the sebaceous gland. While occurrences on the lips are extremely uncommon, there have been a few reported cases in the literature. Our case involves a 47-year-old smoker male who presented with a painless, non-mobile lesion on his upper lip that had been present for 12 months. Upon clinical examination, an ulcerated, exophytic, and irregularly shaped mass was observed on the upper lip. No other intraoral lesions were found. An incisional biopsy was performed, revealing a malignant tumor with a nodular pattern consisting of basaloid cells with obvious sebaceous differentiations and frequent mitoses. The neoplastic cells tested positive for broad-spectrum cytokeratin (AE1-AE3), epithelial membrane antigen (EMA), and P53, while testing negative for S-100 and carcinoembryonic antigen (CEA). Based on these results, a diagnosis of SC of the upper lip was made. This case report and review aimed to describe the histogenesis, unique clinicopathological features, and current treatment options for SC.

Artificial intelligence (AI) technology in pathology has been utilized in many areas and requires supervised machine learning. Notably, the annotations that define the ground truth for the identification of different confusing process pathologies, vary from study to study. In this study, we present our findings in the detection of invasive breast cancer for the IHC/ISH assessment system, along with the automated analysis of each tissue layer, cancer type, etc. in colorectal specimens. Additionally, models for the detection of atypical and typical mitosis in several organs were developed using existing whole-slide image (WSI) sets from other AI projects. All H&E slides were scanned by different scanners with a resolution of 0.12-0.50 μm/pixel, and then uploaded to a cloud-based AI platform. Convolutional neural networks (CNN) training sets consisted of invasive carcinoma, atypical and typical mitosis, and colonic tissue elements (mucosa-epithelium, lamina propria, muscularis mucosa, submucosa, muscularis propria, subserosa, vessels, and lymph nodes). In total, 59 WSIs from 59 breast cases, 217 WSIs from 54 colon cases, and 28 WSIs from 23 different types of tumor cases with relatively higher amounts of mitosis were annotated for the training. The harmonic average of precision and sensitivity was scored as F1 by AI. The final AI models of the Breast Project showed an F1 score of 94.49% for Invasive carcinoma. The mitosis project showed F1 scores of 80.18%, 97.40%, and 97.68% for mitosis, atypical, and typical mitosis layers, respectively. Overall F1 scores for the current results of the colon project were 90.02% for invasive carcinoma, 94.81% for the submucosa layer, and 98.02% for vessels and lymph nodes. After the training and optimization of the AI models and validation of each model, external validators evaluated the results of the AI models via blind-reader tasks. The AI models developed in this study were able to identify tumor foci, distinguish in situ areas, define colonic layers, detect vessels and lymph nodes, and catch the difference between atypical and typical mitosis. All results were exported for integration into our in-house applications for breast cancer and AI model development for both whole-block and whole-slide image-based 3D imaging assessment.

Glioblastoma is the commonest primary malignant brain tumor, with a very poor prognosis and short overall survival. It is characterized by its high intra- and intertumoral heterogeneity, in terms of both the level of single-nucleotide variants, copy number alterations, and aneuploidy. Therefore, routine diagnosis can be challenging in some cases. We present a complicated case of glioblastoma, which was characterized with five cytogenomic methods: interphase fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, comparative genomic hybridization array and single-nucleotide polymorphism, targeted gene panel, and whole-genome sequencing. These cytogenomic methods revealed classical findings associated with glioblastoma, such as a lack of IDH and TERT mutations, gain of chromosome 7, and loss of chromosome 10. At least three pathological clones were identified, including one with whole-genome duplication, and one with loss of 1p and suspected loss of 19q. Deletion and mutation of the TP53 gene were detected with numerous breakends on 17p and 20q. Based on these findings, we recommend a combined approach to the diagnosis of glioblastoma involving the detection of copy number alterations, mutations, and aneuploidy. The choice of the best combination of methods is based on cost, time required, staff expertise, and laboratory equipment. This integrated strategy could contribute directly to tangible improvements in the diagnosis, prognosis, and prediction of the therapeutic responses of patients with brain tumors.

Myeloid sarcoma (MS) occurs when primitive or naive myeloid cells form outside the bone marrow. It occurs mainly in soft/connective tissue and skin; orbital involvement is rare. We report the cases of two female adults, analyze the clinicopathologic characteristics, and review the literature. The average age of both patients was 28 years and they presented unilateral proptosis combined with varying degrees of impaired visual acuity and restricted ocular motility in the affected eye. Despite this, they maintained good overall health and no notable family history. However, the patients had no systemic clinical manifestations of acute myeloid leukemia (AML). Both patients underwent surgical resection of the orbital tumor. Immunohistochemistry showed positive staining for CD43, Leukocyte Common Antigen (LCA), and myeloperoxidase (MPO) and a high level of positive staining for Ki67, which were diagnostic for MS. Bone marrow cytology examination showed no apparent abnormalities. Postoperative chemotherapy, local radiotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) were performed in Case 1, while the second patient underwent adjuvant chemotherapy and radiotherapy. No recurrence or metastasis was found in either patient during follow-up (one more than 5 years, the other more than 10 years). The occurrence of orbital MS is infrequent, with atypical clinical and imaging findings. The diagnosis depends on pathomorphology and immunohistochemical staining, and the prognosis is good with postoperative adjuvant chemotherapy, local radiotherapy, and allo-HSCT.