Clinicopathological and molecular features of renal cell carcinomas with haemangioblastoma-like features distinct from clear cell renal cell carcinoma.

AIMS: Haemangioblastomas arise in the central nervous system. Rarely, haemangioblastomas may develop in extra-neural sites, such as the kidneys. A few reported cases of renal cell carcinomas (RCCs) with haemangioblastoma-like features have exhibited both clear cell renal cell carcinoma (CCRCC)- and haemangioblastoma-like components. The clinicopathological and molecular characteristics of RCCs with haemangioblastoma-like features were analysed, focusing on VHL alterations, in comparison with CCRCCs partially resembling haemangioblastoma. METHODS AND RESULTS: Four RCCs with haemangioblastoma-like features and five CCRCCs partially resembling haemangioblastoma were included. The RCCs with haemangioblastoma-like features were indolent and lacked adverse prognostic factors. All RCCs with haemangioblastoma-like features had a well-circumscribed appearance and a thick fibromuscular capsule, with fibromuscular bundles extending into the tumour to varying degrees in the three tumours. Each RCC with haemangioblastoma-like features exhibited CCRCC-like areas with indistinct tubular structures and foci of haemangioblastoma-like areas, in which vessels and short spindle cells overwhelmed tumour cells. Whereas haemangioblastoma-like areas in the CCRCCs partially resembling haemangioblastoma exhibited sparse vessels and spindle cells and distinct clear cells. The RCCs with haemangioblastoma-like features exhibited a unique immunohistochemical profile, with positive staining for inhibin-α, S100, carbonic-anhydrase-9, keratin7, and high molecular weight keratin and negative staining for (alpha-methylacyl-CoA racemase) AMACR. RCC with haemangioblastoma-like features did not display any VHL alterations, including VHL mutation, 3p LOH, and methylation of the VHL promoter region, and the two tumours harboured a likely oncogenic missense variant of MTOR (c.7280T>G). CONCLUSION: The histopathological, immunohistochemical, and molecular findings suggest that RCC with haemangioblastoma-like features is a distinct entity from CCRCC.

Live attenuated VZV vaccination induces antitumor immunity in ATLL patients.

Adult T cell leukemia/lymphoma (ATLL) is a CD4-positive peripheral T cell lymphoma caused by human T cell lymphotropic virus type 1 (HTLV-1). Although ATLL is quite difficult to be cured, up-regulation of cellular immunity such as HTLV-1 Tax-specific cytotoxic T lymphocytes (CTLs) has been proved to be important to obtain long-term survival. At present, no efficacious method to activate ATLL-specific cellular immunity is available. This study aimed to investigate whether live attenuated varicella-zoster virus (VZV) vaccination to ATLL can activate HTLV-1 Tax-specific cellular immune response. A total of 3 indolent- and 3 aggressive-type ATLL patients were enrolled. All aggressive-type patients had the VZV vaccination after completing anti-ATLL treatment including mogamulizumab, which is a monoclonal antibody for C-C chemokine receptor 4 antigen, plus combination chemotherapy, whereas all indolent-type patients had the VZV vaccination without any antitumor treatment. Cellular immune responses including Tax-specific CTLs were analyzed at several time points of pre- and post-VZV vaccination. After the VZV vaccination, a moderate increase in 1 of 3 indolent-type patients and obvious increase in all 3 aggressive-type patients in Tax-specific CTLs percentage were observed. The increase in the cell-mediated immunity against VZV was observed in all indolent- and aggressive-type patients after VZV vaccination. To conclude, VZV vaccination to aggressive-type ATLL patients after mogamulizumab plus chemotherapy led to the up-regulation of HTLV-1 Tax-specific CTLs without any adverse event. Suppression of regulatory T lymphocytes by mogamulizumab may have contributed to increase tumor immunity in aggressive-type ATLL patients. Japan Registry of Clinical Trials number, jRCTs051180107.

Pathological features of biopsied myocardium in patients clinically diagnosed with peripartum cardiomyopathy.

The etiology of peripartum cardiomyopathy (PPCM) is unknown. Therefore, we evaluated the etiology of patients clinically diagnosed with PPCM using endomyocardial biopsy. We studied five patients diagnosed with PPCM following endomyocardial biopsy (age, 28-42 years; mean age, 35 years). Biopsied samples were evaluated using microscopy, including immunostaining and electron microscopy. The pathological findings were as follows: myocardial hypertrophy, myocardial fibrosis, and cell infiltration. Two patients were diagnosed with lymphocytic myocarditis, one with eosinophilic myocarditis, one with hypertensive heart disease, and one with a combination of hypertension and myocarditis. Endomyocardial biopsy suggested that the causes of PPCM were varied and related to myocarditis and myocardial overload due to hypertension.

Serum Mac-2 binding protein glycosylation isomer as a biomarker of fibrosis in living donor liver transplant graft.

INTRODUCTION: Non-invasive assessment of graft fibrosis is important in liver transplantation. Mac-2 binding protein glycosylation isomer (M2BPGi) has been reported as a diagnostic marker for this purpose, and thus, this predictive ability of M2BPGi was assessed in this study. PATIENTS AND METHODS: In this retrospective study, 236 patients who received living donor liver transplantation (LDLT) from August 1997 to March 2017 were enrolled. Among them, 94 biopsy patients were analyzed. Further, the predictive ability of fibrotic biopsy using M2BPGi, Fibroscan, and Fib-4 index was compared. RESULTS: Of 94 LDLT patients (53 men, 41 women), the median ages of recipients and donors were 57.5 and 33.0 years, respectively. The median M2BPGi values in patients with F0 (n = 11), F1 (n = 38), F2 (n = 35), and F3/4 (n = 10) were 0.680, 0.760, 1.240, and 4.110 COI, respectively. There were significant correlations between the fibrotic stage and M2BPGi levels (Kruskal-Wallis test, P < .0001). The area under the ROC curve for the diagnosis of F ≥ 2 in M2BPGi was 0.778, which was superior to Fibroscan (0.701) and Fib-4 index (0.639). CONCLUSION: M2BPGi is an accurate, non-invasive detection method for significant fibrosis after LDLT.

Histopathological changes of myocytes in restrictive cardiomyopathy.

Restrictive cardiomyopathy (RCM) is a rare primary myocardial disease, and its pathological features are yet to be determined. Restrictive cardiomyopathy with MHY7 mutation was diagnosed in a 65-year-old Japanese woman. Electron microscopy of a myocardial biopsy revealed electron-dense materials resulting from focal myocyte degeneration and necrosis as well as tubular structures and pseudo-inclusion bodies in some nuclei. These features may be associated with the pathogenesis of RCM.

A case of chronic myocarditis.

Chronic myocarditis is sometimes difficult to diagnose using several clinical diagnostic modalities. A 43-year-old Japanese man was admitted to our hospital with heart failure due to a diffusely hypokinetic left ventricle. No abnormal accumulation was seen on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Coronary angiography showed no abnormalities. Endomyocardial biopsy was performed on suspicion of dilated cardiomyopathy, revealing diffuse cell infiltration (more T lymphocytes associated with macrophages than B cells on immunohistochemical staining), myocyte damage, and replacement fibrosis. The pathological diagnosis of biopsy specimen was difficult to differentiate between chronic myocarditis and inflammatory dilated cardiomyopathy without immunohistochemistry. Endomyocardial biopsy offers one of the most useful methods for diagnosing chronic myocarditis.

Viral load and inflammatory cytokine dynamics associated with the prognosis of severe fever with thrombocytopenia syndrome virus infection: An autopsy case.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. The mechanism underlying disease progression remains unknown, and effective treatment strategy for SFTS is yet to be completely established, making its increasing incidence and subsequent mortality a great concern. Here, we present the autopsy case of a patient with rapidly progressed, fatal SFTS infection. Her viral titer and serum cytokines levels were measured daily and compared with the values of a survivor of the infection. Our findings elucidate the clinical features and pathophysiology of SFTS.

[A Case of Giant Adrenal Endothelial Cyst that was Discovered in Pregnancy and Caused Bleeding Three Years Later].

A 39-year-old woman was referred to our hospital after incidental detection of a hypoechoic abdominal mass on ultrasonography at the 11th week of gestation. Magnetic resonance imaging confirmed a 20 cm cystic lesion just cephalad to the left kidney. The patient delivered in the 40th week of gestation without complications. After 3 years of follow-up, she presented with acute left flank pain. Physical examination revealed pale palpebral conjunctiva and abdominal fullness. Contrast-enhanced computed tomography confirmed a 21 × 17 × 15 cm hemorrhagic cyst arising from the left adrenal gland. Laparoscopic left adrenalectomy was performed. Pathological examination revealed a vascular cyst (endothelial cyst) of the adrenal gland. Surgical intervention is indicated for large adrenal cysts which may cause bleeding into the cavity.

Discordance of hormone receptor, human epidermal growth factor receptor-2, and Ki-67 between primary breast cancer and synchronous axillary lymph node metastasis.

PURPOSE: We herein report the discordance rate between primary breast cancer and synchronous axillary node metastasis, its characteristics and its prognostic impact. METHODS: One hundred and four patients with invasive breast cancer with synchronous axillary node metastasis who underwent surgery were included. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2), and Ki-67 were stained by immunohistochemistry in both primary and node metastasis. The cut-off values of the ER/PgR and Ki-67 labeling index were set at 10% and 14%, respectively. HER2 was classified according to the ASCO/CAP guidelines. RESULTS: Cases positive for ER, PgR, and HER2 were 65.4%, 51.0%, and 27.9% and those with a high Ki-67 labeling index were 47.1% in primary breast cancer, respectively, while they were 47.1%, 30.8%, 16.3%, and 75.0% in node metastasis, respectively. The discordance rates between primary and node were 28.8% for ER (positive in primary→negative in node/negative→positive 22.1%/6.7%), 31.7% for PgR (26.9%/4.8%), 13.5% for HER2 (12.5%/1.0%), and 43.3% for Ki-67 (high in primary→low in node/low→high 12.5%/30.8%). The proportions of labeled cells in primary/node were as follows: ER 42.7%/25.2%, PgR 32.1%/14.0%, Ki-67 20.3%/37.1% (p<0.01 each). Regarding the cut-off value of Ki-67 in node metastasis as defined by a receiver operating characteristic (ROC) analysis, the patients with values >33.2% tended to have a poor recurrence-free survival (RFS) (p=0.08). CONCLUSIONS: The expression of hormone receptors tended to weaken while the proliferative status remained strong in axillary metastasis. A high Ki-67 labeling index in axillary lymph node metastasis may be a risk factor for recurrence.

Early stage signet ring cell carcinoma of the colon examined by magnifying endoscopy with narrow-band imaging: a case report.

BACKGROUND: Signet ring cell carcinoma of the colon and rectum is rare, and most cases are detected at an advanced stage. We present a case of primary signet ring cell carcinoma detected at an early stage by magnifying endoscopy with narrow-band imaging (NBI) and crystal violet staining. CASE PRESENTATION: A 73-year-old man visited our hospital for screening colonoscopy. Six years previously, he had undergone endoscopic submucosal dissection (ESD) for early gastric cancer. The pathological diagnosis was a well-differentiated adenocarcinoma, invading into the mucosa without lymphovascular invasion. Colonoscopy revealed a flat elevated lesion with a slightly depressed area, 20 mm in diameter, in the cecum. Further, magnifying endoscopy with NBI revealed that the surface pattern was slightly irregular and microvessels had a regular diameter and distribution in the margin of the lesion, but in the central part of the lesion, irregularity in the tumor surface pattern and form as well as in the diameter and distribution of microvessels was noted. Additionally, due to mucus, avascular areas were also observed. Magnifying endoscopy combined with 0.05 % crystal violet staining showed IIIL and VI pit patterns in the margin of the lesion, and a VI pit pattern in the central part of the lesion; however, due to mucus exudate, this finding could not be established with certainty. The lesion was successfully removed en bloc using ESD without complications. The tumor was composed mainly of signet ring cell carcinoma, partially mixed with moderately differentiated (tub2) and well-differentiated (tub1) adenocarcinomas. The tumor cells infiltrated 250 µm into the submucosal layer and involved lymphatic vessels. Therefore, the patient underwent an additional laparoscopic ileocecal resection, and the resected specimen revealed no residual carcinoma or lymph node metastasis. CONCLUSION: In this case report, we present a case of primary signet ring cell carcinoma detected at an early stage and identified by magnifying endoscopy with NBI and crystal violet staining.

Diverse Findings in Calcified Thrombus Between Histopathology and In Vivo Imaging Including Intravascular Ultrasound, Optical Coherence Tomography, and Angioscopy.

A 46-year-old woman on hemodialysis due to end-stage renal disease was admitted for repeated thrombus formation in previously implanted drug-eluting stents in the right coronary artery. We could successfully aspirate this thrombus, and histopathology revealed a calcified thrombus comprising multiple microcalcifications and fibrinous materials. This is the first report showing how a calcified thrombus is visualized in vivo by intracoronary imaging modalities including intravascular ultrasound, optical coherence tomography, and angioscopy.

Relationships Between Clinical Characteristics and Decreased Plakoglobin and Connexin 43 Expressions in Myocardial Biopsies From Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Reduced expressions of plakoglobin and connexin 43 have been reported in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the relationships between these expression abnormalities and the clinical features of ARVC remain unknown.The expressions of plakoglobin and connexin 43 in myocardial biopsy specimens from 10 patients with confirmed ARVC, and 13 control patients without ARVC (non-ARVC; hypertrophic cardiomyopathy, n = 7; dilated cardiomyopathy, n = 6), were examined by immunostaining to evaluate the relationships between these expressions and the clinical characteristics of ARVC. The ratios of plakoglobin/N-cadherin and of plakoglobin/connexin 43 expressions were significantly lower in the ARVC group than in the control group. Significantly more patients had decreased plakoglobin expression in the ARVC group than in the control group (9/10 versus 7/13; P = 0.0376). Sustained ventricular tachycardia occurred more frequently in patients with ARVC and with decreased expressions of both plakoglobin and connexin 43 than in those with decreased expression of plakoglobin alone (5/5 versus 1/4, P = 0.048).Decreased expressions of both connexin 43 and plakoglobin in the myocardium might be associated with the development of arrhythmia in ARVC.

Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method.

We developed an easy, quick and cost-effective detection method for lymph node metastasis called the semi-dry dot-blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti-pancytokeratin antibody, modifying dot-blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity and accuracy of the SDB method were 100, 98.0 and 98.3%, respectively (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node-negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2-mm intervals and the sensitivity, specificity, accuracy and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy and mean required time of the SDB method were 93.3, 96.9, 96.6 and 43.3 min, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis.

Hand-assisted laparoscopic subtotal colectomy with cecorectal anastomosis for chronic idiopathic colonic pseudo-obstruction: report of a case.

Chronic idiopathic colonic pseudo-obstruction (CICP) is characterized by the chronic disturbance of colonic motility without mechanical obstruction, any underlying disease or medication. Currently, there are no established medical treatments for CICP. A 62-year-old female who had undergone right hemicolectomy for splenic flexure syndrome caused by idiopathic megacolon was referred to our hospital with relapse, experiencing palpitation and abdominal fullness. She was diagnosed with CICP according to findings of marked dilation of the colon without mechanical obstruction, dilation of other parts of the gastrointestinal tract, or underlying disease. The dilated colon was surgically removed by hand-assisted laparoscopic subtotal colectomy, followed by cecorectal anastomosis. Histopathologically, there was no degeneration or lack of ganglion cells in Auerbach's plexus. The patient has experienced no severe symptoms after undergoing the present operation.

Paraganglioma of the cauda equina: a report of two cases with unusual histopathological features.

Paragangliomas of the cauda equina are very rare. Preoperatively, they are usually diagnosed as schwannoma. We report 2 cases that exhibited unusual histopathologic structure as well as a typical Zellballen pattern with a highly vascular stroma. The unusual features included papillary, ribboning, and pseudorosette patterns, ganglion cell nests, and melanin pigment. Pathological diagnosis of paraganglioma may be especially difficult when such unusual histopathological features are seen. Correct histopathological diagnosis is important as paraganglioma has a better prognosis than other tumors included in the differential diagnosis for this location.

Multiple hepatocellular adenomas in a patient with glycogen storage disease type I: various enhancement patterns in MRI with Gd-EOB-DTPA.

The patient is a 20-year-old man with glycogen storage disease type I (GSD-type I). In his teens, multiple focal hepatic masses were detected on abdominal ultrasonography (US), which were diagnosed as multiple hepatocellular adenomas from the imaging. During follow-up, these masses had shown intermittent growth in size. In the evaluation of Gd-EOB-DTPA (gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid) MR imaging, these masses showed various signal intensities from hypo- to hyperintense during the hepatocyte-specific phase. Intermittent growth and elevation of serum PIVKA-II levels indicate the potential for malignant transformation, so the patient underwent partial hepatectomy. The resected masses were all consistent with benign hepatocellular adenomas histopathologically.

Left sleeve pneumonectomy via a clamshell incision for lung cancer with carinal invasion: report of a case.

Surgery for lung cancer involving the carina is challenging as it requires special surgical techniques and airway management. We report how we successfully treated carinal invasion of primary lung cancer by performing left sleeve pneumonectomy through a clamshell incision, as bilateral thoracotomy through a transverse sternotomy. Without a cardiopulmonary assist device, adequate ventilation and oxygenation were maintained across the operative field with a spinal tube. Tracheo-bronchial anastomosis was relatively easy to perform, with an excellent surgical view. The patient had an uneventful postoperative course and was discharged from hospital without oxygen support. There was no evidence of complications at the anastomosis on chest computed tomography and no sign of recurrence during 6 months of follow-up. The clamshell incision approach provided an excellent surgical view without the need to change the position of the patient during the operation. Thus, it could prove a useful procedure for carinal surgery; especially left sleeve pneumonectomy.