Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Neutropenia related to an azathioprine metabolic disorder induced by an inosine triphosphate pyrophosphohydrolase (ITPA) gene mutation in a patient with PR3-ANCA-positive microscopic polyangiitis
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A 68-year-old Japanese man was monitored for chronic kidney disease (CKD), with unknown primary disease starting in 2014. His serum creatinine (sCr) was stable at ~ 2.5 mg/dL for ~ 2 years. Two weeks before admission, he had bloody sputum, and sCr increased to 4.63 mg/dL. Soon after admission, the patient developed a high fever with pigment spots on the legs. A kidney biopsy was performed. The kidney specimens showed necrotizing and crescentic glomerulonephritis without granuloma formation. An additional blood-sampling test revealed high titers of PR3-ANCA, and we diagnosed PR3-ANCA-positive microscopic polyangiitis (MPA). Treatment with intravenous steroid pulse therapy and intermittent pulse intravenous cyclophosphamide therapy was started for remission induction. With these treatments, sCr improved to ~ 3.0 mg/dL. Azathioprine (AZA) was added for remission-maintenance therapy. Three days later, the dose of AZA was increased from 50 to 100 mg/day, and the number of neutrophils decreased to 30/µL. After withdrawal of AZA, neutrophil levels gradually recovered. We suspected that an abnormal metabolism of AZA was responsible for the neutropenia. Therefore, we analyzed three AZA metabolism-associated genes for mutations: thiopurine S-methyltransferase (TPMT), inosine triphosphate pyrophosphohydrolase (ITPA), and nucleoside diphosphate linked moiety X-type motif 15 (NUDT15), and we identified ITPA 94C>A mutation. This was a rare case of PR3-positive MPA with AZA-induced severe neutropenia that was possibly due to an ITPA gene mutation. This case suggests that ITPA gene mutation is related to the adverse reactions of AZA in Japanese patients. We have to pay attention to severe neutropenia when we use AZA, especially in Asian patients with CKD.
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Histological reassessment of the role of bridging fibrosis in the angioarchitectural features associated with lobular distortion of the liver in chronic viral hepatitis.

AIM: To reassess the role of bridging fibrosis in the lobular distortion of the liver from an angioarchitectural aspect. METHODS: Two tissue samples obtained from surgically resected livers with chronic hepatitis and one obtained from an autopsy case with chronic hepatitis were used for the three-dimensional observation of angioarchitecture by histological reconstruction. RESULTS: Samples showed bridging fibrosis with various degrees of severity, without cirrhotic changes. Two different types of portal-portal bridging fibrosis were found. In our samples, the type that developed in the bifurcation region of the portal tracts was more common than the type observed between the distal portions originating from different parent portal tracts. The angioarchitecture tended to be generally maintained in these lesions. Concerning portal-central bridging fibrosis, two types were observed. One type developed in the lesion with partial paucity of the third-step portal branches in the portal tract at a relatively early stage of chronic hepatitis. The other type developed in an advanced lesion with a complete loss of the normal angioarchitecture of the parenchymal portion of the portal veins. The former was likely developed after large-scale necrosis, such as bridging necrosis, while the latter was presumed to be attributable to portal vein damage associated with long standing chronic inflammation. CONCLUSION: As has been previously noted regarding lobular angioarchitecture, portal-central bridging fibrosis clearly affects the lobular structure of the liver more than portal-portal bridging fibrosis. Therefore, portal vein damage may be a critical event in the eventual distortion of the lobular structure.

Malignant melanoma originating on the female nipple: a case report.

We report a very rare case of malignant melanoma arising on a female nipple. A 42-year-old housewife had suffered from a small dark brown nevus on her left nipple for about thirty years without any changes. Six months before her initial visit it had begun to enlarge and rapidly changed from dark brown to black. A small bleeding ulcer was also present in the center of the lesion. Malignant melanoma rather than mammary Paget's disease was suggested based on its clinical course. Excisional biopsy was performed to differentiate between mammary Paget's disease and malignant melanoma. The histopathological examination revealed malignant melanoma, about 4 mm in thickness. She then underwent wide excision with axillary lymph node dissection. The surgical margin was made in a 3 cm radius around the biopsy site. The excision included nipple, areola, and part of the underlying breast parenchyma, adipose tissue and corresponding superficial layer of fascia. Microscopy showed metastasis in one of 13 axillary lymph nodes. After the operation, the patient received adjuvant DAV-Ferron therapy. In such a case, conserving surgery based on correct diagnosis can achieve a good cosmetic result and optimal tumor control.

Perisacral gastrointestinal stromal tumor with intracranial metastasis. Case report.

A 68-year-old woman presented with an extremely rare intracranial metastasis from a gastrointestinal stromal tumor (GIST) manifesting as left hemiparesis 2 years after resection of a sacral tumor adjacent to the coccygeal bone. Magnetic resonance imaging revealed an intracranial tumor in the right parietal lobe. Craniotomy was performed to completely remove the tumor. Although the tumor was located extra-axially, only internal carotid angiography showed mass staining. Seven months after surgery, the tumor recurred. Repeat craniotomy was performed to remove the recurrent tumor. Immunohistochemical analysis showed that the tumor cells were positive for c-kit and CD34, and the tumors were identified as intracranial metastasis of GIST. Following the second intracranial surgery, the patient developed severe lower back pain caused by metastatic tumor invading the lumbar spine and ureter. To avoid surgical complications and to reduce tumor volume, imatinib mesylate (Gleevec) was administered. The severe pain was relieved, although the tumor was not reduced. In this case, the extra-axial tumor was fed only by the internal carotid artery.

Huge cavernous hemangioma arising in a male breast.

We report a rare case of a huge cavernous hemangioma arising in a male breast. A 60-year-old man first noticed 1 x 2 cm elastic hard nodule just below his right nipple ten years previously. It enlarged 5 x 5 cm over six years. When he came to our clinic, it was size of child head (510 mm in circumference),was an elastic hard with a rather smooth surface, and firmly fixed to the chest wall. Magnetic resonance imaging (MRI) and multidetectocomputed tomography (MDCT)showed a large mass infiltrating into the chest wall. Fine needle aspiration cytology (FNA) and core needle biopsy (CNB) failed to obtain proper material except for old bloody fluid or necrotic connective tissue, precluding a correct diagnosis preoperatively. Mastectomy with partial resection of the chest wall was subsequently performed. Histologically, it was found to be a cavernous hemangioma without cellular atypia. In such a case, complete excision is recommended to exclude the possibility of an underlying malignant lesion.

[A case of non-functional pituitary adenoma associated with Rathke's cleft cyst].

A very rare case of non-functional pituitary adenoma associated with Rathke's cleft cyst is reported. A 42-year-old male suffering from visual disturbance and headache was admitted. Visual acuity was 1.2 on the right and 0.5 on the left, and visual field examination showed bitemporal hemianopsia. Endocrinological study disclosed that the basal serum level of prolactin was elevated slightly to 52.6 ng/ml, whereas those of other hormones were within normal limits. MRI showed a dumbbell-shaped cystic sellar mass extending to the suprasellar region beyond the diaphragm sellae, which consisted of two isolated components around the sellar turcica. At the middle of May, the tumor was partially removed by bifrontal craniotomy. The suprasellar tumor tightly adhered to the frontal lobe and the optic nerve, the tumor was grayish cyst and cyst fluid from the suprasellar mass had the appearance of motor oil and the intrasellar tumor contained old hematoma. Histological findings revealed that the suprasellar mass was Rathke's cleft cyst and the intrasellar mass was diagnosed as pituitary adenoma (non-functional). Visual acuity was improved following surgical operation. So far twenty-three cases of pituitary adenoma associated with Rathke's cleft cysts have been reported in the literature, but there was only one case reported of a non-functional pituitary adenoma associated with a Rathke's cleft cyst. Etiology and pathogenesis of the coexistence of non-functional pituitary adenoma and Rathke's cleft cyst in the present case were not elucidated.

Angiogenesis in atherosclerotic plaque obtained from carotid endarterectomy: association between symptomatology and plaque morphology.

Carotid plaque with hemorrhage leads to cerebral embolism and ischemic stroke. Plaque angiogenesis and angiogenetic factors such as vascular endothelial growth factor (VEGF) are critical in the progression of atherosclerotic carotid plaque and intraplaque hemorrhage. The correlation between plaque angiogenesis and presence of clinical symptoms was studied in 41 specimens obtained during carotid endarterectomy from 20 symptomatic and 21 asymptomatic patients treated for carotid artery stenosis. Histological findings using hematoxylin-eosin and immunohistochemical staining against von Willebrand factor and VEGF were examined. Intraplaque hemorrhage, calcification, necrosis, and invasion of foam cells were frequently observed in the carotid plaques from symptomatic patients compared with asymptomatic patients. Higher microvessel density was found in the carotid plaques with necrosis and invasion of foam cells compared with plaques without necrosis and/or foam cell invasion, and higher expression of VEGF was found from symptomatic patients compared with asymptomatic patents. These results suggest that plaque angiogenesis and higher level of VEGF expression may enhance the progression of ischemic symptoms in patients with carotid artery stenosis. Invasive macrophages in the plaque of symptomatic patients increase levels of VEGF and might enhance plaque angiogenesis and atherosclerosis progression.

Metachronous secondary primary occult breast cancer initially presenting with metastases to the contralateral axillary lymph nodes: report of a case.

We report a rare case of a 64-year-old female with metachronous secondary primary left occult breast cancer initially presenting right axillary lymph node metastases. The patient, who had received breast-conserving therapy for left breast cancer at another hospital about 4.5 years ago, came to our hospital complaining of right axillary node swelling. After both breast and systemic examination, she received complete right axillary lymph node dissection. Just after the operation, she was diagnosed with right occult breast cancer by a review of the right axillary lymph nodes and previous left breast cancer. She was followed by radiation and systemic chemoendocrine therapies. One year after axillary lymph node dissection, mammography and ultrasonography showed a new lesion in her left breast. Core needle biopsy revealed similar findings to right axillary lymph node metastasis. After salvage surgery, the diagnosis was revised. We recommend that patients without clinical findings except for axillary lymph node metastasis, especially post-breast-conserving surgery followed by radiation therapy, should be considered not only as having ipsilateral but also contralateral occult breast cancer. If there is no evidence of a primary lesion, axillary lymph node dissection needs to be carried out, and the patient should be offered the choice of radiation therapy or mastectomy followed by proper systemic therapy.

Early cystoadenocarcinoma of vermiform appendix simulating submucosal tumor of the cecum.

Colonoscopy was performed on a 54-year-old man with occult melena in our hospital. A submucosal tumor with a maximum diameter of 5cm was detected in the cecum. The tissue of the submucosal tumor was not obtained by endoscopic biopsy, and tumor diagnosis could not be confirmed by this method. A large, hypodense, cystic structure extending below the inferior wall of the cecum was revealed by computed tomography (CT). Because the tumor was too large to be a benign tumor, we were able to conclude it was malignant. After receiving informed consent from the patient, laparoscopic right colectomy was performed for both diagnosis and treatment in June 2004. As the swollen vermiform appendix pressed the cecum extraluminally, endoscopic examination indicated the possibility of submucosal tumor. Postoperative pathological diagnosis was cystoadenocarcinoma, the tumor was extended within the mucosal layer, and no lymph node metastasis was detected. Cancer cells were not present in the viscous liquid of the vermiform appendix intracavitary, either. The patient left the hospital in 10 days postoperatively. He regularly underwent examinations including CT, and no recurrence was detected for more than 24 months following the laparoscopic operation.

Primary small-cell neuroendocrine carcinoma of the breast: report of a case.

Primary small-cell neuroendocrine carcinoma of the breast is a rare and aggressive neoplasm without an established treatment protocol because so few cases have been described. We report a case of primary small-cell neuroendocrine carcinoma in a 31-year-old woman. The patient came to our hospital 10 days after consulting another clinic, where a diagnosis of locally advanced breast cancer suitable for neoadjuvant chemotherapy had been made. Core needle biopsy under ultrasonographic guidance revealed invasive carcinoma. The doubling time of the tumor progression was calculated as 12 days based on ultrasonographic measurement. After three cycles of chemotherapeutic regimens consisting of adriamycin plus docetaxel, the disease was judged to be progressive and the patient underwent surgery. Definitive histopathological examination revealed primary small-cell neuroendocrine carcinoma. Local and mediastinal recurrence with multiple liver metastases developed only 5 weeks after surgery. Cisplatin plus irinotecan combination chemotherapy was started; however, the patient died of aggressive recurrent tumor progression 6 months after surgery, in spite of the transient tumor regression achieved by chemotherapy. This case reinforces the importance of an early correct diagnosis and the standardization of a treatment regimen for this very rare tumor.