A case of primary ovarian signet-ring cell carcinoma treated with S-1/CDDP therapy.

BACKGROUND: Primary ovarian signet-ring cell carcinoma is extremely rare, with only five recent case reports. Almost all reported cases of ovarian signet-ring cell carcinoma have been treated with TC therapy and none have reported regarding the use of S-1/CDDP therapy. We report a case of primary ovarian signet-ring cell carcinoma treated postoperatively with S-1/CDDP therapy. CASE PRESENTATION: We describe a 55-year-old woman diagnosed with stage IB primary ovarian signet-ring cell carcinoma that was treated with S-1/CDDP therapy. Preoperative transvaginal ultrasonography and contrast-enhanced computed tomography (CT) revealed a solid tumor measuring 10 cm in diameter in the pelvis. The tumor marker levels were as follows: CA125, 41.6 U/mL; CA19-9, < 2.0 U/mL; and CEA, 2.2 ng/mL. Ovarian cancer was suspected, and total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. The left ovary was enlarged to greater than fist-sized, and there was a small amount of clear yellow ascites. Histological examination of the left ovary led to the diagnosis of signet-ring cell carcinoma. Histological examination of the right ovary also showed the presence of a signet-ring cell carcinoma. After surgery, upper and lower gastrointestinal endoscopy and positron-emission tomography-CT were performed to search for a possible primary lesion, but none was found. The patient was diagnosed with primary ovarian signet-ring cell carcinoma with FIGO Stage IB (PT1b, NX, M0). As postoperative adjuvant chemotherapy, S-1/CDDP therapy (S-1120 mg/day/body × 14 days, CDDP 50 mg/m2 day 8, q 21 days) was administered for six cycles. There was no recurrence 27 months after the initial treatment. CONCLUSIONS: We considered S-1/CDDP therapy was effective for primary ovarian signet-ring cell carcinoma. This is the first case report of primary ovarian signet-ring cell carcinoma treated with S-1/CDDP therapy in the world.

[Progression of diagnosis and treatment in pediatric colorectal carcinoma].

Colorectal carcinoma (CRC) is the third most common malignancy in adults. Pediatric colorectal carcinoma (PCRC) is a rare non-embryonal tumor with a significantly lower incidence compared to adults. The clinical manifestations of PCRC are not typical, and pediatricians usually have no enough experience in diagnosis and treatment. Therefore, early diagnosis is extremely difficult, which would always lead to late clinical stages when diagnosis is made. At present, the pathogenesis of PCRC is still not clear, and many countries have started to carry out researches at the level of genes, molecules and cells. In both tumor primary tumors and distant metastases, PCRC has obvious difference in distribution from adults, and the proportion of pathological type of mucous adenocarcinoma (including the signet ring cell carcinoma) was significantly higher than that of adults. Although treated according to adult colorectal cancer guidelines, PCRC has been unable to achieve ideal efficacy with poor prognosis and lower long-term survival rate. The purpose of this paper is to summarize the epidemiological characteristics, pathogenesis, clinical symptoms, pathological types, treatment and prognosis of colorectal cancer in children by reviewing the latest literatures at home and abroad.

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.

Signet-ring cells in the bone marrow as an indication of cryptic metastasis of breast carcinoma: A case report.

RATIONALE: Signet-ring cell is a rare morphological finding in bone marrow, which usually indicates metastatic carcinoma from either the gastrointestinal tract or a primary hematolymphoid neoplasm. Here, we present a very unusual case of lobular breast carcinoma with metastasis to the bone marrow. PATIENT CONCERNS: A 67-year-old female with estrogen receptor (ER)-positive lobular breast carcinoma was staged as T3N3M0, and treated with modified radical mastectomy followed by chemotherapy and radiotherapy. One year after treatment, she was noted to have moderate thrombocytopenia on complete blood count with the remainder of the parameters within normal limits. Radiographic examination revealed no evidence of recurrent disease. DIAGNOSIS: Bone marrow biopsy was performed to exclude therapy-related myelodysplastic syndrome (MDS), which demonstrated hypercellularity with "hyperplastic" hematopoiesis. Upon closer inspection, a few signet-ring cells were identified which morphologically resembled histiocytes. These formed an interstitial infiltrate among the predominantly hematopoietic elements, and could have been easily overlooked. Immunohistochemistry demonstrated that these signet-ring cells were positive for pancytokeratin as well as ER which confirmed metastatic lobular breast carcinoma. On retrospective review of the aspirate smear, rare signet-ring cells were identified. INTERVENTIONS: The patient was treated with additional chemotherapy. OUTCOMES: The patient eventually succumbed to overt dissemination after 14 months. LESSONS: Due to the relative discohesiveness of lobular breast carcinoma, the cells frequently assume single-cell infiltration in bone marrow. This attribute, along with small cell size, bland cytologic features and paucity of tissue response, contributes to its escaping from identification on hematoxylin-eosin (H&E) sections. In this case, the signet-ring cells were hidden in apparently hyperplastic hematopoiesis. Careful inspection raised the possibility of occult metastasis which was readily detected and confirmed with immunohistochemistry.

Occurrence of signet-ring cell carcinoma with cholangiocarcinoma 25 years after choledochal cyst excision: A case report.

RATIONALE: Choledochal cysts are a risk factor for the development of cholangiocarcinoma. Hence, complete surgical excision is the preferred treatment in most cases. However, cholangiocarcinoma still can develop from the remnant biliary system after surgical excision. Signet-ring cell carcinoma is a rare type of cancer of the biliary system, and the occurrence of signet-ring cell carcinoma after surgical excision of choledochal cysts has not been reported in the English literature to date. PATIENT CONCERNS: We report a case of a 32-year-old woman who presented with a 1-month history of abdominal pain,obstructive jaundice, itching, and fever. The patient had undergone choledochal cyst excision and Roux-en-Y hepatico-jejunostomy 25 years previously and had now developed signet-ring cell carcinoma along with cholangiocarcinoma at the anastomotic site. DIAGNOSES:: signet-ring cell carcinoma along with cholangiocarcinoma. INTERVENTIONS: Interventions included laparotomy with evacuation,blood transfusion,and other adjuvant therapy. OUTCOMES: The patient died five months later. LESSONS: Surgery is the best treatment for CCCs, and the surgeon should try to remove as much as of the bile duct cyst as possible.

Clinical and Histopathologic Features of Colorectal Adenocarcinoma in Crohn's Disease.

GOALS: The aim of this study was to assess the histopathologic characteristics of colorectal carcinomas (CRC) in patients with Crohn's disease (CD). BACKGROUND: A higher frequency of microsatellite instability (MSI) is seen in mucinous compared with nonmucinous CRC which suggests that its pathogenesis involves distinct molecular pathways. Several publications reported a higher percentage of mucinous adenocarcinoma in CD patients with CRC. So far, there has been no investigation of MSI in CD patients with mucinous CRC. STUDY: The medical records of patients who underwent surgery for CRC were reviewed and those with a history of CD identified. The data of histologic classification and MSI status of the tumor were investigated. RESULTS: Fourteen patients with CD-associated CRC were identified (5 female, 9 male) resulting in 20 CRC in total. Histologic investigation revealed 7 adenocarcinomas without a mucinous or signet ring cell component. All other CRCs harbored a mucinous (n=11) and/or signet ring cell (n=6) component. All tumors assessed for MSI were found to be microsatellite stable. CONCLUSIONS: Our data indicate that CRCs with signet ring cell and mucinous components were much more common in patients with CD than in patients with sporadic CRC. This observation suggests that CRC in CD represent an own entity with distinct histopathologic and molecular features. This may implicate potential consequences for diagnosis and therapy of CRC in CD in the future as well as new factors to identify patients with an increased risk for developing CRC in CD.

Pathologic features of colorectal carcinomas associated with Crohn's disease in Korean population.

BACKGROUND: Colorectal cancer (CRC) has been known to complicate Crohn's disease (CD). Several reports in Western population revealed that CRC in CD were characterized by much younger onset and equal distribution of tumors along the entire colon. However, clinicopathologic features of CD-associated CRC in Korean population have not been well documented yet. METHODS: Among 2968 Korean CD patients, 16 patients (0.54%) were found to develop CRC during follow up. We reviewed clinicopathologic features of the 16 CRC patients. RESULTS: The mean age at the time of CRC diagnosis was 39.3 years (range 18-59 years) and 14 of the 16 CRCs (87.5%) occurred in anorectal region. Mucinous adenocarcinoma was strikingly frequent (9/16, 56.3%) and eight cases (8/9) of the mucinous adenocarcinoma cases were located at anorectal area. The other cases consisted of 4 tubular adenocarcinomas, 2 signet ring cell carcinomas and 1 neuroendocrine tumor. Thirteen patients (81.3%) had a history of perianal fistula and 8 of them had a histological association between the CRC and the perianal fistula. CONCLUSIONS: CD-associated CRC was characterized by young age at diagnosis, mucinous histology and association with perianal fistula in Korean patients.

Cutaneous clear cell/signet-ring cell squamous cell carcinoma arising in the right thigh of a patient with type 2 diabetes: combined morphologic, immunohistochemical, and etiologic analysis.

BACKGROUND: The clear cell/signet-ring cell variant of cutaneous squamous cell carcinoma (cSCC) is extremely rare. Its carcinogenesis has consistently been linked to ultraviolet radiation and HPV in the literature. However, there is little definite information about the contribution of diabetes mellitus (DM) to cSCC. CASE PRESENTATION: A 78-year-old Chinese woman with type 2 DM presented with a mushroom-like lump in her right thigh. Histological findings revealed that the lesion was mainly composed of clear cells and signet-ring cells. The septa of vacuoles in cytoplasm displayed positivity for periodic acid schiff (PAS) and cytokeratins such as AE1/AE3, CK5/6, CK14, and CK19. Malignant cells did not express CK7, CK8, CK18, CK20, p16, p53, or c-erbB-2, and the Ki-67 index was less than 5 %. We further explored the etiology of clear cell/signet-ring cell cSCC using human papillomavirus (HPV) type-specific PCR and genotyping and confirmed that the patient was not infected with HPV. Nucleus positivity for p63 indicated the involvement of the p53 family in the lesion. Meanwhile, the expression of fibroblast growth factor receptor-2 (FGFR2), a downstream effector of p63, was upregulated in tumor cells. CONCLUSIONS: This study provides the first report on the clear cell/signet-ring cell variant of cSCC found in the right thigh of a patient with type 2 DM. Metabolic imbalance in addition to conventional pathogens such as UV and HPV may contribute to the development of the lesion via p63/FGFR2 axis.

Is there any relationship between drug addiction and the development of a signet ring cell carcinoma of the stomach?

We present three young patients diagnosed with signet ring cell carcinoma of the stomach. All had in common the smoking rather than the injecting route of administration of drugs, such as heroin. In the smoking route, pieces of nickel scourer are mixed with the drug. This heavy metal has known carcinogenic effects. Chronic exposure of the gastric mucosa to nickel, from oropharynx, could be a risk factor for the development of gastric adenocarcinoma in heroin smoking addicts.

Prognosis of Ulcerative Colitis-Associated Colorectal Carcinoma Compared to Sporadic Colorectal Carcinoma: A Matched Pair Analysis.

BACKGROUND: Ulcerative colitis (UC) patients have an increased risk of developing colorectal carcinoma (CRC). In contrast to clinical and pathogenetic differences, little is known about how prognosis compares between these patients and those with sporadic CRC. The aim of this study was to compare their characteristics and prognosis and identify independent risk factors for patients with UC-associated CRC. METHODS: A total of 126 patients who underwent surgery in our department (1984-2010) for UC-associated (n = 63) or sporadic (n = 63) CRC were included in this analysis. Patients were matched according to sex, tumor location, and disease stage. Clinical parameters and overall, recurrence-free, and disease-specific survival were compared. In subgroup analyses, clinical parameters of UC patients were correlated with survival. RESULTS: Median follow-up was 129 months in the UC group and 99 months in the sporadic CRC group. UC patients were significantly younger and had more multifocal, high-grade, and mucinous carcinomas. Five-year overall survival rate for UC-associated and sporadic CRC was similar (65.7 vs. 63.2%, p = 0.98). Recurrence-free survival for International Union Against Cancer (UICC) stage II disease was superior in the sporadic CRC group (p = 0.039). In a subgroup analysis of UC patients, a shorter duration of UC (p = 0.045) and male sex (p = 0.005) were associated with a worse prognosis. CONCLUSIONS: Despite multiple clinical and histopathologic differences between UC-associated and sporadic CRC patients, overall survival and disease-specific survival are similar. In a subgroup analysis of UC patients with CRC, female sex was associated with a significantly better prognosis. This finding implies that estrogens may play a protective role in UC-associated CRC carcinogenesis.

Oesophageal signet ring cell carcinoma as complication of gastro-oesophageal reflux disease.

BACKGROUND: Signet ring cell carcinoma occurs as a histological variant of oesophageal adenocarcinoma. AIM: In a cross-sectional study, to pursue the hypothesis that oesophageal signet ring cell cancers constitute a complication of gastro-oesophageal reflux disease. METHODS: In a large national database of histopathology records, we accumulated 91 802 patients with Barrett's oesophagus (BE), 2817 with oesophageal nonsignet ring adenocarcinoma (EAC) and 278 with oesophageal signet ring cell carcinoma (SRC). The three groups were compared with respect to their clinical and demographic characteristics, as well as socio-economic risk factors (associated with patients' place of residence). RESULTS: About 9% of all oesophageal adenocarcinomas harboured features of signet ring cell carcinoma. Patients with oesophageal adenocarcinoma and signet ring cell carcinoma were characterised by almost identical epidemiological patterns. Patients with either cancer type were slightly older than those with Barrett's oesophagus (EAC 68.0, SRC 66.7 vs. BE 63.7 years), and both showed a striking male predominance (EAC and SRC 85% vs. BE 67%). Both cancer types were associated with a similar set of alarm symptoms, such as dysphagia, pain and weight loss. The distribution by race (Whites vs. Blacks) and socio-economic parameters, such as levels of college education and family income, were similar among the three groups of patients. CONCLUSIONS: Signet ring cell carcinoma is a rare variant of oesophageal adenocarcinoma with similar epidemiological characteristics. The reasons why a minority of reflux patients progress to develop signet ring cell carcinoma, rather than the usual type of oesophageal adenocarcinoma, remain unknown.

[Juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia syndrome in a patient a with SMAD4 mutation].

Germ line mutations in SMAD4 can cause both juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia syndrome. In this case we present a 37-year-old man with a frameshift mutation in SMAD4. The patient had multiple polyps in the gastrointestinal tract and was diagnosed with colon cancer at the age of 21 and gastro-oesophageal junction cancer at the age of 37. Furthermore the patient had telangiectasias and recurrent epistaxis.

Five-year mortality in colorectal cancer patients with ulcerative colitis or Crohn's disease: a nationwide population-based cohort study.

BACKGROUND: The impact of inflammatory bowel disease (IBD) on colorectal cancer (CRC) prognosis, taking into account other comorbidities, is not clear. We studied the overall mortality in CRC patients with a history of ulcerative colitis (UC) or Crohn's disease (CD) compared with non-IBD-CRC patients. METHODS: Data on all CRC and IBD patients diagnosed with CRC between 1977 and 2009 were retrieved from Danish medical registries. One-year and 5-year overall mortality were evaluated with the Kaplan-Meier method and with Cox regression, adjusting for year of CRC diagnosis, sex, Duke's stage, age at CRC diagnosis, and Charlson Comorbidity Index score. RESULTS: We identified 653 CRC patients diagnosed with UC, 238 patients with CD, and 107,024 CRC patients without IBD. The patients with IBD were younger at diagnosis than patients without IBD. The Duke's stage distribution was similar for UC-CRC patients and non-IBD-CRC patients. The CD-CRC patients had a lower frequency of Duke's A and B stage tumors (36% versus 42%), a higher frequency of Duke's C stage tumors (31% versus 27%) and Duke's D-stage tumors (23% versus 21%), and a similar frequency of unknown stage tumors (10%) compared with non-IBD-CRC patients. After 5-years of follow-up, 59% of the UC and the non-UC-CRC patients had died compared with 62% of the patients with CD and 56% of the non-CD-CRC patients. The 5-year adjusted mortality rate ratios for patients with UC or CD were 1.14 (95% confidence interval, 1.03-1.27) and 1.26 (95% confidence interval, 1.07-1.49), respectively, compared with patients without IBD. CONCLUSION: A history of IBD in patients with CRC may be associated with increased mortality.

Ureterosigmoidostomy associated signet ring colon cancer presenting as hip pain.

PURPOSE: We present a case of a young male with a history of ureterosigmoidostomy who presented with hip pain, the subsequent workup of which revealed metastatic bone lesions from a primary sigmoid signet ring cell adenocarcinoma. METHODS: Review of literature was conducted using databases PubMed Medline (1966-current), PubMed Central (1970-current), and EMBASE (1988-2009) to explore previous studies on the topic; used the Surveillance, Epidemiology and End Results Program for epidemiological data; and used the National Comprehensive Cancer Network guidelines for management recommendations. RESULTS: Ureterosigmoidostomy is well-documented risk factor for colonic neoplasms, the reported incidence being 2-41% with a latent period of 10 to 30 years and a risk of occurrence 80-7,000 times higher than in the general population. The most common histological type of colon cancer seen after ureterosigmoidostomy is adenocarcinoma, but cases of signet-ring cell carcinoma have also been described. Signet-ring cell adenocarcinoma occurs predominantly in stomach but may infrequently arise from other organs such as breast, urinary bladder, and small and large bowel. CONCLUSIONS: This case underscores the importance of prolonged screening in patients with ureterosigmoidostomies and also calls for heightened awareness among primary care physicians regarding long-term risks associated with this unique entity.