Large cell neuroendocrine carcinoma of the colon: An unexpected diagnosis: A case report.

INTRODUCTION AND IMPORTANCE: Large cell neuroendocrine carcinomas of the colon (LCNECC) are exceptionally rare, comprising only 0.2 % of all colonic carcinomas. Their diagnosis poses a significant challenge due to their propensity to mimic colonic adenocarcinomas. Typically diagnosed at advanced stages, LCNECCs carry a grim prognosis. Herein, we present a rare case of LCNECC and aim to elucidate its clinico-pathological characteristics. CASE PRESENTATION: A 56-year-old female patient presented with complaints of constipation, abdominal pain, and weight loss. On physical examination, a sizable mass was palpable in the right flank. Colonoscopy revealed a polyp in the descending colon and a friable multinodular stenosing mass in the ascending colon. Microscopic examination of the biopsy from the ascending colon mass exhibited a poorly differentiated large cell carcinomatous proliferation with positivity for synaptophysin and CD56, along with a Ki-67 proliferation index of 50 %. The polyp in the descending colon was consistent with a low-grade dysplastic tubular adenoma. A diagnosis of LCNECC with synchronous low-grade dysplastic tubular adenoma was established. A right hemicoloctomy was performed. Final pathological examination confirmed LCNECC invading the muscularis propria, with lymph node metastases. The tumor was classified as pT2N1M0 (Stage III). CLINICAL DISCUSSION: LCNECCs often mimic adenocarcinomas clinically, endoscopically, and radiologically. Pathological examination is the key for diagnosis. An immunohistochemical study using neuroendocrine markers is imperative to prevent overlooking the diagnosis of LCNECC. CONCLUSION: LCNECCs represent rare aggressive carcinomas. Their diagnosis might be challenging. A better knowledge of this rare entities would enable early diagnosis.

Epidemiological and histopathological characteristics of thyroid carcinoma in a Tunisian health care center.

Background: Thyroid carcinoma (TC) accounts for almost 0.5%-1% of total malignancies. Its incidence is increasing rapidly worldwide. Several studies have drawn up the epidemiological profile of TC and its clinical and pathological features. However, to date, no similar studies have been conducted in Tunisia. Aims: To establish an epidemiological profile of TC in a Tunisian health care institute and to analyze its clinical and histopathological characteristics in our institute. Materials and Methods: We present a retrospective study reviewing the cases of TC diagnosed in our institution in a 4-year period. Results: We collected a sample of 192 cases of TC. It consisted of 31 males and 161 females (83.8%) with a sex-ratio M/F of 0.19. The mean age was 46.4 years. Papillary thyroid carcinoma was the most frequent histological subtype. The multifocality rate was 33.8%. The mean size of TC was 2.2 ± 1.9 cm. 60.9% of TC were staged pT1 and 20.3% had nodal involvement. Papillary thyroid microcarcinomas were noted in 37.5% of cases. Conclusion: Our results were consistent with those of the literature. A high proportion of pT1 and pN0 tumors were noted in our series, suggesting that TC's diagnosis and management was performed at an early stage of the disease in our institution. In addition, our study enabled us to notice the impact of the Coronavirus disease 19 crisis on the management of TC in our institution. Further studies are needed to establish the epidemiological profile of TC in Tunisia and to assess its clinical and pathological features.

A dataset of tumour-infiltrating lymphocytes in colorectal cancer patients using limited resources.

In the realm of cancer research, specifically focusing on colorectal carcinomas (CRCs), a novel diagnostic test referred to as 'Immunoscore' (IS) has emerged. This test relies on assessing the density of tumour-infiltrating lymphocytes, specifically CD3 and CD8, in both the centre of the tumour (CT) and its invasive margin (IM). IS holds promise as a potential prognostic factor. A retrospective descriptive study was conducted within the Pathology Department of Habib Thameur Hospital in Tunis, Tunisia. The study's aim was to evaluate the prognostic efficacy of IS for patients with CRC by means of a comprehensive survival analysis. This publication introduces the immunoscore in colorectal cancer (ISCRC) dataset, which was meticulously compiled during the aforementioned study. The ISCRC dataset comprises digital slide images sourced from biopsies of 104 patients diagnosed with CRC. Using the tissue microarray technique, an immunohistochemical investigation involving anti-CD3 and anti-CD8 markers was performed in regions designated as 'Hot Spots' within the CT and IM. The images were captured using a smartphone camera. Each marker's percentage presence within its respective region was quantified. The IS was estimated utilizing a semi-quantitative method. The ISCRC dataset encompasses anonymized personal data, along with macroscopic and microscopic attributes. The captured images, acquired through manual efforts using smartphones, stand as a valuable asset for the advancement of predictive algorithms Importantly, the potential applications of these models extend beyond mere prediction capabilities. They lay the groundwork for innovative mobile applications that could potentially revolutionize the practices of pathologists, particularly in healthcare settings constrained by resources and the absence of specialized scanning equipment. Database URL: https://figshare.com/s/5b4fa3e58c247a4851d4.

Hemangioma of the umbilical cord: A case report on a rare entity.

Several hundred cases of placental hemangiomas have been reported in the literature. However, the umbilical cord is extremely uncommon as a site of occurrence. We present a case of postnatal discovery of giant hemangioma of the umbilical cord (HUM) in a Coronavirus Disease 2019 (COVID 19) positive mother. To our knowledge, this is the first reported case of HUM synchronous to a maternal infection with COVID 19. We aim, through this case and a review of the literature, to study the clinicopathological characteristics of this singular entity. Our patient, a 37-year-old woman, presented to the Department Of Obstetrics And Gynecology for respiratory distress and loss of fetal movements. Ultrasound examination concluded to intrauterine fetal desmise. After stabilization of the patient, a cesarean section was performed. A macerated fetus was extracted. Placenta showed a giant mass attached to the cord. It was submitted for pathological examination. Gross examination showed that the umbilical cord was inserted eccentrically with a fusiform dilation. Near its placental end, three cohesive solid angiomatous nodules were noted. Microscopic examination revealed lobules of dilated blood-filled capillaries set in a myxoid stroma. The diagnosis of HUM have been established. HUM arise from endothelial cells of the umbilical vessels. Their etiology, physio-pathology and pathways of tumorigenesis are not yet well defined. Further studies are needed to explore the pathways of tumorigenesis and to determin the implication of COVID-19 in HUM.

Sarcomatoid chromophobe renal cell carcinoma revealed by acute pyelonephritis in a diabetic patient.

Chromophobe renal cell carcinoma (CRCC) is a rare tumor comprising 2 types of cells (eosinophilic and clear cells), coexisting in varying proportions. CRCC has an overall good prognosis. However, the rarely encountered sarcomatoid differentiation is associated with a pejorative outcome and must, therefore, be rigorously ruled out. Acute pyelonephritis and other infectious complications rarely occur. We report a case of CRCC with sarcomatoid differentiation in a woman in her sixties which was revealed by acute pyelonephritis and had a lethal outcome.

Evaluating a postgraduate teaching intervention among pathology trainees on medical liability.

BACKGROUND: Pathology is a specialty of high malpractice risk. For that reason, we programmed a training session of the residents in Pathology with an association of traditional methods of learning and case-based brainstorming sessions. OBJECTIVES: We aimed to train them about our national tort law and to make them aware of the different medicolegal errors that they have to avoid in their routine practice. METHODS: Trainees completed a pre-test (3 multiple-choice questions (MCQ) and 4 medical malpractice cases involving pathologists), attended lectures covering standards in pathology, the legal responsibility of pathologists and the notion of medical malpractice error in pathology, brainstormed about legal cases (different than in the pre-test), participated in a conference covering telepathology, digital molecular pathology and social media and finally completed a post-test (same as the pre-test). We tried to assess the impact of the session using a questionnaire that different trainees ( who were present or absent in the training session) fulfilled one month after the training session. Analysis of variance (ANOVA) was conducted to determine whether there were significant differences between the scores among pathologists according to their level of training in the speciality. RESULTS: The results indicated that performance on the post-test significantly improved on questions associated with 2 of the 4 cases.  Trainees were concordant with actual case verdicts at a rate of 38% for pre-test and 54% for post-test.  Most (76.5%) students felt they had an active role in the training and felt they achieved goals (94.1%). CONCLUSION: The association of different methods of learning is helpful in training pathologists about medicolegal malpractice.

KRAS and NRAS pyrosequencing screening in Tunisian colorectal cancer patients in 2015.

BACKGROUND: Mutations in KRAS and NRAS often result in constitutive activation of RAS in the epidermal growth factor receptor (EGFR) signaling pathway. Mutations in KRAS exon 2 (codon 12-13) predict resistance to anti-EGFR targeted therapy in patients with metastatic colorectal carcinoma (mCRC). However, it's currently known that a significant proportion of mCRC have RAS mutations outside KRAS exon 2, particularly in exons 3 and 4 of KRAS and exons 2, 3 and 4 of NRAS. No data about RAS mutations outside KRAS exon 2 are available for Tunisian mCRC. The aim of this study was to analyze RAS, using pyrosequencing, in nine hotspots mutations in Tunisian patients with mCRC. METHODS: A series of 131 mCRC was enrolled. Nine hotspots sites mutations of KRAS and NRAS were analyzed (KRAS: codons 12-13, codons 59-61, codon 117 and codon 146, NRAS: codons 12-13, codon 59, codon 61, codon 117 and codon 146) using Therascreen KRAS and RAS extension pyrosequencing kits. RESULTS: Analysis was successful in 129 cases (98.5%). Mutations were observed in 97 cases (75.2%) dominated by those in KRAS exon 2 (86.6%). KRAS G12V was the most dominated mutation, observed in 25 cases (25.8%), and followed by KRAS G12S and KRAS G12D, each in 17 cases (17.5%). Mutations outside of KRAS exon 2 presented 13.4% of mutated cases and almost a third (28.8%) of KRAS exon 2 wild type mCRC. Among those, 9 cases (69.3%) carried mutations in NRAS exons 2, 3 and 4 and 4 cases (30.7%) in KRAS exons 3 and 4. CONCLUSIONS: RAS mutations outside exon 2 of KRAS should be included in routine practice, since they predict also response to anti-EGFR. That would make certain these patients benefit from appropriate testing and treatment. In addition unjustified expenses of anti-EGFR targeted therapy could be avoided.

Ampullary and pancreatic adenocarcinoma-a comparative study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) and ampullary adenocarcinoma (AAC) are 2 gastrointestinal cancers that share overlapping symptoms. Although some studies have proposed the hypothesis of differences in pathogenesis and prognosis in these 2 cancers; they remain treated similarly. The classification of AAC into three subtypes [pancreatobiliary (PB), intestinal (IT) and mixed (M)] is especially crucial for the 3 axes of patients management (diagnosis, prognosis and therapy). Some studies suggest that PB subtype pathogenesis is comparable to PDAC. The objective of this study was to conduct a comparative analysis between PDAC and AAC; notably PB subtype; via mutational status analysis of 3 oncogenes (KRAS, NRAS and BRAF) hoping to consolidate AAC biology understanding. METHODS: Nine hot spot mutation sites of KRAS, NRAS and BRAF were analysed using pyrosequencing in 39 PDAC and 21 AAC from Tunisian patients. Comparative study was performed using SPSS software. RESULTS: Mutations in oncogenes were detected in almost 43% of AAC, especially in PB (47%) and 95% of PDAC. KRAS was the most mutated oncogene. There were statistical significant differences between PDAC and AAC in tumor differentiation (P<0.001), perineural invasion (P<0.001), vascular emboli (P=0.001), T stage (P=0.007), N stage (P=0.001) and mutational status (P<0.001). When comparing PDAC and PB subtype, there were also significant differences in tumor size (P=0.001), tumor differentiation (P<0.001), perineural invasion (P<0.001), vascular emboli (P=0.001), T stage (P=0.033), N stage (P<0.001) and mutational status (P<0.001). CONCLUSIONS: AAC even PB subtype is different from PDAC. We think that these different tumor types require highly individualized therapy guided by their histomolecular characteristics and that we should stop diagnosing and treating them as a unique entity.

KRAS, NRAS and BRAF analysis of ampullary adenocarcinoma classified using CK7, CK20, MUC1 and MUC2.

BACKGROUND: Ampullary carcinomas are rare and dominated by adenocarcinomas. They account for only 0.5% of all gastrointestinal malignancies. Ampullary adenocarcinoma (AAC) with pancreaticobiliary (PB) histology has a worse outcome than that with intestinal (IT) histology. The mixed subtype contains the two epitheliums. This subclassification remains a challenge for pathologists and induces a reasonable level of disagreement. Genetic features of these subtypes are unclear. In this study, we aimed to reclassify AAC cases then to evaluate differences in prognostic, pathological and molecular parameters including mutational status of three oncogenes between these subtypes. METHODS: AACs from 21 Tunisian patients were used in this study. Reclassification was made based on histology and immunohistochemistry (IHC) using CK7, CK20, MUC1 and MUC2. Mutational analysis included the pyrosequencing of KRAS, NRAS and BRAF. RESULTS: Fifteen cases were PB subtype, 2 cases were IT subtype and 4 cases were mixed subtype. CK20 and MUC2 were associated with N stage, MUC1 and histomolecular subtype with T stage. Nine cases were mutated and 12 were wild-type. Eight cases were KRAS mutated (5 G12D and 3 G12V). Only 1 case was NRAS mutated (G12D). No BRAF mutation was found. Genetic alterations didn't influence prognostic factors. CONCLUSIONS: We validate the prognostic utility of AAC histomolecular classification.

Mercurial hospital waste: management, becoming and recommendations.

INTRODUCTION AND PURPOSE: In hospitals, the use of medical instruments and products containing mercury and the management of mercury waste (MW) collected are regulated in developed countries. In Tunisia, MW end up in landfill and no strategy has so far been adopted. The objective of this study was to quantify MW in two university hospitals in Tunis and to indicate the elimination pathways used and to propose certain recommendations. METHODS: This was a descriptive retrospective study conducted from February to August 2016 and quantifying the MWs from medical products and instruments used by two university hospitals in Tunis during 2015. Semi-structured interviews and focus groups enabled the collection of informations on MW management methods for these products and instruments and their waste and to identify the weaknesses of this management. RESULTS: In 2015, 2,443 mercury thermometers were used by Habib Thameur hospital (HHT) and 7,439 by La Rabta hospital (HLR), releasing 19,764 g of mercury. For dental amalgams, 1,440 g were used at HHT. Their residues (320.4 g) were stored in the original capsules. At HLR, 1,320 g were used but residues, estimated at one-third of the total amount (440g), were discharged into the cuspidor. The total amount released from the amalgams was 380.2g, knowing that half of the volume was mercury. The broken tensiometers (26 at HHT and 113 at HLR) released 183.5g of mercury, the roasted fluorescent lamps (1,627 at HHT and 1,722 at the HLR) 167.4g, Harris Hematoxylin (15 liters at HHT and 18 liters at HLR) 82.5g and used batteries (1,258 at the HHT and 914 at the HLR) 54,3g. In total, with the exception of mercury vapors, the amount of mercury released in 2015 at the two hospitals was approximately 20,632 g. These MW have borrowed the household waste stream (51% of HHT MW and 47% of HLR MW), waste from infectious care activities (47% HHT and 46% of the HLR MW), electrical and electronic waste (1% of HHT and HLR MW), and sewage (1% of HHT MW and 6% of the HLR MW). CONCLUSION: The main supplier of hospital MW is the mercury thermometer (95.8%). The managerial authorities would benefit from the promulgation of a regulatory framework, like the European law of 1998, prohibiting their use on a territorial scale and, by subsidies, replace them with electronic thermometers.

Critical study of pathology theses supported at the medical university of Tunis (2000-2010).

BACKGROUND: Medical writing is a coded language; its purpose is to convey a scientific message. In pathology, specialty involving the study of cell and tissue, quantitative and qualitative production of medical doctoral theses and their thematic focus has not been studied. The aim of this study was to analyze the pathology theses on the level of form, the background and methodology. METHODS: Descriptive retrospective study of medical doctoral theses in the specialty "Pathology", listed in the catalog of theses of the library of the Faculty of Medicine of Tunis and supported between 2000 and 2010. Each thesis has been subject of a direct reading, systematic and thorough. RESULTS: The study involved 189 pathology theses. The average overall productivity per academic pathologist was 5.5 theses. Gastrointestinal pathology was the most studied theme (24.9%). Tumor pathology was addressed in 74.1% of the theses. The IMRAD structure was respected in 57.7% of theses; by assistant professor than by associate professor and professor (p = 0.005). The summary was structured in 88.3% of theses, comparably with the grade of the thesis director (p = 0.5) and with the grade of PhD student (p = 0.08). The transcript of references did not meet the recommendations of Vancouver in 87.8% of theses and irrespective of the rank of director of thesis (p = 0.2). CONCLUSION: The pathology theses presented some shortcomings, particularly in the quality of medical writing. To remedy this problem, our faculty should increase efforts to improve the quality of scientific work, in order to have a better view of medical research in Tunisia.

Impact of pathology theses supported at the medical university of Tunis (2000-2010).

BACKGROUND: The thesis is an research work wish must submit to rigorous scientific criteria. However, this research effort remains inaccessible to international scientific communities. The aims of this study were to determinate the publication rates in indexed journals and factors affecting publication. METHODS: This was a retrospective descriptive study of pathology theses listed in the theses catalog of the library medical university of Tunis whose theses were supported between 2000-2010. Publication had been searched in databases "Pub Med". The number of citations received by each published thesis was recorded in www. Scopus.com. RESULTS: Our study concerned 189 theses. Thirty five original articles were derived from 33 theses (17.5%). Eleven medical indexed journals have made the support of articles, dominated by generalist journal (La Tunisie Médicale: 68.6%), specialist journals (Annales de Pathologies, Pathology, Ultrastructural Pathology: 11.4%). The number of article citations had an average of 1. Theses with informative title had been more publication (p=0.005). Theses with structured introduction had been more publication (p=0.002). CONCLUSION: Publication rate of pathology theses in indexed journals are relatively low. This publication rate could be improved by the organization of seminars and workshops on writing articles from theses or by the improvement of these articles in national competitions.

[Gastric heterotopia: clinical and histological study of 12 cases]. / Hétérotopie gastrique: étude anatomo-clinique de 12 cas

BACKGROUND: Gastric heterotopia is a rare congenital lesion, described everywhere in the body, but involves predominantly the digestive tract. Diagnosis is based on histologic examination and requires the presence of gastric mucosa, especially fundic. This diagnosis is usually easy, but sometimes it can be misinterpreted as gastric metapalsia . This latter is an acquired and frequent lesion of the gastrointestinal tract. AIMS: To determine the relationship between this affection and the other digestive malformations, to describe the clinical characteristics and the evolution of this lesion and to discuss the differential diagnosis particularly the gastric metaplasia. METHODS: Twelve cases of gastric heterotopia were diagnosed over a 12-year period at Habib Thameur Hospital. Clinical data was obtained and all the slides were reviewed. RESULTS: Nine cases were found in Meckel's diverticulum (75%), one case in intestinal duplication, one case in the esophagus and another in the gallbladder. The mean age of patients at diagnosis was 16 years with a peak of incidence at the first decade of life. Intestinal obstruction and digestive bleeding were the most presenting features. Heterotopic gastric mucosa complicates other congenital anomalies such as common mesentery, vestigial polyp of the liver, appendiceal agenesis and heterotopic pancreas. Differential diagnosis consists in gastric metaplasia was found extensively in a patient with Crohn's disease associated with Meckel's diverticulum. CONCLUSION: Gastric heterotopia is frequently associated with congenital anomalies especially with Meckel's diverticulum and digestive duplication. Diagnosis relies on histology, mainly on finding heterotopic fundic glands in normal organizational structure. Sometimes, differentiating between gastric heterotopia and gastric metaplasia requires clinical confrontation.

[An unusual lesion of the nasopharynx: oncocytic metaplasia]. / Une lésion inhabituelle du nasopharynx : la métaplasie oncocytaire.

Oncocytic metaplasia of the nasopharynx is an exceptional lesion which exact etiopathogenesis, although largely discussed, still remains controversial. The purpose of this paper is to present the epidemiological characteristics and clinical signs of this lesion and to study its pathogenesis and its therapeutic modalities. We report two cases that occurred respectively in a 53- and 60-year-old woman. The first presented with pharyngeal dysesthesia and otalgia. The endoscopic examination revealed an irregularity of the posterior wall of the nasopharynx. The second patient presented with tinnitus, discomfort of the left ear and bilateral hearing loss. Endoscopic exam revealed a bilateral structural abnormality to the eardrum. Microscopy showed focal oncocytic metaplasia of the nasopharynx mucosa in both cases. There was a positive outcare for both patients after excisional biopsy. Oncocytic metaplasia seems to be in relation to the stimulation of sympathic neuropeptidergic nerve fibers which target epithelial, connective, endothelial and lymphoid cells.

[Tumors of salivary glands: anatomical study and clinical epidemiology of a series of 180 cases]. / Les tumeurs des glandes salivaires: etude anatomo-clinique et. Epidemiologique d'une série de 180 cas.

BACKGROUND: The salivary gland tumors are rare (less than 3% of all tumors) and poorly known. In fact, they are numerous and histologically difficult to diagnose. AIM: This work aims to point at the different histological types of salivary gland tumors, to draw out the principal epidemiological, clinical, radiological and histological characteristics, and to compare our cases to those of the literature. METHODS: Accordingly, we performed a descriptive type study about 180 cases of salivary gland tumors from the departments of pathology and oto-rhino-laryngology of Habib Thameur hospital during 25 years, extending from April 1979 to December 2004. RESULTS: Benign tumors were predominant (88%), while malignant ones represented 12% of our cases dominated by carcinomas. The sex-ratio was 0.96. Parotid gland location was the most frequent one, and pleomorphic adenoma was the most frequent tumor (62%). CONCLUSION: Histological diversity of salivary tumors results in difficulties for differential diagnosis. These problems can be solved by a precise diagnostic approach and sometimes by an immunohistochemistry study.