Invasive pulmonary aspergillosis due to Aspergillus lentulus in an adult patient: A case report and literature review.

Aspergillus fumigatus is the commonest cause of pulmonary aspergillosis; however, a recently developed molecular genetic technique identified A. lentulus as a sibling species. Most of the isolates were found in solid organ recipients, often associated with a fatal outcome. Moreover, there is concern that A. lentulus has low susceptibility to multiple antifungal agents. Herein, we report an adult immunocompromised patient with proven invasive pulmonary aspergillosis (IPA) caused by A. lentulus, which was identified through molecular genetic analysis. The patient was diagnosed with IPA by bronchoscopy 3 weeks after initiating systemic corticosteroid therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. The clinical course of IPA due to A. lentulus showed improvement after treatment with the antifungal agent voriconazole. In summary, we report an adult immunocompromised patient without a history of transplantation who was diagnosed with IPA due to A. lentulus successfully treated with voriconazole, and we also report the findings of a literature review on IPA caused by A. lentulus.

Idiopathic pulmonary fibrosis as a prognostic factor in non-small cell lung cancer.

BACKGROUND: We investigated the postoperative mortality and long-term survival of lung cancer patients with underlying idiopathic pulmonary fibrosis (IPF). METHODS: The data of 387 primary lung cancer patients treated by surgical resection at our hospital between 1995 and 2008 were retrospectively reviewed. Clinicopathological characteristics such as age, gender, survival, presence/absence of underlying IPF, atypical adenomatous hyperplasia (AAH), and the associations among these factors were examined. RESULTS: Among the 387 patients, 65 (16.8 %) had underlying IPF as detected by histopathology of the resected specimen (IPF group). The percentages of men and squamous cell carcinomas were significantly higher in the IPF group. None of our patients showed concomitant presence of AAH and IPF. Four of the 65 patients showed acute exacerbation of the IPF postoperatively, and all 4 of these patients died in hospital. In patients with non-small cell lung carcinoma, the postoperative survival tended to be lower in the IPF group than in the non-IPF group. Analysis using a Cox proportional hazards model by disease stage revealed that presence of underlying IPF was a risk factor for postoperative mortality in patients with pathological stage I/II but not for stage III/IV. Respiratory failure was the second main cause of death in the stage I/II lung cancer patients of the IPF group. CONCLUSION: Histopathological evidence of IPF was a risk factor for postoperative mortality and poor long-term survival, especially in patients with stage I/II non-small cell lung cancer, with postoperative respiratory failure representing the major cause of death.

[A case of lung cancer resistant to pemetrexed responding to S-1 monotherapy].

Pemetrexed(PEM)and S-1 are both cytotoxic anti-tumor drugs that target thymidylate synthase(TS). Here, we report a case of lung cancer resistant to PEM, but responsive to S-1 monotherapy. A 50-year-old male with lung cancer(adenocarcinoma, EGFR mutation negative)at Stage III B(T4N2M0)received PEM as third-line chemotherapy. However, metastatic mediastinal lymph nodes were increased in size. A switch to gemcitabine(GEM)resulted in further enlargement of the nodes and elevation of the serum CEA level. Introduction of S-1 monotherapy(120mg/body/day divided into two doses, 4-week administration every 6 weeks, 6 courses)reduced the size of the nodes and serum CEA was normalized. Although S-1 as well as PEM, target TS, the mechanisms in these two drugs that lead to resistance are not the same. Furthermore, S-1 induces dysfunction of RNA through the generation of fluoro-uridine monophosphate(FUMP). We conclude that S-1 can be a drug of choice, even in cases that show resistance to PEM.

Lung adenocarcinoma with peculiar growth to the pulmonary artery and thrombus formation: report of a case.

BACKGROUND: Cases of pulmonary artery masses have only rarely been reported, and the optimal type of the diagnosis and treatment is controversial. CASE PRESENTATION: An 81-year-old woman was found to have an abnormal shadow on chest X-ray film. Computed tomography showed an irregularly bordered tumor centered in the hilar region extending from segment 6 to the middle lobe of the right lung. Pulmonary angiography showed complete occlusion of the trunk at the periphery proximal to the bifurcation of the posterior ascending branch. Based on bronchoscopic biopsy of the tumor, an adenocarcinoma was diagnosed. Middle and lower lobectomy was performed. Histopathologically, the adenocarcinoma had invaded the tunica intima of the pulmonary artery and also replaced the endothelium in the same region. Although a large thrombus was found at the vessel invasion site of the adenocarcinoma in the pulmonary artery, there were no malignant findings in the thrombus itself. CONCLUSIONS: This is the first reported case of radical resection of a lung cancer with invasion along the pulmonary artery wherein a benign thrombus had formed. In general, surgery would be the treatment of choice for a pulmonary artery mass.

Combined large cell neuroendocrine carcinoma and spindle cell carcinoma of the lung.

Pleomorphic carcinomas of the lung are rare malignant biphasic tumors composed of carcinomatous and sarcomatous components. The carcinomatous component is usually an adenocarcinoma or a squamous cell carcinoma, and the sarcomatous component is usually a spindle cell carcinoma. Recently, we encountered two patients who underwent surgery for pleomorphic carcinoma whose carcinomatous component was large cell neuroendocrine carcinoma.

Hemangioma in a pulmonary hilar lymph node: case report.

BACKGROUND: Different types of vascular proliferation may occur in lymph nodes, but hemangiomas in lymph nodes are extremely rare. CASE PRESENTATION: A 73-year-old man was found to have a 15-mm nodular shadow in the left lung on computed tomography, and bronchoscopic brush cytology yielded a diagnosis of squamous cell carcinoma. Chest computed tomography showed no evidence of hilar or mediastinal lymphadenopathy. Left lower lobectomy with hilar and mediastinal lymph node dissection was performed. Postoperative histopathological examination revealed squamous cell carcinoma and no lymph node metastasis. On the other hand, a lobar bronchial lymph node presented a small lesion showing the dense proliferation of capillary blood vessels with elastic change. Immunohistochemically, the lesion was positive for factor VIII and CD34, leading to a diagnosis of primary hemangioma of the lymph node. CONCLUSION: To our knowledge, this is the first case reported in the literature of hemangioma in a pulmonary hilar lymph node. Intranodal hemangioma needs to be differentiated from malignant vascular tumors.

Surgery for recurrent inflammatory pseudotumor of the lung.

BACKGROUND: Cases of recurrent inflammatory pseudotumor have only rarely been reported. The treatment for recurrent pseudotumor is surgery. Patients not eligible for surgery require different treatment, and the optimal type of the treatment is controversial. CASE PRESENTATION: A 54-year-old woman was noted to have an abnormal shadow in the right middle lung field on chest X-ray. Computed tomography of the chest revealed an infiltrative lesion in the right segment 4 and a nodule in the right segment 8. She underwent right middle lobectomy and partial resection of the right segment 8. Histopathology revealed non-atypical lymphocytes and plasma cells infiltrates, leading to the diagnosis of the lymphoplasmacytic type of inflammatory pseudotumor. During postoperative follow-up, chest computed tomography revealed a nodular lesion in the left segment 3 and an infiltrative lesion in the right segment 2. Left segment 3 segmentectomy and right segment 2 wedge resection were performed. The histopathological findings were similar to those of the first surgical specimen, leading to the diagnosis of recurrent lymphoplasmacytic type of inflammatory pseudotumor. CONCLUSION: Surgical cases of recurrent inflammatory pseudotumor of the lung have been reported only very rarely. We believe that surgery is the best treatment for recurrent inflammatory pseudotumor of the lung when patients are eligible.

A solitary pulmonary nodule caused by Mycobacterium avium with pleural effusion and pleuritis after transbronchial biopsy: a case report.

BACKGROUND: Pleural effusion and pleuritis are uncommon manifestations of Mycobacterium avium complex pulmonary disease. Pleuritis caused by Mycobacterium avium complex pulmonary disease presenting as a solitary pulmonary nodule is extremely rare. The pathogenesis of Mycobacterium avium complex pleuritis has not been elucidated. However, it has been suggested that secondary spontaneous pneumothorax from Mycobacterium avium complex pulmonary disease is one of the causes of Mycobacterium avium complex pleuritis. CASE PRESENTATION: A 67-year-old Japanese woman who presented with a solitary pulmonary nodule developed a transient pneumothorax after transbronchial biopsy. A definitive diagnosis of solitary pulmonary nodule could not be made on bronchoscopy, so video-assisted thoracoscopic surgery was performed 1 month after bronchoscopy. On the day of hospitalization for the procedure, a left-sided pleural effusion appeared on a chest radiograph. Thickening of the parietal and visceral pleura and numerous scattered white small granules were seen on thoracoscopy. Histologic examination of the resected left lower lobe and a biopsy of the parietal pleura showed Mycobacterium avium complex solitary pulmonary nodule and Mycobacterium avium complex pleuritis. CONCLUSION: Iatrogenic pneumothorax can be a cause of pleuritis in a patient with Mycobacterium avium complex pulmonary disease. Clinicians should watch for the appearance of secondary pleuritis after transbronchial biopsy even in a patient with localized disease such as Mycobacterium avium complex solitary pulmonary nodule.

Solitary pulmonary metastasis from prostate sarcomatoid cancer.

BACKGROUND: Pulmonary metastasis from prostate cancer is considered to be a late event, and patients can be treated with chemotherapy or hormonal manipulation. However, there has been only a few reports on surgical resection for pulmonary metastasis from prostate cancer. CASE PRESENTATION: We present a surgical case of solitary pulmonary metastasis from prostate cancer. A 73-year-old man underwent pelvic evisceration for prostate cancer. Histopathological examination revealed a poorly differentiated adenocarcinoma with a sarcomatoid carcinoma component. During postoperative follow-up, chest computed tomography showed a nodular shadow in the lung, and thoracoscopic wedge resection of the lung was performed. Histopathological examination revealed a histological appearance similar to that of the prostate sarcomatoid carcinoma. This is the first reported case of solitary pulmonary metastasis from prostate sarcomatoid cancer. CONCLUSION: Isolated pulmonary metastasis from prostate sarcomatoid cancer is extremely rare, but surgery could be the treatment of choice.

[A case of pulmonary aspergillosis subacutely forming a cavity during the course of microscopic polyangiitis].

A 77-year-old woman was referred to our department with hemoptysis. Microscopic polyangiitis (MPA) with resultant alveolar hemorrhage was diagnosed because of diffuse infiltrate of the right lung, proteinurea, renal dysfunction and the presence of MPO-ANCA. The disease responded well to corticosteroid therapy. She was discharged, but as corticosteroid was gradually tapered, an irregularly-shaped nodule appeared in the right upper lung field within 2 weeks. She was re-admitted because the nodule increased in size with cavity formation in spite of the administration of antibacterial agent. Pulmonary aspergillosis was diagnosed, since bronchial washing and transbronchial lung biopsy revealed the presence of Aspergillus fumigatus. Serum beta-D-glucan was decreased and the cavity was reduced in size, responding to the treatment with micafungin. However, she died later of systemic infection by a herpesvirus. We report this case because of the interesting course of pulmonary aspergillosis that subacutely formed a cavity.

A Calcified Amorphous Tumor Originating in the Aortic Valve Cusp.

Calcified amorphous tumor (CAT) of the heart is a rare nonneoplastic cardiac tumor. The clinical features of cardiac CATs resemble those of other cardiac tumors that include symptoms related to obstruction or embolization. Cardiac CATs have been found in all chambers of the heart but predominantly present in the left ventricle, mitral annulus, and mitral valve. Here we report an extremely rare case of CAT originating in the aortic valve cusp, which may be related to aortic annular calcification and aortic valve stenosis. We successfully treated this patient with tumor resection and aortic valve replacement.

Correlation of the solid part on high-resolution computed tomography with pathological scar in small lung adenocarcinomas.

OBJECTIVE: To predict the grade of invasion in small (10% ground glass opacity (GGO) area on HRCT. The CT numbers of solid parts were measured on HRCT in each tumor. According to our criteria of histopathological grade of stromal invasion, all tumors were classified into four grades: no evidence of stromal invasion (Grade 0), stromal invasion in the area of bronchioloalveolar growth (Grade 1), stromal invasion localized on the periphery of a fibrotic focus (Grade 2), and stromal invasion into the center of a fibrotic focus (Grade 3). RESULTS: Nineteen cases that had pure GGOs were excluded. In 112 cases that showed a mixed type of both GGO and solid part, the mean CT number of the overt-invasion group was significantly higher than the no invasion and micro-invasion groups. We adopted -40 as a threshold CT number to determine the degree of invasion. Tumors with values <-40 included no case of overt invasion. CONCLUSIONS: Small lung adenocarcinomas with a solid part CT number under -40 in on HRCT usually show no invasion or micro-invasion. Limited surgery may be indicated for such cases because of their good prognosis.

Solitary capillary hemangioma of the lung: report of 2 resected cases detected by high-resolution CT.

We report 2 cases of capillary hemangioma, each presenting as a solitary nodule in the peripheral lung. Both of the patients were asymptomatic with a small solitary nodule that had revealed by computed tomography. In both cases, the nodule was resected surgically under a clinical diagnosis of early lung cancer. Macroscopically, each lesion was ill defined and irregular in shape with a dark brown cut surface. Microscopically, the alveolar septa in both nodules were thickened by accumulations of numerous thin-walled capillary vessels, which characteristically extended along, or infiltrated, each septum. We diagnosed these lesions as "solitary capillary hemangioma" of the peripheral lung. Tumors or tumorlike lesions of capillary vessels in the lung are rare. Among them, pulmonary capillary hemangiomatosis (PCH) has been described as multiple nodules in the lung parenchyma or bronchovascular walls, comprised of infiltrating thin-walled capillary blood vessels. Moreover, PCH-like foci have been found in a retrospective study of autopsy cases. However, the presented cases should be differentiated from PCH in terms of their clinical setting such as history of hypertension or veno-occlusive disease and multiplicity of the lesion. This is a rare case series of solitary capillary hemangioma discovered incidentally during life, and the lesions were difficult to differentiate radiologically from early lung cancer. After the recent advances in imaging diagnosis for early detection of peripheral lung cancer, these lesions are important to bear in mind for differential diagnosis of bronchioloalveolar carcinoma.

Histologic prognostic factors for small-sized squamous cell carcinomas of the peripheral lung.

OBJECTIVE: Although the incidence of peripheral squamous cell carcinomas (SqCCs) of the lung has increased over recent years, histologic prognostic factors for small peripheral SqCCs have not been well established. The aim of this study is to identify clinicopathologic prognostic factors. MATERIALS AND METHODS: We evaluated various clinicopathologic parameters in 101 patients with peripheral lung SqCCs (defined as tumors located in or more peripheral to the fourth branching bronchus), measuring < or = 30 mm in diameter. RESULTS: Multivariate analysis showed that the size of the minimal tumor nest (MTN), a background of usual interstitial pneumonia (UIP) and lymph node metastasis were significant prognostic factors. MTN sizes were defined as large (>6 tumor cells), small (2-5 tumor cells) or single cell. The 5-year disease-free survival rate was significantly worse in patients with single cell nests (50 patients, 69.5%) than in those with small nests (42 patients, 94.1%) (P = 0.0035, log rank test). The MTN size had a significant impact on survival in patients with pathologic stage IA disease and tumors < or = 20 mm in diameter. A background of UIP, which correlated with the presence of a single cell invasive component and pleural involvement, was also a poor prognostic factor, suggesting that peripheral SqCC in UIP is highly malignant even if the tumor is small. CONCLUSION: The MTN size is a useful prognostic factor for small peripheral SqCCs. Tumors with a single cell invasive component appear to be highly malignant, and should be distinguished from invasive cancers with a low malignant potential (tumors with large or small tumor nest components).

The Initial Case Report: Salvage Robotic Assisted Radical Prostatectomy After Heavy Ion Radiotherapy.

Salvage radical prostatectomy is one of treatments after radiation therapy to patients with prostate cancer. To date, no case of the salvage robotic assisted radical prostatectomy (RARP) following heavy ion radiotherapy (HIRT) has been published. We report on a 70-year-old man with a history of HIRT for prostate cancer in 2011. For 3 years after. HIRT, his serum PSA levels were permissible range. However, his PSA levels were increased. We had diagnosis localized prostate cancer after HIRT. We had carried out salvage RARP. Until 10 months after salvage RARP, his PSA level was not detectable.

Identification of genes whose expression is upregulated in lung adenocarcinoma cells in comparison with type II alveolar cells and bronchiolar epithelial cells in vivo.

To identify genes whose expression is upregulated in lung adenocarcinoma (AdC) cells in comparison with noncancerous peripheral lung epithelial cells, type II alveolar cells and bronchiolar epithelial cells, as well as AdC cells, were isolated by laser capture microdissection, and subjected to cDNA microarray analysis of 637 human cancer-related genes. Each of the component cells was obtained from several different individuals and analysed independently. As a comparison, two lung AdC cell lines and two primarily cultured normal lung epithelial cell lines were also subjected to cDNA microarray analysis. Four genes, TOP2A, MMP15, MX2 and KOC1, were commonly upregulated in microdissected AdC cells in comparison with microdissected epithelial cells. Hierarchical clustering analysis revealed that differences in gene-expression profiles were more evident between cultured and uncultured cells than between cancerous and noncancerous cells. To further identify the common molecular targets of AdC cells in vivo, quantitative real-time RT-PCR was performed against the four genes upregulated by cDNA microarray analysis. The TOP2A, MMP15, MX2 and KOC1 genes were overexpressed in 10/10 (100%), 8/10 (80%), 5/10 (50%) and 3/10 (30%) microdissected AdC cell samples, respectively, in comparison with any of nine independently microdissected noncancerous epithelial cell samples. The TOP2A gene was commonly overexpressed in lung AdC cells, as previously reported. In addition, the MMP15 and MX2 genes were identified, for the first time, as being commonly overexpressed in lung AdC cells. These results strongly indicate that the MMP15 and MX2 genes could be novel markers for molecular diagnosis and therapy of lung AdC.

Immunohistochemical KIT (CD117) expression in thymic epithelial tumors.

STUDY OBJECTIVES: It is sometimes very difficult both clinically and pathologically to distinguish thymic epithelial tumors from primary lung carcinoma with massive anterior mediastinal involvement. The expression of KIT (CD117) in thymic epithelial tumors was investigated in order to evaluate its usefulness as a marker supporting differential diagnosis and choice of therapy. METHODS: We examined the immunohistochemical expression of KIT in 70 resected thymic epithelial tumors (thymomas, 50; thymic carcinomas, 20) that had been reclassified on the basis of the World Health Organization histologic classification system. We also compared the expression of KIT and CD5 in 20 thymic carcinomas with their expression in 20 resected pulmonary squamous cell carcinomas that were spreading directly into the mediastinum. RESULTS: Of the 50 thymomas, only 2 (4%) showed positive immunoreactivity for KIT (type A thymoma, 1; type B3 thymoma, 1), whereas 16 of the 20 thymic carcinomas (80%) showed positive immunoreactivity. Testing was positive for CD5 in 14 of the 20 thymic carcinomas (70%). In the pulmonary squamous cell carcinomas, in contrast, the immunohistochemical expression of KIT and CD5 was found in only 4 of 20 carcinomas (20%) and 3 of 20 carcinomas (15%), respectively. Furthermore, of the 40 specimens examined (either thymic or lung carcinoma) all 13 that were positive for both KIT and CD5 were thymic carcinomas, and 13 of the 16 that were negative for both were lung carcinomas. CONCLUSION: KIT expression is a useful immunohistochemical marker for the diagnosis of thymic carcinoma, and its examination in combination with CD5 immunohistochemistry would greatly help in the differential diagnosis of primary thymic carcinoma from pulmonary squamous cell carcinoma. Further investigations at a genetic level should be encouraged, not only to define the role of KIT in the oncogenesis of thymic epithelial tumors, but also to establish target-based therapy.

Clinicopathological significance of epigenetic inactivation of RASSF1A at 3p21.3 in stage I lung adenocarcinoma.

PURPOSE: Chromosome 3p is deleted frequently in various types of human cancers, including lung cancer. Recently, the RASSF1A gene was isolated from the 3p21.3 region homozygously deleted in lung and breast cancer cell lines, and it was shown to be inactivated by hypermethylation of the promoter region in lung cancers. In this study, we investigated the pathogenetic and clinicopathological significances of RASSF1A methylation in the development and/or progression of lung adenocarcinoma. EXPERIMENTAL DESIGN: Association of RASSF1A methylation with clinicopathological features, allelic imbalance at 3p21.3, p53 mutations, and K-ras mutations was examined in 110 stage I lung adenocarcinomas. RESULTS: Thirty-five of 110 (32%) tumors showed RASSF1A methylation. RASSF1A methylation was dominantly detected in tumors with vascular invasion (P = 0.0242) or pleural involvement (P = 0.0305), and was observed more frequently in poorly differentiated tumors than in well (P = 0.0005) or moderately (P = 0.0835) differentiated tumors. Furthermore, RASSF1A methylation correlated with adverse survival by univariate analysis (P = 0.0368; log-rank test) as well as multivariate analysis (P = 0.032,; risk ratio 2.357; 95% confidence interval, 1.075-5.169). The correlation between RASSF1A methylation and allelic imbalance at 3p21.3 was significant (P = 0.0005), whereas the correlation between RASSF1A methylation and p53 mutation was borderline (P = 0.0842). However, there was no correlation or inverse correlation between RASSF1A methylation and K-ras mutation (P = 0.2193). CONCLUSIONS: These results indicated that epigenetic inactivation of RASSF1A plays an important role in the progression of lung adenocarcinoma, and that RASSF1A hypermethylation appears to be a useful molecular marker for the prognosis of patients with stage I lung adenocarcinoma.

A case of primary gastric small cell carcinoma with a rare pattern of lymph node metastasis.

We report a very rare case of primary gastric small cell carcinoma (GSCC) that was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an elevated tumor with a central ulceration in the middle stomach. The patient underwent a distal gastrectomy with lymph node dissection. The pathological examination showed two separated lesions of the stomach, which contained the components of primary GSCC and primary gastric tubular adenocarcinoma. Immunohistochemical (IHC) examination demonstrated that the tumor cells in the small cell carcinoma stained positive for synaptophysin, chromogranin A, and neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells independently metastasized to each regional lymph node. Further studies on the biological behavior of individual tumors may allow the development of new treatment strategies for GSCC.