Gastric Signet Ring Cell Carcinoma Metastasis From Lobular Breast Cancer: A Diagnostic Pitfall.

Breast cancer is the most common type of cancer among women worldwide. Gastric metastasis from invasive lobular carcinoma of the breast is unusual. We report the case of a 66-year-old woman, under follow-up for an invasive classic lobular carcinoma of the left breast treated four years prior, who was admitted for upper abdominal discomfort and worsening constipation. Linitis plastica was suspected at gastroscopy. Histology of gastric biopsies showed a poorly cohesive carcinoma comprising signet ring cells, with no resemblance to the original breast cancer. An adequate immunochemistry panel, including estrogen receptor and GATA-3, eliminated primary gastric cancer and proved that the gastric lesion was a metastasis of the previously diagnosed invasive lobular breast cancer with additional signet ring cell differentiation, which is classified among its rare variants. This challenging case shows the importance of oncologic medical history and immunochemistry in differentiating between metastasis from invasive lobular breast carcinoma and primary gastric cancer. The distinction is necessary as the prognosis and approaches for treatment are different. When encountering a gastric signet ring cell carcinoma, one must keep in mind that it actually can be a metastasis from one of the several primary sites of origin.

[Endoscopic submucosal dissection: advances and perspectives]. / Dissection sous-muqueuse endoscopique : avancées et perspectives.

Endoscopic submucosal dissection (ESD) is a mini-invasive technique allowing to resect superficial lesions of the digestive tract and maintaining organ function. High technical expertise is required as well as a network approach with referring physicians, pathologists, radiologists, surgeons and oncologists. Rigorous selection of cases as well as endoscopic management of potential complications (hemorrhage, perforation) is mandatory. Therefore, ESD should preferably be performed in expert centers with high volumes of cases, in order to maintain competency and offer optimal patient's management. Most frequent indications in the Western world are early cancers of the esophagus, stomach and colon as well as non-non-lifting polyps and gastrointestinal stromal tumors (GIST).

La dissection sous-muqueuse (DSM) est une technique permettant la résection des lésions superficielles du tube digestif, de façon mini-invasive, afin de conserver la fonction de l'organe atteint. L'expertise technique aboutissant à ce geste doit s'accompagner d'un travail en réseau associant médecins référents, pathologistes, radiologues, chirurgiens et oncologues. Elle nécessite une sélection rigoureuse des indications, ainsi que la maîtrise des complications éventuelles (hémorragie, perforation) et doit préférablement être réalisée en centre expert, avec un volume suffisant de cas afin de maintenir la compétence. Les indications les plus fréquentes en Occident concernent les cancers super­ficiels de l'œsophage, de l'estomac et du côlon ainsi que les polypes ne se soulevant pas lors de l'injection sous-muqueuse et les tumeurs stromales gastro-intestinales (GIST).

Degenerated Serous Cystic Tumor of the Pancreas: Case Report and Literature Review of an Aggressive Presentation of a Benign Tumor.

BACKGROUND Serous cystic tumors of the pancreas are known to present a benign nature and course, not requiring surgery in the absence of symptoms. In rare cases, these benign tumors may present aggressive characteristics such as local infiltration and lymph node and distant metastases. In such cases, a surgical approach may be necessary. CASE REPORT We present the case of a 79-year-old woman with an asymptomatic cytologically suggested caudal serous cystic tumor infiltrating the spleen and the splenic vein. This tumor was discovered in a computed tomography scan in the setting of evaluating distant spreading of a primary malignant neoplasm of the rectum. Suspicious malignant signs on imaging dictated a surgical approach and a distal splenopancreatectomy was carried out in the same operative time as the transanal resection of the rectal lesion. The nature of the pancreatic neoplasm was confirmed by histology, but 2 lymph nodes out of 4 retrieved were positive. The postoperative course was uneventful. No adjuvant treatment was proposed. Imaging control 6 months after surgery was not indicative of relapse. CONCLUSIONS Serous cystic adenomas of the pancreas, although generally considered benign neoplasms, may present with characteristics of malignancy. Moreover, they may prove difficult to differentiate from other malignant neoplasms by non-surgical modalities. Although current guidelines and data from the literature provide controversial information regarding management of these clinical entities, in the presence of suspicious radiological aspects, surgical resection could be considered.

Cohort profile: population-based cohorts of patients with colorectal cancer and of their relatives in Geneva, Switzerland.

PURPOSE: Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. Variability between patients in prognosis and treatment response is partially explained by traditional clinicopathological factors. We established a large population-based cohort of patients with CRC and their first-degree and second-degree relatives registered in the Canton of Geneva, to evaluate the role of family history and tumour biomarkers on patient outcomes. PARTICIPANTS: The cohort includes all patients with CRC diagnosed between 1985 and 2013. Detailed information on patient and tumour characteristics, treatment and outcomes were extracted from the Geneva Cancer Registry database, completed by medical records review and linkage with administrative and oncogenetics databases. Next-generation tissue microarrays were constructed from tissue samples of the primary tumour. A prospective follow-up of the cohort is realised annually to collect data on outcomes. First-degree and second-degree relatives of patients are identified through linkage with the Cantonal Population Office database and information about cancer among relatives is retrieved from the Geneva Cancer Registry database. The cohort of relatives is updated annually. FINDINGS TO DATE: The cohort includes 5499 patients (4244 patients with colon cancer and 1255 patients with rectal cancer). The great majority of patients were diagnosed because of occurrence of symptoms and almost half of the cases were diagnosed with an advanced disease. At the end of 2019, 337 local recurrences, 1143 distant recurrences and 4035 deaths were reported. At the same date, the cohort of first-degree relatives included 344 fathers, 538 mothers, 3485 children and 375 siblings. Among them, we identified 28 fathers, 31 mothers, 18 siblings and 53 children who had a diagnosis of CRC. FUTURE PLANS: The cohort will be used for long-term studies of CRC epidemiology with focus on clinicopathological factors and molecular markers. These data will be correlated with the most up-to-date follow-up data.

Study protocol of a phase II study to evaluate safety and efficacy of neo-adjuvant pembrolizumab and radiotherapy in localized rectal cancer.

BACKGROUND: Reshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve cancer treatment. Nevertheless, responsiveness to these treatments is often correlated with the extent of T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor T cell infiltration and, therefore, does not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy has profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immune checkpoint inhibition was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immune checkpoint inhibition have never been tested in these tumors. METHODS: Our clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5 Gy × 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed three weeks after the last pembrolizumab injection. Our clinical trial includes an extensive translational research program involving the transcriptomic and proteomic analysis of tumor and blood samples throughout the course of the treatment. DISCUSSION: Our study is the first clinical trial to combine short-course radiotherapy and immune checkpoint inhibition in rectal cancer, which could potentially result in a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer insights into immunological changes within the tumor and blood and their correlation with patient outcome. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients. TRIAL REGISTRATION: This study was registered with www. CLINICALTRIAL: gov : NCT04109755 . Registration date: June, 2020.

Sexual organ-sparing with hydrogel spacer injections for rectal cancer radiotherapy: a feasibility pilot study.

OBJECTIVES: The aim of this pilot study was to investigate in two rectal cancer patients undergoing neoadjuvant chemo-radiotherapy (nCRT) the implant feasibility and dosimetric benefit in sexual organ-sparing of an injectable, absorbable, radiopaque hydrogel spacer. METHODS: Two rectal cancer patients (one male and one female) underwent hydrogel implant between rectum and vagina/prostate before nCRT and curative surgery. A CT scan was performed before and after injection and a comparative dosimetric study was performed testing a standard (45/50 Gy) and a dose escalated (46/55.2 Gy) schedule. RESULTS: In both patients, the spacer implant in the recto-prostatic or recto-vaginal space was feasible and well tolerated. For the male, the dosimetric benefit with spacer was minimal for sexual organs. For the female however, doses delivered to the vagina were significantly reduced with spacer with a mean reduction of more than 5 Gy for both regimens. CONCLUSIONS: For organ preservation protocols and selected sexually active female patients, use of hydrogel spacers can be considered to spare sexual organs from the high radiotherapy dose levels. ADVANCES IN KNOWLEDGE: For females with advanced rectal tumor, a spacer implant between the rectum and the vagina before nCRT is feasible and reduces doses delivered to the vagina.

Histopathological diagnosis of tumour deposits in colorectal cancer: a Delphi consensus study.

AIMS: Tumour deposits (TDs) are an important prognostic marker in colorectal cancer. However, the classification, and inclusion in staging, of TDs has changed significantly in each tumour-node-metastasis (TNM) edition since their initial description in TNM-5, and terminology remains controversial. Expert consensus is needed to guide the future direction of precision staging. METHODS AND RESULTS: A modified Delphi consensus process was used. Statements were formulated and sent to participants as an online survey. Participants were asked to rate their agreement with each statement on a five-point Likert scale and also to suggest additional statements for discussion. These responses were circulated together with anonymised comments, and statements were modified prior to carrying out a second online round. Consensus was set at 70%. Overall, 32 statements reached consensus. There were concerns that TDs were currently incorrectly placed in the TNM system and that their prognostic importance was being underestimated. There were concerns regarding interobserver variation and it was felt that a clearer, more reproducible definition of TDs was needed. CONCLUSIONS: Our main recommendations are that the number of TDs should be recorded even if lymph node metastases (LNMs) are also present and that nodules with evidence of origin [extramural venous invasion (EMVI), perineural invasion (PNI), lymphatic invasion (LI)] should still be categorised as TDs and not excluded, as TNM-8 specifies. Whether TDs should continue to be included in the N category at all is controversial, and did not achieve consensus; however, participants agreed that TDs are prognostically worse than LNMs and the N1c category is suboptimal, as it does not reflect this.

Pancreas collagen digestion during islet of Langerhans isolation-a prospective study.

The success of pancreas islet isolation largely depends on donor characteristics, including extracellular matrix composition of which collagen is the main element. We hypothesized that isolation yields are proportional to collagen digestion percentage, and aimed to determine a threshold that predicts isolation success. The amount of pancreas collagen (I-V) was determined using colorimetry prior to and after the digestion process in 52 human islet isolations. Collagen I-V and VI were also assessed histologically. We identified a collagen digestion threshold of ≥ 60% as an independent factor beyond which an islet preparation has a ninefold increased odds of yielding ≥ 250 000 islet equivalents (IEQ) (P = 0.009) and a sixfold increased odds of being transplanted (P = 0.015). Preparations with ≥ 60% collagen digestion (n = 35) yielded 283 017 ± 164 214 IEQ versus 180 142 ± 85 397 in the < 60% collagen digestion group (n = 17) (P = 0.016); respectively 62.9% versus 29.4% of those were transplanted (P = 0.024). Common donor characteristics, initial collagen content, enzyme blend, and digestion times were not associated with collagen digestion percentage variations. Donor age positively correlated with the amount of collagen VI (P = 0.013). There was no difference in islet graft survival between high and low digestion groups. We determined that a 60% pancreas collagen digestion is the threshold beyond which an islet isolation is likely to be successful and transplanted.

Whipple's Disease Affecting Ileal Peyer's Patches: The First Case Report.

Whipple's disease is a rare chronic systemic bacterial infectious disease which can affect multiple organs, with a wide clinical spectrum encompassing many symptoms presenting in various forms and combinations. In the cases where the gastrointestinal tract is implicated, the more frequent localizations involve the small bowel, especially the duodenum. A case of a 67-year-old man who underwent clinical investigation after presenting with a progressive weight loss and showing a hypercapting right paracoeliac adenopathy at PET-CT scan is reported herein. A gastroscopy and a colonoscopy were done. The biopsies of the endoscopically normal ileal mucosa encompassed some submucosal Peyer's patches. Histological examination of this lymphoid tissue revealed several foamy macrophages which turned out positive on periodic acid-Schiff special staining. Polymerase chain reaction of the microdissected lymph follicles allowed for confirming Whipple's disease diagnosis. A targeted antibiotic treatment administrated to the patient led to a rapid clinical improvement. This finding of a previously unreported localization of infected macrophages in Whipple's disease suggests that sampling the organized mucosal-submucosal lymphoid tissue may increase the diagnostic yield in endoscopic biopsies.

Biliary Involvement in Type 2 Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is a rare condition classified in 2 subtypes. Their distinction relies on a combination of clinical, serological, morphological and histological features. Type 1 is a pancreatic manifestation of IgG4-related disease characterized by multiorgan infiltration by IgG4 plasmocytes. In this condition, hepatobiliary infiltration is frequent and often mimics cholangiocarcinoma or primary sclerosing cholangitis. On the other hand, type 2 is commonly limited to the pancreas. Herein, we describe the case of a patient who presented a type 2 AIP associated with cholangiopathy, a condition not described in the established criteria. He first developed a pancreatitis identified as type 2 by the typical histopathological features and lack of IgG4 in the serum and tissue. Despite a good clinical response to steroids, cholestasis persisted, identified by MR cholangiography as a stricture of the left hepatic duct with dilatation of the intrahepatic bile duct in segments 2 and 3. Biliary cytology was negative. Evolution was favorable but after steroid tapering a few months later, the patient suffered from recurrence of the pancreatitis as well as progression of biliary attempt, suspicious for cholangiocarcinoma. As the investigations again ruled out neoplastic infiltration or primary sclerosing cholangitis, azathioprine was initiated with resolution of both pancreatic and biliary attempts.

Primordial germ cells as a potential shared cell of origin for mucinous cystic neoplasms of the pancreas and mucinous ovarian tumors.

Mucinous ovarian tumors (MOTs) morphologically and epidemiologically resemble mucinous cystic neoplasms (MCNs) of the pancreas, sharing a similar stroma and both occurring disproportionately among young females. Additionally, MOTs and MCNs share similar clinical characteristics and immunohistochemical phenotypes. Exome sequencing has revealed frequent recurrent mutations in KRAS and RNF43 in both MOTs and MCNs. The cell of origin for these tumors remains unclear, but MOTs sometimes arise in the context of mature cystic teratomas and other primordial germ cell (PGC) tumors. We undertook the present study to investigate whether non-teratoma-associated MOTs and MCNs share a common cell of origin. Comparisons of the gene expression profiles of MOTs [including both the mucinous borderline ovarian tumors (MBOTs) and invasive mucinous ovarian carcinomas (MOCs)], high-grade serous ovarian carcinomas, ovarian surface epithelium, Fallopian tube epithelium, normal pancreatic tissue, pancreatic duct adenocarcinomas, MCNs, and single-cell RNA-sequencing of PGCs revealed that both MOTs and MCNs are more closely related to PGCs than to either eutopic epithelial tumors or normal epithelia. We hypothesize that MCNs may arise from PGCs that stopped in the dorsal pancreas during their descent to the gonads during early human embryogenesis, while MOTs arise from PGCs in the ovary. Together, these data suggest a common pathway for the development of MCNs and MOTs, and suggest that these tumors may be more properly classified as germ cell tumor variants. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Combination of Adenomyoma and Adenomyomatous Hyperplasia of the Ampullary System: A First Case Report.

Adenomyoma and adenomyomatous hyperplasia are benign tumor-like lesions that rarely involve the major or minor duodenal papilla. We report the case of a 73-year-old patient who underwent a cephalic duodenopancreatectomy due to clinical and radiological evidence of underlying malignant neoplasm. The histopathology results revealed the unusual association of a major duodenal papilla adenomyoma and an adenomyomatous hyperplasia of the minor papilla. Because of their resemblance to pancreatic malignancy, the diagnosis of these lesions is particularly challenging. In most cases, it is established postoperatively, after histopathological examination of the surgical specimen.

Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

BACKGROUND: In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. MATERIALS AND METHODS: The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. RESULTS: The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). CONCLUSION: GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC.

The third pathway of colorectal carcinogenesis.

AIMS: The majority of the colorectal carcinomas (CRC) arise in a vast mucosal area built with columnar cells and mucus-producing goblet cells. These carcinomas evolve via the conventional (tubular/villous) adenoma-carcinoma pathway, or the serrated adenoma-carcinoma pathway. Much less frequently CRC arise in the gut-associated lymphoid tissue (GALT) mucosal domain via the third pathway of colorectal carcinogenesis. METHODS: All publications on human colorectal GALT carcinomas in the literature were reviewed. RESULTS: Only 23 GALT-carcinomas found in 20 patients are in record. The GALT carcinomas were detected at surveillance colonoscopic biopsy in 11 patients (four had ulcerative colitis, two were members of a Lynch syndrome family, two of a CRC family, one had familial adenomatous polyposis (FAP), one prior colon adenomas and one a submucosal tumour), or at diagnostic colonoscopic biopsy in the remaining nine patients (three had rectal bleedings, two abdominal pains, one diverticular disease and one protracted constipation. In three, no ground disease or symptoms were provided). In six of the 23 GALT carcinomas, the luminal surface showed tumour cells, ulcerations or no descriptions were given. Ten (66.7%) of the remaining 15 GALT carcinomas showed on top, adenomas (n=8) or high-grade dysplasia (n=2). CONCLUSIONS: The low frequency of GALT carcinomas might be explained by the fact that the colorectal mucosal areas occupied by GALT domains are minute. The finding that two-thirds of the 15 remaining GALT carcinomas (vide supra) were covered by high-grade dysplasia or by conventional adenomas strongly suggest that conventional non-invasive neoplasias might have preceded the majority of the GALT carcinomas in record.

Early closure of fistula using neo-adjuvant intra-arterial chemotherapy in locally advanced anal cancer.

BACKGROUND: Locally advanced anal cancer patients, especially with T4 disease and fistula, have a dismal prognosis. Neo-adjuvant intra-arterial chemotherapy before standard chemoradiation has been shown to be promising in this setting. AIMS: We are reporting results from a larger patient population. METHODS: From 2005 to 2015, 25 consecutive patients with locally advanced anal cancer, 18 of them fistulised, received intra-arterial chemotherapy. RESULTS: Twenty-two of 25 patients (88%) had T4N0-3 disease and 3 (12%) T3N3. An objective tumour response was observed in 24 of 25 patients (96%): 24 partial responses and 1 with stable disease. Fistulas' complete closure was observed in 15 of 18 patients (83.3%). Following intra-arterial chemotherapy, 23 patients underwent chemoradiation. Twenty-one of 25 patients (84%) had a complete remission 6 months after treatment completion. Amongst 22 patients followed for 3 or more years, 18 of them (81%) are colostomy free at 3 years. Five-year overall survival is 75%. Most frequent grade 3-4 toxicity of IAC was neutropenia (25%). CONCLUSIONS: Neo-adjuvant intra-arterial chemotherapy combined to chemoradiation resulted in a high rate of fistulas closure and long-term control of locally advanced anal cancer. This interesting approach in the treatment of fistulised anal cancer, needs a prospective study before being considered a new standard strategy.

[Multidisciplinary management of localized rectal cancer]. / Prise en charge multidisciplinaire du cancer localisé du rectum.

Rectal cancer remains a frequent pathology, with a good prognosis, according to a proper management. During the last decades, we have been confronted with important improvements, notably regarding the diagnosis and the treatment. In the era of highly specialized medicine, it is clear that the management must be multidisciplinary, incorporating not only the surgeon, the oncologist and the radiation oncologist, but also the radiologist, the gastroenterologist, and the pathologist. We aim to review the recent concepts and the future developments in the management of rectal cancer.

Le cancer du rectum demeure une pathologie fréquente, dont le pronostic est heureusement bon. Ces dernières décennies, nous avons été confrontés à plusieurs avancées importantes, que ce soit au niveau du diagnostic ou du traitement. Sa prise en charge fait partie intégrante de la médecine hautement spécialisée, et il est devenu clair que l'approche se doit d'être multidisciplinaire, incorporant aussi bien le chirurgien, l'oncologue et le radio-oncologue, que le radiologue, le gastroentérologue et le pathologue. Dans cet article, les concepts récents ainsi que les perspectives futures sont analysés.