Tetsuya Isaka

Comparison between CT tumor size and pathological tumor size in frozen section examinations of lung adenocarcinoma

OBJECTIVE We examined the appropriate measurement for pathological tumor size by comparing radiological and pathological tumor size of resected lung adenocarcinoma in FSE. MATERIALS AND METHODS We reviewed records of 59 resected specimens of lung adenocarcinoma for FSE from January to December 2008. Specimens were well-inflated with saline by using an injector before cutting into segments. After selecting the tumor segment of maximal diameter, we compared three ways of measuring pathological tumor size by using paired t-test: (I) macroscopic tumor size (MTS), measured with a metal straight ruler, (II) microscopic frozen section tumor size (FSTS), and (III) microscopic paraffin section tumor size (PSTS). We compared each discrepancy rate (DR) [DR=(CT tumor size-pathological tumor size)/CT tumor size×100] (%) between tumors that were air-containing type and solid-density type on CT scans, and also compared the tumors with lepidic component rates (LCR) ≥50% and LCR <50%, by using Mann-Whitney U-tests. RESULTS FSE could diagnose malignancy with 100% accuracy. The mean CT tumor size was 18.36mm, and the mean pathological tumor sizes (MTS, FSTS, and PSTS) were 17.81, 14.29, and 14.23mm, respectively. FSTS and PSTS were significantly smaller than CT tumor size (p<0.001). The DR calculated with PSTS was significantly larger in air-containing than in solid-density tumors, and also larger in LCR ≥50% than in LCR <50% tumors. CONCLUSION FSE with the inflation method diagnosed malignancy with 100% accuracy. The lung specimen must be sufficiently inflated to prevent tissue shrinking, and we propose MTS as the definition for pathological tumor size in FSE. The greater discordance observed between CT tumor size and microscopic tumor size was assumed to be due to shrinkage of the lepidic component in the tumor.

Correlations Between the EGFR Mutation Status and Clinicopathological Features of Clinical Stage I Lung Adenocarcinoma.

Abstract Advanced lung cancers with epidermal growth factor receptor (EGFR) exon 19 deletions (Ex19s) and EGFR exon 21 L858R point mutations (Ex21s) exhibit different clinical behavior. However, these differences are unclear in resectable primary lung tumors. The clinicopathological features of 88 (20.9%) Ex19, 124 (29.4%) Ex21, and 198 (46.9%) EGFR wild-type (Wt) clinical stage I primary adenocarcinomas resected between January 1, 2012 and October 31, 2014 were compared by using Chi-square tests, residual error analysis, analysis of variance, and Tukey tests. Ex21 lesions occurred more frequently in women and never-smokers and had a higher tumor disappearance rate (TDR: 59.6% vs 43.9%; P < 0.001) and lower maximum standardized uptake value (maxSUV: 2.0 vs 3.5; P < 0.01) than Wt lesions; Ex19 lesions had intermediate values (52.8% and 2.6). There was a low frequency of vascular invasion in Ex21 lesions (12.1%; P < 0.05) and a high frequency in Wt lesions (22.7%; P < 0.05). Most Ex19 lesions were intermediate-grade adenocarcinoma (lepidic, acinar, and papillary predominant: 73.9%; P < 0.05). Wt and Ex21 lesions were predominately high-grade (micropapillary or solid predominant, mucinous variant) and low-grade (adenocarcinoma in situ and minimally invasive adenocarcinoma) adenocarcinoma, respectively. Wt lesions had smaller lepidic components (42.1% vs 56.3%; P < 0.001) and larger papillary and solid components (papillary: 15.5% vs 9.0%; P < 0.05; solid: 13.2% vs 3.2%; P < 0.001) than Ex21 lesions. Most Ex19 lesions had intermediate component rates. Most Ex21 lesions were low-grade adenocarcinoma with lepidic growth patterns. Wt high-grade adenocarcinomas included solid and papillary components with vascular invasion. Ex19 lesions were intermediate grade between Ex21 and Wt.

Case of solitary pulmonary capillary hemangioma: Pathological features based on frozen section analysis

Solitary pulmonary capillary hemangioma (SPCH) is a rare benign lung tumor that must be distinguished from small and early lung cancers. Here, we report a case of SPCH for which we performed frozen section diagnosis. The patient was a 55‐year‐old Japanese woman. Five years before the operation, mixed ground‐glass opacity was detected by computed tomography in the left posterior basal segment of the lower lobe (S10). Because the interior tumor density of the ground‐glass opacity increased slightly, video‐assisted thoracic surgery wedge resection was performed. Frozen section diagnosis revealed a benign tumor without proliferation of atypical epithelial cells. The tumor had narrow alveolar lumens, thickened alveolar septa and a clear boundary separating it from normal lung tissue. The proliferated lumens varied in size and were lined with single layers of flat cells. After the operation, immunohistochemical staining of a paraffin section revealed that the thickened alveolar septa resulted from the proliferation of capillary vessels, the flat cells of which were positive for CD31 and CD34 and negative for podoplanin; the tumor was diagnosed as SPCH. Here, we discuss the pathological features of SPCH on frozen sections with reference to this case and review previous related reports.

Prognostic value of EGFR mutations in surgically resected pathological stage I lung adenocarcinoma

With the advent of the molecular‐targeted therapy, rapid progress has been made in the treatment of advanced or recurrent non‐small‐cell lung cancer (NSCLC). Although surgical complete resection remains the standard and most promising treatment, the clinical significance of epidermal growth factor receptor (EGFR) gene mutations in early‐stage NSCLC remains uncertain.

Detection of tumor spread through airspaces by airway secretion cytology from resected lung cancer specimens

It currently remains unclear whether tumor spread through airspaces (STAS) actually exist in vivo or are an artifact. The morphologies of STAS and tumor cell clusters in airway secretions collected from the segmental or lobar bronchus of resected lung adenocarcinomas and squamous cell carcinomas were compared among 48 patients. The EGFR status of tumor cell clusters in airway secretions was also compared with that of the main tumor in EGFR mutant adenocarcinomas. Tumor cell clusters were observed in the airway secretion cytology of ten patients (20.8%), and eight patients were adenocarcinoma (20.0% of adenocarcinoma). The morphology of STAS closely resembled that of tumor cell clusters detected in airway secretion cytology. The positive rates of airway secretion cytology were 83.3%, 100%, and 50% in papillary adenocarcinoma, micropapillary adenocarcinoma, and invasive mucinous adenocarcinoma, respectively. Among three EGFR mutant adenocarcinomas, the EGFR mutation subtypes of the main tumors in FFPE sections and tumor cell clusters in airway secretions were identical. These indicate that STAS may be detected in the airway secretion cytology. STAS is common in papillary or micropapillary adenocarcinoma and may spread as far as the segmental or lobar bronchus at the time of surgery.

Body mass index, C-reactive protein and survival in smokers undergoing lobectomy for lung cancer†

OBJECTIVES Cachexia has been shown to be related to mortality in patients with advanced cancers and chronic obstructive pulmonary disease. Smokers receiving surgery for lung cancer are thought to be at risk of developing cachexia postoperatively. We aimed to investigate whether 2 surrogate variables for cachexia, body mass index (BMI) and C-reactive protein (CRP) level, are predictive of mortality in smokers after complete resection of non-small-cell lung cancer. METHODS We retrospectively examined 678 patients who underwent curative lobar resection for non-small-cell lung cancer at our hospital. Associations between clinicopathological factors and overall survival were assessed in smokers ( N  = 421) and never smokers ( N  = 257). RESULTS Multivariate analysis of the smokers group showed that preoperative BMI ≤ 20.6 kg/m 2 and CRP ≥ 0.13 ng/ml were risk factors for poorer prognosis, independent of age and pathological stage. In never smokers, BMI and CRP were not significantly associated with survival. Smokers in the high-risk group, defined based on preoperative BMI and CRP, had shorter survival after recurrence, although they did not have an elevated recurrence rate. Despite the absence of recurrence, they died more frequently of pneumonia or other cancers. These observations are consistent with the idea that the poor postoperative prognosis could have resulted from the progression of cachexia. CONCLUSIONS In smokers with non-small-cell lung cancer, preoperative low BMI and elevated CRP are predictive factors for poor prognosis after complete resection, probably as a result of cachexia progression. The effective treatment of cachexia might improve postoperative prognosis.

Platinum-Based Adjuvant Chemotherapy for Stage II and Stage III Squamous Cell Carcinoma of the Lung

INTRODUCTION The efficacy of platinum-based adjuvant chemotherapy (PBAC) for pathological stage II and stage III squamous cell carcinoma (SCC) of the lung was analyzed retrospectively. MATERIALS AND METHODS The prognoses of 94 patients with stage II and stage III SCC with or without PBAC (more than three courses of cisplatin-, carboplatin-, and nedaplatin-based adjuvant chemotherapy) were compared. RESULTS The mean observation period was 46.1 months. PBAC was not administered for the following reasons: 39 (55.7%) patients had comorbidities, 25 (35.7%) were older than 75 years, 19 (27.1%) patients underwent surgery before the approval of PBAC, and 3 (4.3%) patients could not continue PBAC (≤2 cycles) because of adverse events. PBAC patients (n = 24) were significantly younger than non-PBAC patients (n = 70; 66.3 vs 69.6 years old, respectively; p = 0.043). Disease-free survival (DFS) did not differ between PBAC and non-PBAC patients (55.0% and 67.1%, respectively; p = 0.266). PBAC patients tended to have worse overall survival (OS) than non-PBAC patients (56.1% and 70.2%, respectively; p = 0.138). PBAC was not prognostic for OS (hazard ratio (HR), 2.11; 95% confidence interval (CI), 0.82%-5.40%; p = 0.120). CONCLUSION PBAC did not improve the prognoses of patients with pathological stage II or stage III SCC in the single institution experience.

Suspected Aerogenous Lung Metastases From Nasopharyngeal Cancer

A 44-year-old man experiencing repeated episodes of epistaxis and respiratory aspiration was diagnosed with nasopharyngeal cancer. Although the tumor completely disappeared after chemoradiation, six pulmonary nodules developed in the right lower lobe within a year. Right lower lobectomy was performed. All nodules were metastases of the nasopharyngeal cancer. Surgery was performed despite a poor prognosis, and there has been no recurrence 12 years postoperatively. Aerogenous metastases were suggested owing to right lower lobe localization and the patients symptoms and prolonged survival. The possibility of aerogenous spread and the efficacy of local therapy should be further studied.

Prediction of lung tumor palpability using high-resolution computed tomography

Background Palpation is the most important means of locating lung tumors and resecting them with sufficient margins. This study aimed to predict the palpability of pulmonary lesions using high-resolution computed tomography. Methods Eighty-six pulmonary lesions were palpated in fresh resected lung specimens from July 2013 to March 2014. The following parameters were compared between 10 impalpable and 76 palpable lesions: maximum tumor size in pulmonary and bone window level settings, consolidation tumor size in pulmonary window level setting, and pleural-tumor distance. In 54 adenocarcinomas, the lepidic component and fibrosis foci rates were compared between the two groups. Results Tumor size in bone window level setting and the consolidation tumor size were significantly smaller in the impalpable group (both p < 0.001), and an operational cutoff of 5 mm was identified by receiver-operating characteristic analysis (sensitivity/specificity was 90.0%/94.7% and 90.0%/86.9%, respectively). Pulmonary lesions were impalpable with 87.5% probability when the tumor size in bone window level setting was ≤5 mm and the pleural-tumor distance was ≥ 5 mm, and with 85.7% probability when the consolidation tumor size was ≤5 mm and the pleural-tumor distance was ≥ 5 mm. Lepidic component and fibrosis foci rates of impalpable/palpable lesions were 96.0%/52.8% and 4.0%/24.7%, respectively (both p < 0.001). Conclusions Tumor size in bone window level setting or a consolidation tumor size ≤5 mm and pleural-tumor distance ≥ 5 mm are simple criteria that are potentially useful indicators for preoperative marking to locate small-sized lepidic-predominant adenocarcinomas with few fibrotic foci.

Plexiform schwannoma involving the trachea and recurrent laryngeal nerve: a case report

Plexiform schwannoma is an infrequent variant of schwannoma characterized grossly and microscopically by multi-nodular growth. Although plexiform schwannoma has such growth patterns, it is a benign tumor as well as a conventional schwannoma. It rarely infiltrates adjacent organs or arises from the organ itself. In this report, we describe a case in which plexiform schwannoma involved the tracheal wall and left recurrent laryngeal nerve to a great extent. As it was expected to be difficult to achieve complete resection even if the longer tracheal resection were performed, we preserved the trachea and resected as much of the tumor as possible. This report is thought to be the first to describe plexiform schwannoma infiltrating or growing from the trachea. Although the treatment decisions we made might be controversial, we believed we could make an accurate diagnosis and adequate treatment decision through surgery.