A Successful Treatment of Broncho-Esophageal Fistula with Esophageal Stenting Using Direct Endoscopic Visualization.

Broncho-esophageal fistula (BEF) is a severe yet relatively rare connection between the bronchus and esophagus usually caused by esophageal and pulmonary malignancies. We present a case report of a 49-year-old man diagnosed with terminal lung carcinoma who developed a BEF. The thoracic computed tomography scan detected a mass in the left bronchi that partially covers and disrupts the bronchial contour in certain regions and extends to the esophageal wall. After thoroughly evaluating alternative treatment approaches, we opt for the stenting procedure due to the advanced stage of the tumor and the significantly diminished quality of life. The treatment involves the use of a partially covered metal stent that is known to exhibit lower potential to migrate. The treatment is highly successful, resulting in a significant enhancement of the patient's quality of life, a lengthening in his survival, and the ability to pursue additional palliative treatment options. In contrast to the typical prosthesis implantation, our procedure uses a direct endoscopic visualization for the proximal deployment of a partially covered stent, offering a cost-effective and radiation-free alternative that can be particularly beneficial for BEF patients in facilities without radiology services.

Collision Tumors of the Colon and Peritoneum: Signet-Ring Cell Carcinoma and Granular Cell Tumor.

Collision tumors, although rare, characterized by two distinctive (morphological, as well immunohistochemical) and spatially independent tumor components at the same location, are always puzzling for clinicians, pathologists, and patients because they do not fit into the usual approaches, being neither diagnostic nor therapeutic. Reviewing the specialized literature, to date, collision tumors have been reported in multiple locations such as the skin, esophagus, stomach, intestine, liver, kidney, bladder, adrenal gland, or thyroid. We report a case of coexistence at the same site of a malignant tumor of the ascending colon and a benign tumor emerging from the peritoneal lining, initially thought by the surgeon to be right-sided serosal carcinomatosis. But histopathological examination reveals that those multiple serosal nodules were benign granular cell tumors that have collided with highly aggressive transparietal signet-ring colon carcinoma. These results put the patient's prognosis and therapeutic strategy in a different light than the clinical and intraoperative evaluation.

Colorectal Carcinomas: Searching for New Histological Parameters Associated with Lymph Node Metastases.

Background and Objectives: Colorectal cancer (CRC) continues to be an essential public health problem. Our study aimed to evaluate the prognostic significance of classic prognostic factors and some less-studied histopathological parameters in CRC. Materials and Methods: We performed a retrospective study on 71 colorectal carcinoma patients who underwent surgery at the "Pius Brînzeu" County Clinical Emergency Hospital in Timișoara, Romania. We analyzed the classic parameters but also tumor budding (TB), poorly differentiated clusters (PDCs) of cells, tumor-infiltrating lymphocytes (TILs), and the configuration of the tumor border on hematoxylin-eosin slides. Results: A high degree of malignancy (p = 0.006), deep invasion of the intestinal wall (p = 0.003), an advanced stage of the disease (p < 0.0001), lymphovascular invasion (p < 0.0001), perineural invasion (p < 0.0001), high-grade TB (p < 0.0001), high-grade PDCs (p < 0.0001), infiltrative tumor border configuration (p < 0.0001) showed a positive correlation with lymph node metastases. Conclusions: The analyzed parameters positively correlate with unfavorable prognostic factors in CRC. We highlight the value of classic prognostic factors along with a series of less-known parameters that are more accessible and easier to evaluate using standard staining techniques and that could predict the risk of relapse or aggressive evolution in patients with CRC.

Invasive Cutaneous Melanoma: Evaluating the Prognostic Significance of Some Parameters Associated with Lymph Node Metastases.

Background and Objectives: This study aimed to assess the clinical-pathological profile of patients with invasive cutaneous melanomas and to identify the parameters with a prognostic role in the lymph nodal spread of this malignant tumor. Materials and Methods: We performed a retrospective study on patients with invasive cutaneous melanomas who underwent surgery in the "Pius Brînzeu" County Clinical Emergency Hospital from Timișoara, Romania, and were evaluated for the status of loco-regional lymph nodes. We selected and analyzed some parameters searching for their relationship with lymph node metastases. Results: We identified 79 patients with invasive cutaneous melanomas (29 men and 50 women, mean age 59.36 years). A percentage of 58.3% of melanomas had Breslow tumor thickness >2 mm; 69.6% of melanomas showed a Clark level IV-V. Tumor ulceration was present in 59.5% of melanomas. A mitotic rate of ≥5 mitoses/mm2 was observed in 48.1% of melanomas. Tumor-infiltrating lymphocytes (TILs), non-brisk, were present in 59.5% of cases and 22.8% of patients had satellite/in-transit metastasis (SINTM). Tumor regression was identified in 44.3% of cases. Lymph nodes metastases were found in 43.1% of patients. Statistical analysis showed that lymph node metastases were more frequent in melanomas with Breslow thickness >2 mm (p = 0.0002), high Clark level (p = 0.0026), mitotic rate >5 mitoses/mm2 (p = 0.0044), ulceration (p = 0.0107), lymphovascular invasion (p = 0.0182), SINTM (p = 0.0302), and non-brisk TILs (p = 0.0302). Conclusions: The Breslow thickness >2 mm, high Clark level, high mitotic rate and ulceration are the most important prognostic factors for lymph nodal spread in cutaneous melanomas. However, some melanomas without these clinical-pathological features can have an unexpected, aggressive evolution, which entails the necessity of close and prolonged clinical follow-up of patients, including those with lesions considered without risk.

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.

Diagnosis of malignant biliary obstruction: pondering over the ERCP, MRCP and histology.

OBJECTIVE: To compare the diagnostic accuracy of endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance pancreatography (MRCP) and histological examination for malignant biliary obstruction. METHODS: This retrospective study included patients admitted for biliary obstruction caused by biliary tree malignancy that underwent ERCP, MRCP and histological examination. Data were collected from the medical records. The primary endpoints were the area under the receiver operating characteristic (AUROC) curve value, sensitivity, specificity and overall diagnostic accuracy of the three procedures in terms of a final diagnosis of obstructive biliary malignancy; and the agreement between ERCP, MRCP and histological examination with the final diagnosis. RESULTS: A total of 160 patients were included in the study (85 males, 53.1%; mean ± SD age, 69.31 ± 10.96 years). Considering the final diagnosis, the performance of MRCP, ERCP and histology in assessing biliary tumours produced AUROC values of 0.88 (95% confidence interval [CI] 0.75, 0.90), 0.94 (95% CI 0.85, 0.99) and 0.80 (95% CI 0.70, 0.82), respectively. ERCP presented higher sensitivity, overall diagnostic accuracy and agreement with the final diagnosis than MRCP and histological examination. CONCLUSION: These current data suggest that invasive methods such as ERCP with biopsy remain more reliable than non-invasive methods.

Three-Dimensional Virtual Pathology Specimens: Decrease in Student Performance upon Switching to Digital Models.

Several alternatives to formalin-stored physical specimens have been described in medical literature, but only a few studies have addressed the issue of learning outcomes when these materials were employed. The aim of this study was to conduct a prospective controlled study to assess student performance in learning anatomic pathology when adding three-dimensional (3D) virtual models as adjunct teaching materials in the study of macroscopic lesions. Third-year medical students (n = 501) enrolled at the Victor Babes University of Medicine and Pharmacy in Timisoara, Romania, were recruited to participate. Student performance was assessed through questionnaires. Students performed worse with new method, with poorer results in terms of overall (mean 77.6% ±SD 11.8% vs. 83.6% ±10.5) and individual question scores (percentage of questions with maximum score 34.6% ±25.6 vs. 47.7 ± 24.6). This decreased performance was generalizable, as it was observed across all language divisions and was independent of the teaching assistant involved in the process. In an open-ended feedback evaluation of the new 3D specimens, most students agreed that the new method was better, bringing arguments both for and against these models. Although subjectively the students found the novel teaching materials to be more helpful, their learning performance decreased. A wider implementation as well as exposure to the technique and use of virtual specimens in medical teaching could improve the students' performance outcome by accommodating the needs for novel teaching materials for digital natives.

Poorly differentiated clusters and tumor budding are important prognostic factors in colorectal carcinomas.

The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - TB (GBd) and poorly differentiated clusters - PDCs (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timișoara. CRC cases were classified based on haematoxylin-eosin slides, using the conventional grading system, GBd and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently,  we evaluated  associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t)  most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p<0.0001), tumor stage (p=0.0003), lymphovascular invasion (p<0.0001), perineural invasion (p=0.005) and the tumor border configuration (p<0.0001). High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC.Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.

Opportunistic Colonoscopy Cancer Screening Pays off in Romania-A Single-Centre Study.

Colorectal cancer (CRC) is the third most diagnosed cancer in men (after prostate and lung cancers) and in women (after breast and lung cancer). It is the second cause of cancer death in men (after lung cancer) and the third one in women (after breast and lung cancers). It is estimated that, in EU-27 countries in 2020, colorectal cancer accounted for 12.7% of all new cancer diagnoses and 12.4% of all deaths due to cancer. Our study aims to assess the opportunistic colorectal cancer screening by colonoscopy in a private hospital. A secondary objective of this study is to analyse the adenoma detection rate (ADR), polyp detection rate (PDR), and colorectal cancer (CRC) detection rate. We designed a retrospective single-centre study in the Gastroenterology Department of Saint Mary Hospital. The study population includes all individuals who performed colonoscopies in 2 years, January 2019-December 2020, addressed to our department by their family physician or came by themselves for a colonoscopy. One thousand seven hundred seventy-eight asymptomatic subjects underwent a colonoscopy for the first time. The mean age was 59.0 ± 10.9, 59.5% female. Eight hundred seventy-three polyps were found in 525 patients. Five hundred and twenty-five had at least one polyp, 185 patients had two polyps, 87 had three polyps, and 40 patients had more than three polyps. The PDR was 49.1%, ADR 39.0%, advanced adenomas in 7.9%, and carcinomas were found in 5.4% of patients. In a country without any colorectal cancer screening policy, polyps were found in almost half of the 1778 asymptomatic patients evaluated in a single private center, 39% of cases adenomas, and 5.4% colorectal cancer. Our study suggests starting screening colonoscopy at the age of 45. A poor bowel preparation significantly impacted the adenoma detection rate.

Immunohistochemical expression of chemokine receptor in neuroendocrine neoplasms (CXCR4) of the gastrointestinal tract: a retrospective study of 71 cases.

AIM: C-X-C motif chemokine receptor 4 (CXCR4) is expressed in many tumor entities, including gastrointestinal neuroendocrine neoplasms (GI-NENs). However, the role of CXCR4 expression in GI-NENs has been less studied. Our objective was to investigate the expression of CXCR4 in a series of GI-NENs with various clinical and pathological features. METHODS: The immunohistochemical (IHC) expression of CXCR4 (clone UMB2) was examined in 71 GI-NENs and a semiquantitative immunoreactivity score (IRS) was calculated taking into consideration the intensity of the IHC reaction and the percentage of the tumor cells which showed positive expression. Results were compared with several clinical and pathological prognostic factors. RESULTS: High CXCR4 expression was noted in 31 (43.7%) cases. Low IRS values were more frequent in NENs from the small intestine (66.7%) and stomach (60%). Also, all appendix tumors had IRS value of zero. High CXCR4 expression was noticed in 52.5% of liver metastases, compared to 40.4% primary tumors. A significant relationship was observed between the CXCR4 expression and the tumor grade (p=0.0216), and high IRS value was correlated with clinical stages III and IV (p=0.0142) and lympho-vascular invasion (p=0.0129). 74.1% of G1 neuroendocrine tumors (NETs) had a low IRS, G3 NETs showed minor differences between low (42.9%) and high (57.1%) expression and 66.7% of neuroendocrine carcinomas (NECs) presented high expression of CXCR4. CONCLUSIONS: The present study highlighted that high CXCR4 expression is associated with high grade and advanced stage GI-NENs, as well as with metastatic cases. In these cases, high CXCR4 expression could serve as an important target for CXCR4 antagonists.

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5.

The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed neuroendocrine-non-neuroendocrine tumors (MiNENs) and classifies goblet cell carcinoid as goblet cell adenocarcinoma. The expression of somatostatin receptors (SSTRs) is the foundation for somatostatin analogue therapy. At present, there are only a few studies that have analyzed the immunohistochemical reactivity of SSTRs in gastrointestinal neuroendocrine neoplasms (NENs). The aim of the present study was to evaluate the immunohistochemical expression of SSTR2 and SSTR5 in gastrointestinal NENs and goblet cell adenocarcinomas and the correlation of these markers with clinical and morphological factors. The study included 67 patients with NENs and 4 patients with adenocarcinoma ex-goblet cell carcinoid diagnosed between January 2008 and December 2018. Tumors were reclassified according to the 2019 WHO classification. Immunohistochemical staining for chromogranin A, synaptophysin, Ki-67, p53, SSTR2, and SSTR5 were performed in all the cases. The results showed that, G1 and G2 neuroendocrine tumors were more common SSTR2-positive in comparison with G3 carcinomas (P<0.0001). In addition, 33.3% of neuroendocrine carcinomas and 2 cases of low-grade adenocarcinoma ex-goblet cell carcinoid were SSTR2-positive. Neuroendocrine carcinomas had significantly lower SSTR2 and SSTR5 expression compared with well-differentiated neuroendocrine tumors (P=0.0130; P=0.0437, respectively). The SSTR2 expression in the early tumor stages was 100%, more often than in advanced stages (55.6%; P=0.0011). The results demonstrated the decrease in SSTR2 expression with increasing malignancy and tumor stage. The SSTR2-positive expression in neuroendocrine carcinomas and adenocarcinoma ex-goblet cell carcinoid provides evidence for the benefits of somatostatin analog treatment associated with surgery and chemotherapy.

Multiple Primary Tumors Originating From the Prostate and Colorectum A Clinical-Pathological and Therapeutic Challenge.

Considering that the incidence of colorectal (CRC) and prostatic cancer (PC) increases with age, metachronous and synchronous tumors can often affect the same patient. Despite the importance of this subject for the diagnosis and management of oncologic patients, in medical literature the data are scarce. The aim of the study was to evaluate the incidence and the characteristics of double/multiple primary malignant tumors (D/MPMTs) with colorectal and prostatic origin, in patients admitted to a reference hospital in West Romania. A 4-year retrospective observational study (2016-2019) was conducted by analyzing the medical records of all patients admitted in the hospital. Demographic and clinical data, as well as tumor-related parameters, were extracted. We identified 413 consecutive hospitalized patients with PC, and 21 (5%) of them also had a primary CRC. At the time of diagnosis, the mean age of the patients with PC was 71.2 ± 6 years, and 71.8 ± 10 years for patients with CRC. Synchronous PC and CRC tumors were identified in 3/21 cases and metachronous tumors in 18/21 cases. Prostate cancer was the first tumor to be diagnosed in 13/18 cases and CRC in 5/18 cases. The most frequent subtype of PC was acinar adenocarcinoma (90%) and for CRC cases, conventional adenocarcinoma (90%). Prostate and colorectal cancers tend to co-occur in a single patient. The diagnosis of one of these two types of tumors should imply the screening for the other one, because these patients require a multidisciplinary and personalized approach.

Sclerosing Extramedullary Hematopoietic Tumor (SEHT) Mimicking a Malignant Bile Duct Tumor-Case Report and Literature Review.

Introduction: Sclerosing Extramedullary Hematopoietic Tumor (SEHT) is a very rare lesion associated with chronic myeloproliferative disorders (CMPD). SEHT can mimic morphologically, both macroscopically and microscopically, a wide variety of tumors/lesions. Case presentation: We present the case of a female patient diagnosed with gallstones for which surgery was decided. Intraoperatively, a malignant tumor of extrahepatic bile ducts was suspected. A frozen section examination raised the suspicion of a mesenchymal tumor or an inflammatory pseudotumor. The histological evaluation of the permanent sections, supplemented with an immunohistochemical investigation (IHC), was the one that established the diagnosis of SEHT, based on the presence of areas of sclerosis, atypical CD31+ megakaryocytes, myeloid and erythroid elements. Conclusions: The authors present the difficulties of a morphological diagnosis on the frozen section and on permanent sections in the absence of relevant clinical information and make a review of the literature data dedicated to the subject.

Different disease characteristics in young patients with colorectal cancer: a large retrospective study in a city in Romania.

OBJECTIVE: In 2018, colorectal cancer (CRC) was the second most frequent malignancy in Romania after lung cancer. Although CRC is typically encountered in patients >50 years old, CRC's global incidence among younger adults has been increasing. We aimed to compare the disease characteristics of patients with CRC aged ≤50 years with those >50 years old. METHODS: We retrospectively evaluated data from patients with CRC who underwent standard surgery at "Pius Brinzeu" Emergency County Hospital, Timisoara, Romania. Patients were divided into two groups: Group 1 (patients ≤50 years old) and Group 2 (patients >50 years old). Six parameters were analyzed (sex, residence location, age, tumor localization, microscopic findings, pathological staging). RESULTS: Data on age-related CRC were available for 1380 patients treated from January 2012 to December 2018. Group 1 included 120 patients while group 2 included 1260 patients. Significantly more Group 1 patients presented with advanced CRC compared with Group 2 patients (94.2% vs. 87.4%). Furthermore, CRC in younger adults was more likely to be diagnosed at an advanced stage. CONCLUSIONS: Monitoring the CRC incidence in younger adults is essential to assess whether screening practices require changes and to raise awareness among clinicians of the increasing CRC incidence among younger patients.

Unexpected diagnosis for a gastric polyp: Granular cell tumor: Case report and review of the literature.

A granular cell tumor (GCT) is a rare neoplasia that originates from Schwann cells. It usually appears in the skin or soft tissues, but it may occur anywhere in the body. The gastrointestinal tract is an unusual developmental site for a GCT, the esophagus being the most common site of origin for this tumor. The stomach is one of the most unique sites of origin for GCT, with less than 80 cases being mentioned in the literature. Histologically, GCTs consist of fusiform and polygonal cells, with granular cytoplasm, arranged in compact 'nests'. Immunohistochemically, these tumors show positivity for S100 protein, CD68, CD56 and, in a smaller percentage, they are positive for other antibodies, most notably inhibin alpha. We report the case of a 52-year-old woman with a solitary GCT that had developed in the gastric cardia, discovered on a routine gastroscopy and successfully treated by endoscopic submucosal dissection.

The Impact of Artificial Intelligence in the Endoscopic Assessment of Premalignant and Malignant Esophageal Lesions: Present and Future.

In the gastroenterology field, the impact of artificial intelligence was investigated for the purposes of diagnostics, risk stratification of patients, improvement in quality of endoscopic procedures and early detection of neoplastic diseases, implementation of the best treatment strategy, and optimization of patient prognosis. Computer-assisted diagnostic systems to evaluate upper endoscopy images have recently emerged as a supporting tool in endoscopy due to the risks of misdiagnosis related to standard endoscopy and different expertise levels of endoscopists, time-consuming procedures, lack of availability of advanced procedures, increasing workloads, and development of endoscopic mass screening programs. Recent research has tended toward computerized, automatic, and real-time detection of lesions, which are approaches that offer utility in daily practice. Despite promising results, certain studies might overexaggerate the diagnostic accuracy of artificial systems, and several limitations remain to be overcome in the future. Therefore, additional multicenter randomized trials and the development of existent database platforms are needed to certify clinical implementation. This paper presents an overview of the literature and the current knowledge of the usefulness of different types of machine learning systems in the assessment of premalignant and malignant esophageal lesions via conventional and advanced endoscopic procedures. This study makes a presentation of the artificial intelligence terminology and refers also to the most prominent recent research on computer-assisted diagnosis of neoplasia on Barrett's esophagus and early esophageal squamous cell carcinoma, and prediction of invasion depth in esophageal neoplasms. Furthermore, this review highlights the main directions of future doctor-computer collaborations in which machines are expected to improve the quality of medical action and routine clinical workflow, thus reducing the burden on physicians.

Prostate carcinomas mimicking a digestive malignancy.

AIM: To report our experience with specific cases of prostate cancer (PC) in which patients presented digestive symptoms, cases that represent a challenge and a source of error regarding the clinical and morphological diagnosis. METHODS: The most important clinical and pathological data were collected from three patients with PC which presented symptoms and/or investigations that initially suggested a digestive malignant tumor. RESULTS: We identified three patients with PC where the prostate tumor was not suspected based on the clinical-imagistic data, the correct diagnosis being the prerogative of the morphological investigation: in the first case, PC was detected during the microscopic examination of the lymph nodes (LN) in the intestinal resection specimen performed for suspected rectal cancer (RC), in the second case, in which the PC was synchronous with a RC, the dominant symptomatology was gastrointestinal, and in the third case, initially, the patient presented a widely disseminated PC, with pleural and bone metastases, as well as LN metastases, and apparent peritoneal involvement. CONCLUSIONS: Unusual forms of PC presentation are not as rare as expected and should be acknowledged by all those involved in diagnosing this neoplasm. PC should always be considered in the differential diagnosis of a rectal tumor. The immunohistochemical (IHC) investigation is essential for establishing the diagnosis in difficult cases. An integrated approach of the interpretation of clinical manifestations, imagistic and serological changes would shorten the diagnostic time and help reduce diagnostic errors.

Clear cell urothelial carcinoma of the urinary bladder - a rare pathological entity. A case report and a systematic review of the literature.

The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). In contrast, the clear cell variant of urothelial carcinoma (CCUC) is quite a rare neoplasm. In this study, we report a case of an 81-year-old male, presenting with gross hematuria and acute urinary retention, which was subsequently diagnosed with CCUC at our pathology department. Furthermore, we provide a short systematic review of the literature (PubMed, Scopus, and Science Citation Index) for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.

Poorly differentiated clusters: prognostic significance in colorectal carcinomas immunohistochemistry images.

Colorectal cancer (CRC) remains a major public health burden worldwide, despite increased knowledge on its pathogenesis and advances in therapy. We aimed to evaluate a new histological grading system based on poorly differentiated clusters (PDCs) counting - the PDCs grade (PDCs-G), and its clinicopathological and prognostic significance, compared to the World Health Organisation (WHO) grading system (WHO grade). We reviewed 71 surgical resection specimens for CRC from the Emergency County Hospital "Pius Brînzeu" Timisoara. The cases were graded using the WHO grade and the PDCs-G, with further analysis of their association with the other recognised prognostic parameters. Using the WHO grade, 9% of the analysed cases were G1, 80% G2, 11% G3, and none of the tumours was graded G4, while in the PDCs-G 16% were G1, 45% G2, and 39% G3. In multivariate analysis PDCs-G was significantly associated with the American Joint Committee on Cancer stage of the disease (AJCC stage) (p = 0.0003), depth of invasion (pT) (p = 0.0084), nodal status (LNM) (p < 0.0001), lymphovascular invasion (LVI) (p < 0.0001), perineural invasion (PNI) (p < 0.0052), and tumour border configuration (p < 0.0001). The novel grading system based on PDCs counting is an additional histological tool in the evaluation of CRC and a promising new prognostic factor for these patients.

Paving the way to tumor budding assessment using digital pathology: a pilot study in Timisoara City (Romania).

BACKGROUND AND AIM: The outcome for some colorectal cancer patients correlates poorly with classical prognostic factors, like tumor stage. Tumor budding (TB) is a promising and intensely studied new prognostic factor. We aimed to evaluate the reliability of bud counting on Hematoxylin-Eosin (HE)-stained and immunohistochemically (IHC)-stained scanned slides. MATERIALS AND METHODS: We evaluated 21 cases of robotic surgery colorectal cancer specimens that were submitted to the Department of Pathology, Emergency County Hospital, Timisoara, Romania. TB was assessed by one experienced (R3) and two junior pathologists (R1, R2), in 10 circular areas at 20× (0.785 mm²) on scanned HE-stained and IHC-stained [cytokeratin (CK) AE1∕AE3] slides. Interobserver agreement (Cohen's kappa) and intraclass correlation coefficient (ICC) were calculated. RESULTS: In the case of HE-stained slides, the inter-item correlation matrix showed values between 0.632 and 0.84, while the ICC on average measures for consistency showed very good correlation [ICC: 0.887, 95% confidence interval (CI): 0.765-0.95)]. The inter-item correlation matrix for IHC-stained slides comprised values between 0.864 and 0.921, while the ICC for average measures for consistency yielded an excellent value (ICC: 0.95, 95% CI: 0.896-0.978). We identified higher values for budding scores on IHC-stained slides, in comparison to the HE-stained slides: in 19∕21 cases for R1 (average increase of 234.85%), 16∕21 cases for R2 (average increase of 114.14%), and 20∕21 cases for R3 (average increase of 66.92%). CONCLUSIONS: We consider the method of buds counting in 10 microscopic fields on scanned slides to be reliable and valuable. TB counts are higher on IHC-stained slides and associate a better interobserver agreement.