Benign clear cell "sugar" tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. CASE PRESENTATION: In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2-associated genetic region was demonstrated. CONCLUSION: To our knowledge, this is the first report of CCST of the lung in a patient with BHDS, indicating that CCST should be added to the spectrum of pulmonary manifestations of BHDS.

Optical characterization of In-flushed InAs/GaAs quantum dots emitting a broadband spectrum with multiple peaks at ~1 µm.

We investigated optical properties of In-flushed InAs quantum dots (QDs) grown on a GaAs substrate by molecular beam epitaxy. By using the In-flush technique for setting the height of self-assembled InAs QDs, we have tuned the emission wavelength of InAs QDs to the ~1 µm regime, which can be utilized as a non-invasive and deeply penetrative probe for biological and medical imaging systems. The controlled emission exhibited a broadband spectrum comprising multiple peaks with an interval of approximately 30 meV. We examined the origin of the multiple peaks using spectral and time-resolved photoluminescence, and concluded that it is attributed to monolayer step fluctuations in the height of the In-flushed QDs. This feature can be advantageous for realizing a broadband light source centered at the ~1 µm regime, which is especially suitable for the non-invasive cross-sectional biological and medical imaging system known as optical coherence tomography.

[Mediastinal cystic lymphangioma; report of a case].

A cystic lymphangioma is a rare mediastinal benign tumor. A 38-year-old male was referred to our hospital because of an mediastinal mass incidentally detected on chest X-ray. The mass had enlarged rapidly during the course of 1 year. Computed tomography (CT) of the chest showed a 7 cm well defined cystic tumor in the left anterior mediastinum. Magnetic resonance imaging (MRI) demonstrated a mass with heterogeneous high signal intensity on enhanced T2-weighted images. The cystic tumor, localized in the mediastinal adipose tissue, was completely resected by a thoracoscopic procedure. A pathological examination confirmed the diagnosis of a cystic lymphangioma.

Successful treatment of ulcerative colitis associated with hypereosinophilic syndrome/chronic eosinophilic leukemia.

A 23-year-old female was diagnosed as having simultaneous ulcerative colitis (UC) relapse and hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL) without FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene. Pathological findings of colon specimens were compatible with UC, however, focal severe infiltration of eosinophils was observed in the rectum, which is unusual in UC, suggesting eosinophil-mediated organ damage. Although imatinib mesylate (IM) is usually ineffective for the treatment of HES/CEL with negative-F/P fusion gene, in the present case it led to the remission of HES/CEL and UC at a higher drug dosage level (400 mg/day). That suggested the presence of unknown tyrosine kinase abnormalities not yet categorized.

Arteriovenous hemangioma in the middle mediastinum: report of a case.

Hemangiomas in the mediastinum are uncommon, and the majority of these tumors are located in the anterior mediastinum. The present report describes an extremely rare case of a hemangioma in the middle mediastinum. A 40-year-old male patient presented with a mass in the left lower lung field on radiographic screening. Chest computed tomography and magnetic resonance imaging revealed a mass measuring 2.5 cm in diameter, which was close to the descending aorta in the left middle mediastinum. The tumor resection was performed by video-assisted thoracic surgery. The thoracoscopic findings revealed a blackish brown mass with a capsule, which had not invaded the descending aorta or cardiac sac. Histologically, the tumor was composed of typical thick-walled vessels and was therefore classified as an arteriovenous hemangioma.

Peripheral T-cell lymphoma that developed during the follow-up of IgG4-related disease.

IgG4-related disease is a recently recognized fibroinflammatory disorder characterized by extensive IgG4-positive plasma cell and lymphocyte infiltration of various organs. The pancreatic manifestation of IgG4-related disease is called autoimmune pancreatitis (AIP), in which autoimmune mechanisms are likely involved. On the other hand, some autoimmune and chronic inflammatory disorders, such as Sjögren's syndrome and rheumatoid arthritis, are associated with increased risks of non-Hodgkin lymphoma (NHL). There have been a few reports of cases with IgG4-related disease that had subsequently developed NHL, however, all of them suffered from B-cell lymphoma. We describe the first case of NHL, compatible with a subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which arose in IgG4-related sclerosing cholangitis. As patients with IgG4-related disease may be at an increased risk of developing NHL, such presentation during the follow-up of IgG4-related disease should be carefully scrutinized to exclude NHL.

A case of syphilis presenting with initial syphilitic hepatitis and serological recurrence with cerebrospinal abnormality.

We present the case of an immunocompetent 50-year-old Japanese man with a cerebrospinal fluid (CSF) abnormality relevant to syphilis; his original presentation was liver dysfunction, the etiology of which was uncertain until positive serology for syphilis was identified. Liver dysfunction was promptly resolved after oral penicillin therapy; however, serological recurrence developed. CSF abnormality associated with syphilis was confirmed by subsequent lumbar puncture. Syphilis should be included in the differential diagnosis of patients with liver dysfunction of unknown etiology, and possible neurosyphilis should be considered when the treatment becomes refractory, even when there is no evidence of neurological manifestations.

Pleuropulmonary paragonimiasis with intrathoracic mass.

Pleuropulmonary paragonimiasis is a food-borne parasitic disease caused by the lung fluke Paragonimus westermani or other species of Paragonimus, which is endemic in Southeast Asia. It presents mainly pleural effusion or intrapulmonary nodules with respiratory symptoms. However, here we describe an exceedingly rare case of Paragonimus westermani with a mass in the pleural cavity. A 47-year-old man, who had presented with chest pain nine months earlier, was found to have right pleural effusion on detection survey computed tomography. He had a history of asbestos exposure and river fishing as a hobby and was confirmed to have Paragonimus westermani by immunodiagnosis. Because of a high level of hyaluronic acid in pleural effusion, he underwent a thoracoscopic examination. The pleura of the thoracic wall thickened greatly and showed no malignant lesion on biopsy. A white mass measuring 8 cm in diameter showed in the pleural cavity, which partially connected with the diaphragm and pulmonary pleura of the lower lobe. The postoperative pathological examination reported that the intrathoracic mass was a lesion that contained necrotic tissue enveloped with a fibrin capsule, which was thought to be formed by paragonimus.

Fulminant hepatic failure accompanied by fatal rhabdomyolysis following exertional heatstroke.

We present a previously healthy 38-year-old Japanese man who developed exertional heatstroke (EHS) following a long-distance run and presented with fulminant hepatic failure (FHF) accompanied by a life-threatening flare-up of rhabdomyolysis. Intensive life-supporting medical procedures, including plasma exchange, hemodiafiltration, steroid pulse therapy, and anticoagulant treatment enabled the patient to survive FHF. Initially, his general condition was thought to be improving; however, smoldering rhabdomyolysis suddenly flared up with a marked increase in creatine kinase levels when the dose of steroids was reduced, subsequent to which his condition deteriorated rapidly, eventually resulting in death. The serum levels of interleukin-6 measured retrospectively were found to be markedly elevated and to have fluctuated synchronously with the disease activity. This case report demonstrates that EHS can cause FHF and severe rhabdomyolysis, the outcome of which was tragic even though FHF was substantially well managed; however, the clinical evidence suggests the possible therapeutic efficacy of steroid therapy for refractory rhabdomyolysis occurring in EHS.

Hepatocellular carcinoma and Crohn's disease: a case report and review.

Hepatocellular carcinoma (HCC) is usually known to develop in patients with underlying high-risk liver diseases such as viral hepatitis, cirrhosis and alcohol abuse, whereas reports dealing with HCC in Crohn's disease (CD) are limited. We present a case of HCC, which developed sequentially within a short period in a 52-year-old Japanese man with a 36-year history of CD without risky conditions for HCC. He also had not taken immunosuppressants such as azathioprine. Although the definitive etiological factors contributing to hepatocarcinogenesis in the present case could not be elucidated, further close surveillance is required.

A variant form of autoimmune pancreatitis successfully treated by steroid therapy, accompanied by von Meyenburg complex.

Diagnostic criteria for autoimmune pancreatitis (AIP) have been proposed and used clinically because, despite its unique clinicopathological features, AIP does not have disease-specific serological tests for confirmation. However, diagnosis of a patient with pancreatic lesions mimicking cancer who deviates from these diagnostic criteria is still difficult. We present herein a patient with a variant form of AIP successfully diagnosed by fine-needle biopsy, whose response to steroid therapy was excellent. A 55-year-old Japanese man was admitted to hospital because of jaundice and pancreatic head mass. AIP was considered as one of the differential diagnoses; however, as the patient showed neither pancreatic duct narrowing nor immunological abnormalities, he did not meet the Japanese diagnostic criteria for AIP. Histopathology of the pancreatic mass demonstrated abundant infiltration by lymphocytes and interstitial fibrosis, which suggested AIP. Immunoreaction to IgG4, which is supposed to be specific to AIP, was not observed; however, response to subsequent prednisolone therapy was good, with dramatic pancreatic head mass regression. Aside from the pancreatic head mass, diffusely spreading small lesions were observed throughout the liver. The likelihood of a potential association with extrapancreatic lesions of AIP was considered and led us to carry out a liver biopsy, which revealed biliary hamartoma, also called von Meyenburg complex (VMC). As IgG4-positive plasma cell infiltration was not demonstrated in the hamartomatous regions, the hepatic condition was thought to have occurred incidentally; however, to the best of our knowledge, this is the first report in which the association between AIP and VMC was investigated and discussed.

An autopsy case of autoimmune pancreatitis after a 6-year history of steroid therapy accompanied by malignant dissemination of unknown origin.

Little is known about the long-term outcome of autoimmune pancreatitis (AIP), and whether AIP possesses malignant potential. We report herein a 68-year-old Japanese AIP patient who rapidly developed systemic malignant dissemination of unknown origin, resulting in death. The patient was diagnosed histopathologically as having AIP in 1999. After a 6-year history of 5 mg/day of prednisolone therapy, a sudden onset of abdominal pain and convulsive seizure occurred, and the patient died on the tenth hospital day owing to diffuse peritoneal disseminations and metastases in the bilateral lungs and brain. Autopsy disclosed that the primary site was renal cell carcinoma, detectable only by autopsy, originating in the left kidney. On microscopy, metastatic cells obtained from the brain, lung, and peritoneum were composed of pleomorphic malignant cells identical to those from the renal cell carcinoma. Unexpectedly, abundant IgG4-positive plasma cell infiltration, suggesting high activity of AIP in pancreatic parenchyma and around dilated bile ducts, was still observed.

Hepatocellular carcinoma with direct invasion to the stomach causing gastrointestinal hemorrhage.

A 54-year-old man had undergone transcatheter arterial embolization (TAE) three times to treat hepatitis B virus-related hepatocellular carcinoma (HCC), but recurrence was found in June 2005. A large tumor in the left lateral portion of the liver showed extrahepatic growth and was attached to the gastric wall. TAE was performed a forth time. In September 2005, the patient was admitted with worsening anemia. Computed tomography and upper gastrointestinal endoscopy revealed that the HCC had directly invaded the stomach and caused gastrointestinal hemorrhage. Endoscopic hemostasis was effective, but the patient died because of worsening hepatic failure.

Late pulmonary metastasis of a rectal cancer resected 20 years after low anterior resection.

A 54-year-old man underwent a low anterior resection for rectal cancer in July 1986. A right pulmonary tumor was pointed out in March 2006 by screening a chest X-ray. Because pulmonary metastasis from colorectal cancer was suspected by transbronchial biopsy, a colonofiberscopy was performed. However, no primary tumor was found. Furthermore, positron emission tomography (PET) revealed no other positive lesion. This tumor was resected in April 2006, and the pathological findings, including immunohistochemical findings, were similar to those of the previously resected rectal cancer. This tumor was therefore diagnosed to be pulmonary metastasis from rectal cancer resected 20 years ago based on a comparison of primary and pulmonary tumors using immunohistochemical examination. This shows that pulmonary metastasis from colorectal cancer is possible even 20 years after the initial operation.

Drug-induced hypersensitivity syndrome associated with reactivation of human herpesvirus 6 presenting with severe hepatic injury.

Little is known about the pathophysiology of liver complication seen in drug-induced hypersensitivity syndrome (DIHS). We describe herein a 32-year-old Japanese man with DIHS due to salazosulfapyridine (SASP) associated with reactivation of human herpesvirus 6 (HHV-6) presenting with severe acute hepatic injury. The patient, with a 1-year history of ulcerative colitis (UC), presented with high fever and abnormally elevated liver enzymes. Six weeks prior to his symptoms, prednisolone (PSL) and SASP had been started because of UC aggravation. Besides fever and liver dysfunction, the appearance of atypical lymphocytes together with eosinophils and generalized erythematous maculopapular skin rash developed sequentially, and a diagnosis of DIHS was established. Despite cessation of SASP and increased dose of PSL, his initial abnormalities continued, and biphasic second alanine aminotransferase (ALT) flare with deep jaundice worsened. Based on the significant increase in the titer of HHV-6 IgG antibodies at the second peak of ALT level without HHV-6 IgM antibody elevation, strongly suggesting reactivation of the virus, HHV-6 was first considered to directly contribute to the deterioration of liver function. However, extensive histological analysis of the liver led to the realization that the cause of the DIHS liver injury was essentially drug-related hepatotoxicity induced by SASP, causing wide-ranging damage to both the hepatocytes and cholangiocytes.

Pulmonary artery obstruction caused by thoracic aortic dissection: a case with unique pathological findings.

Pulmonary artery obstruction is a rare complication of acute thoracic aortic dissection. A 74-year-old woman was admitted to hospital with respiratory distress. Computed tomography scan showed right pulmonary artery occlusion and a thoracic aortic dissection of the Stanford A type. Lung perfusion scan revealed a defect in the entire right lung field. These findings mimicked acute pulmonary thromboembolism accompanying aortic dissection. On the other hand, pulmonary angiography revealed a round smooth defect of the right pulmonary artery, indicating an extrinsic compression. The patient finally died of cardiac tamponade. Autopsy disclosed that the right pulmonary artery was compressed by a hematoma in the adventitial space around the pulmonary artery. Such a mechanism of pulmonary artery obstruction caused by acute aortic dissection is unique, and is distinct from that caused by chronic non-dissecting aortic aneurysms, which themselves compress the pulmonary arteries. This complication inevitably follows aortic rupture; therefore, emergency operation to repair the dissected aorta must be performed to avoid the following catastrophic event.

Thrombopoietin-producing hepatocellular carcinoma.

A 66-year-old man with hepatocellular carcinoma (HCC) showed marked thrombocytosis (110.7 x 10(4)/microl). Bone marrow (BM) aspirates demonstrated an increase of mature megakaryocytes (MgK). The serum thrombopoietin (TPO) level was increased to about 100-fold that of the normal level in the terminal stage. However, the platelet count gradually decreased to 13.5 x 10(4)/microl. The autopsy specimen revealed normoplastic BM with decreased MgK, mainly consisting of the immature type, and it was negative for tumor cells. Liver specimen showed markedly fatty metamorphosis. Immunohistochemical staining of TPO demonstrated that hepatocytes were weakly stained and HCC cells strongly stained, suggesting TPO-producing HCC.

[A case of acute hypersensitivity pneumonitis caused by contact with budgerigars (bird-breeder's lung)].

A 58-year-old woman was admitted to our hospital for repeated episodes of dry cough, low-grade fever, and gradual development of dyspnea on exertion. Chest computed tomography showed diffuse ground-glass opacities in both lung fields. Bronchoalveolar lavage fluid (BALF) showed an increased number of lymphocytes, and transbronchial lung biopsy revealed alveolitis and epithelioid cell granuloma. The acute onset and the patient's living environment suggested summer-type hypersensitivity pneumonitis. However, anti-Trichosporon antibody was negative and a definitive diagnosis could not be made. The patient's condition improved with corticosteroid treatment and, after discharge from the hospital, she moved to a new home. The following year, however, her symptoms returned, and she was readmitted to our hospital. Recurrence of the disease despite the change in environment ruled out summer-type hypersensitivity pneumonitis. Given the patient's history of budgerigar breeding five years earlier, bird breeder's lung was suspected. Anti-bird excreta antibody found in the patient's serum and BALF, along with a positive lymphocyte stimulation test against pigeon serum, strongly suggested an acute onset of bird breeder's lung. We report a rare case of acute bird breeder's lung with radiologic findings of ground-glass opacities, a one-year disease-free period and an acute relapse.

Acute onset of nephrotic syndrome during interferon-alpha retreatment for chronic active hepatitis C.

A 57-year-old woman was scheduled to receive recombinant interferon-alpha retreatment for chronic active hepatitis C. During the course of therapy, the patient showed rapid onset of oliguria, dizziness, edema, and a pre-shock state. She was subsequently admitted to hospital and was diagnosed as having nephrotic syndrome. After admission, albumin-dominant proteinuria persisted despite the discontinuation of interferon therapy. Light microscopy of a renal needle biopsy specimen showed interstitial lymphoid cell infiltration, but no marked changes of the glomeruli and no staining for immunoglobulin or complement. Electron microscopy showed diffuse effacement of the glomerular epithelial foot processes, leading to a diagnosis of minimal change nephrotic syndrome with interstitial nephritis. Proteinuria resolved after the initiation of oral prednisolone therapy (1 mg/kg per day). The number of patients with chronic hepatitis C requiring interferon retreatment is increasing rapidly. We herein report this rare case of acute onset of nephrotic syndrome during interferon-alpha retreatment.