Pathology & Oncology Research最新文献

Plasma cell enrichment plays a pivotal role in the accurate prognosis and molecular characterization of multiple myeloma. The separation is commonly carried out by positive cell selection using CD138 monoclonal antibody conjugated to magnetic beads. Optimally, during the separation procedure, the cells should neither be damaged, nor should their phenotype be significantly altered, as these changes would falsify the results if the isolated cells were subsequently used. For this reason, we investigated the expression patterns of different surface markers by flow cytometry before and after magnetic isolation using bone marrow or peripheral blood samples from 12 patients with plasma cell disorders. The selected markers are not only used as backbone markers in routine diagnostics (CD19, CD38, CD45, CD117, and CD138), but they also play an important role in cell adhesion and connection with microenvironment (CD44, CD49d, CD56, and CD81) or possibly drug resistance (CD69, CD86, and CD184), making them promising targets for myeloma research. Moreover, we examined the effects of separation on cell viability in 8 cases. The intensities of 8 out of the 12 investigated markers were slightly influenced, while CD138, CD38, CD56, and CD184 were changed significantly, however the immunophenotype of the cells was not changed. Positive markers remained positive and negative ones remained negative after the separation procedure. In addition, the number of apoptotic plasma cells was significantly reduced during separation, facilitating further examination of the cells. Our results showed that magnetic isolation can be considered as a reliable option but the immunophenotype of plasma cells should be validated after the separation if the intensities of the markers are important for further experiments.

Purpose: To clarify the prognostic value of lymph node regression (LNR) status including the lymph node regression grade (LNRG) and N downstaging in patients with esophageal cancer receiving neoadjuvant therapy based on available evidence.

Methods: Several databases were searched up to 25 March 2024. The main outcomes included overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined. Subgroup analyses based on the neoadjuvant therapy and pathological type were also conducted.

Results: In total, 14 retrospective studies with 3,212 participants were included. Nine and five studies explored the relationship between LNRG and N downstaging and survival, respectively. Pooled results indicated that complete LNR predicted significantly improved OS (HR = 0.47, 95% CI: 0.41-0.55, P < 0.001) and DFS (HR = 0.42, 95% CI: 0.32-0.55, P < 0.001) and subgroup analysis based on neoadjuvant therapy and pathological type manifested similar results. Besides, N downstaging was also significantly related to improved OS (HR = 0.40, 95% CI: 0.21-0.77, P = 0.006) and CSS (HR = 0.27, 95% CI: 0.12-0.60, P < 0.001).

Conclusion: LNR could serve as a novel and reliable prognostic factor in patients with esophageal cancer receiving neoadjuvant therapy and complete LNR and N downstaging predict better survival.

Background and objectives: Pancreatic cysts have various potential for malignant transformation. Differentiating mucinous from non-mucinous cysts is crucial to make the right decision about further management, since mucinous cysts carry the risk of malignancy. Using endoscopic ultrasound (EUS) guided fine needle aspiration to determine intracystic carcinoembryonic antigen (CEA) levels is the recommended method for identifying mucinous cysts, although intracystic glucose assessment has also proved to be an effective tool. This study aims to compare the diagnostic performance of intracystic glucose and CEA in distinguishing between mucinous and non-mucinous pancreatic cystic lesions.

Methods: In this single center study, we prospectively collected and analyzed the data of 91 consecutive patients who underwent endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with cytological analysis and measurement of intracystic CEA and glucose levels. The cyst type was classified based on radiological and EUS morphology, string sign, CEA, cytological and histological findings in resected cases. The diagnosis was established retrospectively by three experienced gastroenterologists blinded for glucose level in cases without definitive cytology or histology. We calculated the sensitivity, specificity, the positive- and negative predictive value of glucose and CEA respectively, and compared the two methods.

Results: The sensitivity of intracystic glucose versus CEA proved to be 96.2% vs. 69.2% in identifying mucinous cysts, while the specificity of glucose was shown to be 79.5%, compared to 100% for CEA.

Conclusion: Intracystic glucose is a sensitive, easily accessible biomarker in identifying mucinous pancreatic cysts, however, the specificity is lower compared to CEA. The measurement of intracystic glucose level could help in decision-making in daily clinical practice, however the diagnostic performance of the method remains inferior to "through-the-needle" techniques, such as confocal laser endomicroscopy and Moray forceps biopsy.

Cyclic thrombocytopenia (CTP) is a rare disease characterized by the oscillations seen in the platelet count of the patients. The pathomechanism of the disease is poorly understood, several pathological processes have been implied in the background of CTP. In our current study, we aimed to thoroughly investigate the case of a 41-year-old female patient with a 22-year history of CTP. Wide-ranging laboratory testing, histological analyses and genetic investigations were carried out to investigate all the defects and alterations of physiological pathways described in the background of CTP to date. Bone marrow biopsy showed normal hemopoiesis with the abundance of megakaryocytes, some of which displayed hypolobulated nuclei. T-cell receptor rearrangement studies showed a polyclonal pattern with no indication of a monoclonal cell population. Flow cytometric assessment of the platelets revealed large number of immature platelets and decreased expression of glycoprotein IIb and IIIa at platelet zenith. Increased expression of glycoprotein IIb, IIIa and glycoprotein Ib-IX complex was observed at the nadir of the cycle. Whole exome sequencing revealed a heterozygous missense variant of uncertain significance in the SERPINC1 gene, which has been associated with hereditary antithrombin deficiency. The screening of autoantibodies did not reveal signs of autoreactive processes, and no thyroid dysfunction was found. Furthermore, synchronization with the menstrual cycle could not be concluded based on our patient's case. With our results we contribute to the very limited data known about the long-term course of the disease and provide valuable insights into the genetic architecture of CTP.

Advanced melanoma is considered the most aggressive and deadly form of skin cancer whose incidence has been rising over the past three decades. In the absence of treatment, the median overall survival for advanced-stage metastatic disease is less than 6 months. Although most melanomas detected at an early stage can be cured with surgery, a subset of these eventually metastasize. Therefore, a critical need exists to identify unique molecular features that would be predictive of long-term outcome and response to specific therapies. Recent promising therapeutic regimens have included the use of immune checkpoint inhibitors, such as anti-PD1 antibodies. However, the ability to identify responders and non-responders to this therapy remains elusive. To address this challenge at the molecular level, previously our laboratory identified the emergence of a stem cell phenotype associated with advanced melanoma and other aggressive forms of cancer. Underlying this phenotype is the aberrant re-expression of the embryonic morphogen "Nodal". Particularly noteworthy, we have observed Nodal to remain in advanced tumors of non-responders to standard-of-care therapies (i.e., BRAFi). This pilot study is the first proof-of-principle attempt to predict treatment response survival outcome in a small cohort of melanoma patients receiving anti-PD1 immune checkpoint inhibitor therapy - based on their Nodal expression profile. Using advanced multiplex immunohistochemistry-based digital pathology, the major finding of this preliminary study indicates that higher Nodal expression is often associated with poorer overall survival after anti-PD1 therapy, reaching nearly statistical relevance.

Background: Since the seminal publication of the TCGA consortium in 2013, the molecular classification of endometrial cancer has been widely accepted as a new and powerful tool to better understand the natural history of this malignancy. Adoption of routine molecular classification around the world has been limited. We sought to demonstrate our initial experience in incorporating the four molecular subtypes for endometrioid carcinomas.

Methods: This was a retrospective analysis at a single center in Portugal. Molecular classification was determined using immunohistochemical staining for MMR and p53 and Sanger Sequencing to determine POLE mutation status as per published PROMISE method. Descriptive statistics were reported.

Results: 20 patients with endometrioid histology were included. Median age of the cohort was 64 years (range 45-76). Median Body Mass Index (kg/m²) was 29.81 (range 21.3-43.1). In terms of tumor grading, 16 (80%) of the endometrial carcinomas of the cohort were low-grade (either grade 1 or grade 2). 16 (80%) of the cases were FIGO stage I. Regarding the molecular classification the tumors were classified as: MMRd [n = 6 (30%)]; p53 abn [n = 2 (10%)]; NSMP (n = 10 (50%)), POLE ultramut [n = 2 (10%)].

Conclusion: Despite the small sample size, we were able to show that molecular classification is feasible. To our knowledge this is the first cohort of endometroid endometrial carcinomas fully characterized according to the TCGA classification in Portugal, from one single center.

Objective: The topic of this meta-analysis is the comparison of gastric conduit esophageal reconstructions with or without pyloroplasty. Background: Surgical procedures, especially minimal invasive esophagectomy (MIE) can be a curative treatment in the early stages of esophageal cancer. Previously, intraoperative pyloroplasty was routinely performed, but nowadays it became debated again in the light of minimally invasive esophagectomy. Methods: A comprehensive search was performed in multiple databases to identify randomized controlled trials investigating the topic. Two independent authors performed the selection based on predefined criteria. Statistical analysis was performed to assess any significant difference, then the bias and quality of the data were estimated. Results: Nine relevant RCTs consisting of 529 patients with esophageal cancer were identified. No significance was found in mortality [odds ratio (OR): 0.85; p = 0.642], anastomosis leakage (OR: 0.57; p = 0.254), respiratory morbidity (OR: 0.51; p = 0.214) and vomiting (OR: 0.74; p = 0.520), however the results about gastric emptying time (GET) were controversial (weighted mean difference (WMD): -67.71; p = 0.009, OR: 2.75; p = 0.072). Significant heterogeneity was not detected except for GET. Trial sequential analyses (TSA) show that a certain conclusion would require more data except in the binary variables of GET. Conclusion: We conclude that the pyloric drainage procedure is not routinely necessary, but further well-designed studies would be needed, especially in Europe.

Introduction: Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma that occurs at widespread anatomical locations, such as bone, soft tissue, and intracranial sites. The central nervous system (CNS) is one of the most common origins of extraosseous MCS. However, alternative HEY1::NCOA2 fusions have not been reported in this tumor.

Case report: We report a case of intracranial MCS with HEY1::NCOA2 rearrangement. A 52-year-old woman presented with a 15-mm calcified mass around the sella turcica. She initially underwent transsphenoidal surgery for tumor resection and then additional resections for five local recurrences over 5 years. Histologically, the tumor was composed of small round to spindle-shaped cells admixed with well-differentiated hyaline cartilaginous islands. A hemangiopericytoma-like vascular pattern and small sinusoid-like vessels were also observed. RNA sequencing using RNA extracted from formalin-fixed paraffin-embedded samples from the last operation revealed two alternative variants of the HEY1::NCOA2 fusion: HEY1(ex4)::NCOA2 (ex13) and HEY1(ex4)::NCOA2(ex14). Both variants were confirmed as in-frame fusions using reverse transcription-polymerase chain reaction.

Discussion: Cartilaginous components were often not apparent during the recurrences. In addition to the non-typical pathological finding, the correct diagnosis was hampered by the poor RNA quality of the surgical specimens and non-specific STAT6 nuclear staining.

Conclusion: This is the first reported case of intracranial MCS with an alternative HEY1::NCOA2 fusion.

Hereditary breast and ovarian cancer is a well-known genetic condition, inherited mainly in an autosomal dominant way, which elevates the risk of developing malignancies at a young age in heterozygous carriers. Advances in new generation sequencing have enabled medical professionals to determine whether a patient is harbouring mutations in moderate- or high penetrance susceptibility genes. We conducted a retrospective analysis among 275 patients who underwent genetic counselling and multigene panel testing for hereditary breast and ovarian cancer syndrome in our department. From these patients 74.5% (205/275) were affected by some type of malignancy, while the remaining 25.5% (70/275) had a positive family history of different cancers, suggesting a genetic predisposition. These tests confirmed a genetic variant in 29.8% and 28.6% of these patient groups respectively. The results also mirrored our general knowledge concerning the genetic background of hereditary breast and ovarian cancer, as variants in either one of the BRCA1 and BRCA2 genes proved to be the most common cause among our patients with 41.5%. Our test also detected a novel mutation in the CDH1 gene and three patients with double heterozygosity in two different susceptibility genes. This study demonstrates the relevance of genetic counselling and non-BRCA gene sequencing among cancer patients and patients who fulfil the criteria for genetic testing, while also providing important details about the genetic profile of Hungarian patients.

[This corrects the article DOI: 10.3389/pore.2024.1611735.].