Node-by-node diagnosis for multiple ipsilateral nodules by segmental adrenal venous sampling in primary aldosteronism.

OBJECTIVES: In patients with primary aldosteronism (PA), multiple adrenocortical nodules may be present on the surgical side. The aim of this study was to clarify the pathological diagnosis and the node-by-node diagnostic capability of segmental adrenal venous sampling (sAVS). DESIGN: Retrospective study. PATIENTS: A total of 162 patients who underwent adrenalectomy following sAVS were studied. MEASUREMENTS: Multiple nodules on the surgical side were extracted while referring to contrast-enhanced computed tomography images. We also performed a detailed histopathological analysis of the resected specimens from patients undergoing sAVS, which included immunohistochemistry for CYP11B2. RESULTS: In 11 (6.8%) patients, two to three nodules were detected on the surgical side. All patients were diagnosed by sAVS with at least one aldosterone-producing adenoma (APA) for localized aldosterone elevation in tributaries. Seven patients showed a lateralization index value of ≥4 after ACTH stimulation. Histopathologically and clinically, two patients had two or three CYP11B2-positive APAs, and the other nine patients both APAs and non-APAs. The positive predictive value of the most suspected APA, that is, the drainer that showed the highest aldosterone level by sAVS, was 11/11 (100%, 95% confidence interval [CI]: 71.5%-100%), while that for the second and third suspected APA was 3/7 (42.9%, 95% CI: 9.9%-81.6%), and they were significantly different (p = .01). Further, the positive predictive value of non-APA was 4/4 (100%, 95% CI: 39.8%-100%). CONCLUSIONS: The sAVS could correctly diagnose the aldosterone production in multiple ipsilateral adrenal nodules.

LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE RENAL CELL CARCINOMA: RETROSPECTIVE ANALYSIS OF SAFETY AND ONCOLOGICAL OUTCOME.

(Objectives) To evaluate the safety and oncologic efficacy of laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) >7 cm, we retrospectively reviewed the clinical outcome and long-term cancer control of patients who underwent LRN in comparison to open radical nephrectomy (ORN). (Patients and methods) The clinical records of 79 patients with RCC >7 cm, who underwent radical nephrectomy (37 LRN; 42 ORN) between 1993 and 2014, were reviewed. (Results) The 2 groups (LRN and ORN) were comparable regarding age, body mass index and mean tumor size (86.5 mm vs. 94.6 mm).The operative time was significantly longer in the LRN group than ORN group (204 min vs. 168 min; p<0.05) and blood loss was significantly lower in the LRN group than in the ORN group (144 ml vs. 930 ml; p<0.05).No statistically significant difference was found in complication rate (10.8% vs. 23.8%) and the 2-year recurrence-free survival rate (85.6% vs. 83.8%). (Conclusion) Despite the longer operative time, LRN for large RCC was associated with lower blood loss. This study provides evidence of the safety and efficacy of LRN for large RCC.

Angiosarcoma of the gallbladder with hemobilia: a case report.

A 61-year-old woman presented to our hospital with epigastric pain. She underwent abdominal contrast-enhanced computed tomography, which showed signal enhancement in the gallbladder fundus. As biliary obstruction was suspected, endoscopic nasobiliary drainage was performed, which revealed hemobilia. Based on this finding, gallbladder tumor was suspected, and open cholecystectomy was performed. Immunohistological staining of the resected tissue was positive for factor VIII that led to the diagnosis of gallbladder angiosarcoma. Hepatectomy and biliary reconstruction were performed for disease control; however, the patient died due to multiple liver metastases 4 months after the surgery.

Neurodegenerative changes in patients with clinical history of bipolar disorders.

Neurodegeneration in bipolar disorder (BPD) is poorly understood. Therefore, the current study was designed to assess the immunohistochemical changes in neurodegenerative markers in patients with BPD. Eleven consecutive autopsy cases diagnosed with BPD were analyzed. Sections were obtained from archival paraffin blocks of representative areas and stained using conventional methods, as well as immunostained with several antibodies to screen for neurodegenerative diseases. Age- and non-argyrophilic grains (AGs) degeneration matched controls were selected for each case. Clinical information was retrospectively collected from medical charts. All patients were men, and the average age of death was 70 years. Neuropathological diagnoses included dementia with grains (2), argyrophilic grain disease (2), corticobasal degeneration (CBD, 1), Lewy body disease (1), hypoxic encephalopathy (1) and cerebral infarction (1). All cases showed AGs to various degrees. Three patients died in their 50s; one demonstrated dementia with Lewy bodies, while the other two showed abundant AGs in the thalamus and amygdala. Of the three patients who died in their 60s, one showed AGs preferentially in the thalamus and amygdala, while the others demonstrated limbic predominance. The patients who died in/after their 70s demonstrated AGs similar to controls, except for the patient with CBD. Our data provides potentiality that neurodegenerative diseases may be an underlying pathology in certain cases of BPD.

A case of crystalglobulin-induced nephropathy wherein M protein was identified by mass spectrometry and immunoglobulin G subclass staining.

Crystalglobulin-induced nephropathy is a rare disease that causes the deposition of crystallized monoclonal immunoglobulins into the glomerular capillary and arteriole spaces. Here, we report the case of a patient who presented with skin ulcers, urinary protein, and renal dysfunction. The patient underwent renal and skin biopsies, and the biopsy tissue samples were subjected to mass spectrometry. The patient was diagnosed with crystalglobulin-induced nephropathy. A literature review suggested that pathological examinations using electron microscopy, mass spectrometry, and immunofluorescent staining of paraffin-embedded biopsy samples treated with pronase may be useful for the diagnosis of this condition.

Inflammatory Myopathy Associated with Anti-mitochondrial Antibody-negative Primary Biliary Cholangitis Diagnosed by a Liver Biopsy.

Anti-mitochondrial antibody (AMA)-associated myopathies represent a homogeneous disease entity with severe arrhythmia and slowly progressive proximal muscle weakness with lordotic posture, irrespective of the presence of primary biliary cholangitis (PBC). We herein report a case of myositis associated with PBC without AMAs. A 48-year-old woman presented with clinical features very similar to AMA-associated myositis, despite negative AMAs. PBC, ascertained by a liver biopsy performed based on mildly elevated liver enzymes, and the efficacy of steroid therapy on muscle weakness confirmed the diagnosis of immune-mediated myositis. When AMAs are negative, a liver biopsy is indispensable for diagnosing treatable PBC-associated myositis.

Active surveillance criteria for prostate cancer: can they be applied to Japanese patients?

Prostate-specific antigen screening has significantly increased the percentage of men who are diagnosed with low-risk prostate cancer. All men undergoing retropubic radical prostatectomy for primary treatment of prostate cancer from April 2004 to September 2010 in our hospital were examined in order to determine whether active surveillance criteria could be applied to Japanese men. From pathological data of prostate biopsies, whether these men met five published criteria for active surveillance (Johns Hopkins Medical Institution, Prostate Cancer Research International: Active Surveillance Study, University of California, San Francisco, Toronto and Kakehi criteria) was evaluated. Men who met any of the criteria had a statistically significant lower extracapsular extension rate and organ-confinement rate. From the view of the possibility of Gleason upgrading and organ-confinement rate, the Johns Hopkins Medical Institution and Prostate Cancer Research International: Active Surveillance Study criteria showed to be appropriate for Japanese patients. However, the present study had limitations of selection bias and a limited number of cases.

[A case of small intestinal stage IV gastrointestinal stromal tumor in which long-term disease control was maintained for more than 10 Years through a multidisciplinary team approach].

The prognosis of metastatic or recurrent gastrointestinal stromal tumors (GISTs) accompanied by multiple hepatic metastases and peritoneal dissemination is very poor. We encountered a case of stage IV small intestinal GIST with multiple hepatic metastases and peritoneal dissemination that were observed after resection of the primary lesion. Multidisciplinary treatments were performed over time, including hepatic resection, radiotherapy, imatinib therapy, sunitinib therapy, and transcatheter arterial chemoembolization, and the disease had been brought under control following resection of a primary lesion 14 years ago. The patient was a 49-year-old woman diagnosed with hemorrhagic stool in July 1998, when a computed tomography scan revealed an 8-cm-diameter tumor in her small bowel. Partial resection of her small bowel was performed and the pathological diagnosis was a high-risk GIST showing 15 mitoses per 50 high power fields. Several metastases developed in the S4 and S5 segments of the patient's liver 3 years after resection of the primary lesion, and a central two-segmental resection of the liver was performed. Furthermore, 1 year after this procedure, peritoneal dissemination developed near the pancreas, for which radiotherapy was performed. Four months later, the patient again developed multiple liver metastases and was started on treatment with 400 mg imatinib per day, achieving a partial response(PR). Five years and 6 months after imatinib initiation, resistance emerged in one of the liver metastases. The patient was switched to sunitinib(50 mg per day), but was diagnosed with progressive disease at the end of the second course and the procedure was discontinued. Treatment with 400 mg of imatinib per day was resumed, and transcatheter arterial chemoembolization was performed twice over a 17-month period for the resistant hepatic region and a PR was achieved each time. We were able to maintain a PR in this patient; other metastases indicated the effectiveness of imatinib therapy. Therefore, a multidisciplinary team approach can be effective in achieving long-term disease control in patients with metastatic or recurrent GIST.

Characteristics of aldosterone-producing adenomas in patients without plasma renin activity suppression.

Primary aldosteronism (PA) usually accompanies suppressed plasma renin activity (PRA) through a negative feedback mechanism. While some cases of PA with unsuppressed PRA were reported, there have been no studies about the characteristics of PA with unsuppressed PRA; thus, these characteristics were examined herein. Nine patients with unsuppressed PRA and 86 patients with suppressed PRA were examined. All patients underwent segmental adrenal venous sampling (sAVS) and adrenalectomy, and were pathologically confirmed to have cytochrome P450 11B2 (CYP11B2)-positive aldosterone-producing adenoma according to international histopathology consensus criteria. Unsuppressed and suppressed PRA were defined as PRA levels of > 1.0 and ≤ 1.0 ng/mL/hr, respectively, in multiple blood samples obtained in the resting position. The unsuppressed PRA group had higher morning cortisol levels (12.6 [8.5, 13.5] vs. 8.5 [7.1, 11.0] µg/dL, P = 0.03) and higher cortisol levels after a 1 mg dexamethasone suppression test (DST) (2.2 [1.6, 2.5] vs. 1.3 [1.0, 1.9] µ g/dL, P = 0.004) than the suppressed PRA group. The unsuppressed PRA group also showed higher aldosterone levels on the non-surgical side during sAVS (P = 0.02 before adrenocorticotropic hormone (ACTH) stimulation, P = 0.002 after ACTH stimulation), a higher intensity of CYP17 expression in the resected adrenal gland (P = 0.02), and a lower clinical complete success rate 1 year after surgery (P = 0.04) compared with those in the suppressed PRA group. These findings suggest that PA should not be ruled out by unsuppressed PRA among patients with hypertension, particularly when their cortisol levels remain unsuppressed in the 1 mg DST. Meanwhile, it should be acknowledged that patients with unsuppressed PRA have higher aldosterone levels on the non-surgical side, and a lower likelihood of postoperative complete clinical success is to be expected.

A case of matrix-producing carcinoma of the breast treated with preoperative chemotherapy.

Background: Matrix-producing carcinoma (MPC) is a rare tumor accounting for 0.1% of all breast cancers. Although MPC is usually triple-negative breast cancer, there have been few reports of preoperative chemotherapy for MPC that is considered chemotherapy-resistant. Herein, we report a case of MPC that was successfully treated with preoperative chemotherapy. Case Description: The patient was a 47-year-old woman diagnosed with right multiple breast cancer, clinical stage IIA. One of the tumors was identified as MPC and the other was invasive ductal carcinoma. The maximum tumor diameter of MPC was 3.8-cm. On immunohistochemistry, the tumor cells of MPC tested negative for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). The Ki67 index was 90%. Preoperative chemotherapy was performed. EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) was administered every 3 weeks for a total of 4 courses, followed by 12 courses of weekly paclitaxel (80 mg/m2). Then, she underwent right skin-sparing mastectomy, sentinel lymph node biopsy, and deep inferior epigastric perforator flap reconstruction. There was no metastasis to the sentinel lymph nodes. Postoperative pathological results showed that the residual tumor of the MPC measured only 0.1 cm. On the other hand, the residual tumor of the invasive ductal carcinoma was 0.7 cm. Endocrine therapy with oral tamoxifen was initiated for the invasive ductal carcinoma. Three years after surgery, no recurrence was observed. It has been reported that prognosis was correlated with residual cancer after preoperative chemotherapy. In addition, preoperative chemotherapy is of high clinical significance for the selection of postoperative treatment. Conclusions: Although our case of MPC was successfully treated with preoperative chemotherapy, the standard of care for MPC remains uncertain. Development of a new targeted therapy for MPC is warranted.

[A case of lung cancer with endometrial metastasis].

A 50-year-old woman was admitted because of chest pain and lumbago. A chest X-ray film showed a 4-cm mass in the left lower lung field. Computed tomography scans revealed a nodule with spicule formation in the left lower lobe, and therefore we strongly suspected lung cancer. Fiberoptic bronchoscopy yielded a diagnosis of adenocarcinoma. However, since she had metrorrhagia we performed an endometrial biopsy. Histologically, the endometrium was similar to the lung lesion, with positive staining for thyroid transcription factor-1 (TTF-1), and lung cancer with endometrial metastasis was therefore diagnosed. Although lung cancer with endometrial metastasis is rare, it should be included in the differential diagnosis in patients with gynecological symptoms such as metrorrhagia.

Hereditary pheochromocytoma/paraganglioma syndrome with a novel mutation in the succinate dehydrogenase subunit B gene in a Japanese family: two case reports.

BACKGROUND: Pheochromocytoma and paraganglioma caused by succinate dehydrogenase gene mutations is called hereditary pheochromocytoma/paraganglioma syndrome. In particular, succinate dehydrogenase subunit B mutations are important because they are strongly associated with the malignant behavior of pheochromocytoma and paraganglioma . This is a case report of a family of hereditary pheochromocytoma/paraganglioma syndrome carrying a novel mutation in succinate dehydrogenase subunit B. CASE PRESENTATION: A 19-year-old Japanese woman, whose father died of metastatic paraganglioma, was diagnosed with abdominal paraganglioma, and underwent total resection. Succinate dehydrogenase subunit B genetic testing detected a splice-site mutation, c.424-2delA, in her germline and paraganglioma tissue. Afterwards, the same succinate dehydrogenase subunit B mutation was detected in her father's paraganglioma tissues. In silico analysis predicted the mutation as "disease causing." She is under close follow-up, and no recurrence or metastasis has been observed for 4 years since surgery. CONCLUSIONS: We detected a novel succinate dehydrogenase subunit B mutation, c.424-2delA, in a Japanese family afflicted with hereditary pheochromocytoma/paraganglioma syndrome and found the mutation to be responsible for hereditary pheochromocytoma/paraganglioma syndrome. This case emphasizes the importance of performing genetic testing for patients with pheochromocytoma and paraganglioma suspected of harboring the succinate dehydrogenase subunit B mutation (that is, metastatic, extra-adrenal, multiple, early onset, and family history of pheochromocytoma and paraganglioma) and offer surveillance screening to mutation carriers.

Multisystem Langerhans cell histiocytosis in an adult non-smoker treated with steroid therapy.

We describe the case of a 29-year-old female non-smoker who was treated with steroid therapy for a subacute exacerbation of multisystem Langerhans cell histiocytosis (MS-LCH) with worsening lung, skin, and oral mucosal lesions. The patient developed pneumonia, and computed tomography (CT) showed multiple thin-walled cavities. Transbronchial lung cryobiopsy (TBLC) specimens revealed Langerhans cells, which were positive for CD1a and S-100 expression. Similar histological findings were detected in the submandibular gland, skin, and tooth. On the basis of these findings, the patient was diagnosed with MS-LCH and subsequently treated with steroid therapy. From the literature review, case reports of non-smokers with pulmonary lesions that worsened and required treatment are rare. Almost all cases recurred and needed additional treatment. This case study contributes to our understanding of the potential role of steroid therapy in MS-LCH treatment. Additionally, TBLC is a novel, potentially safer, diagnostic tool that has not been previously described for LCH.

Clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenza-associated encephalopathy.

BACKGROUND: Influenza-associated encephalopathy (IAE) is one of the most serious CNS complications of an influenza virus infection, with unclear pathophysiology. Clasmatodendrosis is a complex of morphological changes in astrocytes characterized by fragmentation of the distal processes and swollen cell bodies. Although pathologists in Japan have long been aware of the presence of clasmatodendrosis in IAE brains, no details of the phenomenon have been published to date. We aimed to confirm the existence, and characterize the spatial distribution of clasmatodendrosis in postmortem IAE brains. METHODS: Autopsied brains from 7 patients with IAE and 8 non-IAE subjects were examined immunohistochemically. In addition, immunofluorescent staining and electron microscopy were performed. RESULTS: Clasmatodendrosis was present in all examined regions of the IAE brains, but none of the control brains. Fragmented processes of astrocytes in IAE brains were closely adjacent to synapses on the dendritic spines, with the fragmentation especially prominent in the cerebellar molecular layer. In addition, the clasmatodendrotic astrocytes were negative for autophagy markers. Furthermore, whereas aquaporin 4 was predominantly detected in the perivascular endfeet of astrocytes in the control brains, its primary localization site shifted to the fragmented perisynaptic processes in the IAE brains. CONCLUSION: Clasmatodendrosis was distributed diffusely in the IAE brains in close association with synapses, and was not caused by astrocyte autophagy. Clasmatodendrosis may be a suggestive pathological feature of IAE.

Differentiating sclerosing cholangitis caused by autoimmune pancreatitis and primary sclerosing cholangitis according to endoscopic duodenal papillary features.

BACKGROUND: Differentiating primary sclerosing cholangitis (PSC) and sclerosing cholangitis caused by autoimmune pancreatitis (SC-AIP) is often challenging. Recently, endoscopic findings of the duodenal papilla in cases with AIP or PSC were reported by Unno and Parlak, although the endoscopic differentiation of these 2 conditions has not yet been fully clarified. OBJECTIVE: Our purpose was to clarify the endoscopic findings of the duodenal papilla in patients with SC-AIP and those with PSC and to determine criteria for the differentiation of these conditions. DESIGN: Case series. SETTING: Retrospective. PATIENTS: Twenty-seven patients with SC-AIP and 12 patients with PSC who had undergone ERCP were identified from our database. We reviewed these records to determine whether the duodenal papillary findings (swollen papilla/normal papilla/small papilla) might be potentially useful for differentiating SC-AIP and PSC. Immunohistopathological findings for the duodenal papilla were also examined by using immunoglobulin G4 (IgG4) among the infiltrating plasma cells. INTERVENTIONS: ERCP, biopsy specimen taken from duodenal papilla. MAIN OUTCOME MEASUREMENTS: The presence of a swollen duodenal papilla with IgG4-positive plasma cells was useful for discriminating SC-AIP from with PSC. RESULTS: A swollen duodenal papilla was observed in 63% (17/27) of the patients with SC-AIP, whereas there was no swelling of the duodenal papilla of the patients with PSC. A small papilla was recognized in 50% (6/12) of the patients with PSC. IgG4-positive plasma cells in the duodenal papilla were significantly detected in the patients with SC-AIP but not in the patients with PSC. LIMITATION: Single-center study. CONCLUSIONS: Characteristic duodenal endoscopic papillary features in patients with SC-AIP, such as a swollen duodenal papilla and positive immunostaining for IgG4, might be helpful for discriminating this condition from PSC.

Clinicopathologic study of resected cases of primary carcinoma of the cystic duct.

BACKGROUND/AIMS: There have been few reports of primary carcinoma of the cystic duct (CCD) included in advanced cases. The aim of this study was to elucidate the clinical features of resected CCD. METHODOLOGY: Six cases of CCD were diagnosed in which the main carcinomatous component arose from the cystic bile duct, even if these carcinomas were accompanied by invasion beyond the cystic duct. Histopathologic findings (i.e., H.E. staining and cell proliferating potency assessed by ki-67 staining) were compared between the main lesion and invasive lesion of the CCD. RESULTS: Abdominal ultrasonography revealed swelling of the gallbladder in 3 of the 6 patients, but not in the remaining 3, who were later diagnosed as having adenomyomatosis of the gallbladder, dystelectasis due to the carcinomatous infiltration, and atrophic gallbladder, respectively. On computed tomography, 4 of the 6 cases with nodular-type lesions fulfilling Farrar's criteria, the tumors showed contrast enhancement. Direct cholangiography demonstrated unilateral obstruction of the common bile duct in 4 out of the 6 cases. Intraductal ultrasonography revealed CCD in only 1 of the 6 cases. Advanced CCD shows 2 patterns of invasion; the hepatic hilum pattern and the confluence invasive pattern. The hepatic hilum pattern of invasion tends to be associated with a poorer prognosis. Histopathological study revealed papillary and/or well differentiated adenocarcinoma in the cases where the lesion predominantly involved the cystic duct, whereas those lesions which extended beyond the cystic duct were composed of moderate and/or poorly differentiated tubular adenocarcinoma. The latter was associated with a high cellular proliferative activity as assessed by immunocytochemical examination for ki-67. Invasion of the perineural space was often observed in the cases with advanced CCD. CONCLUSIONS: CCD showed the hepatic hilum and/or confluence pattern of invasion when the tumor extended beyond the cystic duct. CCD extending beyond the cystic duct was associated with more aggressive characteristics of the tumors, with perineural infiltration and histopathologic features resembling those of pancreatic cancer. It is concluded that CCDs extending beyond the cystic duct are more aggressive and associated with a poorer prognosis.

Neuroendocrine differentiation in stage D2 prostate cancers.

OBJECTIVES: Chromogranin A (CgA) and neuro-specific enolase (NSE) are gaining acceptance as markers of several types of neuroendocrine tumors and the concentration of CgA and NSE have been reported to be elevated in relation to neuroendocrine differentiation of prostate cancer. The aim of the present study was to examine the correlation between the immunohistochemical (IHC) findings and serum value for CgA and NSE in untreated stage D(2) prostate cancer patients. METHODS: Immunohistochemistry was carried out using antibodies against CgA and NSE in 58 patients and, pretreatment serum CgA and NSE levels were measured by monoclonal immunoradiometric assay in 18 patients with stage D(2) prostate cancer treated by androgen ablation. We examined the relationship of the pretreatment serum level to IHC findings for CgA and NSE in prostate cancer patients to clinicopathological parameters, and prognosis. Also, we evaluated the correlation of IHC findings to serum levels for CgA and NSE. RESULTS: There was a statistically significant correlation between CgA positivity and serum CgA level (P = 0.0421). However, there was no statistically significant correlation between NSE positivity and serum NSE level (P > 0.05). We divided stage D(2) patients into three groups according to IHC positivity of CgA and NSE. The cause-specific survival was significantly poorer in patients with strongly positive (++) patients for independent CgA and combined CgA with NSE (P = 0.0379). Multivariate analysis of cause-specific survivals in patients with stage D(2) prostate cancer demonstrated that strong IHC stain was considered as independent variable associated with greater risk of death (P = 0.0142). CONCLUSION: Neuroendocrine differentiation in stage D(2) prostate cancer has attracted considerable attention as a potentially findings prognosis. Thus, CgA had a stronger relationship between serum levels and IHC positivity in contrast to NSE, suggesting clinical usefulness as a tumor marker in predicting the extent of neuroendocrine differentiation in prostate cancer.

Amiodarone-induced Thyrotoxicosis with Cardiopulmonary Arrest.

We describe a case of amiodarone-induced thyrotoxicosis (AIT) with cardiopulmonary arrest (CPA) in a 49-year-old woman. The patient had been treated with amiodarone for non-sustained ventricular tachycardia. Two weeks prior to her admission, she developed thyrotoxicosis and prednisolone (PSL, 30 mg daily) was administered with the continuation of amiodarone. However, she was admitted to our hospital for CPA. We performed total thyroidectomy to control her thyrotoxicosis and the pathological findings were consistent with type 2 AIT. She gradually improved and was discharged on day 84. This case demonstrates the importance of considering immediate total thyroidectomy for patients with uncontrollable AIT.

A case of PR3-ANCA-positive anti-GBM disease associated with intrarenal arteritis and thrombotic microangiopathy.

Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) is occasionally reported and termed "double positive" disease. Interestingly, the majority of "double positive" ANCA is myeloperoxidase (MPO)-ANCA, and some of the MPO-ANCA-positive cases reveal intrarenal arteritis indicating an ANCA-associated renal lesion. In contrast, proteinase 3 (PR3)-ANCA-positive "double positive" disease had rarely been reported, and as far as we know, none of the cases showed intrarenal arteritis. Herein, we report a case of PR3-ANCA-positive "double positive" anti-GBM disease presenting with pulmonary-renal syndrome and hemolytic uremic syndrome. The kidney biopsy showed crescentic glomerulonephritis, intrarenal arteritis, and thrombotic microangiopathy. This case newly describes PR3-ANCA-associated intrarenal arteritis in "double positive" anti-GBM disease.

Clinical characteristics of aldosterone-producing microadenoma, macroadenoma, and idiopathic hyperaldosteronism in 93 patients with primary aldosteronism.

Primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a form of surgically curable secondary hypertension, and distinguishing APA from idiopathic hyperaldosteronism (IHA) is important for treatment. We made a differential diagnosis between APA and IHA using imaging tests such as adrenal CT and MRI as well as adrenal venous sampling (AVS) in all 93 cases of PA presenting at our institutions over the last decade. We identified 27 patients with aldosterone-producing microadenoma (APmicroA), all of whom could be diagnosed by AVS but not by the imaging tests. Then, we compared the clinical and roent-genological findings of these 27 patients with those of 42 patients with aldosterone-producing macroadenoma (APmacroA) and of 24 patients with IHA. Using surgically removed adrenal tissues, histopathological examinations and immunohistochemical analyses of steroidogenic enzymes were conducted. The findings for APmicroA were similar to those for APmacroA, except with respect to the diameter of the adrenal adenomas. Endocrinological and roentgenological findings for APmicroA were similar to those for IHA, but not to those for APmacroA. The rate of cure of hypertension was much greater in patients with APmicroA than in patients with APmacroA after the unilateral adrenalectomy (odds ratio, 4.0; p=0.028). In conclusion, it is important to accurately diagnose APmicroA, in which the laterality of the hyperproduction of aldosterone is only detectable by AVS, and to treat these patients by unilateral adrenalectomy in order to avoid long-term medical treatment and prevent hypertensive vascular complications.