Identification of Recurrent TERT Promoter Mutations in Intrathyroid Thymic Carcinomas.

Intrathyroid thymic carcinoma (ITTC) is a rare malignant neoplasm considered to be a eutopic thymic carcinoma (TC) arising ectopically in the thyroid. Histopathologically, ITTC resembles squamous cell carcinoma of the thymus with positive TC markers such as CD5 and c-KIT. Despite these similar histological findings, ITTC is clinically less aggressive than TC. In this study, we compared clinical, histological, and genetic characteristics of ITTCs and TCs. We collected 9 ITTCs and 8 TCs with their clinicopathological profiles. Immunohistochemistry for CD5, p63, CD117/c-KIT, Ki-67, p53, TTF-1, thyroglobulin, PAX8, EGFR, and PD-L1/CD274 plus in situ hybridization for EBER was performed. We further investigated mutation status of KIT, EGFR, BRAF, and TERT promoter using Sanger sequencing. In our study, ITTCs affected significantly younger patients than TCs. After a mean follow-up of 86 months, all patients with ITTC were alive, while two patients with TC had died. Immunohistochemistry showed ITTCs and TCs had a similar immunophenotype except for EGFR and p53. Genetic analysis did not identify KIT or BRAF mutations in any ITTCs or TCs. EGFR mutations were positive in 11% (1/9) of ITTCs and 25% (2/8) of TCs. Notably, TERT promoter C228T mutation was identified in 22% (2/9) of ITTCs but none of the TCs. There were no significant differences in age, tumor size, or sex between TERT-mutated and TERT-wild-type ITTCs. Collectively, ITTC and TC have similar histopathologic and immunophenotypic features but different clinical outcomes. Recurrent TERT promoter mutation may be a key event related to cancer progression in ITTCs and warrants further investigation.

Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion.

ATF1, CREB1, and CREM constitute the CREB family of transcription factors. The genes encoding these factors are involved in gene fusion events in human tumors. EWSR1-ATF1 and EWSR1-CREB1 are the 2 most characterized fusions, whereas EWSR1-CREM has been less studied. To better understand the phenotypic spectrum of mesenchymal tumors associated with the EWSR1-CREM fusion, we investigated archival cases using fluorescence in situ hybridization and/or RNA sequencing. Among 33 clear cell sarcomas of soft tissue tested, we found 1 specimen, a hand tumor bearing the rearrangements of EWSR1 and CREM, with classic histology and immunophenotype. None of 6 clear cell sarcoma-like tumors of the gastrointestinal tract tested harbored the EWSR1-CREM fusion. Among 11 angiomatoid fibrous histiocytomas, we found that 3 tumors of myxoid variant harbored the rearrangements of EWSR1 and CREM. All 3 tumors occurred in middle-aged men and involved the distal extremities (N=2) and the lung (N=1). Prominent lymphoid cuff, fibrous pseudocapsule, and amianthoid fiber were present in 3, 2, and 2 tumors, respectively, whereas none showed pseudoangiomatoid spaces. All 3 tumors were immunohistochemically positive for epithelial membrane antigen and desmin. These cases suggested a closer relationship between angiomatoid fibrous histiocytoma and a recently proposed novel group of myxoid tumors with CREB family fusions. Our cohort also included 2 unclassifiable sarcomas positive for EWSR1-CREM. One of these was an aggressive pediatric tumor of the abdominal cavity characterized by proliferation of swirling spindle cells immunopositive for cytokeratin and CD34. The other tumor derived from the chest wall of an adult and exhibited a MUC4-positive sclerosing epithelioid fibrosarcoma-like histology. Our study demonstrates that a wider phenotypic spectrum is associated with the EWSR1-CREM fusion than previously reported.

Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer.

AIM: To study how lymph node metastasis (LNM) risk is stratified in undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations of risk factors. METHODS: Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using clinicopathological factors of patient age, location, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by conventional statistical analysis and data-mining analysis. RESULTS: LNM was positive in 44 of 567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis. In preoperatively evaluable factors excluding LVI, sm and > 2 cm were independent factors. According to the depth and size, cases were categorized into the low-risk group [m and ≤ 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%; and sm and ≤ 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than 28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases even in the moderate- and high-risk groups. CONCLUSION: LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively. Among these factors, LI was the most significantly correlated factor.

[Case of leptomeningeal carcinomatosis with esophageal carcinoma presenting with neurological signs].

A 72-year-old male was admitted because of hearing impairment, blurred vision, right hemifacial numbness, and difficulty walking. Brain magnetic resonance imaging revealed two enhancing lesions with infiltration around the cranial nerves indicating either metastatic brain tumors or meningeal carcinomatosis. Cytological examination of the cerebrospinal fluid revealed malignant cells with keratotic changes. Upper gastrointestinal endoscopy was performed, which revealed type 1 squamous cell carcinoma of the esophagus;this led to the diagnosis of leptomeningeal carcinomatosis. In this report, we present a rare case of esophageal carcinoma accompanied by meningeal carcinomatosis diagnosed on the basis of neurological symptoms.

A case of idiopathic giant cell myocarditis with a past history of sarcoidosis.

A 70-year-old woman with back pain and breathlessness was referred to our hospital for suspected myocardial infarction. Coronary angiogram was normal and endomyocardial biopsy showed inflammatory cell infiltrates consisting of eosinophils and multinucleated giant cells. The clinical course was hemodynamically fulminant, but steroid therapy improved the cardiac function. Interestingly, this patient had a past history of sarcoidosis. We diagnosed this case with idiopathic giant cell myocarditis (IGCM) from its clinical course. However, whether IGCM and cardiac sarcoidosis belong to the same histological entity has been debated. This case is important with respect to the pathogenic association between these two disorders. .

Acute effect of sodium nitroprusside on microvascular dysfunction in patients who underwent percutaneous coronary intervention for acute ST-segment elevation myocardial infarction.

Even in the era of thrombus aspiration and distal protection for ST-segment elevation acute myocardial infarction (STEMI), microvascular dysfunction does exist and improvement of microvascular dysfunction can improve the prognosis and/or left ventricular dysfunction. We evaluated the acute effects of nitroprusside (NTP) on coronary microvascular injury that occurred after primary percutaneous coronary intervention (PCI) for STEMI in 18 patients. The final Thrombolysis in Myocardial Infarction trial (TIMI) flow grade after PCI was 3 in 17 patients and 2 in 1 patient. The index of microcirculatory resistance (IMR) was improved significantly from 76 ± 42 to 45 ± 37 (P = 0.0006) by intracoronary NTP administration. IMR improved to the normal range (IMR < 30) in 9 patients (50%). Higher TIMI flow grade and lower IMR at baseline were observed more frequently in patients whose IMR recovered to normal range after NTP administration. NTP improved the microcirculatory dysfunction at the acute phase in patients who underwent PCI for STEMI and had final TIMI 3 flow in almost all cases.

Sodium bicarbonate for the prevention of contrast-induced nephropathy: the efficacy of high concentration solution.

BACKGROUND: The appropriate dose of sodium bicarbonate to prevent contrast-induced nephropathy (CIN) has not been established. METHODS AND RESULTS: To determine the efficacy of high-concentration sodium bicarbonate, 123 consecutive patients with renal dysfunction undergoing coronary angiography with/without intervention were administrated either high-concentration (group H: 833 mEq/L, n = 87) or low-concentration (group L: 160 mEq/L, n = 36) sodium bicarbonate at the rate of 3 mL/kg/h for 1 hour before the contrast exposure, and followed by 1 mL/kg/h for 7 hours. A total of 77 patients (group H, n = 54; group L, n = 23) without prophylactic continuous hemodiafiltration were analyzed in this study. Urine pH (n = 10 for each group and n = 5 for control) was increased by concentration and time-dependent manner in each group. Urine pH at 3 hours after administration of sodium bicarbonate was significantly higher in group H than group L and control (8.50 ± 0.94 vs 6.95 ± 1.17 vs 5.70 ± 0.97, respectively; P<.001). Incidence of CIN (0% vs 17.3%; P=.005) was lower in group H than group L. Percent change in creatinine within 48 hours was significantly lower in group H than group L (-2.65 ± 9.83% vs 9.14 ± 14.0%; P=.001). Percent change in estimated glomerular filtration rate within 48 hours was significantly higher in group H than group L (3.97 ± 11.8 vs -7.43 ± 13.3; P<.001). CONCLUSION: Administration of a higher concentration of sodium bicarbonate was more effective for urine alkalization and prevention of CIN.

Ruptured plaque in a bare-metal stent 8 years after implantation-Comparison of IVUS and OCT findings.

Optical coherence tomography (OCT) and intravascular ultrasound tomography (IVUS) findings in a patient with very late in-stent restenosis that was manifested as acute coronary syndrome 8 years after bare-metal stent implantation are presented. This case clearly shows the disruption of thin fibrous cap associated with a white thrombus by OCT. A superficial high signal with deep attenuation by OCT, composing more than half of the plaque, was expressed as heterogeneous tissue, mainly composed of echolucent lesion including outside the struts by IVUS. OCT was very useful, like it is for de novo vulnerable plaques, to evaluate vulnerable plaque that had formed in a previously implanted stent. On the other hand, tissue outside the stent struts could be visualized by IVUS. Combined use of OCT and IVUS was useful for understanding the plaque characteristics of ruptured vulnerable plaque that had formed in a previously implanted bare-metal stent even after stabilization of neointimal hyperplasia.

Late in-stent restenosis after sirolimus-eluting stent implantation is related to thrombus formation-Insight from a case with IVUS, OCT, and histological findings.

We experienced a case of very late in-stent restenosis of a sirolimus-eluting stent (SES) (3.0 mm × 18 mm) in the left anterior descending coronary artery in a 62-year-old man with type 2 diabetes mellitus, dyslipidemia, and hypertension. Angina pectoris recurred 39 months after the index percutaneous coronary intervention (PCI). We performed PCI with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) guidance. OCT showed very eccentric low signal plaque with a high signal thin cap on the delayed healing stent struts without intimal coverage. IVUS showed that the plaque was eccentric and hypoechogenic with a "black hole appearance." We used a filter wire (Filtrap™, Nipro, Osaka, Japan) to prevent distal embolism. Filter no-reflow occurred after predilatation. We deployed a paclitaxel-eluting stent followed by postdilatation. After aspiration and Filtrap™ withdrawal, thrombolysis in myocardial infarction 3 flow was obtained. Histopathological analysis revealed that the main tissue was composed of fibrin deposits with scarce inflammatory cells and proteoglycans. This case revealed that fibrin formation is related to very late in-stent restenosis and OCT and IVUS characteristics of this case are shown.

Spontaneous and selective CO2 sorption under ambient conditions in seemingly nonporous molecular crystal of azacalix[5]arene pentamethyl ether.

Described are the syntheses, crystal structures, and solid-gas adsorption behaviors of azacalix[4]arene tetramethyl ether and azacalix[5]arene pentamethyl ether. While the former compound exhibited no adsorption of four main atmospheric components, the latter selectively and rapidly adsorbed CO(2) at ambient temperature and pressure. X-ray crystallographic and potential energy distribution analysis revealed that azacalix[5]arene created an energetically favorable space for CO(2) in its seemingly nonporous crystal, leading to the observed selective CO(2) uptake under ambient conditions.

Localized mucinous bronchioloalveolar carcinoma of the lung: thin-section computed tomography and fluorodeoxyglucose positron emission tomography findings.

PURPOSE: The aim of this study was to evaluate thinsection computed tomography (CT) and fluorodeoxyglucose positron emission tomography (FDG-PET) findings of localized pulmonary mucinous bronchioloalveolar carcinomas (BACs). METHODS AND MATERIALS: From February 2000 to February 2009, there were seven patients with pulmonary localized mucinous BACs that were pathologically confirmed in the surgical specimens. Their CT findings were assessed regarding location, extent (percent) of groundglass opacity (GGO), margin characteristics, and the presence of air-containing spaces and contractive changes. We evaluated the presence of the "angiogram sign" in the patients who underwent enhanced CT. The maximum standardized uptake value (SUVmax) on FDG-PET was measured in four cases. RESULTS: All tumors were located in the lower lobes. The percentages of GGOs ranged from 0% to 70% (average 20%). The tumor margins were well defined in five cases and ill-defined in two cases. Air-containing spaces were seen in all cases. Evidence of contractive change was seen in two of the seven cases. The angiogram sign was identified in one of five patients who underwent enhanced CT. The SUVmax on FDG-PET ranged from 0.93 to 1.97 (mean 1.53). CONCLUSION: The imaging features of localized mucinous BACs include solid or partly solid attenuation, the presence of air-containing spaces, lack of contractive changes, and lower lobe predominance. Additionally, the SUVmax is markedly low on FDG-PET.

T1N0 laryngeal sarcomatoid carcinoma that showed rapid systemic metastases after radical radiotherapy: a case report and review of literature.

Sarcomatoid carcinomas of the larynx account for less than 1% of all malignant laryngeal tumors and there is currently no consensus regarding the clinical course or appropriate management of this disease. A case of sarcomatoid carcinoma of the larynx displaying rapid systemic progression after radiotherapy and a brief review of the literature are presented.

Mucinous carcinoma (poorly differentiated carcinoma with extensive extracellular mucin deposition) of the thyroid: a case report with immunohistochemical studies.

We report on a case of mucinous carcinoma of the thyroid in an 82-year-old Japanese woman. The 3 x 2 x 2-cm thyroid tumor located in the patient's right lateral lobe was soft and yellowish gray on the cut section. Microscopically, the tumor was composed entirely of strands or solid clusters accompanied by extensive extracellular mucin. Extracellular mucin was positive with Alcian blue stain and negative with periodic acid-Schiff stain. Immunohistochemically, the tumor cells were positive for thyroglobulin, thyroid-specific transcription factor 1, and low-molecular-weight cytokeratin but negative for carcinoembryonic antigen, calcitonin, and high-molecular-weight cytokeratin. The MIB-1 labeling index was rather high (11%), and immunoexpression of p53 was detectable in the nuclei of carcinoma cells. From these findings, we classified the present tumor as a mucinous carcinoma of the thyroid (poorly differentiated thyroid carcinoma producing massive extracellular mucin). The patient died of multiple metastases 4 years after the initial operation.

Stromal tumor of the pancreas with expression of c-kit protein: report of a case.

We report on a case of a stromal tumor, similar to a gastrointestinal stromal tumor, originating from the pancreas. The patient was a 54-year-old woman, who was seen at the Kofu Municipal Hospital because of an abdominal tumor. On abdominal computed tomography and splenic arteriography, the tumor was detected in the pancreatic tail. The patient underwent distal pancreatectomy with splenectomy. Macroscopically, the cut surface of the tumor showed almost completely surrounded by the normal pancreatic tissue. Microscopically, the tumor composed of spindle-shaped cells that were immunoreactive for vimentin, CD34, and c-kit protein. Therefore, the tumor was diagnosed as a stromal tumor of the pancreas. The expression of c-kit protein suggests that this pancreatic stromal tumor may originate from primitive mesenchymal cells which can be a logical candidate for the origin of gastrointestinal stromal tumors and extra-gastrointestinal stromal tumors.

Mixed papillary adenocarcinoma and transitional cell carcinoma of the uterine cervix.

A mixed papillary adenocarcinoma and transitional cell carcinoma (MAcTcc) was discovered in the uterine cervix of a 38-year-old woman. A condylomatous papillary lesion was found in the uterine cervix during a colposcopic study and histopathological examination showed that the tumor was composed of two different neoplastic subtypes. One was an adenocarcinoma (AC) component showing papillary and tubular structure with endocervical and intestinal differentiation; the other was a transitional cell carcinoma (TCC) component showing papillary excrescence mimicking papillary TCC of urothelial origin. To characterize the tumor, an immunohistochemical study of cytokeratins (CK) was performed. The AC component showed immunoreactivities similar to conventional adenocarcinomas: positive immunoreactivity of low-molecular-weight cytokeratins 7, 8 and 19, and negative immunoreactivity of CK20 and high-molecular-weight cytokeratin (34betaE12). The lower epithelial layer of the TCC component showed different immunoreactivity, but the superficial epithelial layer had similar immunohistochemical findings to the AC component. These findings indicate that the TCC component had the cellular character of AC rather than that of TCC or squamous cell carcinomas. This is thought to be the first report of a MAcTcc of the uterine cervix.

Air-containing space in lung adenocarcinoma: high-resolution computed tomography findings.

OBJECTIVE: To disclose imaging features of air-containing spaces other than air bronchograms in lung adenocarcinoma on high-resolution computed tomography (HRCT). MATERIALS AND METHODS: We retrospectively reviewed HRCT scans of 42 consecutive patients with surgically proved lung adenocarcinoma correlating with pathologic specimens. RESULTS: Air-containing spaces were seen in 17 (40%) of cases on HRCT. The air-containing spaces appeared as multiple air densities (16 cases [94%]) with variable shapes and had a relatively larger size than that of air bronchograms. Internal septi were often noted (11 cases [65%]). CONCLUSION: Our results demonstrate that multiplicity, larger diameter, and internal septi are the features of air-containing spaces. These findings could be a key to the definitive diagnosis of lung adenocarcinoma, distinguishing it from the mimics such as organizing pneumonia, tuberculoma, or malignant lymphoma.

Bronchiolitis obliterans organizing pneumonia after tangential beam irradiation to the breast: discrimination from radiation pneumonitis.

We report a case of bronchiolitis obliterans organizing pneumonia (BOOP) secondary to tangential beam irradiation to the breast, which occurred seven months after the completion of radiotherapy. Although radiation pneumonitis is an alternative consideration, BOOP could be differentiated from it by its relatively late onset and extensive distribution, which did not respect the radiation field. This disease should always be kept in mind in patients with a history of tangential beam irradiation to the breast.