Chiho Ohbayashi

Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes

Abstract Although usual interstitial pneumonia (UIP)-like IP has been known as the most serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP associated with HPS (HPSIP). The salient histopathologic features of HPSIP observed were: (1) alveolar septa displaying florid proliferation of type-2 pneumocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around respiratory bronchioles, occasionally showing constrictive bronchiolitis; and (3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over accumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic disruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secretion process of surfactant by the 2PCs in HPS, which may well be the triggering factor for the HPSIP development. Other factors, such as macrophage dysfunction, may be working synergistically for further acceleration of the inflammatory process.

STIR turbo SE MR imaging vs. coregistered FDG‐PET/CT: Quantitative and qualitative assessment of N‐stage in non‐small‐cell lung cancer patients

To conduct a prospective comparison of the accuracy of short inversion time (TI) inversion‐recovery (STIR) turbo spin‐echo (SE) imaging and coregistered 2‐[fluorine‐18] fluoro‐2‐deoxy‐D‐glucose (FDG)–positron emission tomography (PET) with computed tomography (CT) (coregistered FDG‐PET/CT) to assess the N‐stage in non‐small‐cell lung cancer (NSCLC) patients.

Differentiation of metastatic versus non-metastatic mediastinal lymph nodes in patients with non-small cell lung cancer using respiratory-triggered short inversion time inversion recovery (STIR) turbo spin-echo MR imaging

OBJECTIVES To differentiate between metastatic and non-metastatic lymph nodes in patients with non-small cell lung cancer using respiratory-triggered short inversion time inversion recovery (STIR) turbo spin-echo (SE) MR imaging. METHODS AND PATIENTS One hundred and forty mediastinal lymph nodes were detected in 25 patients with non-small cell lung cancer who underwent respiratory-triggered STIR turbo SE imaging. Ratios of signal intensity of lymph nodes to 0.9% saline phantoms (lymph node-saline ratio) were compared by Students t-test using the pathological diagnosis as the gold standard. The threshold value of the lymph node-saline ratio was determined for a positive test, and tested for its capability to provide a differential diagnosis. RESULTS One hundred and forty lymph nodes were diagnosed and classified into two groups: metastatic lymph node (n=21) and non-metastatic lymph node (n=119). The mean lymph node-saline ratio in the non-metastatic lymph node group (0.42+/-0.01; mean+/-standard error) was significantly lower than that of the metastatic lymph node group (0.77+/-0.02, P<0.0001). When 0.6 was adapted as the threshold for a positive test, sensitivity, specificity, and accuracy for differentiating metastatic lymph node from non-metastatic lymph node per lymph nodes were 100, 96, and 96%, and sensitivity, specificity, and accuracy for differentiating metastatic lymph node from non-metastatic lymph node per patients were 100, 75, and 88%, respectively. CONCLUSIONS Both metastatic and non-metastatic lymph nodes in patients with non-small cell lung cancer were well differentiated using respiratory-triggered STIR turbo SE imaging.

Dynamic MRI, dynamic multidetector-row computed tomography (MDCT), and coregistered 2-[fluorine-18]-fluoro-2-deoxy-D-glucose–positron emission tomography (FDG-PET)/CT: Comparative study of capability for management of pulmonary nodules

To compare the nodule management capabilities of dynamic MRI, dynamic multidetector‐row computed tomography (MDCT) and coregistered positron emission tomography (PET)/CT.

Carcinosarcoma of the gallbladder with chondroid differentiation

Carcinosarcoma of the gallbladder is an uncommon neoplasm. We herein report the case of a patient with carcinosarcoma of the gallbladder with chondroid differentiation, treated by cholecystectomy with liver segmentectomy and lymph node dissection for a tumor which occupied the entire gallbladder and spread to the liver. Histologically, the tumor contained two distinct components: a mixture of both well and poorly differentiated tubular adenocarcinoma and sarcomatoid tissue with chondroid differentiation. From a review of the literature, it was seen that carcinosarcomas of the gallbladder could be divided into two groups: one group with apparent sarcomatous differentiation, such as chondroid, osteoid, and rhabdomyosarcomatous differentiation, and the other group, of carcinosarcomas with a sarcomatous portion composed of anaplastic spindle cells. Each group had a poor prognosis in spite of surgical resection of tumors. Our patient died of peritoneal dissemination 7 months after surgery.

Novel marker D2-40, combined with calretinin, CEA, and TTF-1: an optimal set of immunodiagnostic markers for pleural mesothelioma.

Malignant pleural mesothelioma is a challenging disease with regard to diagnosis and treatment; early and accurate diagnosis would lead to appropriate therapeutic strategies, including extrapleural pneumonectomy. Immunohistochemistry has proven valuable for the diagnosis of the most common epithelioid mesothelioma, although it is often difficult to differentiate it from pulmonary or metastatic adenocarcinoma with absolute certainty if a single antibody is employed. The current study was designed to identify an immunodiagnostic panel for pleural mesothelioma.

Transthoracic CT-guided biopsy with multiplanar reconstruction image improves diagnostic accuracy of solitary pulmonary nodules☆

OBJECTIVE To evaluate the utility of multiplanar reconstruction (MPR) image for CT-guided biopsy and determine factors of influencing diagnostic accuracy and the pneumothorax rate. MATERIALS AND METHODS 390 patients with 396 pulmonary nodules underwent transthoracic CT-guided aspiration biopsy (TNAB) and transthoracic CT-guided cutting needle core biopsy (TCNB) as follows: 250 solitary pulmonary nodules (SPNs) underwent conventional CT-guided biopsy (conventional method), 81 underwent CT-fluoroscopic biopsy (CT-fluoroscopic method) and 65 underwent conventional CT-guided biopsy in combination with MPR image (MPR method). Success rate, overall diagnostic accuracy, pneumothorax rate and total procedure time were compared in each method. Factors affecting diagnostic accuracy and pneumothorax rate of CT-guided biopsy were statistically evaluated. RESULTS Success rates (TNAB: 100.0%, TCNB: 100.0%) and overall diagnostic accuracies (TNAB: 96.9%, TCNB: 97.0%) of MPR were significantly higher than those using the conventional method (TNAB: 87.6 and 82.4%, TCNB: 86.3 and 81.3%) (P < 0.05). Diagnostic accuracy were influenced by biopsy method, lesion size, and needle path length (P < 0.05). Pneumothorax rate was influenced by pathological diagnostic method, lesion size, number of punctures and FEV1.0% (P < 0.05). CONCLUSION The use of MPR for CT-guided lung biopsy is useful for improving diagnostic accuracy with no significant increase in pneumothorax rate or total procedure time.

Oncogenic phosphatase Wip1 is a novel prognostic marker for lung adenocarcinoma patient survival.

DNA damage response pathways are important for maintaining genomic stability. The oncogenic phosphatase Wip1 plays a crucial role in DNA damage response by inhibiting several cell cycle proteins, including p53. Although Wip1 gene amplification has been reported in various primary tumors, including lung cancer, its biological significance for survival of primary lung tumor patients remains unclear. We investigated the expression of Wip1 in cancer epithelial cells immunohistochemically in 84 consecutive resected cases of lung adenocarcinoma. Increased Wip1 expression was observed in 54 (64.3%) of the 84 cases. Wip1 expression was found to be correlated significantly with two clinicopathological factors: γ‐H2AX expression, and invasion to the pulmonary vein. A univariate analysis and log–rank test indicated a significant association between Wip1 expression and lower overall survival rate (P = 0.019 and P = 0.0099, respectively). A multivariate analysis also indicated a statistically significant association between increased Wip1 expression and lower overall survival rate (hazard ratio, 4.3; P = 0.026). The Ki67 index level was higher in the Wip1‐positive group than in the negative group (P < 0.04, Mann–Whitney U‐test). Moreover, in a subgroup analysis of only stage I patients, increased Wip1 expression was also significantly associated with a lower overall survival rate (P = 0.023, log–rank test). These results indicate that the increased expression of Wip1 in cancer epithelial cells has significant value for tumor progression and the clinical prognosis of patients with primary lung adenocarcinoma. (Cancer Sci, 2011; 102: 1101–1106)

Pathogenesis of multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis and association with tuberous sclerosis genes TSC1 and TSC2

Tuberous sclerosis (TSC) is a rare, genetically determined disorder / familial tumor syndrome, currently diagnosed using specific clinical criteria proposed by Gomez, including the presence of multiorgan hamartomas. Pulmonary involvement in TSC is well known as pulmonary lymphangioleiomyomatosis (LAM), which has an incidence of 1–2.3% in TSC patients. LAM has immunohistochemical expression of both smooth‐muscle actin and a monoclonal antibody specific for human melanoma, HMB‐45. It has recently been reported that multifocal micronodular pneumocyte hyperplasia (MMPH) associated with TSC should be considered as a distinct type of lung lesion, whether it occurs with or without LAM. Two predisposing genes have been found in families affected by TSC; approximately half of the families show linkage to TSC1 at 9q34.3, and the other half show linkage to TSC2 at 16p13.3. TSC genes are considered to be tumor suppressor genes, and mutations in them may lead to abnormal differentiation and proliferation of cells. Tuberin, the TSC2 gene product, has recently been found to be expressed in LAM and MMPH. In this article we discuss the histogenesis and genetic abnormalities of neoplastic lesions associated with TSC, and we review the current understanding of the pathogenesis of pulmonary hamartomatous lesions such as LAM and MMPH in TSC.

Overexpression of Necl-5 correlates with unfavorable prognosis in patients with lung adenocarcinoma

Nectin‐like molecule‐5 (Necl‐5) is an immunoglobulin (Ig)‐like molecule that is up‐regulated in many types of cancer cells. It was shown experimentally that Necl‐5 enhances cell migration, proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl‐5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl‐5. The relationship between expression of Necl‐5 and clinicopathological features was analyzed, and the influence of Necl‐5 expression on outcomes in these patients was assessed. A strong expression of Necl‐5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl‐5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease‐free survival rate in patients with positive Necl‐5 overexpression was significantly lower than that in patients with negative Necl‐5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl‐5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the disease‐free survival rate of the Necl‐5‐positive group was significantly lower than that of the Necl‐5‐negative group (P = 0.0192). These results indicate that Necl‐5 plays a role in mediating tumor cell invasion and that the overexpression of Necl‐5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma.