Two cases of histopathologically advanced (stage IV) early gastric cancer]

Various minimally invasive surgical techniques in some cases of early gastric cancer are becoming common practice. However, there are rare cases of advanced cancer with distant metastasis although the invasion of the gastric wall is limited to the mucosa and/or submucosa (defined as early gastric cancer according to UICC-TNM classification). We report two cases of early gastric cancer with distant metastasis (stage IV). Both tumors were defined as early cancer because they were confined to the submucosa. One was a type IIa early cancer, histologically classifiable as a signet ring cell carcinoma (according to the Japanese Classification of Gastric Carcinoma and UICC-TNM classification); the other was a surface spreading type IIb + IIc, classifiable as a signet ring cell carcinoma, too. Stage IV factors were ovarian metastasis (Krukenberg tumor) in the former and N3 in the latter case.     

SYNCHRONOUS MULTICENTRIC SIGNET‐RING CELL CARCINOMA OF THE STOMACH

A case of simultaneous multicentric signet‐ring cell carcinoma (SRC) of stomach is presented. Initially, an early gastric cancer (IIc) was diagnosed and this was cured with distal gastrectomy. Thirty‐eight months after the operation, follow‐up endoscopy revealed a tiny mucosal discoloration lesion, which was diagnosed as a minute SRC focus with biopsy. This was successfully treated with endoscopic mucosal resection (EMR). Nine months later, gastroscopy discovered another small mucosal lesion and it was again diagnosed as a tiny SRC lesion, which was also successfully treated with EMR. After a further 2 months, endoscopy showed three small mucosal lesions (discoloration) similar to previous lesions, two of which proved to be SRC with biopsy. As these lesions distributed widely over the remnant stomach, total gastrectomy of the residual stomach was performed. Pathological examination demonstrated a total of 22 simultaneous multifocal SRC lesions, which were all very small mucosal cancer. These cancers, including previously EMR‐treated ones, seemed to develop in a multicentric manner, as they were diagnosed within 11 months. This case also indicated that even subtle endoscopic findings should vigorously be sought and, if in doubt, be biopsied in order to locate gastric cancer early enough for minimal invasive curative treatment to be feasible.     

Gastric cancer with metastasis to the gingiva

The present case report describes a gastric cancer which showed unusual metastasis in the oral region. A 56-year-old male patient underwent total gastrectomy and splenectomy due to advanced gastric cancer in the upper third of the stomach. Fifteen months later, he presented with anorexia and gingival swelling of durations of approximately 3 and 1 month, respectively. The gastric tumor was histologically a signet ring cell and a poorly differentiated cancer with a moderate degree of vascular invasion. Biopsy specimens from the gingival tumor revealed a signet ring cell cancer. Other metastatic sites were the brain, limb bones and abdominal lymph nodes. A bone scintigram revealed an abnormal uptake in the limb bones, while it did not exhibit any abnormality in the oral region. Correlation between the histology of the gingival tumor with that of the gastric cancer, as well as the absence of a gingival tumor at the time of prior gastrectomy, led to a diagnosis that the gingival tumor was a metastasis from gastric cancer. Gastric cancer metastasizing to the oral region, either the osseus or the oral soft tissue, is very rare. Although it cannot be proved without an autopsy, negative findings in the mandible by bone scanning in the present case suggest that direct gingival metastasis can be considered, rather than mandibular metastasis involving the gingiva. Hematogenous spread could be a mechanism of metastasis for this unusual tumor.     

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.     

A case of gastric hamartomatous inverted polyp (submucosal tumor type) accompanied by gastric cancer]

Endoscopic examination of a 39-year-old woman revealed a flat-elevated submucosal tumor (SMT) in the upper third area of the stomach and a IIc lesion in the anterior wall of the lower third of the stomach. Endoscopic ultrasonography findings suggested an aberrant pancreas. Both lesions were resected by distal gastrectomy. Histological examination of the SMT revealed the dilated glands with cyst formation and proliferation of smooth muscle bundles in the submucosal layer, and it was diagnosed as a gastric hamartomatous inverted polyp. The IIc lesion was a signet ring cell carcinoma. Cases of gastric hamartomatous inverted polyps coexistent with gastric cancer have been rarely reported in Japan.     

Multiple early gastric cancer with gastritis cystica profunda showing various histological types

We report a case of multiple early gastric cancer showing varied histological types associated with gastritis cystica profunda (GCP). A 61-year-old man who had early gastric cancer associated with GCP underwent a distal gastrectomy with lymphadenectomy. Histological examination showed various histological types of cancer -well differentiated, moderately differentiated, poorly differentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma- that had developed independently in the mucosal and submucosal layers of the resected specimen. Furthermore, multiple cysts with a single layer of columnar epithelium were present in the submucosa around the cancerous lesions. However, no neoplastic changes were found in those epithelial cells. Helicobacter pylori was detected in the residual stomach 3 months after surgery. Although the mechanism of the relationship between gastric carcinoma and GCPs is obscure, we speculate that repeated erosion and regeneration induced by chronic inflammation causes multicentric carcinogenesis as well as an aberration of the gastric glands. GCPs may be a risk factor for multiple gastric cancer.     

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.     

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.     

Extensive bone marrow necrosis associated with carcinomatosis 7 years after operation for gastric cancer

A case of extensive bone marrow necrosis due to cancer metastasis is reported. A 55-year-old female, who had a history of subtotal gastrectomy for signet ring cell carcinoma of the stomach 7 years ago, was admitted to our hospital with a complaint of lumbago on October 25, 1987. Red blood cell count was 92 X 10(4)/microliters, hemoglobin 2.7 g/dl, hematocrit 8.0%, platelet 6.4 X 10(4)/microliters, and white blood cell count 13,400/microliters with leukoerythroblastosis. Bone marrow aspiration of the sternum, left iliac crest, and bilateral posterior superior iliac supine showed extensive bone marrow necrosis. Serum ALP was increased to 7410IU/l, dominated isozyme of bone type. Hemostatic findings suggested a complication of consumption coagulopathy. Skull, vertebrae, iliac and pelvic bone X-ray showed multiple osteolytic lesions, and irregular isotope uptake was recognized on the bone scintigraphy using 99mTc. Sixth bone marrow examination at the right iliac crest revealed signet ring cell carcinoma metastasis. In spite of detailed examinations, there was no evidence of primary carcinoma, including the remnant of stomach. We speculated that the signet ring cells were originated from the respected gastric cancer. The patient has received anti-cancer chemotherapy with UFT and OK432, and is still alive 9 months after diagnosis.     

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。     

Metastases from gastric carcinoma to colon in the form of multiple flat elevated lesions: a case report

Gastric carcinoma is a common malignancy worldwide. Advanced stages of the disease may result in metastases to many other organs of the body. However, colonic metastases are rare. We report a case of gastric carcinoma with symptoms of abdominal fullness and weight loss. The serum carcinoembryonic antigen level was elevated. Esophagogastroduodenoscopy revealed giant folds occupying the whole gastric body and poor expansion of the stomach. Histologic examination of biopsy specimens from the giant fold demonstrated poorly differentiated adenocarcinoma with signet ring-cell differentiation. Total colonoscopy revealed five or six discrete flat elevated lesions in the distal transverse, descending, and sigmoid colons. These lesions were characterized by a clear margin of 3-5 mm in diameter and erosions on the tips. Polypectomy specimens demonstrated signet ring-cell carcinoma, which was histologically similar to the specimens taken from the gastric lesion. We conclude that this was a rare case in which gastric signet ring-cell carcinoma had metastasized to the colon in the form of flat elevated lesions, combined with rapid and wide lymphatic spread to the thorax and abdomen in a clinical course as short as 46 days.     

Ulcerative colitis-associated colorectal cancer

The association between ulcerative colitis(UC) and colorectal cancer(CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC(UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, lowgrade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC.     

GASTRIC CANCER RETROSPECTIVELY INVESTIGATED FOR 9 YEARS AND 6 MONTHS: A CASE OF LINITIS PLASTICA

This report presents a rare case of a patient with gastric cancer whose clinical course with the development of tumor from early cancer type IIc to advanced cancer of linitis plastica was observed for 9.5 years. The cancer remained in early stage for 3 years and 8 months after the patient’s first endoscopy. At 5 years and 10 months after initial endoscopy, the lesion progressed to advanced cancer, and after 6 years and 7 months sclerotic changes in the gastric wall were detected at the lesion site. After 9 years, advanced gastric cancer of linitis plastica was present throughout the stomach. The initial stage of linitis plastica is considered to be early gastric cancer type IIc with histologically undifferentiated cancer cells. It is widely accepted that a period of 6–8 years is required for this type of cancer to develop from carcinogenesis to completion of lesions. The present case is valuable in that development from early gastric cancer type IIc to linitis plastica during approximately 10 years of follow up was clinically observed, and will contribute to knowledge of the natural history of gastric cancer.     

Characterization of a newly established cell line (JR-St) derived from human gastric signet ring cell cancer, producing tumor markers.

Despite the importance of in vitro study of gastric cancer, there are very few established cell lines derived from human gastric carcinoma. We have recently established a new cell line derived from human gastric cancer which has the ability to produce tumor markers. This cell line has been designated JR-St. This cell line was derived from the cerebrospinal fluid of a 37-yr-old female patient who had metastatic brain tumor of signet ring cell gastric adenocarcinoma. This cell line has been maintained for more than 24 months through 80 passages with stable growth. PAS staining showed intracellular mucin granules. Transmission and scanning electron microscopy revealed cells with numerous microvilli and fine projections as well as intracellular granules, indicating mucin. This cell line had the ability to produce high concentrations of tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. Thus Thus this cell line should provide a very useful tool for the investigation of gastric cancer such as analysis of tumor markers as well as effects of anti-cancer drugs or growth factors.     

CONCURRENT GASTRIC AND COLONIC LOW‐GRADE MUCOSA‐ASSOCIATED LYMPHOID TISSUE LYMPHOMATA IN A PATIENT WITHOUT HELICOBACTER PYLORI INFECTION

Mucosa‐associated lymphoid tissue (MALT) lymphomata observed simultaneously in the stomach and colon are rare. We report concurrent gastric and colonic low‐grade MALT lymphomata that originated from the same clone in a 58‐year‐old Japanese man without Helicobacter pylori infection. Endoscopy showed multiple erosive lesions in the gastric body and antrum, and a single flat elevation with an irregular margin in the sigmoid colon. Histopathological findings of both lesions suggested low‐grade MALT lymphoma. Lymphoepithelial lesions were evident in the gastric lesions, but not in the colonic lesion. Southern blot analysis of lymphoma cells revealed the same immunoglobulin heavy‐chain rearrangement pattern. The chromosomal translocation t(11;18)(q21;q21) was also observed. After six courses of cyclophosphamide, doxorubicin, vincristine and predonisolone, the gastric lesions disappeared endoscopically, while the colonic lesion persisted. A sigmoidectomy was consequently performed. The chromosomal translocation may be related to the pathogenesis of the present MALT lymphoma case without H. pylori infection. It is interesting that the gastric and colonic lesions differed in response to treatment and in their endoscopic and histologic features, despite having the same origin.     

Small gastrointestinal stromal tumor concomitant with early gastric cancer： A case report

The term gastrointestinal stromal tumors (GISTs)is defined diagnostically as the main group of mesenchymal tumors with spindle or epithelioid cells arising from the wall of the gastrointestinal tract with immunohistochemical reactivity for CD117 antibody.Previous studies revealed that cells in GISTs express a growth factor receptor with tyrosine kinase activity (termed c-kit), which is the product of the c-kit protooncogene. The most specific and practical diagnostic criteria for GISTs are: immunohistochemically determined c-kit (CD117) expression; mitotic score; and tumor size.A small GIST concomitant with early gastric cancer is rarely encountered clinically. Herein we have reported a case of a 1.1-cm GIST detected by esophagogastroduo denoscopy concomitant with a Ⅱc type of early gastric cancer (signet ring cell type). It was detected during a routine physical health examination. To our knowledge,this is the first report of a small GIST concomitant with a signet ring cell type of early gastric cancer.     

Korean experience of superficial depressed‐type early colorectal cancer

Background: Unlike the adenoma–carcinoma sequence theory, the de novo carcinoma theory has been highlighted recently because of the emergence of superficial depressed‐type early colorectal cancers. In addition, some flat‐elevated or sessile‐type early colorectal cancers have been identified as originating from superficial depressed‐type early colorectal cancers. Thus, studies of superficial depressed‐type early colorectal cancers may provide an opportunity to clarify the morphogenesis of colorectal cancers in the foreseeable future. Methods: The authors studied 231 cases of early colorectal cancer from 1997 to 2000. Among them, 17 cases (7.4%) were superficial depressed‐type. According to Kudo's classification, the 17 lesions were classified as three types based on their growth patterns: IIc, IIa + IIc, and Is + IIc. They were also classified as sm‐s (sm₁) and sm‐m (sm_2–3) cancers based on the depth of submucosal invasion according to Kudo's classification. They were analyzed with emphasis on size, depth of submucosal invasion and treatment. Results: Type IIc lesions were 11 mm in diameter on average; types IIa + IIc and Is + IIc had diameters of 15 mm and 11 mm on average, respectively. Sm‐m cancers' diameters were all larger than 10 mm. Fifty‐seven percent (57%) of type IIc cancers were submucosally invasive, while 90% of type IIa + IIc and type Is + IIc cancers together were submucosally invasive. The overall surgical resection rate was 41.2%, and surgical resection was performed in 80% of the sm‐m cases. Conclusion: Recognition of superficial depressed‐type early colorectal cancers, especially type IIa + IIc and type Is + IIc cancers, is important because their biological behavior will most likely be different from that of the usual protruding early cancers. Accordingly, the treatment modality should be selected prudentially, and early detection is imperative in order for their sizes to be less than 10 mm.     

Intramucosal poorly differentiated and signet‐ring cell components in patients with ulcerative colitis‐associated high‐grade dysplasia

Despite the rarity of colorectal poorly differentiated adenocarcinoma (Por) and signet‐ring cell carcinoma (Sig), they are more frequent in patients with ulcerative colitis (UC). However, little is known about these components of early colitis‐associated cancer due to the difficulty of detection at an early stage. Here, we reviewed colitis‐associated high‐grade dysplasia/cancer with Por/Sig components within the submucosa among 103 lesions of 79 UC patients who presented between 1997 and 2017. In total, one Sig in situ, three intramucosal and two submucosal carcinomas (8.7%) were identified among 69 lesions within the submucosa. Depressed appearance, loss of crypt architecture and amorphous surface pattern suggested the presence of Por/Sig, rather than submucosal infiltration. All lesions were located in the rectosigmoid colon and included high‐grade dysplasia. While the surrounding noncancerous mucosa expressed E‐cadherin and MUC5AC, the expression of E‐cadherin was reduced and the expression of MUC5AC was negative in all of the carcinomas except for the Sig in situ. The gastric type metaplasia associated with altered MUC5AC profiles may be a sign of the stepwise accumulation of molecular alterations, including TP53 defects and a reduced expression level of E‐cadherin.     

Breast cancer metastasizing to the stomach mimicking primary gastric cancer: A case report

Breast cancer with stomach metastasis rare with an incidence of 1% or less among metastatic breast cancer patients. We experienced a case of breast cancer metastasizing to the stomach in 65-year-old female patient. She experienced dyspepsia and poor oral intake before visiting the clinic. Diffuse infiltration with nodular mucosal thickening of the stomach wall was observed, suggesting advanced gastric cancer based on gross endoscopic finding. Spread of poorly cohesive tumor cells in the gastric mucosa observed upon hematoxylin and eosin stain resembled signet ring cell carcinoma, but diffuse positive staining for GATA3 in immunohistochemical stain allowed for a conclusive diagnosis of breast cancer metastasizing to the stomach. Based on the final diagnosis, systemic chemotherapy was administered instead of primary surgical resection. After 2 cycles of docetaxel administration, she showed a partial response based on abdominal computed tomography scan. This case is an unusual presentation of breast cancer metastasizing to the gastrointestinal tract.