Cancer emerging from the recurrence of sessile serrated adenoma/polyp resected endoscopically 5 years ago.

Since the serrated neoplastic pathway has been regarded as an important pathway of colorectal carcinogenesis, few reports have been published on clinical cases of cancer derived from sessile serrated adenoma/polyp, especially on recurrence after resected sessile serrated adenoma/polyp. An elderly woman underwent endoscopic mucosal resection of a flat elevated lesion, 30 mm in diameter, in the ascending colon; the histopathological diagnosis at that time was a hyperplastic polyp, now known as sessile serrated adenoma/polyp. Five years later, cancer due to the malignant transformation of the sessile serrated adenoma/polyp was detected at the same site. The endoscopic diagnosis was a deep invasive carcinoma with a remnant sessile serrated adenoma/polyp component. The carcinoma was surgically removed, and the pathological diagnosis was an adenocarcinoma with sessile serrated adenoma/polyp, which invaded the muscularis propria. The surgically removed lesion did not have a B-RAF mutation in either the sessile serrated adenoma/polyp or the carcinoma; moreover, the initial endoscopically resected lesion also did not have a B-RAF mutation. Immunohistochemistry confirmed negative MLH1 protein expression in only the cancer cells. Lynch syndrome was not detected on genomic examination. The lesion was considered to be a cancer derived from sessile serrated adenoma/polyp recurrence after endoscopic resection, because both the surgically and endoscopically resected lesions were detected at the same location and had similar pathological characteristics, with a serrated structure and low-grade atypia. Furthermore, both lesions had a rare diagnosis of a sessile serrated adenoma/polyp without B-RAF mutation. This report highlights the need for the follow-up colonoscopy after endoscopic resection and rethinking our resection procedures to improve treatment.

An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.

To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers.

Pulmonary fibrosis in an individual occupationally exposed to inhaled indium-tin oxide.

Despite the increasing industrial use of indium-tin oxide (ITO) to manufacture flat-panel displays, such as liquid-crystal displays or plasma display panels for televisions, little is known about the potential health hazard induced by occupational exposure to indium compounds. The current study describes a case of fibrotic lung disease that developed after a 4-yr exposure to ITO. The pathology of the lung demonstrated pulmonary fibrosis with the presence of cholesterol granulomas. In conclusion, more attention needs to be paid to the possible toxic effects of indium compounds, and maximum healthcare measures should be taken to protect industry workers from these toxicities.

A rare case of alpha-fetoprotein-producing early gastric cancer.

Most of the alpha-fetoprotein-producing gastric cancer is advanced at the time of presentation, and alpha-fetoprotein-producing early gastric cancer is extremely rare. Alpha-fetoprotein-producing early gastric cancer was confirmed by immunohistochemistry and serum analysis of alpha-fetoprotein concentration. Alpha-fetoprotein carbohydrate chain microheterogeneity was further evaluated by lectin binding specificity. A 71-year-old-male patient underwent total gastrectomy due to a depressed type of gastric cancer in the upper third of the stomach. There was no evidence of synchronous liver metastasis and hepatitis. Histological examination revealed that the tumor invasion was limited to the submucosal layer, and that the tumor consisted of both well-differentiated, papillo-tubular growth areas and trabecular and medullary growth areas resembling hepatoid carcinoma. Immunohistochemically, alpha-fetoprotein and cytokeratin localization were confirmed in the cancer cells, whereas simultaneous localization of carcinoembryonic antigen, carbohydrate antigen 19-9, and human chorionic gonadotropin could not be observed. The elevated preoperative serum alpha-fetoprotein concentration (113 ng/mL) promptly decreased to and remained within normal levels postoperatively (3.6 ng/mL). The predominance of a strong-bound fraction with lectin, which was demonstrated by lens culinalis agglutinin affinity chromatography, suggests that the alpha-fetoprotein carbohydrate chain species in the present case was a hepatic type. The patient received adjuvant intravenous chemotherapy consisting of 5-fluorouracil and cisplatin, and has been further supported by oral 5-fluorouracil administration. The patient has been disease free for 15 months following surgery. We report here a rare case of alpha-fetoprotein producing early gastric cancer. The alpha-fetoprotein carbohydrate phenotype analysis helps to consider the primary differentiation of alpha-fetoprotein-producing gastric cancer.

Bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type.

PURPOSE: To report a patient with bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type. METHODS: Case report. RESULTS: A 55-year-old woman complained of visual field loss and decreasing vision. Seven months earlier, uterocervical carcinoma of the squamous cell type was diagnosed and treated with chemotherapy and irradiation. Serous retinal detachment and choroidal masses were present in both eyes. Retinal detachment was lessened in both eyes after radiotherapy. The patient died of respiratory insufficiency 3 months after the appearance of choroidal metastases. At autopsy, there was no second cancer to cause the choroidal metastases. Tumor embolization was present in the choriocapillaries. CONCLUSION: Choroidal metastasis may develop from hematogenous spread of uterocervical squamous cell carcinoma.

Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin.

The histological differentiation of thyroid carcinoma is known to correlate with prognosis. Ras oncogene mutations, which have been identified in various human cancers, have been suspected playing an important role in carcinogenesis and tumor progression. The purpose of this study was to clarify the mechanism of thyroid tumor progression, focusing on ras oncogenes. We examined ras mutations using nested polymerase chain reaction (PCR) and direct sequencing methods. The ras oncogene product was also examined immunohistochemically. Our results indicated that the incidence of ras mutations correlated with the histological differentiation of thyroid cancer. Three poorly differentiated carcinomas showed a higher rate of ras mutations than did 17 well-differentiated counterparts. Hot spots were not identified except for a relative accumulation of the N-ras gene at codon 61. There was a correlation between the immunoreactivity of the ras oncogene product and ras mutation, although the immunoreactivity of ras-p21 did not correlate with the histological differentiation. Mutation of the ras gene seemed to be one of the important events in the progression from well-differentiated carcinoma to poorly differentiated thyroid carcinoma.

Dedifferentiated chondrosarcoma of the rib with a malignant mesenchymomatous component: an autopsy case report.

A rare variant of dedifferentiated chondrosarcoma with malignant mesenchymomatous component in a 57-year-old male is reported. The patient presented with a posterior mediastinal mass arising from the left eighth and ninth ribs showing well differentiated, low-grade chondrosarcoma. Five years later, local recurrence occurred and an excised specimen also showed the same histological features as the primary tumor. Another 6 years later, the tumor recurred and metastasized to the multiple organs, the patient dying 4 months later. Autopsy revealed that the recurrent and metastatic tumors showed malignant mesenchymomatous 'dedifferentiation' of chondrosarcoma composed of rhabdomyosarcoma, angiosarcoma, chondrosarcoma, osteosarcoma, and leiomyosarcoma, in addition to fibrosarcomatous areas. Although the less differentiated component of dedifferentiated chondrosarcoma usually shows the histological features of malignant fibrous histiocytoma and fibrosarcoma, multilineage differentiation can occur in that component. The phenomenon of 'dedifferentiation' in chondrosarcoma and the relationship to and distinction from malignant mesenchymoma of soft tissue and bone are discussed.

Fulminant septicemic syndrome of Bacillus cereus in a leukemic patient.

We report a rapidly fatal Bacillus cereus septicemia in a leukemic patient receiving remission-induction therapy. Symptoms resembling food poisoning and fever preceded coma accompanied by neurologic abnormalities. Autopsy revealed necrotizing leptomeningitis with subarachnoid hemorrhage and coagulation necrosis of the liver with bacterial infiltration. These clinicopathologic findings were closely similar to those of reported cases. Because of a rapidly fatal clinical course, suspicion of this syndrome early in the course is important to determine an appropriate treatment. Therefore, we propose that this type of septicemia should be termed as fulminant septicemic syndrome of Bacillus cereus.

Necrotizing Bacillus cereus infection of the meninges without inflammatory reaction in a patient with acute myelogenous leukemia: a case report.

A 64-year-old man in a severely immunocompromised state due to acute myelogenous leukemia died, respirator-unaided, about 10 h after the abrupt onset of coma. An earlier blood culture had yielded Bacillus cereus. The autopsy, performed 2 h after death, demonstrated diffuse subarachnoid hemorrhage without berry aneurysms, and the formalin-fixed brain was tinged with gray-brownish discoloration. The sections of the brain presented a whitish tint of the surface layer of all portion of the cerebral cortices, even those in the sulci. Histological examination of the brain revealed leptomeningeal B. cereus dissemination, and widespread necrosis of the leptomeninges and arachnoid vessels without inflammatory cell reaction. The grossly recognizable whitish surface layer of the cerebral cortex showed overt hyperchromatism, and contained neurons more degenerative than those located in the deeper cortical layer. The total absence of inflammatory reaction may be explained by a combination of the immunocompromised state of the patient and the character of B. cereus infection, which in itself induces little inflammatory reaction. The prominent lesions were confined to the cerebral surface layer and leptomeningeal tissue including the arachnoid vessels, which were all bathed in the cerebrospinal fluid, suggesting that some necrotizing toxins had been secreted into the fluid by the B. cereus. The necrosis of arachnoid vessels is thought to have in turn caused diffuse subarachnoid hemorrhage and marked disturbance of the cerebral blood flow, resulting in the terminal coma.

Neuroendocrine tumors of the liver and pancreas associated with elevated serum prostatic acid phosphatase.

A 58-year-old man was revealed to have multiple liver tumors with elevated prostatic acid phosphatase (PAP) during a medical examination. The tumors were of neuroendocrine nature, but no abnormal findings were obtained in other organs in which neuroendocrine tumors develop frequently. Repeated transarterial embolization was partially effective. However, the tumors became resistant to the therapy three years later, continued growing and ruptured. Autopsy disclosed neuroendocrine tumors in the pancreas, which were immunohistologically positive for PAP. Neuroendocrine tumors of the pancreas and liver producing PAP are rare; this case is reported with a review of literature.