Pleomorphic carcinoma of the lung with mediastinal extension following malignant lymphoma: report of a case.

In following up a patient with non-Hodgkin's lymphoma, we encountered a case of pulmonary pleomorphic carcinoma with mediastinal direct invasion. A 65-year-old man with hemoptysis was found to have an abnormal shadow in the right upper lung field. A 6.4 x 4.8-cm tumor adjacent to the upper mediastinum occupied the right anterior segment of the upper lobe (S3) and invaded the superior vena cava (SVC). The serum level of neuron-specific enolase was elevated to 11.9 ng/ml. A specimen from a transbronchial lung biopsy of the right B3b bronchus revealed giant tumor cells. A right upper lobectomy with SVC reconstruction was performed. The resected tumor was diagnosed as a pulmonary pleomorphic carcinoma with a large component of giant and spindle cells, and it is considered to be a rare histologic type.

Endobronchial neurogenic tumors treated by transbronchial electrical snaring and Nd-YAG laser abrasion: report of three cases.

Neurogenic benign tumors arising from the trachea and bronchus are relatively rare. We experienced three cases of neurofibroma of the bronchus which were successfully treated by transbronchial electrical snaring and Nd-YAG laser abrasion. The first was a 67-year-old man with right lung cancer, who was pointed out to have a neurofibroma in the left main bronchus. The second was a 34-year-old man with an obstruction in the right main bronchus due to neurofibroma. The third was a 66-year-old woman with a complete obstruction in the left main bronchus due to schwannoma. All patients were successfully treated to remove the tumors and obtain a patency of the bronchus by transbronchial electrical snaring and Nd-YAG laser abrasion. We also review 23 reported cases of endobronchial neurogenic tumors and discuss the efficacy of endoscopic treatments for endobronchial neurogenic tumors.

Double primary lung carcinoma consisting of large cell neuroendocrine carcinoma and squamous cell carcinoma: report of a case.

We report a rare case of double primary lung carcinoma including large cell neuroendocrine carcinoma (LCNEC). A 67-year-old man underwent an annual medical checkup in 2000, pulmonary carcinoma was strongly suspected by sputum cytology and radiological images. Preoperative diagnosis was double primary lung carcinoma with a squamous cell carcinoma in the right lower lobe and non-small cell carcinoma in the right upper lobe. The histological carcinoma type in the right upper lobe could not be determined preoperatively. The patient underwent a right lower lobectomy and wedge resection of the right upper lobe. Histologically, the tumor in the right upper lobe was LCNEC and the tumor in the right lower lobe was a moderately differentiated squamous cell carcinoma. The patient had right supraclavicular lymph node metastases of LCNEC and died of multiple pulmonary metastases 10 months after the operation.

Biological features of bronchial squamous dysplasia followed up by autofluorescence bronchoscopy.

Some dysplasias in the bronchial epithelium are thought to be precancerous lesions that can develop into squamous cell carcinomas. In this investigation, we assessed the biological behavior of bronchial squamous dysplasia in order to define which dysplasias have the potential to progress to squamous cell carcinoma. Using autofluorescence bronchoscopy, we followed up periodically localized dysplasias and examined for correlation between histological outcome and smoking status during the follow-up period, telomerase activity, Ki-67 labeling index, and p53 immunoreactivity of initial biopsy specimens. Ninety-nine dysplasias from 50 participants mainly with sputum cytology suspicious or positive for malignancy were followed up. Of 99 dysplasias, 3 dysplasias progressed to squamous cell carcinoma, 41 dysplasias remained as dysplasia, 6 dysplasias changed to metaplasia, 14 dysplasias changed to hyperplasia, and 35 dysplasias regressed to bronchitis or normal bronchial epithelium. There were no significant associations between histological outcome and smoking status. Mean initial telomerase activity and Ki-67 labeling index values in the dysplasias increased in proportion to the severity of the histological outcome at the second biopsy. There was also a significant difference between p53-positive and p53-negative dysplasia in terms of histological outcome at the second biopsy. Our results suggested that dysplasias with high telomerase activity, increased Ki-67 labeling index, and p53-positivity tended to remain as dysplasia and might have the potential to progress to squamous cell carcinoma. Patients with dysplastic lesions with these characteristics should be carefully followed up.

Genetic alterations in early-stage pulmonary large cell neuroendocrine carcinoma.

BACKGROUND: Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are high-grade malignant neuroendocrine tumors. Histologic differentiation between SCLC and LCNEC is difficult in some cases and to the authors' knowledge, genetic alterations associated with LCNEC have not been identified. Therefore, the authors studied genetic alterations found in LCNEC and compared them with those of SCLC and classic large cell carcinoma (CLCC). METHODS: Twenty-two patients with UICC TNM Stage I LCNEC, 12 patients with Stage I CLCC, and 11 patients with SCLC with limited disease were studied. All tumors were resected completely. Loss of heterozygosity (LOH) of the tumor cells was detected using fluorescent primers. Methylation status of the p16 gene and expression of the p53 protein, retinoblastoma protein, and p16 protein were evaluated immunohistochemically. RESULTS: LOH at TP53 and 13q14 was observed in most patients. The prevalence of LOH at D3S1295, D3S1234, and D5S407 was significantly higher in patients with LCNEC and SCLC than in patients with CLCC. The prevalence of LOH at D5S422 was higher in patients with CLCC and in patients with SCLC than in patients with LCNEC. Expression of the p16 protein was observed more frequently in SCLC than in CLCC or LCNEC. Hypermethylation of the p16 gene was observed more frequently in LCNEC than in SCLC. Patients with allelic losses at D3S1234 and D10S1686 had poorer prognoses compared with patients without allelic losses at these sites. CONCLUSIONS: Genetic alterations of LCNEC were akin to those of SCLC. However, allelic losses at 5q and abnormalities in the p16 gene may differentiate LCNEC from SCLC.

Imprint cytologic features of pulmonary large cell neuroendocrine carcinoma: Comparison with classic large cell carcinoma.

The World Health Organization (WHO) categorized large cell neuroendocrine carcinoma (LCNEC) as a variant of large cell carcinoma in 1999. However, cytologic features of these tumors have not yet been adequately characterized. The cytologic features of 24 cases of LCNEC were analyzed and compared to the features of 16 cases of classic large cell carcinoma (CLCC). Giant cells, neutrophils and cytophagocytosis were observed more frequently in CLCC than in LCNEC (p<0.05), whereas the unclear border of tumor cells was seen more frequently in LCNEC (p<0.05). The presence of nuclear atypia, such as anisokaryosis, nuclear budding, irregularity of nuclear margins, and multinucleation (having three or more nuclei), was observed less frequently in LCNEC. Characteristic arrangements of tumor cells, such as rosette formation, and palisading, were observed only in LCNEC cases. In morphometric studies, the nuclear areas, cytoplasmic areas, and nuclear rotundity ratios were significantly higher in CLCC cells than in LCNEC cells (p<0.05). However, N/C ratios were significantly higher in LCNEC than in CLCC. LCNEC cells have less nuclear atypia than CLCC cells, and have the characteristic arrangements of tumor cells, such as palisading and rosette. It is possible to preoperatively differentiate LCNEC from CLCC by careful cytologic characterization.

Small cell carcinoma of the prostate expressing prostate-specific antigen and showing syndrome of inappropriate secretion of antidiuretic hormone: an autopsy case report.

An autopsy case of primary small cell carcinoma (SCC) of the prostate in a 68-year-old man is reported. The patient was admitted to hospital because of a bloody stool and suspected rectal cancer. However, a diagnosis of prostate cancer was made on the basis of a digital rectal examination, the serum level of prostate-specific antigen, and a needle biopsy of the prostate. The patient also experienced a syndrome of inappropriate secretion of antidiuretic hormone. He died 29 days after admission. At autopsy, the tumor had invaded the rectum, bladder and pelvic peritoneum. Metastases to the heart, vertebrae and lymph nodes were observed. Microscopically, the tumor was composed of small round cells that showed a solid growth pattern. Rosette formations were observed. Immunohistochemically, the tumor cells were positive for a prostatic epithelial marker and neuroendocrine markers. A high level of antidiuretic hormone was detected in the tumor tissue. To our knowledge, this is the first reported case of SCC of the prostate in which both a prostatic epithelial marker and neuroendocrine markers have been found in the same tumor. This finding supports the hypothesis that SCC of the prostate originates from a multipotential stem cell of the prostatic epithelium.

Fatal infectious mononucleosis with evidence suggestive of the development of B cell lymphoma.

A 4-year-old girl presented to a local hospital in August 1999 with fever and cervical lymphadenopathy. A diagnosis of Epstein-Barr virus (EBV) infection was made and the patient was treated with corticosteroids. One month later she developed dyspnea secondary to tonsilar swelling, and underwent tonsillectomy and adenoidectomy. Her dyspnea increased, however, and by mid September she required mechanical ventilation. Six weeks later, she was transferred to Chiba Children's Hospital (Chiba, Japan). Despite vigorous treatment, she died within four weeks of admission. At autopsy, microscopic examination revealed numerous histiocytes with frequent hemophagocytosis in her lungs, liver, spleen, thymus, and lymph nodes. The tentative diagnosis was EBV-associated hemophagocytic syndrome (EBVAHS). A proliferation of atypical lymphocytes was observed in the lymph nodes, the majority of which stained positive with CD79a antibody. A whitish nodule, 8 mm in diameter, was noted in her right ovary. It consisted of a proliferation of pleomorphic lymphoid cells expressing CD79a antigen. In situ hybridization detected EBV RNA within CD79a antigen-positive cells in the lungs, spleen, thymus, bone marrow, lymph nodes, and the right ovary. Polymerase chain reaction analysis of DNA from the ovarian nodule demonstrated a monoclonal rearrangement of the immunoglobulin heavy chain gene indicating that it consisted of a clone of B lymphocytes. We suggest that EBVAHS develops into polyclonal and monoclonal lymphoproliferative disorder in a short period, and that EBVAHS is a preneoplastic condition that may result in B cell lymphoma.

Preoperative carbon ion radiotherapy for non-small cell lung cancer with chest wall invasion--pathological findings concerning tumor response and radiation induced lung injury in the resected organs.

The purpose of this study was to make a pathological evaluation of the tumor response and the lung injury of non-small cell lung cancer (NSCLC) patients after carbon ion therapy. We enrolled four NSCLC patients with chest wall invasion but without nodal and distant metastasis (T3N0M0). Only primary lesions were irradiated with carbon ions, followed by surgical resection. The patients consisted of three males and one female varying by age from 54 to 73 (average 66.3). Total treatment dose was 59.4 and 64.8 GyE, respectively, administered in 18 fractions over 6 weeks, or 72.0 GyE in 16 fractions over 4 weeks. Resection after radiation therapy was performed as a combination of lobectomy, lymph node dissection and chest wall surgery. After fixation, the lung was sliced into thin sections to match the CT image. Each slice was anatomically identified and the slices were compared with each other subjected to pathological analysis. No tumor cells were observed in two cases. The other two cases exhibited only a few tumor cells sparsely distributed in the lung tissue. There was evidence of dense pulmonary fibrosis in the limited space surrounding primary tumors, but its density was found to rapidly decrease in the narrow area toward the outside. The rate at which its density subsided mirrored the rapid decrease in the planning CT dose distribution. Microscopy showed no evidence of fibrosis in any of the fields irradiated with less than 15 GyE. Microscopy confirmed an outstanding tumor response with limited pulmonary fibrosis. This substantiates the superior dose localization and strong biological effect of carbon ion beams with a Bragg peak in the lung. The pathological findings have thus provided evidence of the safety and effectiveness of carbon beam therapy in the treatment of NSCLC.

Small solitary pulmonary metastasis detected before primary sigmoid colon cancer: report of a case.

We report the case of a 60-year-old woman referred to us after chest X-ray and mobile computed tomography screening detected an 8-mm nodule in right S2. Transbronchial aspiration cytology suggested a pulmonary metastasis from colorectal cancer. Therefore, we performed a colonoscopy and found a polypoid lesion, 2 cm in diameter, in the sigmoid colon. An analysis of a biopsy specimen from this polypoid lesion confirmed adenocarcinoma. Surgical resection of the primary sigmoid colon cancer was subsequently performed, followed 4 weeks later by a right S2 segmentectomy to remove the lung metastasis. The patient is currently well without any clinical signs of recurrence, 44 months after her operation.

Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer.

BACKGROUND: The cigarette smoking status of patients before surgery is an important prognostic factor in evaluation of stage I non-small cell lung cancer, and the proliferative activity of lung tumors is also related to the patient's prognosis. This study evaluates relationships between various clinicopathologic factors, including tumor proliferative activity and smoking status, and the patient's prognosis in stage I non-small cell lung cancer. METHODS: One hundred eighty-seven stage I adenocarcinoma and squamous cell carcinoma cases were evaluated. The patients underwent complete resection between 1988 and 1993 at Chiba University Hospital. Expression levels of Ki-67 nuclear antigen, p53 protein, and retinoblastoma protein were determined immunohistochemically, and postoperative survival rates for patients in the categories of clinicopathologic factors were estimated. RESULTS: The mean Ki-67 labeling index (LI) for all cases was 19.3%. Labeling index values were significantly higher in squamous cell carcinoma than in adenocarcinoma (p < 0.0001). Postoperative survival of adenocarcinoma patients was significantly related to the LI values and to the patient's smoking status (p = 0.0164 and 0.0268, respectively). The LI values were also related to smoking status and the extent of histologic differentiation (p = 0.0112 and p < 0.0001, respectively). For non-smoking adenocarcinoma patients, higher LI values were associated with abnormalities in p53 expression (p = 0.0048). Retinoblastoma protein abnormalities were not related to LI values. CONCLUSIONS: In smokers with stage I pulmonary adenocarcinoma, tumor proliferative activity and smoking status before surgery were important prognostic determinants. The LI values were related to several clinicopathologic factors.

Pulmonary large cell carcinoma with rhabdoid phenotype.

A 70-year-old woman presented with a coin lesion in her left lung. The tumor was well circumscribed and had a large area of central necrosis with a thin rim of viable tumor cells. It showed a solid growth pattern of polygonal cells with eosinophilic intracytoplasmic inclusion bodies. Immunohistochemically, the tumor cells were positive for vimentin, neural cell adhesion molecule, neuron-specific enolase, and vascular endothelial growth factor. Electron microscopy revealed intracytoplasmic inclusion bodies consisting of whorled intermediate filaments. Based on histological and immunohistochemical findings, the patient was diagnosed as having pulmonary large cell carcinoma with rhabdoid phenotype (LCCRP). The patient was in stage IA, and the histological findings may be the prototype of pure LCCRP. The tumor recurred after 6 years, and the second tumor had more apparent intracytoplasmic inclusion bodies. It is worthwhile detecting and recognizing the significance of these intracytoplasmic inclusions because of the poor prognosis of this tumor.

Proliferative activity and apoptosis in thymic epithelial neoplasms.

The classification of thymic epithelial tumors is controversial because prediction of the biological behavior of these tumors from their morphologic appearance is difficult. The aim of this study was to evaluate the proliferative activity and rate of apoptosis of thymic epithelial tumors classified according to World Health Organization histological classification. We also attempted to determine the importance of a number of proapoptotic factors in these processes. We investigated 46 surgically resected thymic epithelial tumors (8 Type A, 8 Type AB, 7 Type B1, 7 Type B2, 6 Type B3, and 10 Type C). Immunohistochemical staining was performed to determine the tumor expression of p53 protein, Bax, Bcl-2, and survivin. In addition, the Ki-67 labeling index (LI) and apoptotic index (AI) of these tumors were evaluated. Type C thymoma had a higher LI (16.55 +/- 12.12%) than did the other histological subtypes. Stage IV thymoma (12.36 +/- 9.99%) had a higher LI than did Stage I tumor. The AI was significantly elevated in Type B1 thymoma (1.47 +/- 0.55%). Overexpression of p53 protein was observed in Type B3 and C thymomas. p53 protein-positive tumors had a higher LI than did p53 protein-negative tumors (P <.0001). Bcl-2 expression was observed in Type A, AB, and C thymomas. Bcl-2-positive thymoma had a lower AI than did Bcl-2-negative thymoma (P =.0157). These results suggest that overexpression of p53 protein is associated with a higher tumor proliferative activity and that Bcl-2 acts as an inhibitor of apoptosis in thymoma. Bcl-2 and p53 protein expression may be useful markers in differentiating thymoma subtypes.

Evidence of neoangiogenesis and an increase in the number of proliferating cells within the bronchial epithelium of smokers.

BACKGROUND: Normal bronchial epithelium gradually acquires cellular and genetic changes that result in the formation of invasive tumors. The objective of this study was to evaluate the degree of proliferative change and the amount of neovascularization in both normal and preneoplastic lesions in smokers who were at high risk for developing lung carcinoma. METHODS: The authors studied bronchial biopsy specimens from 7 nonsmokers and 52 smokers. Immunohistochemical staining of the specimens with antibodies for the presence of p53 protein, Ki-67 and CD34 antigens, and vascular endothelial growth factor was performed. The proliferation index (PI) was assessed by immunohistochemical staining for Ki-67 antigen. RESULTS: Overexpression of p53 protein was observed frequently in regions of squamous dysplasia and in squamous cell carcinoma tissue. The PI of normal epithelium from smokers was increased compared with nonsmokers, and the difference was statistically significant (P < 0.05). The microvessel count (MC) in normal mucosa obtained from smokers was higher compared with the MC in normal mucosa obtained from nonsmokers (P < 0.05). A significant difference in MC also was observed between regions of squamous metaplasia or dysplasia with projections of capillary loops into the bronchial mucosa and similar lesions without capillary loops (P < 0.005); however, there was no difference in either the PI or the incidence of p53 overexpression between these groups. CONCLUSIONS: These results show that smoking appears to induce both a proliferative response and neovascularization in bronchial mucosa. The projection of capillary loops into the bronchial mucosa also may be a result of neovascularization occurring within the lamina propria of the bronchial wall.

Antibody binding to fas ligand attenuates inflammatory cell infiltration and cytokine secretion, leading to reduction of myocardial infarct areas and reperfusion injury.

Fas ligand (FasL) induces apoptotic cell death when bound to Fas antigen. The engagement of FasL has anti-inflammatory effects through the prevention of cell proliferation and cytokine secretion. However, the role of FasL in myocardial ischemia/reperfusion (MI/R) injury is unclear. We examined the expression of FasL mRNA in the myocardium of MI/R rats by ligating the left coronary artery for 30 minutes and allowing reperfusion to occur for 0, 1, 3, and 24 hours. The expression of FasL mRNA was enhanced 1 hour after reperfusion, and enhanced levels were consistently seen after 24 hours of reperfusion. FasL immunostaining was observed on neutrophils, macrophages, T cells, and vascular endothelial cells. We then assessed the potential role of FasL in the cell proliferation and cytokine production seen in MI/R injury after 24 hours of reperfusion. Rats were divided into three groups; Group A, without treatment; Group B, treated with nonspecific rabbit IgG; and Group C, treated with anti-FasL antibody. Anti-FasL antibody or rabbit IgG were administered intravenously before coronary artery occlusion. In Group C, interleukin-1beta and interleukin-2 mRNA levels were decreased, and neutrophil and T cell accumulation was attenuated. The infarct area determined by triphenyltetrazolium chloride staining was significantly smaller in Group C (18 +/- 4%) than in Group A (34 +/- 2%) or Group B (33 +/- 4%) (p< 0.0001). However, there was no significant difference in the prevalence of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling-positive cardiomyocytes among the three groups. These findings suggest that the cardioprotective effect of anti-FasL antibody is due to its anti-inflammatory action, rather than antiapoptotic action. The Fas/FasL system may be involved in the development of MI/R injury.

Imprint cytologic features of pulmonary sclerosing hemangioma: comparison with well-differentiated papillary adenocarcinoma.

BACKGROUND: Sclerosing hemangiomas (SH) of the lung are uncommon tumors and are thought to be benign. However, histogenesis of these tumors has not yet been characterized adequately. Moreover, there are few reports dealing with their cytologic features, and it is generally considered difficult to make accurate diagnoses of sclerosing hemangiomas that have a predominantly papillary pattern. METHODS: Cytologic features were analyzed for 15 sclerosing hemangiomas, and cytologic features of sclerosing hemangioma were compared with features of 22 cases of well-differentiated papillary adenocarcinoma classified as pathologic Stage 1A. RESULTS: Blood and round cells were observed more frequently in SH than in adenocarcinomas (P < 0.05), whereas necrosis was seen more frequently in adenocarcinomas than in SH (P < 0.05). The presence of nucleoli, nuclear indentations, irregularities of nuclear margins, nuclear polymorphisms, and high nuclear-cytoplasmic (NC) ratios of tumor cells were observed less frequently in SH. Polynuclear (having three or more nuclei) tumor cells were observed only in adenocarcinoma cases. In morphometric studies, the nuclear areas, cytoplasmic areas, NC ratios, long axes of nuclei, short axes of nuclei, and nuclear rotundity ratios were significantly higher in adenocarcinoma cells than in SH cells (P < 0.05). CONCLUSIONS: The presence of polymorphous cells and tumor cells with bland nuclei are characteristic cytologic findings associated with sclerosing hemangioma. It is possible to make accurate diagnoses for SH cases preoperatively by careful cytologic characterization.

Prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung.

BACKGROUND: The relative incidence of adenocarcinoma of the lung is increasing and some patients with lung carcinoma, detected at an early stage, still develop recurrent disease despite complete resection of the tumor. Recently, neuroendocrine differentiation in large cell carcinoma of the lung has been reported to be of prognostic significance. Therefore, we have evaluated the prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung. METHODS: A total of 90 resected specimens of adenocarcinoma of the lung measuring 3 cm or less (T1 N0 M0 or T2 N0 M0) were reviewed histologically and immunohistochemical staining was performed to determine the degree of neuroendocrine differentiation. RESULTS: Seven adenocarcinomas exhibited neuroendocrine differentiation in 10% or more of tumor cells. The disease-free survival rate for these patients was significantly lower than that of patients with tumors exhibiting neuroendocrine differentiation in less than 10% of tumor cells or with absent neuroendocrine differentiation (p < 0.0005). Other conventional pathologic factors such as vascular invasion (p < 0.0005), lymphatic invasion (p < 0.05), and pleural involvement (p < 0.05) were also of prognostic significance. In multivariate analysis, the presence of 10% or more neuroendocrine marker-positive tumor cells, vascular invasion, and lymphatic invasion were found to be significantly adverse prognostic factors (p = 0.0162, p = 0.0111, and p = 0.0173, respectively). CONCLUSIONS: Neuroendocrine differentiation of tumor cells is a prognostic factor in lung adenocarcinoma. It is suggested that the identification of neuroendocrine differentiation as well as vascular invasion by tumor in small peripheral adenocarcinoma of the lung may predict the prognosis of these patients.

Pulmonary large cell carcinomas with neuroendocrine features are high-grade neuroendocrine tumors.

BACKGROUND: In 1999, the World Health Organization (WHO) categorized large cell carcinoma with neuroendocrine features as variants of large cell carcinoma and reclassified neuroendocrine lung tumors, especially typical and atypical carcinoid tumors. However, to date, the clinical relationship between these categories of neuroendocrine lung tumors has not been clearly defined. METHODS: We analyzed 133 cases of neuroendocrine tumors from primary lung carcinoma cases surgically resected. Using electron microscopy and immunohistochemical staining, we classified these cases as typical carcinoid (TC), atypical carcinoid (AC), large cell carcinoma with neuroendocrine features (LCNF), or small cell lung carcinoma (SCLC) based upon the WHO classification. RESULTS: TC and AC tumors were not related to smoking (p < 0.001) and, unlike LCNF, were found in younger patients (p < 0.001) without a male predominance (p < 0.001). Multivariate analysis revealed that LCNF predicted poorer overall and disease-free survivals comparable with SCLC (overall survival, p = 0.019, hazards ratio, 6.34; disease-free survival, p = 0.007, hazards ratio, 8.19). CONCLUSIONS: The prognoses of LCNF are comparable with those of SCLC, and LCNF should be classified as high-grade neuroendocrine tumors.

Alpha-fetoprotein-producing lung carcinoma: report of three cases.

Three cases of alpha-fetoprotein (AFP)-producing lung carcinoma were studied histologically and immunohistochemically. Samples were obtained from two men and one woman who ranged in age from 64 to 71 years. Serum AFP levels for the three samples were 9826, 74.4 and 24.3 ng/mL. One case was classified as stage IIIA and two as stage IIIB. Two cases were diagnosed as large cell neuroendocrine carcinoma, and AFP expression was detected immunohistochemically. One of these samples showed differentiation to a hepatoid carcinoma, while the other was combined with a squamous cell carcinoma. The remaining case was a squamous cell carcinoma, and AFP was detected in only some of the tumor cells. All patients died within 2 years. The Ki-67 labeling indices of the AFP-producing pulmonary carcinomas (30.2 +/- 4.6%) were significantly higher than those of AFP-negative pulmonary carcinomas (P < 0.05). The high proliferative activity, advanced stage at presentation, vascular endothelial growth factor expression and vascular invasion observed in these tumors may explain the poor prognosis of AFP-producing lung carcinomas.

Correlation between endobronchial ultrasonography (EBUS) images and histologic findings in normal and tumor-invaded bronchial wall.

The aim of this study was to examine the ability of endobronchial ultrasonography (EBUS) to image the bronchial wall structure in order to assess the depth of bronchial tumor invasion. Sixty-one patients who underwent lobectomy, pneumonectomy or forceps biopsy were included in this study. In 21 patients with bronchoscopically visible bronchial malignant tumors, EBUS was performed during bronchoscopy. In the remaining 40 patients, ultrasonography was performed on the resected specimens. The EBUS findings obtained using thin ultrasonic probes (20 MHz radial scanner) were compared with the macroscopic and histologic findings of the corresponding areas in the resected specimens. When the bronchial walls were imaged while immersed in normal saline, six ultrasonically distinct layers were detected in the cartilaginous and membranous portions. A similar wall structure was imaged when EBUS was performed during bronchoscopy using a latex balloon sheath. The image of the lamina propria and submucosa was occasionally compressed and mixed with a balloon echo due to the latex balloon sheath, whereas the cartilage layer was always distinctly imaged. A good correlation was observed between the EBUS-determined cartilage thickness and the actual histologic measurement, as measured with vernier calipers. Malignant tissues were imaged as hypoechoic areas, and tumor invasion of the cartilage layer was clearly detected. In conclusion, using high-resolution (20 MHz) ultrasonic probes, the bronchial wall structure could be imaged as six distinct layers. The cartilage layer was easily identified and could be used as a reference to evaluate the rest of the bronchial wall structure.