[Growing Mixed Squamous Cell and Glandular Papilloma Difficult to Differentiate from Primary Lung Cancer:Report of a Case].

A 76-year-old woman was referred to our hospital due to abnormal chest radiography findings. Chest computed tomography (CT) revealed a nodule in the right lower lobe. Fluorodeoxyglucose-positronemission tomography (FDG-PET) showed abnormal accumulation in the nodule. Bronchoscopy did not provide a definitive diagnosis. Since the nodule tended to increase in size, primary lung cancer was suspected and surgery was performed. During the surgery, pathological diagnosis of squamous cell carcinoma was made, and a right lower lobectomy was performed. Subsequently, a pathological diagnosis of mixed squamous cell and glandular papilloma (mixed papilloma) was made. She has had no sign of recurrence for approximately four years since the surgery.

[Diffuse Pulmonary Meningotheliomatosis Needed to be Differentiate from Metastatic Lung Tumor:Report of a Case].

A 77-year-old woman was found to have multiple granular shadows in the bilateral lungs and a right mammary mass on chest computed tomography (CT) scan for preoperative check of colorectal cancer. The right mammary mass was diagnosed as breast cancer as a result of vacuum-assisted breast biopsy. Fluorodeoxyglucose-positron emission tomography( FDG-PET) showed no abnormal uptake in the lung fields. Since a transbronchial lung biopsy did not establish a diagnosis, an incisional biopsy was performed via a thoracoscopic approach. The histology of the pulmonary nodules revealed minute pulmonary meningothelial-like nodules (MPMNs) and the patient was diagnosed with diffuse pulmonary meningotheliomatosis (DPM). When multiple pulmonary nodules are found in patients with coexisting malignancy, DPM should be considered in addition to metastatic lung tumors.

[Mediastinal Dedifferentiated Liposarcoma Resected with Partial Resection of Pericardium].

An anterior mediastinal tumor was detected by computed tomography (CT) in a 66-year-old man who complained of left flank pain, and the surgical treatment was performed. At surgery, partial resection of the pericardium was also conducted because the pericardial inversion was suspected. The histopathological diagnosis was dedifferentiated liposarcoma. The patient is well without adjuvant chemotherapy 23 months after the surgery.

[A Case of Sarcoidosis Associated with Esophageal Cancer].

A 67-year-old man was diagnosed with esophageal cancer. Computed tomography(CT)revealed multiple sites of bilateral mediastinal lymph node swelling. Serum levels of soluble interleukin-2 receptor(sIL-2R)were elevated; however, serum levels of angiotensin-converting enzyme(ACE)were normal. Thus, we could not confirm a diagnosis of sarcoidosis. Esophagectomy with neck lymph node dissection was performed. The resected specimen, comprising the mediastinal lymph nodes, showed noncaseating epithelioid cell granuloma; this supported the diagnosis of sarcoidosis. Cases of sarcoidosis associated with esophageal cancer are rare. It is difficult to distinguish between metastasis and sarcoid-like reactions from swollen lymph nodes using preoperative CT or positron emission tomography(PET). It is possible to differentiate lymph node metastasis from its sarcoid reaction it the patient received.

[Primary Synovial Sarcoma in the Anterior Mediastinum;Report of a Case].

We report a rare case of synovial sarcoma in the anterior mediastinum. A 43-year-old man consulted our hospital with a complaint of dyspnea and chest discomfort. Chest computed tomography revealed an anterior mediastinal mass. Small open biopsy was performed, and the pathological examination revealed spindle-shaped cells with severe atypia. Tumor resection was performed. On pathology, fascicular and storiform patterns of spindle-shaped cells with severe atypia were noted. The tumor cells were positive for cytokeratin 7, vimentin, Bcl -2 and CD99, and the amplification of SYT-SSX fusion gene was also found. Therefore it was diagnosed as a synovial sarcoma.

[Intravascular papillary endothelial hyperplasia of the lung].

We report a rare case of pulmonary intravascular papillary endothelial hyperplasia. The patient was a 63-year-old male. Multiple lung nodules were noted on chest computed tomography( CT) at preoperative check for gastric cancer. Metastatic lung tumor was suspected, and partial resection of the right lung was performed. Histopathologic examination revealed papillary proliferation lined by endothelial cells and a hematoma. Immunohistochemically, the endothelial cells were positive for CD31/CD34 and factor VIII related antigen.

[Comparison of HER2 immunohistochemical results for advanced gastric cancer obtained on using 3 different antibodies].

We compared the results of immunohistochemical assessment of HER2 expression in 107 samples of advanced gastric cancer on using 3 currently used antibodies. Expression was scored as 0 to 3+, and equivocal or discordant cases were subjected to fluorescence in situ hybridization(FISH)analysis. HER2 scores of 2+or 3+were noted in 16.8% of cases(18/ 107)using SV2-61g, in 29.9% of cases(32/107)using Dako HercepTest, and in 34.6% of cases(37/107)using 4B5. The results of the HER2 test differed according to the antibodies used for immunohistochemistry preceding FISH analysis, and the HER2 positive rates after the FISH analysis were 14.0%(15/107)using SV2-61g, 19.6% (21/107)using Dako HercepTest, and 22.4% (24/107)using 4B5. Thus, therapeutic decisions might be considerably influenced by the antibody used for the HER2 test.

Comparison of HER2 immunohistochemical results using a monoclonal antibody (SV2-61γ) and a polyclonal antibody (for Dako HercepTest) in advanced gastric cancer.

We compared a monoclonal antibody (SV2-61γ) and a polyclonal antibody (Dako HercepTest) in immunohistochemical assessments of human epidermal growth factor receptor 2 (HER2) expression in 73 samples of advanced gastric cancer. Results were scored as 0 to 3+, and equivocal or discordant (SV2-61γ/Dako HercepTest = 0/2+, 0/3+, 1+/3+ or 2+/3+) cases were subjected to fluorescence in situ hybridization (FISH) analysis. The frequencies of HER2 scores of 2+ or 3+ were 15.1% (11/73) using SV2-61γ and 38.4% (28/73) using Dako HercepTest. All of the equivocal or discordant cases with a HER2 score of 3+ using Dako HercepTest exhibited amplification of the HER2 gene regardless of the HER2 score determined with SV2-61γ. The results of the HER2 tests differed according to the antibodies used for immunohistochemistry that preceded FISH analysis, being 15.1% (11/73) using SV2-61γ and 23.3% (17/73) using Dako HercepTest. Thus, therapeutic decisions might be markedly influenced by the selection of antibody used in the HER2 test.

[Huge unresectable multiple hepatic metastases of rectum cancer responding to combined therapy with FOLFIRI +bevacizumab - a case report].

We report a patient with a huge multiple hepatic metastases of rectal cancer treated by combination of infusional 5-FU, Leucovorin, irinotecan(FOLFIRI), and bevacizumab(BV). The patient was a 60-year-old man with cancer of the rectum, with huge multiple hepatic metastases. The serum carcinoembryonic antigen(CEA)level was 3,979.6 ng/mL, and the carbohy- drate antigen(CA)19-9 level was 66,562.6 U/mL. The patient received combined chemotherapy with FOLFIRI and BV. After completion of 8 courses, abdominal CT scans revealed that those low-density areas of the liver had reduced. The patient was judged to have achieved PR. He received combined therapy for 42 courses, and his response is SD at this point. No grade 2 adverse event occurred throughout chemotherapy. This case suggests that combined therapy with FOLFIRI+BV may be an effective regimen for advanced rectal cancer with huge multiple hepatic metastases.

[A case of posterior gastric arteriovenous malformation causing massive intraperitoneal hemorrhage].

We report abdominal bleeding caused by arteriovenous malformations (AVM) of the posterior gastric artery. A 38-year-old man visited our hospital complaining of epigastralgia. Enhanced abdominal CT revealed a high density spot in a huge low density mass. Angiographic study showed AVM of the posterior gastric artery. Transcatheter arterial embolization was performed and we successfully treated the AVM which was accompanied by abdominal bleeding.

A rare case of fibrohistiocytic hepatic inflammatory pseudotumor with cholecystocholangitis showing positive IgG4 staining.

Inflammatory pseudotumor (IPT) is a rare benign mass characterized by infiltration of inflammatory cells and proliferation of fibrous tissues. Consistent with increasing knowledge about IgG4-related disease (RD), it has been implicated in the etiology of hepatic IPT, which is pathologically classified into two categories with respect to the proportion of IgG4-positive plasma cells: fibrohistiocytic- and lymphoplasmacytic-type. A 66-year-old man was admitted for treatment of cholecystocholangitis. Incidentally, abdominal computed tomography (CT) revealed an ambiguous low-density mass within segment 4 (S4) of the liver. Magnetic resonance imaging (MRI) showed the typical images of hepatic IPT within S4. Together with CT and MRI imaging, we suspected hepatic IPT, and had the opportunity to biopsy the S4 lesion during surgery for cholecystitis. Histopathological examination of liver tissue showed diffuse fibrous tissues, dense lymphoplasmacytic infiltration, and obliterative phlebitis with no evidence of malignancy. Despite infiltration of IgG4-positive plasma cells, these histological findings corresponded with fibrohistiocytic-type hepatic IPT. Similarly, in the resected gallbladder, relatively abundant IgG4-positive cells were observed, but not entirely consistent with IgG4-RD criteria. Although IgG4 immunostaining can be useful for the classification of hepatic IPT, the present histological tissues were borderline condition defined by IgG4-RD criteria. This rare case of hepatic IPT suggests a future focus on the borderline histological features of IgG4-RD.

Programmed death ligand 1 protein expression is positively correlated with the solid predominant subtype, high MIB-1 labeling index, and p53 expression and negatively correlated with epidermal growth factor receptor mutations in lung adenocarcinoma.

Programmed death ligand 1 (PD-L1) protein expression is a proposed predictive biomarker of immunotherapy; thus, identification of the clinicopathological and molecular characteristics associated with PD-L1 expression is important and necessary. We examined PD-L1 immunohistochemical expression and its relationships with the clinicopathological and molecular characteristics of patients with surgically resected nonsmall cell lung carcinoma. PD-L1 expression differed according to the histological subtype. Among 633 patients with adenocarcinoma, 523 (82.6%) had no PD-L1 expression, 78 (12.3%) low expression, and 32 (5.1%) high expression. PD-L1 expression was more common in men (p < 0.001), in smokers (p = 0.002), and in patients with a more advanced stage (p = 0.002), the solid predominant subtype (p < 0.001), no epidermal growth factor receptor(EGFR) mutations (p < 0.001), a high MIB-1 labeling index (p < 0.001), and positive p53 immunohistochemical expression (p < 0.001). In a multivariate logistic regression analysis, the solid predominant subtype (odds ratio [OR] = 4.92, 95% confidence interval [CI]: 2.72-8.89, p < 0.001), no EGFR mutations (OR = 2.27, 95% CI: 1.35-2.7, p = 0.002), a high MIB-1 labeling index (OR = 2.78, 95% CI: 1.72-4.55, p < 0.001), and p53 positivity (OR = 2.13, 95% CI: 1.34-4.36, p = 0.042) were significantly and independently associated with PD-L1 expression. The combination of the solid predominant subtype with a high MIB-1 labeling index was strongly associated with positive expression of PD-L1. In the 193 patients with squamous cell carcinoma, 92 (47.7%) had no PD-L1 expression, 57 (29.5%) low expression, and 44 (22.8%) high expression. There were no significant correlations between PD-L1 expression and the evaluated clinicopathological or molecular characteristics of these patients. These results, indicating associations of PD-L1 with various clinicopathological or molecular characteristics in adenocarcinoma but not squamous cell carcinoma, may be useful for selecting patients with a good response to immune checkpoint inhibitors.

The Frequency of DNA Mismatch Repair Deficiency Is Very Low in Surgically Resected Lung Carcinoma.

INTRODUCTION: DNA mismatch repair (MMR) deficiency leads to changes in the length of nucleotide repeat sequences of tumor DNA. In that situation, DNA replicational errors occur and accumulate during DNA replication. As a result, this mechanism frequently affects the coding regions of oncogenes and tumor suppressor genes and causes carcinogenesis. Recently, DNA MMR deficiency has been recognized as a predictive biomarker for immunotherapy. The aim of this study is to examine the frequency of DNA MMR deficiency and clinicopathological characteristics in surgically resected lung carcinoma (LC) and their correlation. METHODS: A total of 1153 LCs were examined. Tissue microarrays were constructed. The status of MMR deficiency was evaluated by immunohistochemical analysis of MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2). Microsatellite instability analysis, BRAF mutation, and MLH1 methylation analysis were performed for cases that showed MMR deficiency. RESULTS: Only 2 of the 1153 cases (0.17%) showed a loss of hMLH1/hPMS2 protein expression. They also had high levels of microsatellite instability (MSI-H), had neither MLH1 promoter methylation nor BRAF mutation, and were male smokers. Histopathologically, one was a squamous cell carcinoma, and the other was combined small cell carcinoma with squamous cell carcinoma. Regarding PD-L1 protein expression, one had high expression, and the other had none. CONCLUSION: The frequency of MMR deficiency was very low in LC. However, our two cases were non-adenocarcinoma and differed from previous studies. Because of its very low frequency, MMR deficiency is not a practical biomarker to predict the effect of immune checkpoint inhibitors in LC.

[Successful internal jugular vein puncture with ultrasound guidance for a terminal life stage patient in sitting position].

We experienced an internal jugular vein cannulation of a terminal life stage patient suffering from serious peritonitis carcinomatosa with severely edematous limbs. He could not lie down on a bed because of dyspnea due to high abdominal pressure caused by massive ascites. We examined his internal jugular vein with ultrasound device, and found that it kept high venous pressure even in his inspiratory phase, although in sitting position. Internal jugular vein cannulation was successfully performed at first attempt by using ultrasound guide with no complications including air embolism, pneumothorax and bleeding. We considered that positive pressure of jugular vein during a respiratory cycle of the patient was obtained from his unconscious Valsalva's maneuver by increasing intrathoracic pressure following high abdominal pressure. Ultrasound-guided vascular access technique is useful and safe even in terminal life stage patients under palliative care.

Parathyroid carcinoma with anaplastic feature: association of a p53 gene mutation with anaplastic transformation.

Parathyroid carcinoma is a rare neoplasm that accounts for only 1-3% of cases of primary hyperparathyroidism. Parathyroid carcinoma is a well-differentiated tumor that is sometimes difficult to differentiate histopathologically from its benign counterpart, parathyroid adenoma. The molecular mechanism of parathyroid carcinogenesis remains unknown, and investigators have reported that abnormalities of the p53 gene do not play a significant role in parathyroid carcinogenesis, unlike in other human malignancies. The present report describes parathyroid carcinoma with anaplastic transformation of differentiated parathyroid carcinoma in a patient with primary hyperparathyroidism. Nuclear accumulation of p53 protein was found in anaplastic carcinoma cells but not in differentiated carcinoma cells. Polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing showed that anaplastic carcinoma cells carried a missense mutation at codon 248 (CGG to CAG) of the p53 gene, while the remaining differentiated carcinoma cells had the wild-type p53 gene. These findings suggest that the p53 gene mutation is associated with anaplastic transformation of parathyroid carcinoma.

Tumor spread through air spaces is a useful predictor of recurrence and prognosis in stage I lung squamous cell carcinoma, but not in stage II and III.

OBJECTIVES: Tumor spread through air spaces (STAS) is a newly identified invasion pattern in lung adenocarcinoma. This study aimed to analyze and validate the clinical impact of tumor STAS in surgically resected lung squamous cell carcinoma (SQCC). MATERIALS AND METHODS: We retrospectively reviewed 220 patients with lung SQCC. Tumor STAS was defined as detached tumor cells within the air spaces in the lung parenchyma beyond the edge of the main tumor. Statistical analyses were conducted to investigate the proportion of STAS and the relationship between the presence of STAS and clinicopathological factors, including clinical outcome. RESULTS: STAS was identified in 42 of 220 patients (19.1%). The patients with STAS had a significantly worse 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) than those without STAS (5-year RFS: 37.4% vs. 68.4%; p = 0.0006; 5-year OS: 50.2% vs. 71.4%, p = 0.0078) in stage I, but not in stage II and III. A multivariate analysis showed that the presence of STAS was an independent predictive factor of recurrence (hazard ratio = 3.27; 95% confidence interval, 1.7-6.29; p = 0.0004) and an independent prognostic factor (hazard ratio = 3.01; 95% confidence interval, 1.54-5.89; p = 0.0013) in stage I, but not in stage II and III. CONCLUSION: We found that STAS was detected in 19.1% of surgical resected SQCC, and it was associated with recurrence and worse survival in stage I SQCC, but not in stage II and III SQCC. Therefore, we suggest that STAS is a useful predictor of recurrence and prognosis in stage I lung SQCC.