The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment.

Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a "leather bottle appearance". LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management.

Primary gastric amyloidosis associated with linitis plastica and delayed progression to systemic amyloidosis and multiple myeloma.

We report the case of a woman in her 50s who underwent, 5 years prior, a total gastrectomy after neoadjuvant chemotherapy for diffuse-type gastric cancer diagnosed during a workup for isolated gastric primary light chain (AL) amyloidosis. At the time of diagnosis, immunoglobulins light chain measurements and bone marrow biopsy were performed to rule out multiple myeloma and came back normal. Three years later, the patient developed systemic amyloidosis involving the heart and the lungs, after which she developed multiple myeloma. Isolated amyloid deposits in the stomach are a rare finding. While AL amyloidosis is frequently found in concomitance with multiple myeloma, late progression of primary AL amyloidosis to systemic amyloidosis and multiple myeloma is uncommon.

pCLE detects mucosal neoplastic vascular pattern in gastric linitis plastica.

Linitis plastica (LP) is a very aggressive and rare carcinoma with a scirrhous stroma that affects the submucosal and muscular layers of the stomach even without mucosal alterations. Lack of timely diagnosis is a crucial problem related to its prognosis and treatment. In this study, we investigated the LP-associated vascular pattern as a possible means to improve the diagnosis of these patients. During standard endoscopy, mucosal architecture, tortuosity and enlargement of vessels, as well as the presence of vascular leakage and efficiency of the blood flow were assessed in six LP patients using probe-based Confocal Laser Endomicroscopy (pCLE). In all LP patients, we detected abnormal changes in vasculature. The aberrant features of the vascular network were common to all LP patients examined and consisted of vessel enlargement, tortuosity, and leakage associated with the affected submucosal layer. This is the first study to highlight the presence of marked vascularization associated with LP, characterized by the presence of abnormal and non-functional vessels, similar to what is observed in neoplastic tissues. Therefore, the analysis of LP by pCLE may provide a new endoscopic approach and strategy to better define these patients.

[Chronic ischemic gastropathy as a simulator of plastic linitis]. / Gastropatía isquémica crónica como simuladora de linitis plástica.

Chronic ischemic gastropathy is a rare entity, being the atheroesclerotic vascular the most prevalent cause. Clinical and endoscopic manifestations are unspecific and may simulate more frequent pathologies. Cardiovascular risk factors allow us to diagnose and treat these patients earlier. We present the case of a patient with chronic ischemic gastropathy that manifested abdominal pain, weight loss and endoscopic findings as a simulator of linitis plastica. The diagnosis was made with an endoscopic block biopsy after two inconclusive biopsies.

La gastropatía isquémica es una entidad rara, cuya etiología más frecuente es la obstrucción al flujo sanguíneo secundaria a aterosclerosis. Sus manifestaciones clínicas y endoscópicas son inespecíficas, pudiendo simular afecciones más prevalentes. La sospecha clínica en pacientes con factores de riesgo cardiovascular permite un diagnóstico precoz y tratamiento adecuado. Presentamos el caso de una paciente con gastropatía isquémica crónica que se manifestó con dolor abdominal, pérdida de peso y hallazgos endoscópicos compatibles con linitis plástica. Se arribó al diagnóstico con una biopsia endoscópica en bloque luego de haber obtenido dos biopsias previas no concluyentes.

Emlorák hasüregi áttétei - Egy szokatlan entitás klinikopatológiai jellemzoi.

Case report: A sixty-five-year-old female patient underwent surgery for severe gastrointestinal symptoms, following an alarming CT image. Laparotomy revealed irresectable gastric cancer and peritoneal carcinosis. Palliative gastro-jejunostomy and ileo-descendostomy were performed. The endoscopic diagnosis - linitis plastica - and the intraoperative macroscopic appearance matched and agreed on the histologically presumed shigillocellular carcinoma. Three years following the initial abdominal symptoms, histological samples taken from newly detected cutaneous metastases which developed during oncological palliative treatment verified occult lobular breast carcinoma. Histological revision of the sample taken from abdominal exploration confirmed the latter diagnosis. The hormone receptor positive, human epidermal growth factor receptor-2 negative malignancy showed very good regression for the palliative hormone treatment. Discussion: About ten percent of breast cancer cases are lobular carcinomas, which are more often multicentric, bilateral, occult and have a propensity to metastasize to serous membranes, abdominal and pelvic viscera. Due to the increasing survival of breast cancer patients, the number of abdominal metastases of breast cancer is expected to increase. Histological confirmation is indispensable even in case of advanced abdominal malignancies, especially in the case of an unusual medical history. The currently rare case demonstrates the need for multidisciplinary cooperation in all diagnostic and therapeutic fields of breast cancer.

Development and internal validation of a diagnostic score for gastric linitis plastica.

BACKGROUND: There is no consensual definition for gastric linitis plastica (GLP). We aim to construct a diagnostic score to distinguish this rare tumor from usual gastric adenocarcinomas. METHODS: In this retrospective study, all patients who had gastrectomy for cancer between 2007 and 2017 in French tertiary centers were included. The outcome was a diagnosis of GLP based on pathological review of the surgical specimen. The diagnostic score was created by using variables that were most frequently associated with GLP using penalized logistic regression on multiply imputed datasets. We used discrimination measures to assess the performances of the score. Internal validation was performed using bootstrapping methods to correct for over-optimism. RESULTS: 220 patients including 71 linitis plastica (female 49%, median age 57 years) were analyzed. The six parameters retained in the diagnosis score were the presence of large folds and/or parietal thickening on at least one segment, pangastric infiltration and presence of gastric stenosis on the upper endoscopy, circumferential thickening on at least one segment and thickening of the third hyperechogenic layer on endoscopic ultrasound and the presence of signet ring cells on endoscopic biopsies. The area under the ROC curve (AUC) was 0.967 with a sensitivity of 94% [89.9-97.3] and a specificity of 88.7% [81.7-95.8] for a threshold of 2.75. After internal validation, the corrected AUC was 0.959. CONCLUSION: It is the first study validating a pre-therapeutic diagnostic score (Saint Louis linitis score) with an excellent ability to discriminate GLP from non-GLP adenocarcinomas. An external validation is necessary to confirm our data.

Valor del ultrasonido endoscópico en el diagnóstico de la linitis plástica gástrica / Value of endoscopic ultrasound in the diagnosis of gastric plastic linitis

Fundamento: la linitis plástica gástrica es una forma avanzada de cáncer gástrico de pronóstico desfavorable y diagnóstico complejo. Objetivo: presentar el caso de un paciente con linitis plástica gástrica cuya evaluación inicial no fue concluyente para diagnóstico. Presentación del caso: paciente masculino de 51 años de edad que presenta dolor abdominal en epigastrio, vómitos, pérdida de peso y decaimiento. Se realiza estudios analíticos que concluyen linitis plástica gástrica difusa con posible carcinosis peritoneal. Conclusiones: la linitis plástica gástrica es una enfermedad infrecuente con alta morbi-mortalidad y que requiere en algunos casos de estudios especiales como el ultrasonido endoscópico en los pacientes con alta sospecha diagnóstica (AU)

Background: gastric plastic linitis is an advanced form of gastric cancer with an unfavorable prognosis and a complex diagnosis. Objective: to present the case of a patient with gastric plastic linitis whose initial evaluation was inconclusive for diagnosis. Case report: a 51-year-old male patient presented with abdominal pain in the epigastrium, vomiting, weight loss and decay. Analytical studies are performed and they conclude diffuse gastric plastic linitis with possible peritoneal carcinosis. Conclusions: gastric plastic linitis is an infrequent disease with high morbidity and mortality and in some cases requires special studies such as endoscopic ultrasound in patients with high diagnostic suspicion (AU)

Primary signet-ring cell carcinoma of the urinary bladder: A report of two cases.

INTRODUCTION: Primitive bladder adenocarcinomas account for about 2% of urinary bladder tumors. Primary signet-ring cell carcinoma is a rare variant of bladder adenocarcinoma. It is characterized by a late diagnosis and a poor prognosis. The aim of the study was to discuss the clinical, pathological and evolutive features of this rare entity. Clinical Observations: We report two patients a 53-year-old man and a 70-year-old woman. The main reason for consultation was right back pain, mictional burn and total hematuria. Abdominal ultrasound showed a thickened bladder wall measuring 8 mm in thickness. Ultrasonography revealed a budding intravesical lesion with a calculation of the lower left ureter measuring 5mm of great diameter. Cystoscopy showed an atypical tissular lesion frayed whitish and solid in the cut. Pelvic MRI performed in women showed a cervix ill-limited tissue mass invading the anterior vaginal wall. A transurethral resection of the bladder tumor was performed in one case and a biopsy of the bladder lesion for the other case. The immunohistochemical study showed positive tumoral cells to CK7. The diagnosis of signet ring cell adenocarcinoma of the bladder was established. CONCLUSION: Signet ring cell adenocarcinoma of the bladder is an aggressive tumor of rapid development and poor prognosis. Its management is multidisciplinary and involves surgery. Adjuvant chemotherapy should be discussed even if consensual attitude has not been set.

Linitis plastica of the bypassed stomach 7 years after Roux-en-Y gastric bypass: a case report.

Laparoscopic Roux-en-Y gastric bypass (RYGB) is currently the preferred surgical procedure to treat morbid obesity. It has proven its effects on excess weight loss and its positive effect on comorbidities. One of the main issues, however, is the post-operative evaluation of the bypassed gastric remnant. In literature, cancer of the excluded stomach after RYGB is rare. We describe the case of a 52-year-old woman with gastric linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass, diagnosed by means of laparoscopy and Single-Balloon enteroscopy, and it is clinical importance. Linitis plastica of the excluded stomach after RYGB is a very rare entity. This case report shows the importance of long-term post-operative follow-up, and the importance of single-balloon enteroscopy for visualization of the bypassed stomach remnant, when other investigations remain without results. This case report is only the second report of a linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass.

A case report of gastric linitis plastica diagnosed by endoscopic ultrasound-guided fine needle aspiration.

RATIONALE: There is currently no consensus on the ideal method for obtaining deep tissue biopsy material of advanced gastric LP. EUS-FNA has potential as a useful diagnostic method. Thus, we report the case of a 46-year-old male with advanced gastric linitis plastica (LP) who was diagnosed using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). PATIENT CONCERNS: The patient underwent esophagogastroduodenoscopy (EGD) because of epigastric pain at a local clinic. The gastric fold swelling was pointed out by the EGD and despite the suspected advanced gastric LP, biopsy indicated Group 1. Repeat biopsy did not suggest malignancy. The patient was referred to our institution. DIAGNOSES: Endoscopic ultrasound indicated gastric wall thickening mainly in the greater curvature of the gastric corpus. Low-level echoes were detected throughout the entire gastric wall, and gastric wall layers had been disappeared. EUS-FNA of the gastric wall indicated signet ring cell carcinoma. INTERVENTIONS: As a result of EUS - FNA, it became a policy to administer chemotherapy. In accordance with the patient's wishes, he was referred to another institution for chemotherapy. OUTCOMES: Normal biopsy did not give a definitive pathological diagnosis, and final diagnosis of LP was obtained with EUS-FNA. LESSONS: We expect that EUS-FNA can be utilized as a relatively non-invasive, highly sensitive, and specific pathological diagnostic procedure for advanced gastric LP. EUS-FNA should be considered as one way to obtain a deep tissue biopsy of advanced gastric LP.

Accuracy of staging laparoscopy in detecting peritoneal dissemination in patients with gastroesophageal adenocarcinoma.

Despite staging laparoscopy (SL) with peritoneal lavage is recommended in US Guidelines in patients with potentially resectable gastroesophageal adenocarcinoma, this procedure is not systematically proposed in French Guidelines. Therefore, we decided to analyze the results of systematic SL in patients considered for preoperative chemotherapy. From 2005 to 2011, 116 consecutive patients with distal esophagus, esogastric junction, and gastric adenocarcinoma ≥T3 or N+ without detectable metastatic dissemination by computed tomography (CT) scan imaging underwent SL before neoadjuvant chemotherapy. Positive and negative SLs were compared according to tumor characteristics. SL was positive in 15 cases (12.9%) including 14 with peritoneal seeding (localized in five, diffuse in nine). SL was positive in 7 (24.1%) of 29 patients with poorly differentiated tumor, in 9 (32.1%) of 28 patients with signet ring cells, in 7 (50%) of 14 patients with gastric linitis tumor, and in 15 (16.3%) of 92 patients with T3 or T4 tumor. All the lesions of distal esophagus extending to the cardia had a negative SL. Among the 14 patients with peritoneal carcinomatosis at SL, nine (65%) had signs of peritoneal seeding on initial CT scan. One (0.8%) patient had a small bowel perforation closed laparoscopically. If systematic SL before preoperative chemotherapy does not seem justified because of its low accuracy, it should be performed in patients with poorly differentiated tumor, signet ring cell, and gastric linitis plastica components on biopsy and when CT scan is suggestive of T4 tumor, ascites, or peritoneal nodule.

Primary Linitis Plastica of the Rectum: Focus on Magnetic Resonance Imaging Patterns and Treatment Options.

BACKGROUND: Rectal linitis plastica (RLP) is a rare disease with poor outcome. It is often accompanied by a delayed histopathological diagnosis, primarily due to submucosal disease. A concentric ring pattern or "target sign" on T2-weighted magnetic resonance imaging (MRI) has been proposed as being characteristic for early suspicion. Even though RLP is more aggressive and has poorer survival than other rectal adenocarcinomas, no specific treatment is recommended. In this case report of 3 patients, we challenge the sensitivity of the characteristic radiological pattern, and we review the existing data for a treatment strategy. CASE REPORT: One patient presented classic clinical characteristics of RLP with young age and advanced stage at diagnosis, with chemo-refractory disease and rapid fatal evolution. Biopsies confirmed the RLP with the presence of signet-ring cells (SRC) in a strong desmoplastic stromal reaction. However, the characteristic concentric ring pattern was absent. Instead, he had a large vegetative lesion with important tumor infiltration in mesorectum and pelvic organs, with major lymph node involvement. The 2 other patients presented resectable locally advanced disease with characteristic concentric ring pattern. No clinical and radiological responses were observed to neo-adjuvant chemoradiotherapy (CRT), including 1 patient with non-resectable disease at surgery and another with upstaged disease at pathological specimen after resection. However, data suggest 2 types of RLP: about half of patients are extremely sensitive to CRT with pathological complete response, and the other half are highly resistant with no response to CRT. Current data are insufficient to distinguish between these 2 populations. CONCLUSIONS: The absence of a concentric ring pattern should not eliminate the suspicion of RLP, especially in young patients with aggressive clinical presentation. There are probably 2 types of RLP in terms of chemoradiosensitivity, and neoadjuvant CRT could delay the curative-intent surgery in refractory patients. Future molecular analysis of the tumor and its environment are required to characterize the 2 different forms of RLP to develop more personalized treatment strategies.