Microangiopathic hemolytic anemia (MAHA) as paraneoplastic syndrome in metastasized signet ring cell carcinomas: case reports and review of the literature

We report on two spontaneous cases of microangiopathic hemolytic anemia (MAHA) as first manifestation due to metastasized signet ring carcinoma, one of gastric and one of unknown origin. The patients presented with an acute onset of Coombs negative hemolytic anemia and fragmentocytes in the peripheral blood smear which are typical for MAHA. These case reports present MAHA as a rare paraneoplastic syndrome in patients with metastasized signet ring carcinoma. Parallel to symptomatic treatment we started chemotherapy treatment (ELF and PLF regimen, respectively). In both cases we were able to control the MAHA and cancer progression.     

Pedunculated gastric carcinoma demonstrating a gastric foveolar phenotype

We report a case of gastric cancer complicated with very well differentiated adenocarcinoma containing signet ring cells. An endoscopic examination revealed a pedunculated polyp in the fornix of the stomach. A surgical operation was performed and the pathological findings showed very well differentiated adenocarcinoma mimicking gastric foveolae with a poorly differentiated component containing signet ring cells. This is the first case of pedunculated gastric cancer complicated with very well differentiated adenocarcinoma containing signet ring cells and also demonstrating a gastric foveolar phenotype.     

Minute signet ring cell carcinoma occurring in gastric hyperplastic polyp

We describe a 45-year-old woman with minute signet ring cell carcinoma occurring in a gastric hyperplastic polyp. A biopsy specimen obtained from the gastric hyperplastic polyp revealed signet ring cell carcinoma. Endoscopic mucosal resection （EMR） was performed to confirm the diagnosis. Histological examination of the EMR specimen revealed focal signet ring cell carcinoma in the hyperplastic polyp. There are few cases of gastric hyperplastic polyp associated with signet ring cell carcinoma.     

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.     

Coexistence of multifocal gastric adenocarcinoma with signet-ring cell morphology and a gastrointestinal stromal tumour in a stomach with hp-associated gastritis

A 79-year-old man was admitted because of anemia during marcumar therapy with suspected bleeding in the gastrointestinal tract. Endoscopy revealed a large mutifocal poorly differentiated gastric signet ring cell adenocarcinoma. After staging by the usual oesophagogastroduodenoscopic method, a total D 2 gastrectomy was performed. In the pathological resection specimen of the stomach, a multifocal poorly differentiated signet ring cell adenocarcinoma, infiltrating the submucosa (so called early cancer of sm-type) and an incidental gastroinstinal stromal tumour, 0.8 cm in diameter, was diagnosed. This is the first case report of the synchronous occurrence of a multifocal poorly differentiated gastric adenocarcinoma with signet-ring cell morphology (diffuse type according to the Lauren classification) and a GIST incidentally within a stomach with Hp-associated gastritis.     

A case of Sister Mary Joseph's nodule as a presenting sign of gastric cancer]

The cutaneous metastasis of a visceral malignancy to the umbilicus is known as "Sister Mary Joseph's nodule (SMJN)". It is considered to be a predictor of poor prognosis because it mostly occurs in advanced, metastasizing cancer. However, it is a very rare condition as an initial presenting sign of primary cancer. We recently encountered a 48-year-old man presented with an umbilical lump. The lesion was a firm, ill-delineated, painful nodule with regular surface in the umbilicus. Abdominal computed tomography showed a 2.2 cm sized, ill-defined, delayed enhancing mass at the periumbilical area accounting for umbilical nodule. Diffuse irregular thickening of peritoneum and diffuse wall thickening of stomach implied the diagnosis of gastric cancer. Esophagogastroduodenoscopy revealed diffuse nodular infiltrative lesion from cardia through body of the stomach, compatible with Bormann type 4 advanced gastric cancer. Later, histopathologic confirmation showed a presence of signet ring cell adenocarcinoma from biopsy specimens. We experienced a case presenting with an umbilical metastasis as the first sign of gastric adenocarcinoma. It is thought that direct extension of tumor through the peritoneum might be the route for umbilical metastasis. Careful examination of all umbilical lesions must be needed for the early diagnosis of internal malignancy.     

Endoscopic features of early-stage signet-ring-cell carcinoma of the stomach

AIM: To identify the features of early signet ring cell gastric carcinoma using magnification endoscopy with narrow band imaging (NBI).METHODS: A retrospective review was conducted of 12 cases of early signet ring cell gastric carcinoma who underwent treatment in a single institution between January 2009 and April 2013. All patients had magnification endoscopy with NBI and indigo carmine contrast to closely examine the mucosal architecture, including the microvasculature and arrangement of gastric pits. Histologic examination of the final endoscopic submucosal dissection or gastrectomy specimen was performed and compared with the endoscopic findings to identify patterns specific to signet ring cell carcinoma.RESULTS: Twelve patients with early signet ring cell gastric carcinoma were identified; 75% were male, and average age was 61 years. Most of the lesions were stage T1a (83%), while the remainder were T1b (17%). The mean lesion size was 1.4 cm². On standard endoscopy, all 12 patients had a pale, flat lesion without any evidence of mucosal abnormality such as ulceration, elevation, or depression. On magnification endoscopy with NBI, all of the patients had irregularities in the glands and microvasculature consistent with early gastric cancer. In addition, all 12 patients exhibited the “stretch sign”, an elongation or expansion of the architectural structure. Histologic examination of the resected specimens demonstrated an expanded and edematous mucosal layer infiltrated with tumor cells.CONCLUSION: The “stretch sign” appears to be specific for signet ring cell carcinoma and may aid in the early diagnosis and treatment of this aggressive pathology.     

Metastases of a gastric adenocarcinoma presenting as colonic polyposis

The authors report a case of multiple colonic metastases of a gastric signet ring cell adenocarcinoma, presenting as colonic polyposis revealed by diarrhea, iron deficiency anemia, and left supraclavicular lymph node.     

Signet-ring cell carcinoma arising from a fundic gland polyp in the stomach

Fundic gland polyps (FGPs) are currently the most common type of gastric polyps and are usually benign. However, although rare, gastric adenocarcinoma of FGP has been recently proposed as a new variant of gastric adenocarcinoma. Here we report the first case of a 49-year-old woman with focal signet ring cell carcinoma that arose from an FGP of the stomach. The tumor was completely excised by endoscopic snare polypectomy. FGPs should therefore be evaluated for malignant changes although they occur rarely, if the FGP has an erosive or irregular surface.     

Primary rectal signet ring cell carcinoma with peritoneal dissemination and gastric secondaries

Disseminated signet ring cell carcinomas frequently arise from the stomach. However, primaries in the colon and rectum have also been reported. We present a 68 year old lady who presented with a change in her bowel habit. Colonoscopy showed a stenosing rectal tumour at 7 cm to 8 cm from the anal verge. Multiple scattered ulcers were also noted along the entire length of the colon. Biopsy of the lesions revealed signet ring cell adenocarcinoma. Gastroscopy showed multiple nodules with ulceration over several areas of the stomach which were similar in appearance to the colonic lesions. However, no primary tumour of the stomach was seen. Biopsy of the gastric lesions also showed signet ring cell adenocarcinoma. Computed tomography scan of the abdomen and pelvis revealed circumferential tumour at the rectosigmoid junction with possible invasion into the left ischiorectal fossa. The overall picture was that of a primary rectal signet ring cell carcinoma with peritoneal dissemination. The patient was referred for palliative chemotherapy in view of the disseminated disease. In the present report, we discuss this interesting pathological entity and review the role of various histolological techniques in helping to identify the primary tumor.     

肺转移性印戒细胞癌1例并文献复习

目的研究胃印戒细胞癌肺转移的临床特点。方法介绍1例对肺转移性印戒细胞癌的病例,并进行文献复习。结果以慢性咳嗽患者影像学上支气管周围斑片状阴影及多发纵隔淋巴结肿大并伴有外周血嗜酸粒细胞的增多,应考虑消化道肿瘤的可能。结论恶性度极高的黏液细胞型胃癌,可以跳跃转移到肺及纵膈。如果慢性咳嗽的患者,外周血嗜酸粒细胞的增多时,应尽早行肿瘤标记物及内窥镜的检查,以提高肿瘤的早期诊断率。     

A Small Gastric Cancer in Association with Menetrier Disease

Abstract: We studied a 57-year-old man who was diagnosed as having giant rugae at a mass-screening for gastric cancer. He was examined endoscopically for check-up purposes. In addition to giant rugal folds which occurred throughout the entire fundus and body of the stomach, a type IIc lesion was noted in the posterior lower wall of the gastric body. A biopsy revealed signet ring cell carcinoma. A total gastrectomy was performed. A resected specimen was serially sectioned and underwent histopathological examination; hypertrophy and cystic elongation of the gastric glands indicative of so-called giant hypertrophic gastritis was seen. The histological type of the type IIc lesion was undifferentiated adenocarcinoma with the signet ring cells being confined to the mucosal layer. This patient had a rare case of Menetrier's disease complicated by intramucosal carcinoma.     

A case of gastric metastasis of breast carcinoma resembling early gastric cancer]

Many patients suffering from breast carcinoma have metastases at initial diagnosis. The common metastatic sites are skeleton, liver and lung. Metastases to stomach are rare and only three cases have been reported in Korea. The endoscopic features of gastric metastases from breast carcinoma can be divided into three main categories: diffuse infiltration, external compression, and localized tumor deposition with ulceration or with a polypoid mass. However, metastatic gastric lesions which resemble early gastric carcinoma are rare. Typically, gastric metastases are confined to submucosa and muscularis, so that mucosal biopsy specimens might be false-negative. We report a case of gastric metastasis from infiltrative lobular carcinoma of the breast in a 66-year-old woman who had undergone left mastectomy with postoperative radiotherapy 17 years earlier. Initial diagnosis was early gastric carcinoma, signet ring cell type on gastric biopsy findings. However, definitive diagnosis of metastatic breast cancer was confirmed after endoscopic mucosal resection of a presumed primary early gastric carcinoma.     

The diagnostic role of endoscopic submucosal dissection for gastric lesions with indefinite pathology

Abstract Objective. Endoscopic forceps biopsy is a fundamental modality for the histologic diagnosis of gastric neoplasms. However, the pathologic findings are not always concordant with the endoscopic interpretations. Currently, repeat endoscopic biopsy is the only way to manage lesion of indefinite pathology such as Category 2 according to the revised Vienna classification. We aimed to elucidate the role of endoscopic submucosal dissection (ESD) in clarifying the final pathologic diagnosis. Method. Among the 2304 gastric ESD cases, a total of consecutive 30 patients with 31 lesions (1.3%) that had a forceps biopsy with indefinite pathology discrepant from the endoscopic findings underwent endoscopic submucosal dissection (ESD) for confirmative diagnosis and treatment. Results. The final pathologic diagnoses of the ESD specimens were as follows: low-grade dysplasia in 3 patients (9.7%); high-grade dysplasia in 2 patients (6.5%); adenocarcinoma in 15 patients (48.4%); and a benign lesion in 11 patients (35.5%). Cases with adenocarcinoma included nine well-differentiated lesions, four moderately differentiated lesions, and two lesions with signet ring cell carcinoma. The complete en bloc resection rate for neoplastic lesions was 95.0%, and the incidence rates of ESD-related bleeding and perforation were 5.0% and 5.0%, respectively. Conclusion. ESD can be considered an effective and safe alternative therapeutic and diagnostic tool for gastric lesions in cases where the forceps biopsy pathology is discrepant from the endoscopic findings. The overall final neoplastic diagnosis rate after ESD was 64.5%, and ESD should be performed for lesions with red coloration and friability.     

青年人与老年人胃癌临床病理及预后对比分析

目的探讨青年与老年胃癌的临床、内镜、术后病理特点及预后。方法回顾性总结我院2003年12月～2012年12月经胃镜检查,手术确诊的青年人(≤35岁)胃癌51例及老年人(≥65岁)胃癌284例,进行临床表现、内镜表现、术后病理分型及预后等对比分析。结果近年来,胃癌患病总人数下降,同期内老年人胃癌总人数多于青年人;青年组胃癌以女性多,老年组以男性多;青年组多在胃下1/3,老年组多在胃上1/3;内镜下青年组多表现为Borrmann Ⅲ、Borrmann Ⅳ,术后病理以低分化腺癌、黏液腺癌、印戒细胞癌为主;老年组以Borrmann Ⅰ、Borrmann Ⅲ为主,术后以高-中分化腺癌居多;两组胃癌手术方式无差异性;老年组1年、3年生存率高于青年组。结论青年人胃癌临床症状隐匿,病理分化差,预后差。早期胃镜检查、定期复查、幽门螺杆菌根除、手术是青年人胃癌治疗的关键。     

Ultrastructural cytochemical study of enzymes expressed by signet ring cells in gastric cancer

AIM: To study the ultrastructural localization of five marker enzymes (ALPase, ACPase, G6Pase, TPPase and CCOase) in gastric cancer signet ring cells to demonstrate their biologic behaviors.METHODS: Five marker enzymes were examined in signet ring cells of seven gastric cancer patients by ultrastructural enzyme cytochemical techniques.RESULTS: The number of corresponding organelles and the activities of marker enzymes, especially ACPase and TPPase, increased, leading to stronger mucus synthesis, secretion and digestion in gastric cancer signet ring cells. There was a lack of collagenous fibers in the stroma around the cancer nests.CONCLUSION: Signet ring cell carcinoma is very invasive with metastasis rates due to the secretion of proteolytic enzymes.     

Signet Ring Cell Histology Is Not an Independent Predictor of Poor Prognosis After Curative Resection for Gastric Cancer: A Propensity Analysis by the KLASS Group

Whether signet ring cell (SRC) histology carries a worse prognosis than other forms of gastric adenocarcinoma has been questioned. The present study investigated the differences in clinicopathologic features and survival between SRC and non-SRC adenocarcinoma. The prospectively collected data of 2643 patients who had undergone curative gastrectomy between 1998 and 2005 by 10 surgeons were reviewed. Additionally, we employed analysis of covariance, propensity-score risk adjustment, and propensity-based matching to account for possible selection bias. The baseline characteristics of prematched patients with SRC or non-SRC adenocarcinoma histology differed: SRC presented in younger patients and less often in men, was more likely found in the middle stomach, and was more likely to be Stage I. After applying the propensity-score strata and propensity-score matching, there was no difference in the baseline characteristics, and SRC was not an independent risk factor for mortality in the same stage. SRC is not an independent predictor of poor prognosis after curative resection for gastric cancer in Korea.     

胃癌印戒细胞电镜酶细胞化学研究

目的对胃癌印戒细胞５种细胞器标志酶（ＡＬＰａｓｅ，ＡＣＰａｓｅ，Ｇ６Ｐａｓｅ，ＴＰＰａｓｅ和ＣＣＯａｓｅ）进行超微水平的定位观察，探讨胃癌印戒细胞的生物学行为及其发生机理．方法应用电镜酶细胞化学技术对５例印戒细胞癌，２例伴有印戒细胞的粘液腺癌进行５种细胞器标志酶的电镜观察．结果胃癌印戒细胞粘液的合成、分泌和消化功能增强，相应细胞器数目增多，酶活性增强，其中尤以ＡＣＰａｓｅ，ＴＰＰａｓｅ为显著．癌周间质缺乏胶元纤维．结论胃癌印戒细胞在功能上属高分化，但其形态与功能不协调，出现了畸形分化．其侵袭力强、转移率高的原因与癌细胞分泌的酶对细胞连接的影响和溶解癌周间质密切相关．     

A case of early gastric cancer with bone metastases: are bone marrow micrometastases significant?

Gastric adenocarcinoma is currently the 14th cause of death worldwide. Early gastric cancer, defined as cancer not penetrating deeper than the submucosa, is considered to carry an excellent prognosis with 5-year survival rates reaching more than 90%. Cases of bone metastases due to intramucosal gastric cancer are very rarely described. A case of a 70-year old male presenting with confirmed bone metastases 7 years after a curative resection for a mucosal gastric carcinoma is discussed. The patient was investigated with bone marrow biopsy and bone scan and showed no other signs of disease. The clinicopathologic features included poor differentiation, signet ring cells presence, no lymph node involvement and a negative second laparotomy two years after the initial surgery. Studies concerning the presence of residual disease in the form of bone marrow micrometastases are briefly reviewed emphasizing that intramucosal gastric cancer still carries the p sibility for metastasis, many years after a curative resection, mandating long term alertness from the attending physician.     

Schistocytes in erythroleukemia

A patient whose initial hematologic evaluation suggested the diagnosis of a microangiopathic hemolytic anemia (MAHA) was further evaluated and found to have erythroleukemia (DiGuglielmo's syndrome). This prompted us to review retrospectively the peripheral blood morphology of 12 patients with erythroleukemia. Anisocytosis, poikilocytosis, macrocytosis, and nucleated red cells have been described in patients with erythroleukemia; however, changes characteristic of a microangiopathic hemolytic process (schistocytes) have not been previously described. Our patients with erythroleukemia had prominent helmet and fragmented red cells, as well as elliptocytosis. Six of our 12 patients with erythroleukemia did not have blasts on their peripheral smear, and platelets were decreased (platelet count ranged from 2 to 92 X 10(3)/microliter), resulting in changes similar to patients with MAHA due to thrombotic thrombocytopenic purpura (TTP), traumatic RBC lysis, and disseminated intravascular coagulation. Our data indicate the RBC changes characteristic of MAHA are commonly seen in erythroleukemia, and that as many as half of these patients may not have white cell changes suggestive of leukemia on the peripheral smear. Patients presenting with microangiopathic hemolytic anemia require a bone marrow examination to confirm or exclude a myelodysplastic syndrome.