Pulmonary infarction caused by sarcoidosis vascular involvement: A case report.

Sarcoidosis is a systemic granulomatous disease. In pulmonary sarcoidosis, granulomatous vascular involvement is a common feature that occurs in all types of vessels, including large elastic arteries to venules, but sarcoidosis complicated with pulmonary infarction has not been reported. We report a case of a 60 years old female, who was operated on a clinical diagnosis of lung cancer, and histological examination revealed a pulmonary infarction and sarcoidosis. In the pulmonary elastic arteries, granulomas infiltrated the adventitia and media, and caused elastic fiber collapse and destruction. Arterial occlusion by granulomas was observed in the edge of the infarcted area. It was considered that the arterial sarcoidosis granuloma involvement was the cause of pulmonary infarction. Sarcoidosis is a significant risk factor for cardiovascular events. However, pulmonary infarction is an extremely rare complication of sarcoidosis. Our case suggests that sarcoidosis may cause vascular events in the lungs.

The microRNA expression signature of small cell lung cancer: tumor suppressors of miR-27a-5p and miR-34b-3p and their targeted oncogenes.

Small cell lung cancer (SCLC) constitutes approximately 15% of all diagnosed lung cancers. SCLC is a particularly lethal malignancy, as the 2-year survival rate after appropriate treatment is less than 5%. The patients with SCLC have not been received a benefit of the recently developed molecular targeted treatment. Therefore, a new treatment strategy is necessary for the patients. The molecular mechanisms underlying the aggressiveness of SCLC cells and their development of treatment-resistance are still ambiguous. In this study, we newly constructed a microRNA (miRNA) expression signature of SCLC by analysis of autopsy specimens. Based on the resultant signature, four miRNAs (miR-27a-5p, miR-485-3p, miR-34-5p and miR-574-3p) were found to be candidate anti-tumor miRNAs. To investigate their functional importance, we first validated the downregulation of miR-27a-5p and miR-34b-3p in SCLC clinical specimens. Next, we demonstrated that ectopic expression of both miR-27a-5p and miR-34b-3p significantly inhibited cancer cell aggressiveness. Our in silico analyses showed that four genes (topoisomerase 2 alpha (TOP2A), maternal embryonic leucine zipper kinase (MELK), centromere protein F (CENPF) and SRY-box 1 (SOX1) were identified as miR-27a-5p- and miR-34b-3p-regulated genes. Based on immunohistochemical analysis, TOP2A, MELK and CENPF were involved in SCLC pathogenesis. These genes might contribute to high proliferation and early metastatic spread of SCLC cells. Elucidation of differentially expressed miRNA-mediated cancer pathways based on SCLC signature may provide new insights into the mechanisms of SCLC pathogenesis.

Napsin A levels in epithelial lining fluid as a diagnostic biomarker of primary lung adenocarcinoma.

BACKGROUND: It is crucial to develop novel diagnostic approaches for determining if peripheral lung nodules are malignant, as such nodules are frequently detected due to the increased use of chest computed tomography scans. To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma. METHODS: In consecutive patients with indeterminate peripheral lung nodules, ELF samples were obtained using a bronchoscopic microsampling (BMS) technique. The levels of napsin A and carcinoembryonic antigen (CEA) in ELF at the nodule site were compared with those at the contralateral site. A final diagnosis of primary lung adenocarcinoma was established by surgical resection. RESULTS: We performed BMS in 43 consecutive patients. Among patients with primary lung adenocarcinoma, the napsin A levels in ELF at the nodule site were markedly higher than those at the contralateral site, while there were no significant differences in CEA levels. Furthermore, in 18 patients who were undiagnosed by bronchoscopy and finally diagnosed by surgery, the napsin A levels in ELF at the nodule site were identically significantly higher than those at the contralateral site. In patients with non-adenocarcinoma, there were no differences in napsin A levels in ELF. The area under the receiver operator characteristic curve for identifying primary lung adenocarcinoma was 0.840 for napsin A and 0.542 for CEA. CONCLUSION: Evaluation of napsin A levels in ELF may be useful for distinguishing primary lung adenocarcinoma.

Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis.

BACKGROUND AND AIM: There is a paucity of data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Using propensity score matching, we retrospectively analyzed the additional diagnostic value of LBC compared to a conventional Papanicolaou smear (CPS) for samples of solid pancreatic lesions obtained by EUS-FNA. METHODS: This cohort study included 126 matched patients who underwent initial EUS-FNA for solid pancreatic lesions between January 2009 and August 2014. CPS was used for cytology of EUS-FNA samples obtained until May 2012 (63 patients). Subsequently, LBC was used for cytological analysis (63 patients). Diagnostic yields of CPS and LBC for malignancy were compared. Risk factors for cytological misdiagnosis with LBC were investigated. RESULTS: Overall rate of malignancy was 86% after matching. LBC had higher diagnostic sensitivity and accuracy than CPS (96.6% vs 84.0%, P = 0.03; and 96.8% vs 87.3%, P = 0.05). LBC was significantly more sensitive for diagnosing pancreatic head lesions (96.4% vs 78.1%, P = 0.04). The sensitivity for pancreatic ductal adenocarcinoma (PDAC) with LBC was higher (98.1% vs 83.0%, P = 0.009). Multivariate analysis revealed that malignant tumors other than PDAC (P = 0.004) and lesion size ≤20 mm (P = 0.046) were risk factors for LBC misdiagnosis in all participants. CONCLUSIONS: For solid pancreatic lesions, LBC of EUS-FNA samples contributes to the diagnosis of malignancy. Malignant tumors other than PDAC and small tumors are difficult to diagnose using EUS-FNA and LBC.

Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease.

BACKGROUND: Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. METHODS: We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. RESULTS: Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. DISCUSSION: This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. CONCLUSION: These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.

Immunohistochemistry May Not Replace Immunofluorescence in Paraffin-embedded Tissue for Detecting Masked Monoclonal Immunoglobulin Deposits.

An 84-year-old man developed a membranoproliferative glomerulonephritis pattern of injury, and the most likely cause detected during a workup was monoclonal IgG-λ in the urine and serum. Predominant IgG and λ light chain deposition was confirmed only by immunofluorescence using formalin-fixed, paraffin-embedded tissue and not by immunohistochemistry. A smaller and non-linear dynamic range of immunohistochemistry makes it less quantitative than immunofluorescence staining and may explain why immunohistochemistry failed to detect the light chain restriction. This case suggests that immunohistochemistry may not serve as a substitute for immunofluorescence on formalin-fixed, paraffin-embedded tissue in detecting masked monoclonal immunoglobulin deposits, although further research is warranted.

Thoracoscopic esophagectomy for stenosis of thoracic esophagus due to acute esophageal necrosis associated with alcoholic ketoacidosis.

Acute esophageal necrosis (AEN) is a rare disease characterized by the appearance of diffuse black mucosa on upper gastrointestinal endoscopy; the condition often progresses to esophageal stenosis in the chronic phase. A 70-year-old man was admitted to a neighborhood hospital with the diagnosis of alcoholic ketoacidosis and an upper gastrointestinal endoscopy performed to investigate the symptom of esophageal tightness revealed AEN. The patient developed esophageal stenosis with scarring in the chronic phase and was referred to our hospital for surgery 6 months after the diagnosis of AEN. We performed thoracoscopic esophagectomy with the patient in the prone position. Although the esophagus was thickened and strong adhesions were present around the esophagus due to inflammation, we were able to complete the surgical procedure thoracoscopically. In patients presenting with benign esophageal stenosis developing after AEN, thoracoscopic esophagectomy may be a useful treatment option, even in the presence of severe fibrosis.

Thymic Dedifferentiated Liposarcoma Having a Leiomyosarcomatous Dedifferentiated Component.

We report an extremely rare case of 42-year-old man, d iagnosed with thymic dedifferentiated liposarcoma (DDL) having a leiomyosarcomatous dedifferentiated component. The tumor was composed of atypical spindle cells. The morphological atypia was also observed around thymic adipose tissue. Immunohistochemically, the spindle cells were positive for desmin, smooth muscle actin, MDM2 and CDK4. MDM2 and CDK4 were also positive for the thymic adipose tissue. MDM2 amplification was confirmed by fluorescence in situ hybridization. Although there are some reports of mediastinal leiomyosarcoma, DDL may be overlooked. For accurate diagnosis of mediastinal mesenchymal tumor, careful observation of thymic adipose tissue is required with immunohistochemical study.

Enteric-type thymic adenocarcinoma: a case report and literature review focusing on prognosis based on histological subtypes.

Thymic adenocarcinoma is a rare disease and enteric-type thymic adenocarcinoma is even more rarely found. We report a resected case of a non-mucinous, enteric-type thymic adenocarcinoma in a 53-year-old woman. The operation was performed by median sternotomy, and the tumor was stage II in the Masaoka classification. Six months after the operation, recurrence-free follow-up is currently underway. Knowledge of enteric-type thymic adenocarcinoma can prevent misdiagnosis of metastatic tumors. We also determined the prognosis of enteric-type thymic adenocarcinoma based on histological subtypes through our literature review.

Eosinophilic granulomatosis with polyangiitis after treatment with dupilumab.

Eosinophilic granulomatosis with polyangiitis (EGPA) in association with the use of asthma medications has been reported. We report the first Asian case of EGPA developed after dupilumab administration in a 77-year-old Japanese woman and discuss the association between dupilumab and EGPA.

Cryptogenic Fibrosing Pleuritis with Rapidly Progressive Restrictive Ventilatory Dysfunction.

Cryptogenic bilateral fibrosing pleuritis is a rare condition, and its pathogenesis and clinical course are poorly understood, with no established therapy available. A 61-year-old man presented with bilateral pleural thickening and lymphocytic exudative effusions. The patient was diagnosed with fibrosing pleuritis with no evidence of a known etiology on a surgical pleural biopsy. Within 16 months from the onset of respiratory symptoms, restrictive ventilatory impairment progressed rapidly, resulting in hypercapnic respiratory failure requiring home oxygen and non-invasive positive pressure ventilation therapies.

Histopathological bronchial reconstruction of human bronchiolitis obliterans.

To clarify the morphological mechanisms of airway obliteration in bronchiolitis obliterans (BO) associated with various causes, we conducted a retrospective study of 9 patients with a histological diagnosis of BO. The morphological characteristics were analyzed by histopathological bronchial reconstruction. BO was classified into two major morphologic subtypes: constrictive BO (CoB) and cellular/destructive BO (CDB). CoB is characterized by concentric narrowing of the airway lumen due to submucosal fibrosis. In contrast, in CDB the narrowing of the airway lumen is due to intraluminal, mural, and peribronchiolar infiltration of inflammatory cells as well as proliferation of granulation tissue. The histopathological diagnosis was CoB in 6 patients and CDB in 3 patients. Macroscopic bronchial reconstruction in CoB demonstrated that the beginnings of bronchial obliterations were in the 4th to 7th branches, numbering from each segmental bronchus and the lesions were distributed intermittently. Histopathologically, the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal obliteration in CoB, whereas the primary lesions in CDB revealed more continuous obliteration of the bronchiolar lumen than observed in CoB. In conclusion, this bronchial reconstruction study demonstrated marked morphological differences in the mechanisms of airway obliteration between two major morphologic subtypes of BO.

Hydrophilic Polymer in Thrombus Specimens Obtained During Thrombus Aspiration in the Setting of Percutaneous Interventions in Japan.

Although hydrophilic polymer (HP) is used on vascular catheters to prevent medical device-related complications, HP emboli are well established as a potentially fatal iatrogenic phenomenon. HP embolus is thromboembolism by HP, which is mechanically disrupted from catheter during procedure. We reviewed 119 thrombus specimens obtained by percutaneous interventions from the coronary artery, vessels of inferior and superior limbs, cerebral artery, carotid artery, and renal vein. The frequency of HP was 28.6% (34/119 cases); 26.4% (24/91 cases), coronary artery; 50% (6/12 cases), artery of the lower limb; 28.6% (2/7 cases), vein of the lower limb; 0% (0/2), artery of the upper limb; 33.3% (1/3 cases), cerebral artery; 50% (1/2 cases), pulmonary artery; 0% (0/1 case), carotid artery; and 0% (0/1 case), renal vein. The range of numbers and diameter of HP was 1 to 127 per case and 10 to 934 µm, respectively. This is the first study concerning HP in thrombus specimens in Japan. We think that this study is significant because HP in thrombus specimens obtained from coronary artery in Japan seems to be of lower frequency than that of Europe. Although we suspect that the difference was caused by types of catheter, protocol, and procedure time of percutaneous interventions, we could not investigate correlation of HP in thrombus specimens with these factors. For future investigation, we should accumulate thrombus specimens obtained by routine procedure and device to clarify specific device-associated risk of disruption of HP.

Collision tumor of primary malignant lymphoma and adenocarcinoma in the colon: report of a case.

This report presents the case of a 62-year-old man with a collision tumor of primary malignant lymphoma and adenocarcinoma in the cecum. All regional mesenteric lymph nodes that were removed surgically were found to be occupied by lymphoma cells and no lymph nodes contained any cancer cells, although the primary carcinomas did exhibit lymphatic invasion. Malignant lymphoma was also seen in the duodenum. Systemic chemotherapy was administered for the malignant lymphoma, and a complete response was thus obtained. However, just after chemotherapy multiple liver metastases of adenocarcinoma emerged, and chemotherapy against adenocarcinoma was therefore continued. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectum is rare. Furthermore, collisions of these different entities are also extremely unusual; so far only five such case reports have been published. The accurate clinical determination of the dominant tumor and a close follow-up is required for proper treatment in these cases.

[A case report of anorectal malignant melanoma showing a complete response after DTIC/ACNU/VCR therapy].

We report herein the case of a 64-year-old male who presented with hematochezia. The patient was diagnosed with malignant melanoma of the anorectum using colonoscopy. Preoperative studies revealed no distant metastases, and he underwent Miles operation. Pathological exams revealed that the tumor had invaded the submucosa with lymphatic and venous invasion. Cancer cells were found in regional lymph nodes. Post-operative CT scan demonstrated multiple metastases in the liver, and he received two courses of combined chemotherapy, DAV regimen (dacarbazine: DTIC 100 mg iv days 1-5, nimustine hydrochloride: ACNU 100 mg iv day 1, vincristine sulfate: VCR 1 mg iv day 1), leading to a complete response. However, malignant melanoma cells were found in hernia contents at the operation for left inguinal hernia, which led to a diagnosis of recurrent malignant melanoma. The patient has subsequently been well without any sign of recurrence including liver metastases. To our knowledge, this is the first report of a complete response in a patient with multiple liver metastases of anorectal malignant melanoma after DAV regimen.

Clinicopathological features of hydrophilic polymer emboli in Japanese autopsy cases.

Hydrophilic polymer is used on multiple endovascular devices to decrease friction between these devices and vessel walls. Although it can prevent medical device-related complications, hydrophilic polymer emboli (HPE) has recently been established as a potentially fatal iatrogenic phenomenon. HPE can cause tissue injury in numerous sites, including the brain, heart, lung, skin, and intestines. Most HPE reports have been from Europe and the USA. Therefore, we investigated the frequency, site distribution, and degree of tissue injury of HPE in 227 Japanese autopsy cases. HPE was noted in 3.1% (7/227 cases), and was only found in the lung or heart. There were no cases with tissue injury, such as vasculopathy, ischemia or infarction, associated with HPE. This is the first series study of HPE in Japanese autopsy cases. Unlike in reports from Europe and USA, HPE was only seen in the lung or heart and did not injure the surrounding tissue.

CK7/CK20 Double-Negative Pulmonary Enteric Adenocarcinoma With Histopathological Evaluation of Transformation Zone Between Enteric Adenocarcinoma and Conventional Pulmonary Adenocarcinoma.

We report a rare case of pulmonary enteric adenocarcinoma (PEA) exhibiting a immunohistochemical feature of CK7/CK20 double-negativity by evaluating the transformation zone between PEA and conventional pulmonary adenocarcinoma (CPA). A 75-year-old man was found to have a mass, 40 mm in diameter, in the right lower lobe on chest computed tomography, and underwent right lower lobectomy. Histologically, the tumor was composed of a PEA and CPA component. The dominant PEA component had medium to large complex glands with tall columnar cells with eosinophilic cytoplasm and brush-border. The CPA component comprised small to medium glands with cuboidal cells. Moreover, intermediate glands (INT), which had cuboidal to tall columnar cells, with morphological features between PEA and CPA, was also observed in the transformation area. Immunohistochemically, the PEA component was negative for CK7, CK20, and TTF-1, and positive for CDX2 and SATB2 (weak): the CPA component was negative for CK20, CDX2, and SATB2, and positive for CK7 and TTF-1: the INT were negative for SATB2, with intermingled positive signals for CK7, CK20, TTF-1, and CDX2. The final diagnosis was PEA based on the CPA component and not colorectal carcinoma. To distinguish CK7-negative PEA from metastatic colorectal carcinoma, careful examination for a CPA component is very useful along with clinical information. There are no reports that discuss about process of oncogenesis, de novo sequence or transformation from CPA of PEA. This is the first reported case of CK7/CK20 double-negative PEA, with analysis of the transformation zone between PEA and CPA components.

Pulmonary Adenocarcinoma Mimicking Desquamative Interstitial Pneumonia: Report of 2 Cases With Genetic Analysis.

We report 2 cases of pulmonary adenocarcinoma mimicking desquamative interstitial pneumonia (DIP) with genetic analysis occurring in a 74-year-old woman and a 76-year-old woman. In both cases, the tumor was mainly composed of discohesive tumor cells, which filled and floated in the alveolar space in a DIP-like pattern. The tumor cells had abnormally large round to oval nuclei with fine chromatin and relatively abundant eosinophilic cytoplasm lacking pigmentation. Immunohistochemically, tumor cells in both cases were positive for CK7, TTF-1, napsin A, E-cadherin, ß-catenin, and PD-L1 (one case had high expression and the other had low expression), and negative for CK5/6, CK20, p40, and ALK. However, the positive pattern of E-cadherin and ß-catenin was incomplete on the circumference of the cell membrane in both cases and in one case, respectively. On genetic analysis, EGFR alteration (exon 21, L858R mutation) was observed in one case and ALK translocation was not observed in either. To the best of our knowledge, this is the first report of pulmonary adenocarcinoma mimicking DIP with genetic analysis.