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 fusions have not been reported in this tumor.

The topic of this meta-analysis is the comparison of gastric conduit esophageal reconstructions with or without pyloroplasty. 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. 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. Nine relevant RCTs consisting of 529 patients with esophageal cancer were identified. No significance was found in mortality [odds ratio (OR): 0.85; = 0.642], anastomosis leakage (OR: 0.57; = 0.254), respiratory morbidity (OR: 0.51; = 0.214) and vomiting (OR: 0.74; = 0.520), however the results about gastric emptying time (GET) were controversial (weighted mean difference (WMD): -67.71; = 0.009, OR: 2.75; = 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. We conclude that the pyloric drainage procedure is not routinely necessary, but further well-designed studies would be needed, especially in Europe.

Melanoma incidence is increasing globally. Although novel therapies have improved the survival of primary melanoma patients over the past decade, the overall survival rate for metastatic melanoma remains low. In addition to traditional prognostic factors such as Breslow thickness, ulceration, and mitotic rate, novel genetic and molecular markers have been investigated. In our study, we analyzed the expression of G-protein coupled estrogen receptor 1 (GPER1) and the endodomain of collagen XVII (COL17) in relation to clinicopathological factors in primary cutaneous melanomas with known lymph node status in both sexes, using immunohistochemistry. We found, that GPER1 expression correlated with favorable clinicopathological factors, including lower Breslow thickness, lower mitotic rate and absence of ulceration. In contrast, COL17 expression was associated with poor prognostic features, such as higher tumor thickness, higher mitotic rate, presence of ulceration and presence of regression. Melanomas positive for both GPER1 and COL17 had significantly lower mean Breslow thickness and mitotic rate compared to cases positive for COL17 only. Our data indicate that GPER1 and COL17 proteins may be of potential prognostic value in primary cutaneous melanomas.

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.

[This retracts the article DOI: 10.1007/s12253-018-00570-4.].

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 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 and 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 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.

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.

By 2021, the FDA approved the use of the drugs pembrolizumab and atezolizumab in the first-line treatment of patients with high positivity of programmed death ligand-1 (PD-L1) in locally advanced and metastatic non-small-cell-lung cancer (NSCLC). This approval was the result of statistically significant evidence from international, multicentric clinical studies that all reported increasing progression-free survival (PFS) and overall survival (OS) in these patients. In our study, we reported the demographic and clinical characteristics of 79 patients diagnosed with NSCLC with expression of PD-L1 ≥50% from January 2019 to December 2022 at the Institute for Pulmonary Diseases of Vojvodina, who received pembrolizumab therapy as the first-line treatment. Patients were divided according to the histological type of lung cancer as adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of the lung. In 52 of the 79 patients, PFS and in 32 of them overall survival (censored OS) was shown according to the histological type of tumor, the tumor proportion score (TPS) of PDL-1 expression, and the metastatic status within the Tumor Nodes Metastasis (TNM) disease classification. Independent factors of death outcome were shown by multivariable proportional hazard regression analysis. The study included 79 patients diagnosed with NSCLC with an expression of PD-L1 ≥50%, 50 (63.3%) patients with ADC, and 29 (36.7%) patients with SCC, whose 55 (69.6%) PDL-1 expression was obtained from broncho biopsy (BB). The majority of patients, 49 (62%), had a TPS PD-L1 score of 51%-79%. Median, PFS for adenocarcinoma was 22 months and censored OS was 27 months, while for squamous cell carcinoma, median PFS was 12 months, and censored OS was 21 months. M1b disease stage, which was the most common in patients, had a PFS of 16 months and a censored OS of 18 months. Pembrolizumab monotherapy in patients with NSCLC in the fourth stage of the disease and with the positivity of the immune checkpoint protein TPS PD-L1 above 50% represents a safe therapy that allows a satisfactory period without disease progression and overall survival with acceptable treatment complications.

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.

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.

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.

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.

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.

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 and genes proved to be the most common cause among our patients with 41.5%. Our test also detected a novel mutation in the gene and three patients with double heterozygosity in two different susceptibility genes. This study demonstrates the relevance of genetic counselling and non- 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.

Accurate lymph node (LN) retrieval during colorectal carcinoma resection is pivotal for precise N-staging and the determination of adjuvant therapy. Current guidelines recommend the examination of at least 12 mesocolic or mesorectal lymph nodes for accurate staging. Traditional histological processing techniques, reliant on visual inspection and palpation, are time-consuming and heavily dependent on the examiner's expertise and availability. Various methods have been documented to enhance LN retrieval from colorectal specimens, including intra-arterial methylene blue injection. Recent studies have explored the utility of indocyanine green (ICG) fluorescence imaging for visualizing pericolic lymph nodes and identifying sentinel lymph nodes in colorectal malignancies. This study included 10 patients who underwent colon resection for malignant tumors. During surgery, intravenous ICG dye and an endoscopic camera were employed to assess intestinal perfusion. Post-resection, intra-arterial administration of ICG dye was performed on the specimens, followed by routine histological processing and an ICG-assisted lymph node dissection. The objective was to evaluate whether ICG imaging could identify additional lymph nodes compared to routine manual dissection and to assess the clinical relevance of these findings. For each patient, a minimum of 12 lymph nodes (median = 25.5, interquartile range = 12.25, maximum = 33) were examined. ICG imaging facilitated the detection of a median of three additional lymph nodes not identified during routine processing. Metastatic lymph nodes were found in four patients however no additional metastatic nodes were detected with ICG assistance. Our findings suggest that intra-arterial administration of indocyanine green dye can augment lymph node dissection, particularly in cases where the number of lymph nodes retrieved is below the recommended threshold of 12.

Despite the availability of many novel therapies for multiple myeloma, it remains an incurable disease with relapse fated in almost all patients. In the era of modern agents, second autologous stem cell transplantation still holds its role in patients relapsing after first-line autologous transplant. The authors reviewed a single-center experience with a second auto-SCT for relapsed multiple myeloma. Thirty patients had received a salvage auto-SCT at the institution. The median follow-up after diagnosis was 86 months, and the median time between transplants was 59.1 months. Response before second ASCT was the following: CR - 11 cases, VGPR - 9 cases, PR - 10 cases. Most patients received reduced dose (140 mg/m2) of melphalan as a conditioning regimen for the second auto-SCT. Treatment-related mortality was 3%. With a median follow-up time of 34 months after the second transplant, median progression-free survival was 24 months. The median PFS in the patients achieving CR or VGPR at day 100 after the second transplantation was 32 months. By 15 months, all patients achieved only partial remission progressed, with a median PFS of 8.5 months. During the follow-up period, no MDS or AML developed, and the frequency of second malignancy was also low, 3%. In conclusion, second autologous stem cell transplantation is a well-tolerated and effective treatment option for relapsed multiple myeloma in selected patients, though with a shorter PFS than in first remission.

() gene amplification and subsequent protein overexpression is a strong prognostic and predictive biomarker in invasive breast carcinoma (IBC). ASCO/CAP recommended tests for HER2 assessment include immunohistochemistry (IHC) and/or hybridization (ISH). Accurate HER2 IHC scoring (0, 1+, 2+, 3+) is key for appropriate classification and treatment of IBC. HER2-targeted therapies, including anti-HER2 monoclonal antibodies and antibody drug conjugates (ADC), have revolutionized the treatment of HER2-positive IBC. Recently, ADC have also been approved for treatment of HER2-low (IHC 1+, IHC 2+/ISH-) advanced breast carcinoma, making a distinction between IHC 0 and 1+ crucial. In this focused study, 32 IBC with HER2 IHC scores from 0 to 3+ and HER2 FISH results formed a calibration dataset, and 77 IBC with HER2 IHC score 2+ and paired FISH results (27 amplified, 50 non-amplified) formed a validation dataset. H&E and HER2 IHC whole slide images (WSI) were scanned. Regions of interest were manually annotated and IHC scores generated by the software QuantCenter (MembraneQuant application) by 3DHISTECH Ltd. (Budapest, Hungary) and compared to the microscopic IHC score. H-scores [(3×%IHC3+) +(2×%IHC2+) +(1×%IHC1+)] were calculated for semi-automated (MembraneQuant) analysis. Concordance between microscopic IHC scoring and 3DHISTECH MembraneQuant semi-automated scoring in the calibration dataset showed a Kappa value of 0.77 (standard error 0.09). Microscopic IHC and MembraneQuant image analysis for the detection of amplification yielded a sensitivity of 100% for both and a specificity of 56% and 61%, respectively. In the validation set of IHC 2+ cases, only 13 of 77 cases (17%) had discordant results between microscopic and MembraneQuant images, and various artifacts limiting the interpretation of HER2 IHC, including cytoplasmic/granular staining and crush artifact were noted. Semi-automated analysis using WSI and microscopic evaluation yielded similar HER2 IHC scores, demonstrating the potential utility of this tool for interpretation in clinical practice and subsequent accurate treatment. In this study, it was shown that semi-automatic HER2 IHC interpretation provides an objective approach to a test known to be quite subjective.

Herein, we detail a multidisciplinary approach and sequential treatment for two infants with congenital granular cell epulis (CGCE). Ultrasonic examinations at 34 weeks of gestation revealed prominent oral masses in both fetuses. To devise a carefully considered treatment strategy, a comprehensive multidisciplinary consultation including oral and maxillofacial surgeons, pediatricians, obstetricians, and anesthesiologists was convened. Following cesarean sections, the lesions were successfully removed, measuring approximately 30 × 15 mm and 30 × 20 mm in size, respectively. Immunohistochemical analysis showed that vimentin was positive, S-100 protein was negative, and NSE protein and CD68 protein were negative. These findings underscore the importance of prenatal diagnosis of congenital granular cell epulis for the effective management of these rare benign conditions.

Castleman disease is a rare and atypical lymphoproliferative disorder characterized by diverse clinical manifestations. It has both unicentric and multicentric forms, the latter with further subdivisions, i.e., human herpesvirus 8-associated and idiopathic forms. The diagnosis of Castleman disease is often delayed, as it is rare, and because it shares clinical features with different autoimmune, inflammatory, and malignant lymphoproliferative disorders. The first-line treatment in unicentric form is mainly surgical, while in idiopathic Castleman disease, anti-interleukin-6 treatment is the therapy of choice. In virus-associated diseases, antiretroviral therapy and rituximab are recommended. In Hungary, only a few cases of Castleman disease have been published. This report presents our two decades of experience in the challenging diagnosis and management of this rare disorder, most properly underdiagnosed in Hungary. We provide insights into seven unicentric and five idiopathic multicentric Castleman disease cases, the latter ones especially highlighting the diagnostic and therapeutic challenges due to the variable and unique clinical features both of patients and diseases, e.g., bronchiolitis obliterans, stage IV diabetic renal failure, anti-HBc positivity, siltuximab treatment period, respectively.

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

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 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.