[Enteritis cystica profunda]. / L'entérite kystique profonde.

Enteritis cystica profunda is a rare and benign disease defined as the invagination of the intestinal epithelium into the submucosa and more profound layers of intestinal wall leading to the formation of mucin-filled cystic spaces. We reported the case of a 45-year-old female, suffering from a Crohn's disease, with a Koenig's syndrome, diarrhea, abdominal pain and weight loss. The colonoscopy and the abdominopelvic scan showed a terminal ileal stenosis, with parietal calcifications. A surgical ileocecal resection was decided. Gross examination of the ileocecal resection showed a thickening of the ileal wall, with many mucin-filled cysts measuring 1mm to 2cm, with some calcifications. The ileal mucosa was ulcerated, and showed a stenotic sector extending over 3cm. Histological examination showed acute ulcerated ileitis lesions, with chronic ileitis lesions and stenosis, compatible with the known diagnosis of Crohn's disease. There were also many cysts into the ileal wall. They were lined with a regular ileal epithelium. The cysts contained mucus, with some calcifications. Some cysts were ruptured, with extravasation of mucus within the wall. Cystica profunda can be found anywhere along the digestive tract. The physiopathology is not yet well understood, but it seems to be favored by chronic aggression of the intestinal wall. This pathology most often coexists with Crohn's disease. The main differential diagnosis is mucinous adenocarcinoma. Cystica profunda does not require any specific treatment.

[Inflammatory bowel diseases and upper gastrointestinal tract]. / Les maladies inflammatoires chroniques intestinales (MICI) et tube digestif haut.

Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis are inflammatory diseases with a flare-up evolution and an unknown etiology. Inflammatory lesions of the upper gastrointestinal tract are more and more often described in Crohn's disease and ulcerative colitis. The aim of this article was to review the inflammatory lesions of the esophagus, stomach and duodenum currently described in the IBD.

[Drug induced gastro-intestinal tract lesions: A pathologist point of view]. / Lésions iatrogènes du tube digestif vues par le pathologiste.

The number of drugs available to clinicians, especially targeted therapies, grows continuously. Some drugs are known to cause frequent digestive adverse effects, which may affect the gastro-intestinal tract in a diffuse or localized manner. Some treatments may leave relatively pathognomonic deposits, but histological lesions of iatrogenic origin are mostly non-specific. The diagnostic and etiological approach is often complex because of these non-specific aspects and also because (1) a single type of drug may cause different histological lesions, (2) different drugs may cause identical histological lesions, (3) the patient may receive different drugs, and (4) drug-induced lesions may mimic other pathological entities such as inflammatory bowel disease, celiac disease, or graft versus host disease. The diagnosis of iatrogenic gastrointestinal tract injury therefore requires close anatomic-clinical correlation. The iatrogenic origin can only be formally established if the symptomatology improves when the incriminating drug is stopped. This review aims to present the different histological patterns of gastrointestinal tract iatrogenic lesions, the potentially incriminate drugs, as well as the histological signs to look for in order to help the pathologist to distinguish an iatrogenic injury from another pathology of the gastrointestinal tract.

[Rectal leiomyosarcoma, a rare malignant tumor diagnosed in ulcerative colitis]. / Le léiomyosarcome rectal, une tumeur maligne rare diagnostiquée au cours de la rectocolite ulcéro-hémorragique.

Patients with chronic inflammatory diseases (IBD) of the digestive tract are known to have an increased risk of colorectal cancer. These are usually adenocarcinomas, and the occurrence of malignant mesenchymal tumours, particularly leiomyosarcomas, is exceptional. We report one case in a 40-year-old woman, followed for 9 years for ulcerative colitis. The tumour measured 2cm in length and infiltrated the entire rectal wall as far as the subserosa. It was composed of fusiform cells, with 5 mitoses for 10 fields at ×400 magnification, and expressing actin, desmin and caldesmone under immunohistochemical study. We review the 2 cases of leiomyosarcomas associated with Crohn's disease and 3 cases developed during ulcerative colitis published in the literature.

Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma.

BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs. METHODS: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling. RESULTS: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA ("Nestin High", >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies. CONCLUSION: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. LAY SUMMARY: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.

[Gastric mucosal calcinosis]. / Calcinose de la muqueuse gastrique.

The gastric mucosal calcinosis is a benign condition corresponding to calcium deposits in the gastric mucosa. A 39-year-old women, with an history of transplantation, transplant rejection and hemodialysis, treated with corticosteroids and calcium/phosphoremic supplements, had chronic diarrhea. Gastroduodenal fibroscopy found an atypical atrophic gastritis appearance with small focal whitish deposits in the gastric mucosa. Histological examination revealed brown and gray-bluish crystalline deposits in superficial chorion, stained by Von Kossa, leading to a diagnosis of gastric mucosal calcinosis. This lesion can be categorized as systemic, dystrophic, iatrogenic and idiopathic. In our observation, gastric mucosal calcinosis was probably mixed, linked to renal disorders, and mainly to exogenous phosphocalcic drug intakes. The gastric mucosal calcinosis is commonly found  in kidney transplant patients reaching a frequency of 15 to 29%.

[Gastric glomus tumors. Interest of ultrasound endoscopic biopsies for the diagnosis. About two cases]. / Les tumeurs glomiques gastriques. Intérêt des biopsies sous échoendoscopie pour le diagnostic. À propos de deux cas.

Glomus tumors are rare mesenchymal tumors, mostly benign, although a few malignant cases have been described in the literature. These tumors are usually localized subcutaneously or subcutaneously, however they may exceptionally be gastric localized. We report two new observations diagnosed on biopsies performed by echo endoscopy. The first was a 66-year-old man and the second a 78-year-old man. In both cases, the lesions were on astral, nodular, and very limited location. The biopsies revealed a tumor proliferation of trabecular architecture, composed by monomorphic cells, with eosinophilic cytoplasm, medium size, with a rounded, regular nucleus, without mitosis or necrosis, with distended and branched capillaries on the periphery. In immunohistochemical studies, tumor cells expressed smooth muscle actin and caldesmone. The proliferation index KI 67 was very low. In practice, however, preoperative diagnosis remains difficult because there is no typical appearance in imaging or echo-endoscopy to distinguish them from other gastric parietal tumors. To date, there is no consensus on the therapeutic management of gastric glomus tumors. However, endoscopic resection by dissection under the mucosa associated with endoscopic monitoring seems to be a method of choice as well as a way to postpone open or laparoscopic surgery, especially when these tumors are small (<30mm).

[Relevance of oesophageal biopsies during graft-versus-host disease]. / Intérêt des biopsies œsophagiennes au cours de la maladie du greffon contre l'hôte.

INTRODUCTION: Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation. It frequently affects the digestive tract. Oesophageal damage is not part of its typical clinical picture. The objective of this study was to determine whether oesophageal lesions could be found in this condition. MATERIAL AND METHODS: Cases coded as GVH at the CHU of Amiens in anatomopathology were identified from 2004 to 2019. Each patient who had an oesophageal biopsy was included. The slides were re-read by 2 pathologists to assess the lesions. RESULTS: A total of 24 patients were included. A total of 79.1 % of the biopsies showed inflammatory lesions: 25 % erosions, 37.5 % a cleavage between the lamina propria and squamous epithelium, 41.7 % a lichenoid inflammatory infiltrate, 54.1 % apoptotic cells and 54.1 % epithelial vacuolations. 25 % of the biopsies were classified as Lerner's grade 4 (used in dermatopathology to assess cutaneous GVH lesions), 12.5 % as grade 3, 25 % as grade 2, 16.7 % as grade 1, and 20.8 % of the biopsies did not show oesophageal GVH lesions. None of the histological lesions observed were correlated with the prognosis, however erosions and epithelial cleavage were more frequently associated with death. CONCLUSION: Lesions evocative and probably specific for acute GVH can be found in the esophagus. They could help and be part of the diagnosis. A protocol for oesophageal biopsy sampling, and the exclusion of other causes of esophagitis, should be performed in the future during suspicion of acute GVH.

[Pathologist occupational hazards: Results of a survey for the French case]. / Risques professionnels chez les pathologistes : résultats d'une enquête française.

INTRODUCTION: The profession of pathologist exposes to various risks, notably infectious, physical and chemical. The objective of this study was to make an inventory of these occupational risks to which pathologists are subjected and to evaluate the pathologies that they presented. A particular attention was given to microscopic and screen work as they can induce musculoskeletal or ophthalmic disorders, and stress-related psychological disorders. METHOD: An anonymous online questionnaire containing 54 questions had been sent by mail to pathologists via the French Society of Pathology and the Syndicate of French Pathologists. RESULTS: Five hundred and twelve pathologists responded to the survey. Thirty-eight percent reported musculoskeletal disorders in the last 6 months. Visual disturbances concerned 73.4% of respondents. In the last 12 months, 33.3% of pathologists had been injured or had had mucosal projections during macroscopic or autopsy specimens. The frequency of infectious diseases was low (6.2%) as well as that of cancers (3.9%). Psychological disorders such as depression or burnout were reported by 16.7% of respondents. Pathologists seemed happy at work and had a good overall lifestyle. Few doctors had medical follow-up and few had benefited from ergonomic advice and training on the risks of chemicals. CONCLUSION: The results of this study showed the interest of a medical surveillance adapted to the pathologies presented by the pathologists. Educational and preventive measures should be introduced early in the career, focusing on ergonomics and learning about chemical and biological hazards.

[Immunohistochemical diagnosis of colonic spirochetosis with anti-treponema antibody in patients consulting for chronic diarrhea. Results of a prospective study conducted in 137 patients]. / Diagnostic immunohistochimique de la spirochétose colique avec l'anticorps anti-tréponème chez les patients consultant pour une diarrhée chronique. Résultats d'une étude prospective menée chez 137 patients.

AIM: To assess the incidence of colonic spirochetosis, diagnosed by immunohistochemical stain with anti-Treponema pallidum antibody, in a prospective study of colonic biopsies of patients presenting with chronic diarrhea. MATERIAL AND METHODS: From March 2017 to March 2018 the colonic biopsies of patients presenting with chronic diarrhea were stained with Hematoxylin Eosin and anti-Treponema pallidum antibody. The positive cases were also stained with Steiner stain. RESULTS: A total of 137 colonic biopsies were assessed and 3 cases were positive for immunohistochemical stain with anti-Treponema pallidum antibody (2% of the patients). One case was easy to diagnose with HE stain but the 2 other cases were not. The bacteria were stained with Steiner stain, but less easily seen than with the immunohistochemical stain. No patient was treated with antibiotics. DISCUSSION AND CONCLUSION: The colonic spirochetosis can be easily diagnosed by pathologists with immunohistochemical stain with anti-Treponema pallidum antibody. The bacteria are more easily diagnosed with immunohistochemical stain than with HE stain or Steiner stain. However, colonic spirochetosis is rarely diagnosed on colonic biopsies of patients presenting with chronic diarrhea (2% of the patients in our study). Due to the rarity of the entity, and the cost of immunohistochemical stain and the weak benefit for the patient (no patient in our study was treated with antibiotics for colonic spirochetosis) we cannot advise to perform systematic immunohistochemical stain with anti-Treponema pallidum antibody in all the colonic biopsies of patients presenting with chronic diarrhea.

[Venous invasions in colonic adenocarcinoma: Value of elastic stain]. / Invasions veineuses dans l'adénocarcinome colique : intérêt d'une coloration des fibres élastiques.

The aim of our study was to assess the value of Elastic stain in the diagnosis of venous invasion (VI) in colonic adenocarcinoma. MATERIAL AND METHODS: All patients who undergone surgery for colonic adenocarcinoma at the University Hospital of Amiens, between 2004 and 2007, were included. Hematein-phloxin-saffron (HPS) stained slides of colectomy specimens were reviewed by two pathologists. Tumor blocks were stained with Elastic Stain (Roche - Ventana®). The presence or absence of VI, their number and localization were correlated with overall survival. RESULTS: Two hundred and thirty-one cases were investigated and 3274 slides were examined. VI were more often diagnosed by Elastic Stain than HPS stain (66% vs. 40%). Ninety percent of VI were revealed within the first 6 HPS slides, and from the first 5 in Elastic Stain. The presence of VI revealed by Elastic Stain and/or HPS was significantly associated with decreased overall survival in multivariate analysis (P=0.029), especially for stage IIA tumors (P=0.016). Tumor differentiation (P=0.006) and pTNM stage (P=0.001) were also independent prognostic factors. The localization and the number of VI were not prognostic factors. CONCLUSION: Our study confirms the prognostic value of VI, revealed by an elastic stain, in colonic adenocarcinoma. A systematic elastic stain of all tumor blocks (number at least 5) could be considered in the future, during pathological examination of colectomy for adenocarcinoma.

Incidence, Clinical Presentation, and Associated Factors of Microscopic Colitis in Northern France: A Population-Based Study.

OBJECTIVE: To date, there are no epidemiological data on microscopic colitis (MC) in France. The aim of this study was to determine the incidence of MC in the Somme department in Northern France, to evaluate clinical characteristics, and to search for risk factors for both collagenous colitis (CC) and lymphocytic colitis (LC). DESIGN: Between January 1, 2005, and December 31, 2007, four pathology units in the Somme department recorded all new cases of MC diagnosed in patients living in the area. Colonic biopsies were reviewed by 4 pathologists together. For each incident case, demographic, clinical, endoscopic, and biological data were collected according to methodology of the EPIMAD registry. RESULTS: One hundred and thirty cases of MC, including 87 CC and 43 LC, were recorded during the three-year study. The mean annual incidence for MC was 7.9/105 inhabitants, 5.3/105 inhabitants for CC, and 2.6/105 inhabitants for LC. Annual standardized incidence of Crohn's disease and ulcerative colitis in the EPIMAD registry during the same period (2005-2007) were 7.4/105 and 4.9/105, respectively. Median age at diagnosis was 63 years for MC, 70 for CC, and 48 for LC. The female-to-male gender ratio was 3.5 for MC, 4.1 for CC, and 2.6 for LC. Median time to diagnosis was 8 weeks. Chronic diarrhea and abdominal pain were, respectively, present in 93 and 47 % of the cases. An autoimmune disease was associated in 28 % of MC cases. At diagnosis, proton pump inhibitor treatment was more often reported in CC than in LC (46 vs 16 %; p = 0.003). Budesonide was effective on diarrhea in 77 % of patients, and thirteen percent of patients became steroid dependent. CONCLUSION: This population-based study shows that the incidence of MC in France is high and similar to Crohn's disease incidence and confirms that this condition is associated with female gender, autoimmune diseases, and medications.

Increased tumor infiltration by mucosal-associated invariant T cells correlates with poor survival in colorectal cancer patients.

The infiltration of tumors by lymphocytes is a prognosis factor in colorectal cancer (CRC). The magnitude and quality of this infiltration have emerged as important component of the clinical outcome in these patients. Specifically, markers associated with functional cell-mediated immunity, i.e., a Th1 immune response, are independent markers of better prognosis, whereas Th17-associated components are deleterious and correlate with poorer survival. Mucosal-associated invariant T (MAIT) cells are a recently described T cell subset with tissue-homing properties. They display a restricted TCR repertoire specific for widely conserved microbial ligands, and display anti-bacterial properties upon release of Th1-like, Th17-like, and/or cytotoxic granules. MAIT-cell-specific transcripts have been found in kidney and brain cancer, but have not been studies in other sites. In this study, we retrospectively analyzed by confocal microscopy the presence of MAIT cells within colorectal tumors as compared with paired healthy tissues. We observed a significant although variable increase, both in density and in proportion of overall tumor-infiltrating T lymphocytes inside the tumors. Importantly, survival curves as well as multivariate analysis showed that patients displaying a higher recruitment of MAIT cells in their tumor, as compared with the neighboring healthy tissue, showed a less favorable clinical outcome. This study suggests that including MAIT-cell-specific markers or transcripts in the analysis of tumor-infiltrating lymphocytes could be a benefit to the diagnosis and follow-up of CRC patients.

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group.

INTRODUCTION: As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection. METHODS: Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (<12 months) after a resection. RESULTS: The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24-85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis. CONCLUSION: The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.

Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis.

BACKGROUND: Mortality among patients with severe acute alcoholic hepatitis is high, even among those treated with glucocorticoids. We investigated whether combination therapy with glucocorticoids plus N-acetylcysteine would improve survival. METHODS: We randomly assigned 174 patients to receive prednisolone plus N-acetylcysteine (85 patients) or only prednisolone (89 patients). All patients received 4 weeks of prednisolone. The prednisolone-N-acetylcysteine group received intravenous N-acetylcysteine on day 1 (at a dose of 150, 50, and 100 mg per kilogram of body weight in 250, 500, and 1000 ml of 5% glucose solution over a period of 30 minutes, 4 hours, and 16 hours, respectively) and on days 2 through 5 (100 mg per kilogram per day in 1000 ml of 5% glucose solution). The prednisolone-only group received an infusion in 1000 ml of 5% glucose solution per day on days 1 through 5. The primary outcome was 6-month survival. Secondary outcomes included survival at 1 and 3 months, hepatitis complications, adverse events related to N-acetylcysteine use, and changes in bilirubin levels on days 7 and 14. RESULTS: Mortality was not significantly lower in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months (27% vs. 38%, P = 0.07). Mortality was significantly lower at 1 month (8% vs. 24%, P = 0.006) but not at 3 months (22% vs. 34%, P = 0.06). Death due to the hepatorenal syndrome was less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months (9% vs. 22%, P = 0.02). In a multivariate analysis, factors associated with 6-month survival were a younger age (P<0.001), a shorter prothrombin time (P<0.001), a lower level of bilirubin at baseline (P<0.001), and a decrease in bilirubin on day 14 (P<0.001). Infections were less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group (P = 0.001); other side effects were similar in the two groups. CONCLUSIONS: Although combination therapy with prednisolone plus N-acetylcysteine increased 1-month survival among patients with severe acute alcoholic hepatitis, 6-month survival, the primary outcome, was not improved. (Funded by Programme Hospitalier de Recherche Clinique; AAH-NAC ClinicalTrials.gov number, NCT00863785 .).