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1/56. Multiple primary cancers of the esophagus and thyroid gland.

    The occurrence of multiple primary cancers in the aerodigestive tract is a well known phenomenon that has been explained by the concept of 'field carcinogenesis'. Metachronous or synchronous esophageal cancer has usually been identified in patients with head and neck cancer, gastric cancer or colon cancer. The incidence of multiple primary cancers of the esophagus and thyroid gland is very low. We treated four patients with synchronous cancers of the cervical esophagus and the thyroid gland. Histologically, all of the esophageal cancers were squamous cell carcinomas. Thyroid cancers were evaluated as papillary carcinoma or follicular carcinoma. Both the esophageal cancer and the thyroid cancer frequently metastasized to lymph nodes. All patients had multiple lymph nodes metastasis from the esophageal or the thyroid cancer. In one patient, both the esophageal and the thyroid cancers were detected in the same lymph node. Three of four patients died from recurrence of esophageal cancer. The prognosis of these patients was poor. In the treatment of esophageal carcinoma, cancers of other organs including the thyroid gland should be carefully investigated.
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ranking = 1
keywords = carcinogenesis
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2/56. Genetic analysis of multiple sporadic colon carcinomas from a single patient.

    At least two separate genetic pathways of carcinogenesis in sporadic colon cancer involving the accumulation of mutations at various genetic loci have been described. About 15% of sporadic colorectal carcinomas arise via a mechanism associated with microsatellite instability (MSI) and mutations in transforming growth factor beta receptor II (TGFbetaRII), insulin-like growth factor ii receptor (IGFIIR) and BAX, whilst the remaining 85% are associated with aneuploidy and gross chromosomal rearrangements. An 81-year-old woman had a sigmoid colon carcinoma resected and 18 months later developed two additional carcinomas of the caecum and transverse colon. To investigate whether there was a common genetic mechanism of carcinogenesis for the three lesions, MSI status was assessed, TGFbetaRII, IGFIIR and BAX were analysed for mutations and protein expression of transforming growth factor beta1 (TGFbeta1) and p53 were studied using immunohistochemistry. The caecal and transverse colonic carcinomas were both MSI positive but different mutations were identified in each lesion. No genetic abnormalities were identified in the sigmoid colonic carcinoma. This suggests that each carcinoma arose via a separate genetic mechanism of carcinogenesis.
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ranking = 3
keywords = carcinogenesis
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3/56. Primary tracheal mucosa-associated lymphoid tissue lymphoma accompanying lung cancer. Common tumorigenesis or coincidental coexistence?

    We report a 67-year-old patient with coexistent tracheal non-Hodgkin's lymphoma and lung cancer the first case, to our knowledge, of this concomitant incidence in the literature. Chest radiography showed a mass in the right lung and pulmonary fibrosis. biopsy of the unanticipated tracheal irregularity revealed non-Hodgkin's lymphoma, compatible with mucosa-associated lymphoid tissue lymphoma. After right upper lobectomy, chemotherapy for non-Hodgkin's lymphoma was conducted, but the patient died 11 months postoperatively of pulmonary fibrosis. pulmonary fibrosis was suspected of having progressed from drug-induced pneumonitis caused by anticancer drugs. A common tumorigenetic factor may thus exist between tracheobronchial mucosa-associated lymphoid tissue lymphoma and lung cancer.
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ranking = 6.2995942903919
keywords = tumorigenesis
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4/56. hyperthyroidism in a patient with TSH-producing pituitary adenoma coexisting with thyroid papillary adenocarcinoma.

    A 27-year-old woman who presented with a left thyroid nodule was found to have hyperthyroidism caused by a syndrome of inappropriate secretion of TSH. The levels of free T3, free T4 and TSH were 9.50 pg/mL, 4.05 ng/dL and 2.16 microU/mL, respectively. magnetic resonance imaging of the head revealed a pituitary macroadenoma. The TSH response to TRH stimulation was normal and responses of other anterior pituitary hormones to stimulation tests were also normally preserved. Administration of octreotide with iodine successfully reversed hyperthyroidism prior to total resection of pituitary adenoma, which was followed by hemithyroidectomy of the left thyroid five months later. Histologically, the resected pituitary adenoma was a TSH-producing adenoma (TSH-oma) and the thyroid nodule was a papillary adenocarcinoma. serum TSH diminished to undetectable levels immediately following pituitary adenomectomy but gradually normalized over nine months. Coexistence of a TSH-oma with thyroid cancer is very rare and only two similar cases have previously been documented. This combination raises the possibility that TSH may be involved in tumorigenesis in the thyroid gland.
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ranking = 1.574898572598
keywords = tumorigenesis
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5/56. Widespread cutaneous carcinomas associated with human papillomaviruses 5, 14 and 20 after introduction of methotrexate in two long-term PUVA-treated patients.

    BACKGROUND: PUVA treatment for patients with severe psoriasis has been demonstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in patients with long-term puva therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented. case reports: Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term puva therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification. CONCLUSION: These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis.
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ranking = 1
keywords = carcinogenesis
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6/56. Malignant fibrous histiocytoma of the ileum at a site of previous surgery: report of a case.

    Sarcomas rarely arise in the intestinum, and leiomyosarcoma represents the majority of cases. With only seven cases reported in the available English literature up to now, malignant fibrous histiocytoma of the small intestine is exceedingly rare. Moreover, follow-up data are almost completely unavailable. We present herein the unique case of a malignant fibrous histiocytoma arising in a postoperatively adherent intestinal loop. To the best of our knowledge, this is the first such case ever to be described. The clinical history and the intraoperative findings suggested that chronic postoperative repair processes might have been a promoting factor in the tumorigenesis of this neoplasm, on the analogy of malignant fibrous histiocytoma arising at different sites. The patient recovered well but 9.5 years after surgical removal, a solitary recurrent tumor developed in the urinary bladder and progressed rapidly, highlighting the need for long-term, possibly life-long, surveillance of patients with this rare type of intestinal cancer.
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ranking = 1.574898572598
keywords = tumorigenesis
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7/56. Differences in EBNA2 and LMP-1 carboxy terminal region sequences of Epstein-Barr virus type A between the tumors in a multiple cancer patient.

    Using PCR, type A Epstein-Barr virus (EBV) infection was demonstrated in a squamous cell carcinoma of the maxilla (in a 52-year-old man) and the tongue of the same patient 18 years later (at the age of 70). Furthermore, at the age of 72, this patient developed an EBV-infected anaplastic large cell lymphoma. Analysis of the terminal regions of the EBV genome revealed a monoclonal proliferation of EBV-infected lymphoma cells. However, sequence analysis of the EBV revealed a slight difference in the EBNA2 regions between the virus-infected lymphoma and the squamous cell carcinomas. The mutations at 48991 (G-->T) and 48998 (C-->A) were demonstrated in the lymphoma. Although the squamous cell carcinoma of the tongue occurred after an interval of 18 years, the mutation site in the carcinomas was the same, 49137 (A-->G), as compared with B95-8 strain EBV EBNA2. The mutations at 48991 and at 49137 were associated with amino acid changes, Arg-->Met and Thr-->Ala, respectively, but the alteration at 48998 was a silent mutation. Thirty-bp deletion in the LMP-1 carboxy terminal region was demonstrated in the virus-infected lymphoma, but not in the squamous cell carcinomas. On the other hand, HTLV-1 proviral DNA (tax, gag and env) was not detected in the lymphoma, nor was HPV demonstrated in the squamous cell carcinomas, although Okinawa is known as an HTLV-1 and HPV prevalence region. The T-cell receptor beta gene rearrangement was demonstrated in the lymphoma, but the t(2;5) fusion transcript was not detected using PCR. cytogenetic analysis of the lymphoma cells showed a complex hypertriploid karyotype with 76XY. The type A EBV infection might play a role in the carcinogenesis of the tumors of our patient. Interestingly, the infected virus genome sequences, the EBNA2 and LMP-1 regions, which were closely associated with carcinogenesis in the squamous cell carcinomas and the lymphoma, showed slight differences.
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ranking = 2
keywords = carcinogenesis
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8/56. Multistep carcinogenesis in anaplastic thyroid carcinoma: a case report.

    We previously established an anaplastic thyroid carcinoma cell line (KOA2) that had double mutations: an N-ras mutation and a p53 gene mutation. To clarify multistep carcinogenesis, we analysed surgical material from the patient from whom KOA2 was derived for abnormalities in the N-ras and p53 genes. The resected material had two histologically different lesions: a follicular neoplasm and an anaplastic carcinoma. The N-ras mutation was observed in both lesions, but the p53 gene mutation only in the anaplastic lesion. These facts indicate that an N-ras mutation may induce follicular neoplasm and a subsequent p53 mutation may have caused the follicular neoplasm to transform to anaplastic carcinoma in this patient. This report suggests direct evidence for multistep carcinogenesis in anaplastic thyroid carcinoma.
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ranking = 6
keywords = carcinogenesis
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9/56. A novel germline mutation of hMLH1 in a patient with hereditary non-polyposis colorectal cancer.

    dna mismatch repair genes, hMLH1 and hMSH2, assigned on chromosome 3p21-23 and 2p21-22 are involved in hereditary non-polyposis colorectal cancer (HNPCC). The heterozygous carrier of the mutated allele results in a mutator phenotype and accelerating tumorigenesis, which especially causes carcinomas in the gastrointestinal and genitourinary tracts. We screened germline mutations of mismatch repair genes hMLH1 and hMSH2 in a patient with multiple primary neoplasms (multiple stomach cancers, colon cancer and brain tumor) in a cancer clustered HNPCC family. Screening by long RT-PCR from the rna extracted from puromycin-treated heparinized blood showed skipping of the exon 2 in hMLH1. The analysis of the genomic DNA showed a GT deletion in the splice-donor site of the exon 2, which is compatible with the splicing variant detected by long RT-PCR analysis. This is a novel germline mutation that has not been reported previously.
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ranking = 1.574898572598
keywords = tumorigenesis
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10/56. Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two different dysplastic nodules.

    We present the first reported case of explant cirrhotic liver that had synchronous cholangiocarcinoma and hepatocellular carcinoma arising in two different high-grade dysplastic nodules. The patient was a 55-year-old woman who had hepatitis b virus-associated liver cirrhosis for 3 years. The moderately differentiated cholangiocarcinoma occurred in high-grade dysplastic nodule with a 1.7-fold cell density compared with that of cirrhotic nodule. The hepatocellular carcinoma arose in a nodule-in-nodule pattern within a peripherally low-grade and centrally high-grade dysplastic nodule and had a 2.7-fold cell density compared with that of cirrhotic nodule. By immunohistochemistry, the tumor cells of the cholangiocarcinoma as well as bile ductular cells in dysplastic nodule were diffusely positive for cytokeratin 7, whereas hepatocellular carcinoma cells and dysplastic hepatocytes were negative for cytokeratin 7. The c-kit-positive hepatic progenitor cells were singly scattered between hepatocytes, and their number was highest in cirrhotic nodule and decreased in dysplastic nodule, whereas they were absent in cholangiocarcinoma and hepatocellular carcinoma arising in dysplastic nodules. Proliferation indices were progressively increased in cirrhotic nodule, dysplastic nodule, and cholangiocarcinoma or hepatocellular carcinoma, sequentially. These observations indicate that cholangiocarcinoma as well as hepatocellular carcinoma can develop in dysplastic nodule and that hepatic progenitor cells might play a role in the early stage of cholangiocarcinogenesis and hepatocarcinogenesis.
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ranking = 2
keywords = carcinogenesis
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