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The case is an 80-year-old woman with Sjögren's syndrome. During the follow-up of multiple pulmonary nodules, an enlarged nodule was observed in the peripheral of the right S3 interlobar region. Fluorodeoxyglucose- positron emission tomography (FDG-PET) showed FDG accumulation only in the S3 nodule, which led to suspicion of primary lung cancer. Because of its difficult location to reach by bronchoscopy, a right lung S3 segmentectomy was performed. Intraoperative findings revealed a hard yellowish- white nodule just below the pleura. Pathological examination showed that the nodule consisted of an acidophilic structureless material, which was positive for Congo red staining and disappeared after permanganate treatment. Based on the above findings, we diagnosed amyloid A( AA)-type amyloidosis. In this case, the nodule was located just below the pleura and we could observe it by thoracoscopy. There have been few reports of thoracoscopic observation of pulmonary amyloidosis, and we report with intraoperative findings.

A 79-year-old man had undergone endoscopic colorectal resection for colon cancer and partial resection of right S2 for lung cancer in 2007. Two years later, enlargement of a small nodule in the right S10 detected by chest computed tomography was noted. Partial lung resection was performed in April 2009, and the pathological diagnosis was localized nodular pulmonary amyloidosis.

A 78-year-old man presented with subacute progressive proximal weakness and dysphagia. A biopsy specimen from the left biceps femoris revealed evidence of necrotic and regenerating muscle fibers, but lymphocyte infiltration was not noted. The patient was diagnosed with necrotizing myopathy with anti-signal recognition particle (SRP) antibodies. Concomitant therapy with prednisolone and azathioprine caused the serum CK level to return to normal and it caused clinical manifestations to abate. One year later, however, muscle weakness worsened. Immunoelectrophoresis of serum revealed IgG M protein, and muscle pathology revealed amyloid deposits in numerous blood vessels and at the periphery of a few muscle fibers, and deposits stained positive for anti-λ light chain antibody. The patient was diagnosed with amyloid myopathy, and therapy for systemic amyloid light chain amyloidosis caused muscle weakness to diminish. Amyloidosis is believed to be the primary pathology in this case based on the patient's response to treatment reaction, but the significance of a case involving both amyloid myopathy and necrotizing myopathy warranted examination.

Patients with renal insufficiency receiving long-term hemodialysis often develop so-called hemodialysis amyloidosis characterized by systemic β 2-microglobulin amyloid lesions, while patients with renal cell carcinoma may develop amyloid A(AA) amyloidosis. Herein, we present a 67-year-old man on thirty-yearlong hemodialysis who was diagnosed to have left renal cell carcinoma coincident with a large spaceoccupying lesion adjacent to the psoas muscle in the pelvic cavity. An ultrasound-guided percutaneous needle biopsy was performed at the time of laparoscopic radical nephrectomy. The pathological work-up on the needle biopsy specimen revealed that the lesion was not an AA amyloidoma but a β2-microglobulin amyloidoma, which is a rare manifestation of hemodialysis amyloidosis.

A 79-year-old man was diagnosed to have primary amyloid light-chain (AL) amyloidosis with associated liver damage and prominent hepatomegaly. He was followed up without any treatment. One year after the diagnosis, he was taken to the hospital with a sudden onset of features of shock. Computed tomography revealed hepatic rupture, and he was treated by emergent transcutaneous arterial embolization. However, the procedure was unable to save his life. AL amyloidosis with prominent hepatomegaly is considered to be a risk factor for spontaneous liver rupture and intra-abdominal hemorrhage.

Background: Amyloidosis is a spectrum of disorders characterized by the deposition of amyloid that causes severe damage to many organ systems. However, conjunctival amyloidosis is thought to be the manifestation of a local immunologic disorder and rarely affects the organ systems. We present two cases of conjunctival amyloidosis found as unilateral ptosis at initial visit. Case 1: 43-year-old-woman presented with unilateral ptosis and discomfort for the left eye. She had been treated with topical antihistamines and corticosteroids for allergic conjunctivitis. However, as symptoms persisted she was referred to us. At initial visit, unilateral ptosis, subconjunctival hemorrhage and waxy-yellow mass were found. Incisional biopsy was performed and histpathological examination revealed amyloid in the conjunctival stroma. Case 2: 31-year-old woman presented with unilateral ptosis and discomfort of palpebral superior conjunctiva in the left eye. At initial visit, the examination of the left superior palpebral conjunctiva showed waxy-yellow mass and hemorrhage. Incisional biopsy was performed and histopathological examination revealed amyloid in the conjunctival stroma. Conclusion: Unilateral ptosis may be an indication of conjunctival amyloidosis.

A woman in her 70s presented with dehydration and malnutrition due to watery diarrhea. She was examined and diagnosed with gastrointestinal amyloidosis accompanied by a protein-losing gastroenteropathy secondary to rheumatoid arthritis. She first underwent treatment with an anti-tumor necrosis factor alpha (TNF-α) antibody for secondary amyloidosis, but due to lack of adequate response, she was switched to an anti-interleukin (IL)-6 receptor antibody. Her clinical symptoms subsequently improved, and endoscopy revealed a marked decrease of amyloid protein deposits in the digestive tract. She was followed up for 3 years while continuing to receive the anti-IL-6 receptor antibody, with no recurrence. Although secondary amyloidosis is a fatal disease associated with chronic inflammatory diseases, clinical symptoms and prognosis have recently been improved by intervention with biological therapies. In particular, anti-IL-6 receptor antibodies have been reported to be superior to anti-TNF-α antibodies in the treatment of secondary amyloidosis and are expected to play a central role in treating secondary amyloidosis in the future.

A 42-year-old female visited our hospital with the chief complaint of macrohematuria and left lateroabdominal pain. Computed tomography and retrograde pyelogram showed left hydronephroureter and obstructive uropathy which was 20 mm in diameter in the middle ureter. Urine cytology was negative. Ureter biopsy revealed amyloidosis. Our diagnosis was localized amyloidosis of the ureter, because amyloid was not found in other places in her whole body inspection. Partial ureterectomy was performed. Left renal function was preserved. The patient has been free of recurrence for 18 months after surgery.

Amyloidosis refers to disorders that cause organ failure due to amyloid deposition. Deposited amyloid is clearly stained by Congo red and is detected by apple-green birefringence under polarized light. Amyloid fibril proteins are very stable, but several recent studies have revealed that amyloid deposition and the clearance of fibrils cause the steady turnover of deposited amyloid proteins. Therefore, in several amyloidosis disorders, especially primary AL, reactive AA, and transthyretin-related amyloidosis, effective therapies are expected to cause the regression of tissue-deposited amyloid.

Amyloidoses are a group of protein conformational diseases in which soluble precursor proteins form insoluble amyloid fibrils in the extracellular space. Amyloidoses are roughly classified in terms of their localized or systemic deposition, and are further grouped based on the types of precursor proteins. As of today, 27 different proteins have been recognized as amyloid precursor proteins. Amyloidoses are diagnosed by histopathological analysis using Congo red staining and/or electron microscopy, and the disease classification is made based on immunohistochemistry, proteomics, and gene analyses. The four main types of systemic amyloidosis are light-chain amyloidosis, reactive amyloid A amyloidosis due to chronic inflammatory diseases, β2-microglobulin amyloidosis associated with long-term hemodialysis, and hereditary transthyretin-related amyloidosis caused by mutations in the transthyretin gene. There are a many types of localized amyloidosis including cerebral endocrine, and cutaneous amyloidosis. In recent years, the treatment strategies for amyloidoses have greatly improved, and several forms of these are now treatable. Therefore, it is increasingly important to make an early diagnosis and begin treatment at the earliest, based on the precise disease classification of amyloidoses.

An 82-year-old woman with a history of bronchiectasis for 20 years was admitted to our hospital with anorexia and diarrhea. Sigmoidoscopy showed multiple mucosal erythematous areas and erosions. Histologic examination with Congo red stain revealed massive amyloid deposition around the submucosal vessels as well as in the parenchyma of the mucosa and submucosa. With immunohistochemistry, the diagnosis of secondary/reactive AA amyloidosis was confirmed. Esophagogastroduodenoscopy demonstrated diffuse dark brown mucosa, establishing the diagnosis of acute necrotizing esophagitis. Ischemia associated with amyloid deposition of the vessels in the esophagus was considered to be a possible etiology of acute necrotizing esophagitis. Additionally, gastric outlet obstruction and gastroesophageal reflux associated with gastroduodenal erosions caused by amyloid deposition were supposed to be another factor. Amyloid deposition in the esophageal mucosa may cause a reduction in mucosal defense that is responsible for the pathogenesis. We report the first case of acute necrotizing esophagitis associated with amyloidosis.

A 68-year-old man, with a history of type 2 diabetes mellitus and chronic kidney impairment, had been suffering from progressive knee joint contracture and dysesthesia of the lower extremities for 4 years. When he walked, his knees remained bent owing to contracture of the knee joints. There was no evidence of muscle pseudohypertrophy, intramuscular nodules, or muscle weakness. Clinical examination revealed IgA λ M-protein, reticular high-signal intensity lesions demonstrated by magnetic resonance T2-short TI IR(STIR) imaging of the lower extremity muscles, and a mixture of neurogenic and myogenic changes demonstrated by needle electromyography. A biopsy specimen from the vastus lateralis muscle identified Aλ amyloid deposits around the vessels, establishing a diagnosis of amyloid myopathy based on systemic AL amyloidosis. This case demonstrated that joint contracture and reticular lesions shown by magnetic resonance STIR imaging of the muscles can alert the physician to consider muscle biopsy to investigate deposition of amyloid in the skeletal muscles even in the absence of muscle pseudohypertrophy or weakness, both of which are characteristic of amyloid myopathy.

A 55-year-old man was referred to our department with the chief complaint of left flank pain. Computed tomography and magnetic resonance imaging demonstrated a left hydronephroureter due to the ureteral stenosis with a mass. We considered the possibility of a malignant neoplasm, and performed laparoscopic left total nephroureterectomy. Microscopic appearance showed ureteral wall thickening and perivascular deposition of heterogeneous amyloid. It stained positive by immune-histochemical staining using Congo-red. In addition, it stained positive by immune-histochemical staining with an anti-AA antibody. These findings indicated that the amyloid was type AA. AA amyloidosis is a systemic amyloidosis that arises secondarily to an inflammatory disease. He had been treated for systemic lupus erythematosus. It is compatible to secondary amyloidosis. Eighty seven months after diagnosis, he died of lung cancer. There were no signs or symptoms of deposition of the AA amyloid proteins.

A 60-year-old man presented with fever and fatigue in a medical clinic and was given a diagnosis of cholangitis with mild cholangiectasis. The cholangiectasis remained even after treatment with an appropriate antibiotic agent. When the patient was transferred to our hospital for further examination, he was newly suffering from orthostatic hypotension and peripheral facial nerve palsy. Computed tomography (CT) scan revealed multiple low-density areas in the liver and intrahepatic bile duct dilatation. We performed percutaneous liver biopsy, and histopathological findings showed amyloid deposition around the portal vein. We diagnosed his condition as AL amyloidosis. Oral administration of melphalan and dexamethasone improved his clinical features and CT findings. We consider this case as rare in that the deposition of amyloid protein caused cholangiectasis.

A 26-year-old man was introduced to our hospital with a complaint of macrohematuria. Endoscopic examination showed a small tumor in the anterior urethra. Microscopic examination of a biopsy specimen taken under lumbar anesthesia showed amyloid deposition in the urethral submucosa. On Congo red staining, amyloid was visualized as orange material, showing characteristic birefringence under polarized light. Amyloidosis of the urethra was diagnosed. Because the patient refused to undergo duodenal or rectal biopsy, the possibility of systemic amyloidosis could not be completely excluded. No recurrence has been noted since the endoscopic examination, and no further symptoms have been reported.

We present three long-term survivors treated with high-dose melphalan with autologous peripheral blood stem cell transplantation(auto PBSCT)for primary AL amyloidosis. Because melphalan toxicity is dose-related, patient age and the extent of organ involvement are very important factors for the success of high-dose melphalan treatment with PBSCT. The patients were therefore given high-dose melphalan using the risk-adapted approach to melphalan dosing. They received 3 courses of a vincristine, doxorubicin and dexamethasone(VAD)regimen, along with high-dose melphalan(100-200mg/m2)with auto PBSCT. There were no serious complications or transplantation-related mortalities. Patients survived for an average of 68 months(22-100 months)in partial response. A risk-adapted approach to melphalan dosing with PBSCT is an effective treatment in patients with primary AL amyloidosis.

A 75-year-old man was admitted to our hospital with progressive weakness in the lower extremities for 7 months. Immunoelectrophoresis of serum detected IgA λ type M protein and bone marrow examination detected an increase in monoclonal plasma cells, thus leading to a diagnosis of IgA λ type multiple myeloma. Subsequent muscular CT scan showed severe fatty infiltration of vastus lateralis muscles, and histopathological examinations of biopsied muscle specimens an abundance of abnormal "ring-fiber-like" appearance, positive staining by Congo red and the presence of anti-λ light chain antibody. This led to a diagnosis of amyloid myopathy. No depositions were seen in rectal mucosa, cardiac muscle, or sural nerve. The results of double immunohistochemical staining using anti-dystrophin antibody and anti-λ light chain antibody suggested the possibility of direct injury by amyloid to muscle fibers. The case presented here was thus amyloidosis confirmed by deposition of amyloid only in muscles. In conclusion, when amyloidosis is suspected and there is evidence of muscle injury, muscle biopsy should be performed.

Amyloidosis is characterized by extracellular deposition of abnormal insoluble fibrils, which cause structural and functional disorders. Amyloidosis is classified into systemic and localized amyloidosis. Localized amyloidosis in individual organs is uncommon. We report a rare case of localized form of primary amyloidosis of the urinary bladder. A 76-year-old male visited our hospital with a complaint of macroscopic hematuria. Cystoscopy showed submucosal hematoma in the anterior wall and broad-based mass occupying the trigone without normal mucosa covered by calcification. Transurethral biopsy and resection were performed. Histopathological diagnosis was AL type amyloidosis occupying submucosal extracellular space. We gave the patient occlusive dressing with dimethyl sulfoxide. In 12 months, cystoscopy and magnetic resonance imaging revealed improvement of the mass-like lesion in the bladder wall.

A 78-year-old woman was referred to our hospital with chief complaint of colicky right flank pain. Computed tomography (CT) demonstrated right hydronephrosis and a wall thickening in the right ureteropelvic junction. Right nephroureterectomy was performed under a clinical diagnosis of invasive ureteral cancer. Histological examination revealed immunoglobulin light chain (AL) amyloidosis of the ureter. Although amyloid deposition seemed to be localized to the ureter alone, bone marrow biopsy revealed primary macroglobulinemia. After 23 months, no signs or symptoms suggesting the progression of amyloidosis or macroglobulinemia have been pointed out. AL amyloidosis arising secondarily to plasma cell disorder is called immunocytic amyloidosis. In general, immunocytic amyloidosis accompanies deposition of the amyloid protein to various organs of the whole body, and causes multiple clinical symptoms related to amyloid deposition. Even though the clinical manifestation indicates the localized disease like the presented case, close examination of immunocytic amyloidosis is important.

Primary amyloidosis of the seminal vesicle is a rare disease entity. We report here a case of localized seminal vesicle amyloidosis with hematospermia. A 66-year-old man visited our hospital with a chief complaint of hematospermia. T2 weighted magnetic resonance imaging (MRI) showed a hypointensity mass in the left seminal vesicle. Needle biopsy revealed amyloidosis of the seminal vesicle. Without any specific treatment, the mass lesion disappeared on MRI, and hematospermia was improved.

Deposition of insoluble amyloid fibrils in tissues is a common hallmark of a wide range of human diseases referred to as amyloidoses, including Alzheimer's disease, type II diabetes mellitus. The amyloid deposits cause cell dysfunction, death, and subsequently severe impairment in tissues. Elucidation of amyloid formation mechanisms is essential for prevention of the onset and development of amyloidoses. Accumulated experimental evidence demonstrates that membrane lipids enhance the fibril formation of amyloidogenic proteins. Our group demonstrated that amyloid formation by amyloid β-protein (Aβ) was facilitated by gangliosides in lipid raft-like model membranes. Phosphatidylserine and phosphatidylglycerol were also reported to trigger fibril formation by human islet amyloid polypeptide (hIAPP). However, it is not verified whether the proposed lipid-protein interactions can occur on plasma membranes of live cells. The author developed a method for visualizing amyloid fibrils on live cell membranes and investigated the roles of gangliosides and cholesterol in lipid rafts for amyloid formation. Congo red, an amyloid-specific dye, was found to be a promising compound for staining amyloids in live cells. Aβ was accumulated on cholesterol-dependent ganglioside-rich domains in PC12 neuronal cells in a time- and concentration-dependent manner, leading to cell death. Nerve growth factor-induced differentiation of PC12 cells increased both gangliosides and cholesterol and thereby greatly potentiated the accumulation and cytotoxic effect of Aβ. Amyloid formation by hIAPP was also facilitated by gangliosides in lipid rafts. Membrane lipid compositions, in this case, gangliosides in lipid rafts, actually caused striking change in amyloid formation on cell membranes.

A 67-year-old woman, who had been treated for Sjögren syndrome and rheumatoid arthritis for 10 years, was consulted for examination of multiple nodular pulmonary nodules. She has been pointed out multiple pulmonary nodules on chest computed tomography (CT) for 7 years, of which the number and the size gradually increased. When visuting our hospital, approximately 20 nodules up to 10 mm in size were noted. Thoracoscopic resection of the nodule was performed and histological diagnosis was amyloid, which was negative for A- and P- component and positive for transthyretin. Neither amyloid deposition in other organs nor abnormal protein in serum and urine was detected. The diagnosis of localized nodular pulmonary amyloidosis was established. As far as our knowledge, this is the 1st report of transthyretin amyloidosis with Sjögren syndrome.

Here, we present a case of mucosa-associated lymphoid tissue (MALT) lymphoma in the thymus with multiple amyloid nodules in both lung. A 66-year-old woman was incidentally found to have an abnormal shadow on mass-screening chest roentgenogram. A chest computed tomography (CT) demonstrated a mass of 50 mm in diameter with a smooth margin adjacent to the heart in the anterior mediastinum and multiple small nodules in both lung. As a differential diagnosis, thymic carcinoma with multiple lung metastases was firstly considered from these clinical informations. To make a definite diagnosis, the operation via a thoracoscopy was done. As a result, it turned out that pulmonary nodules were amyloidosis and the thymic tumor was MALT lymphoma. Postoperative course was uneventful and she was treated with chemoradiotherapy. In addition, she was diagnosed with Sjögren's syndrome 1 and half years later. Four years later the patient has been well without recurrence.

AL amyloidosis is the most common form of systemic amyloidosis. Although kidney biopsy often is the method by which the disease is identified, small amounts of amyloid in kidney biopsy specimens may be missed on routine examination unless specifically investigated. We present here a previously healthy 60-year-oldmissed on routine examination unless specifically investigated. We present here a previously healthy 60-year-old man who developed nephrotic syndrome. His first renal biopsy showed minimal change nephrotic syndromeman who developed nephrotic syndrome. His first renal biopsy showed minimal change nephrotic syndromesuggesteda subtle depost ommon formsystemicamyloidfibrilhediminationof an early lesion of renal amyloido-s (MCNS). Proteinuria remained refractory to immunosuppressive treatments. Six months later, a repeat renal biopsy clearly showed AL amyloidosis. Re-examination of the first biopsy in the light of the final diagnosis again suggested a subtle deposition of amyloid fibrils. The discrimination of an early lesion of renal amyloidosis with MCNS may often be difficult. It is necessary to maintain a high level of alertness for amyloidosis especially in aged patients with nephrotic syndrome and to consider a repeat biopsy in steroid-resistant cases.

A 57-year-old woman who had been given a diagnosis of Sjögren syndrome at age 53 consulted a nearby doctor because of bloody sputum. He noted her chest abnormal shadows and referred her to our hospital. Her chest radiograph and high-resolution computed tomograph showed multiple nodules and cysts in both lung fields. Video-assisted thoracoscopic lung biopsy revealed patchy fibrosis, cystic change, AL type amyloid deposition and mild lymphoid hyperplasia and a diagnosis of Sjögren syndrome-associated-pulmonary-disease was established.

A 71-year-old male consulted our hospital complaining of right tonsil enlargement. Tonsillectomy was performed. Histological analysis demonstrated AL amyloid deposits obliterating the tonsillar structures. Foreign body giant cell reaction and morphologically normal plasma cells mainly containing light chain lambda were present around the amyloid. Serum immunoglobulin levels were normal and M-proteins were not detected. Urinary test for Bence Jones proteins was negative. Bone marrow aspirates did not demonstrate any signs of multiple myeloma. Amyloidosis of the stomach, colon, heart, and skin was ruled out. We report an extremely rare case of amyloidosis localized in the tonsil and review the literature.

We synthesized new chemical compounds to detect amyloid fibrils named (trans, trans) -1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy) styrylbenzene (BSB) and 1-fluoro-2,5-bis (3-carboxy-4-hydroxystyryl) benzene (FSB). We used these compounds to detect amyloid fibrils in autopsy and biopsy samples from patients with systemic amyloidosis, such as familial amyloidotic polyneuropathy, amyloid A (AA) amyloidosis, light chain (AL) amyloidosis, and dialysis-related amyloidosis, and localized amyloidosis, such as familial prion disease (Gerstmann-Straussler-Scheimker syndrome: GSS). BSB showed reactions in all Congo red positive and immunoreactive regions of the samples examined in the study, and some amyloid fibrils in the tissues could be detected more precisely with BSB and FSB than with the other methods. In the mouse model of AA amyloidosis, injected BSB reacted with amyloid in all regions in the serial sections in which Congo red staining was positive. A highly sensitive 27-MHz quartz crystal microbalance analysis revealed that BSB showed a significant affinity for amyloid fibrils purified from familial amyloidotic polyneuropathy and dialysis-related amyloidosis samples and suppressed formation of transthyretin amyloid in vitro. These results suggest that BSB and FSB may become valuable tools for detection of amyloid deposits in amyloidosis and of the mechanism of amyloid formation.

The patient was a 64-year-old asymptomatic man. His chest X-ray film, at age 61, showed a solitary nodule in the right middle lobe. Thoracoscopic surgery was performed. The nodule was pathologically diagnosed as a solitary nodular amyloidosis. After 3 years, his chest CT showed a solitary nodule in the left upper lung. Thoracoscopic surgery for the pulmonary nodule was performed again, and it was also pathologically diagnosed as a solitary nodular amyloidosis with AA type amyloid protein. Solitary nodular pulmonary amyloidosis is usually AL type, and few cases of solitary AA type amyloidosis have been reported. We reported a rare case of recurrence of solitary pulmonary amyloidosis.

We reported a case of Sjögren's syndrome with pulmonary involvement diagnosed by video-assisted thoracoscopic lung biopsy. The patient was a 54-year-old woman with antiphospholipid syndrome. Her chest radiograph and CT scan showed multiple nodules with or within cystic lesions. The thoracoscopic lung biopsy specimens revealed nodular amyloid deposits associated with bronchiolitis. The mechanism of bulla formation appeared to be a check-valve mechanism caused by the narrowing of the airway due to bronchiolitis with mononuclear cell infiltration. She has no symptoms without respiratory failure or functional impairment, therefore we are following her closely without therapy.

A 66-year-old female was admitted to our hospital because of chest abnormal shadow. Chest X-ray and chest computed tomography (CT) on admission showed a nodule in the right middle lobe. The nodule was not diagnosed preoperatively by a bronchoscopy. She underwent partial lung resection including the nodule with video-assisted thoracoscopic surgery. The pathological diagnosis was amyloidosis, and we diagnosed her illness as localized nodular pulmonary amyloidosis, since the amyloid substance was type AL. In addition, electron microscopy showed amyloid as straightly fibrous materials in alveolus. It is difficult to differentiate amyloidosis from lung cancer by radiology, and the lung biopsy with video-assisted thoracoscopic surgery is useful and a safety way to establish diagnosis.

A 78-year-old woman was admitted to our hospital for treatment of liver cirrhosis and an esophageal varix. Endoscopy revealed a protruding nodular lesion with a transparent smooth surface proximal to the pylorus, which was accompanied by a partly yellow-whitish spot. A depressed lesion with an even edge was found. Histologically, the protruding lesion and depressed lesion showed amyloid deposits, mainly in the mucosal layer. The lesions were found to correspond to AL type amyloidosis by immunochemical analysis. General examination showed no other amyloid deposits. Thus, we diagnosed localized amyloidosis of the stomach.

For the diagnosis of amyloidosis, histological evidence of amyloid deposition is essential. Histologically, an amyloid deposit is stained orange red with Congo red and shows green birefringence under polarized light. When amyloidosis is clinically suspected, endoscopic biopsy of the stomach, duodenum or colon, or aspiration biopsy of abdominal fat is usually performed. If clinicians suspect amyloidosis, they should advise pathologists. Identification of the chemical type of amyloid is necessary with respect to treatment and prognosis. Immunohistochemical examination of amyloid in formalin-fixed, paraffin-embedded sections is simple to perform in most pathological laboratories. In Japan, almost all cases of systemic amyloidosis are classified as AL, AA, ATTR or Abeta2M amyloidosis, so the use of anti-immunoglobulin light chain, anti-amyloid A, anti-transthyretin and anti-beta2 microglobulin antibody is recommended for the classification of systemic amyloidosis. Formic acid pretreatment, which is often used for immunohistochemical detection of amyloidosis, is useful and easy for antigen retrieval. Amyloid deposits of AL amyloidosis are sometimes not immunostained well with commercial anti-immunoglobulin light chain antibody. Previously, we generated polyclonal antibodies against synthetic peptides corresponding to positions 118-134 of immunoglobulin lambda light chain and positions 116-133 of immunoglobulin kappa light chain. These antibodies are very useful for detecting AL amyloidosis because they react with amyloid deposits on formalin-fixed, paraffin-embedded specimens in almost all AL amyloidosis cases. Exact diagnosis and typing of amyloidosis are necessary for therapy.

We report an 80-year-old woman who had rheumatoid arthritis and antiphospholipid syndrome. She was treated for rheumatoid arthritis since her thirties. At 76 years of age, she was diagnosed antiphospholipid syndrome serologically. She felt It. limb weakness and dysarthria and was admitted to the hospital on July 18, 2003. The brain MRI showed T2 hyperintensity signal on the rt. pre-central lobe. She was treated by the argatroban, edaravone, glycerol, and aspirin. However, she became bedridden and fed by NG-tube because her symptoms progressed in spite of the therapy. Progression of stroke stopped by adding heparin at last. After that, she repeated pneumonia. She was found dead on the bed August 2, 2003. The patient was discussed in a CPC. The chief discussant arrived at a conclusion that the cause of infarction was angitis due to rheumatoid arthritis. Other possibilities were multiple thrombus due to antiphospholipid syndrome, amyloid angiopathy, and atherosclerotic infarction. Post-mortem study revealed sputum obstruction in her bronchus, string deposition in her organs. The brain showed infarction on the rt. pre-central lobe. There were multiple thrombus in the leptomeningeal artery, but few atherosclerotic changes of the small arteries. Amyloid didn't deposit in the brain artery and the parenchyma. Pathologist concluded that her infarction was induced with multiple thrombus due to antiphospholipid syndrome.

Background: Histopathological evaluation of primary congenital glaucoma with extensive corneal amyloidosis., Clinical Findings: A three-month-old infant. At the first examination, corneal diameter was 12 mm in both eyes, intraocular pressure (IOP) 43 mmHg in the right eye and 47 mmHg in the left eye. A diagnosis was made of primary congenital glaucoma. At 4 months of age bilateral goniotomy, at 1 year and 2 months of age bilateral goniotomy, and at 2 years and 2 months of age bilateral trabeculectomy and the superficial keratectomy of the right eye were done. At 14 years and 11 months of age the enucleation of the right eye was done because of corneal opacity, visual loss, and figure. HISTOPATHOLOGICAL FINDINGS: In the cornea disappearance of Bowman's membrane, accumulation of amyloid in the rough endoplasmic reticulum of the basal cells and subepithelial fibroblasts, and thickeniny of Descemet's membrane could be seen. At the peripheral anterior synechia new Descemet's membrane was spread over the anterior surface of the peripheral iris., Conclusion: Unilateral corneal amyloidosis might have been present in infancy, amyloid produced in the rough endoplasmic reticulum of the basal epithelium and subepithelial fibroblasts and deposited in the subepithelial region. At puberty amyloid might have been produced in the subepithelial fibroblasts. The poor IOP control at puberty might have been due to the complication of neovascular glaucoma.

We report a case of localized amyloidosis of the renal pelvis and upper ureter arising in a 74-year-old man who presented at our hospital with gross hematuria. The intravenous pyelogram showed right hydronephrosis and stenosis of right renal pelvis and upper ureter. The cystoscopy view was normal, but the right retrograde-ureteropyelogram showed a long irregular stricture of the renal pelvis. Ureteroscopy was performed and rubbing biopsy of edematous, bleeding lesion suggested class IIIb, transitional cell carcinoma. With the diagnosis of a right renal pelvic tumor, right nephroureterectomy was performed. The histology report stated "massive deposits of amyloids are seen in the segment of macroscopically abnormal renal pelvis". Amyloidosis of the renal pelvis is a rare entity and 12 cases were reported in the Japanese and English literature.

A 73-year-old man was admitted to our hospital because of fever, productive cough and dyspnea on exertion in March 1998. He had been treated at our hospital for interstitial pneumonia. Chest radiographs showed consolidations and honeycomb shadows in both lungs. He also had a chronic subdural hematoma. After admission his respiratory state deteriorated and the chronic subdural hematoma increased in size and as a result, artificial respiration was needed. During intubation for bronchoscopy, we found protuberant white lesions in the tracheal mucous membrane, a biopsy of which showed amyloid deposition. Immuno-histochemistry revealed AL-amyloid, although there was no amyloid deposition else where. This was an idiopathic case in which localized tracheal amyloidosis probably developed in association with interstitial pneumonia.

A 53-year-old male was admitted to the hospital because of progressive paralysis of inferior limb. Chest X-ray film and chest computed tomography (CT) on admission showed a small nodule with bullae in the right lower lung field. After CT-guided marking, partial lung resection including the nodule was performed. The cut surface of the resected specimen showed a tumor (10 mm in diameter) in a bullae measuring 14 mm in diameter. The tumor was diagnosed as amyloidosis. Fourty-six cases of primary localized pulmonary amyloidosis were reported in Japan. However, primary localized pulmonary amyloidosis with bullae is extremely rare, only 3 cases have been reported.

A 53-year-old man was diagnosed as primary amyloidosis by biopsy specimens of the mucosa in rectum, spleen and bone marrow (BM). BM examination showed 5.5% of plasma cells with some dysplasia. Immunoglobulin heavy chain gene rearrangement was detected by polymerase chain reaction using third-complementary-determining region (CDR 3) specific primers in BM mononuclear cells and spleen cells embedded in paraffin. The sequence analysis revealed that monoclonal B cells existed in the both, BM and spleen. Flowcytometric analysis using two-color staining showed the phenotype of plasma cells with the expression of CD19+/-, CD27+/-, CD56+/- and CD138+ and CD38++. This phenotype is similar to those of monoclonal gammopathy of undetermined significance (MGUS). Therefore, primary amyloidosis is considered to have two plasma cell populations including normal plasma cells and monoclonal plasma cells in BM. Given that there are two types of plasma cells in patients with primary amyloidosis, amyloid protein is expected to originate from immunoglobulin light chain produced by monoclonal plasma cells.

Primary amyloidosis of the urinary bladder is a rare disease entity. A total of 61 cases have been reported in the Japanese literature, and most of them were AL type amyloidosis. We report here a case of primary AA type amyloidosis. A 52-year-old man presented with a chief complaint of asymptomatic gross hematuria. Cystoscopy revealed yellowish elevated lesions, transurethral mucosal biopsies were performed, and the histopathological diagnosis indicated a primary AA type amyloidosis of the urinary bladder. Systemic amyloidosis was clinically eliminated. The yellowish lesions in the bladder through cystoscopy disappeared spontaneously one year later without any specific treatment, but periodical work-up may be necessary to rule out recurrence of the disease or bladder tumor.

In our experience, QS pattern of poor R wave progression and atrio-ventricular block of varying degrees on electrocardiogram, cardiomegaly with pleural effusion on chest X-ray film, left ventricular wall thickening, pericardial effusion and findings suggesting left ventricular diastolic dysfunction on echocardiogram and increased right ventricular end-diastolic pressure in cardiac catheterization were frequently observed in patients with cardiac amyloidosis. Though none of these findings are specific, we should suspect cardiac amyloidosis as a possibility when some of these signs are observed in patients with chronic cardiac failure of unknown etiology. Left ventricular mass obtained from echocardiography could be useful predictive parameter of prognosis in patients with cardiac amyloidosis.

Primary Sjögren's syndrome (primary SS) is characterized by lymphocytic and plasma cell infiltration of the lacrimal and salivary glands, sometimes extending to extraglandular sites. An increased incidence of B-cell lymphoproliferative disorders has been observed in patients with primary SS. We recently studied an unusual case of primary SS associated with multifocal nodular AL amyloidosis (amyloidomas), located in the lower respiratory tract and oral mucosa. A 66-year-old woman with primary Sjögren's syndrome since 1966 was hospitalized in 1996 because of multifocal nodular shadows on a chest radiograph. An open lung biopsy specimen was obtained, revealing a large mass of amorphous eosinophilic material with green birefringence when stained with Congo red. Numerous plasma cells surrounded the amyloid deposits, aggregated in nodules and around blood vessels. The cytoplasm of these cells stained monotypically with anti-lambda light chain, using a peroxidase technique. Amyloid material did not stain with antibodies directed against kappa and lambda light chains, or against IgG, IgA and IgM heavy chains. Immunofixation of the serum and concentrated urine did not demonstrate monoclonal immunoglobulins. AL-amyloidomas might be a manifestation of local immunoglobulin production and amyloid formation within extramedullary plasmacytoma. This plasmacytoma might be burned out, namely, overcome by the deposits and no longer recognizable.