Chronic Thromboembolic Pulmonary Hypertension Complicated by Giant Pulmonary Artery Aneurysm.

A pulmonary artery (PA) aneurysm is an extremely rare condition that can be idiopathic or secondary. Only a few reports on giant PA aneurysms associated with chronic thromboembolic pulmonary hypertension (CTEPH) are available in the literature. Here, we present a case of CTEPH associated with a secondary giant PA aneurysm detected by autopsy. A 68-year-old woman was diagnosed with pulmonary hypertension (PH) and a PA aneurysm with a diameter of 7.5 cm 7 years before admission. CTEPH was suspected as the cause of PH; however, she refused to undergo surgical treatment. Although her condition improved temporarily with pulmonary vasodilators, she had recurrence of heart failure and died because of the deterioration of her general condition. An autopsy revealed a giant PA aneurysm without medial degeneration, suggesting a secondary PA aneurysm associated with PH. Histological findings indicated multiple organized thrombi with recanalization in the PA bilaterally, and CTEPH was diagnosed as the cause of PH. Although rare, when a PA aneurysm is detected, it is important to consider that CTEPH might be associated with a giant PA aneurysm. A better understanding of this condition is necessary to improve the therapeutic strategy.

Detection rate of clinically significant prostate cancer in magnetic resonance imaging and ultrasonography-fusion transperineal targeted biopsy for lesions with a prostate imaging reporting and data system version 2 score of 3-5.

OBJECTIVES: To evaluate the detection rates of clinically significant prostate cancer classified according to the prostate imaging reporting and data system scoring system using magnetic resonance imaging/ultrasound rigid fusion targeted biopsy. METHODS: A total of 339 patients underwent transperineal magnetic resonance imaging/ultrasound rigid fusion targeted biopsy in our institution between January 2015 and July 2017. Patients with prostate imaging reporting and data system category 1 or 2 and those with a pre-biopsy prostate-specific antigen value of >30 ng/mL were excluded from this study. Finally, 310 patients were recruited. RESULTS: The detection rates of clinically significant prostate cancer with prostate imaging reporting and data system category 3, 4, and 5 were 1.0% (1/98), 35.1% (47/134) and 73.1% (57/78), respectively. The factors affecting the detection of clinically significant prostate cancer with prostate imaging reporting and data system categories 4 and 5 were: (i) prostate imaging reporting and data system category 5; (ii) prostate volume <40 cc; (iii) no previous biopsy; (iv) lesion located in the peripheral zone; and (v) prostate-specific antigen density >0.35 ng/mL/mL. CONCLUSIONS: The detection rate of clinically significant prostate cancer on magnetic resonance imaging/ultrasound rigid fusion targeted biopsy is very low in patients with prostate imaging reporting and data system category 3; therefore, patients with this classification should not undergo targeted biopsy. Prostate-specific antigen density, prostate volume, locations of suspected cancer and history of biopsy should be considered to predict the detection rate of clinically significant prostate cancer with prostate imaging reporting and data system categories 4 and 5.

[Malignant Transformation of Cerebellopontine Angle Epidermoid Cyst:A Case Report].

Intracranial epidermoid cysts are benign cystic lesions that typically exhibit slow growth. Their malignant transformation into squamous cell carcinoma is rare. We report a 77-year-old woman who was admitted to our hospital because of a near-drowning incident due to a seizure sustained in her bathtub. Magnetic resonance imaging(MRI)revealed an extra-axial tumor occupying the right cerebellopontine angle. The lesion appeared hyperintense in diffusion-weighted images and exhibited contrast enhancement after gadolinium injection. Cerebrospinal fluid examination revealed noninfectious meningitis, presumably due to the ruptured epidermoid cyst. Tumor resection was performed and histopathological examination revealed squamous cell carcinoma, which was indicative of malignant transformation of the cyst. The patient underwent adjuvant radiotherapy and has no signs of recurrence 9 months postsurgery. Rapid neurological deterioration and contrast enhancement on MRI are key signs of malignant transformation of epidermoid cysts.

Various Cardiac Abnormalities Caused by Bacterial Myocarditis.

A 69-year-old woman without any past disease history was hospitalized for heart failure. After hospitalization, she showed myocardial infarction, atrioventricular dissociation, and cardiac dysfunction, and finally she passed away despite intensive care. Autopsy revealed that the cardiac abnormalities were due to bacterial myocarditis possibly resulting from urinary tract infection by E. coli. Although bacterial myocarditis is rare in developed countries, we should consider its possibility when patients show various cardiac abnormalities with bacterial infection.

A prospective study of magnetic resonance imaging and ultrasonography (MRI/US)-fusion targeted biopsy and concurrent systematic transperineal biopsy with the average of 18-cores to detect clinically significant prostate cancer.

BACKGROUND: This study compared the detection rates for clinically significant prostate cancer (CSPC) between magnetic resonance imaging and ultrasonography (MRI/US)-fusion-targeted biopsy (TB), systematic biopsy (SB) and combination of TB and SB. METHODS: This prospective study evaluated simultaneous TB and SB for consecutive patients with suspicious lesions that were detected using pre-biopsy multiparametric MRI. A commercially available real-time virtual sonography system was used to perform the MRI/US-fusion TB with the transperineal technique. The prostate imaging reporting and data system version 2 (PI-RADS v2) was assigned to categorize the suspicious lesions. RESULTS: A total of 177 patients were included in this study. The detection rate for CSPC was higher using SB, compared to TB (57.1% vs 48.0%, p = 0.0886). The detection rate for CSPC was higher using the combination of TB and SB, compared to only SB (63.3% vs 57.1%, p = 0.2324). Multivariate analysis revealed that PIRADS v2 category 4 and an age of <65 years were independent predictors for TB upgrading (vs. the SB result). CONCLUSIONS: PI-RADS v2 category 4 and an age of <65 years were predictive factors of upgrading the Gleason score by MRI/US-fusion TB. Thus, MRI/US-fusion TB may be appropriate for patients with those characteristics. TRIAL REGISTRATION: This study was retrospectively registered at the University Hospital Medical Information Network ( UMINID000025911 ) in Jan 30, 2017.

[A case of bladder cancer arising after augmentation cystoplasty using ileal patch for interstitial cystitis].

A 62-year-old man, who was refractory to repeated hydrodistentions for interstitial cystitis, underwent augmentation cystoplasty using ileal patch. Pathological examination revealed no malignancy. Computed tomography (CT) scan showed multiple pelvic and para-aortic lymph-node swellings at 14 months after the operation. CT-guided lymph-nodes biopsies and transurethral bladder biopsies revealed invasive urothelial carcinoma with lymph node metastasis. In patients with symptoms of interstitial cystitis, bladder cancer should be kept in mind despite negative findings of cytology and bladder biopsies.

Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling.

Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a definitive diagnosis. In this case study, we report a 69 year-old female patient for whom the integration of multi-layered molecular analyses contributed to making the diagnosis. The disease exhibited aggressive clinical behavior, requiring two sequential surgeries because of rapid regrowth within a short period. Primary and recurrent tumors exhibited similar histological features, in which spindle-shaped cells arranged in interlacing fascicles without any specific architectures, implicating sarcomatous tumors. In immunohistochemistry testing, tumor cells were immunopositive for vimentin but lacked any specific findings that contribute to narrowing down the differential diagnoses. Seeking further diagnostic clues, we performed DNA methylation-based analysis. The copy number analysis revealed MDM2 gene amplification and loss of heterozygosity of 22q. Moreover, dimension reduction clustering analysis implicated a methylation pattern comparable to aggressive types of sarcomas. In addition, an in-house next-generation sequencing panel ("Todai-OncoPanel") analysis identified somatic mutations in DICER1, NF2, and ATRX genes. Taken all together, we finally made the diagnosis of primary intracranial spindle cell sarcoma, DICER1-mutant, with MDM2 gene amplification. This case report suggests that even for the tumors with insufficient morphological and immuno-histological diagnostic clues, integration of multi-layered molecular analyses can contribute to making the diagnoses as well as to understanding the rare tumors by elucidating unexpected genetic and epigenetic features.

Follicular dendritic cell sarcoma with microtubuloreticular structure and virus-like particle production in vitro.

Neoplasm of follicular dendritic cells (FDC), follicular dendritic cell sarcoma (FDCS), is a rare tumor of intermediate to high-grade malignancy in lymph nodes and visceral organs. Reported herein is a case of FDCS arising from cervical lymph nodes in a 16-year-old Japanese boy, who died of the disease 3 years after diagnosis. The tumor cells were pale eosinophilic and elongated with euchromatic nuclei and were positive for CD21, clusterin, and CNA-42 on immunohistochemistry, as well as desmosome-like junctions on electron microscopy. The presence of microtubuloreticular structures (MTRS) in the tumor cells and associated lymphocytes characterized this case, suggesting some viral infection, although qualitative polymerase chain reaction of genomic and complementary DNA obtained from the tumor failed to demonstrate any viral infection at the laboratory level. The stimulation of dispersed tumor cells and peripheral blood mononuclear cells with mAb to CD3 and interleukin-2 was attempted; and the cell line established by the authors (FDCS-Sa) was stimulated with iododeoxyuridine. Virus-like particles (VLP) were successfully induced from each cellular source. The VLP, 100 nm in diameter, showed an electron-dense thorny envelope and granular core. This is the first case of FDCS with MTRS accompanying VLP production in vitro.

Resection of a lateral supratentorial endodermal cyst complicated by postoperative seizures: A case report.

BACKGROUND: Endodermal cysts are uncommon cystic lesions usually located at the ventral aspects of the spine. A lateral supratentorial location of such cysts is extremely rare. A unique case of a lateral supratentorial endodermal cyst that required surgical intervention due to uncal herniation, complicated with postoperative seizures, is presented. CASE DESCRIPTION: A 48-year-old man presented with transient motor aphasia and diplopia. Magnetic resonance imaging showed a cystic lesion occupying the left frontal and temporal convexity with midline shift and uncal herniation. Cyst resection was performed, and cyst contents with mucous-like components were aspirated. Histopathological examination showed an endodermal cyst. The patient showed no neurological deficits immediately after surgery but developed tonic-clonic seizures 9 h after surgery. Sedation and intubation were required to control the seizures. After administering multiple antiepileptic drugs, he was extubated on the 5th day after surgery. He was discharged home in a month with mild impairment in dexterity of his right hand. CONCLUSIONS: Surgical intervention for endodermal cysts can be complicated by postoperative seizures caused by chemical irritation of brain cortex due to spillage of cyst contents. It is important to irrigate the cyst wall very well intraoperatively and pay attention not to spill the cyst fluid to unaffected locations. Preoperative administration of antiepileptic drugs should also be considered if endodermal cysts, not simple arachnoid cysts, are suspected preoperatively.

Intramedullary and intratumoral hemorrhage in spinal hemangioblastoma: Case report and review of literature.

BACKGROUND: Intramedullary hemorrhages involving spinal hemangioblastomas are rare. They are frequently associated with devastating neurologic outcomes, despite with emergent surgical intervention. Here, we presented an example of an intramedullary hemorrhage occurring in a spinal hemangioblastoma, where the patient markedly improved with surgery. Additionally, the appropriate literature was reviewed (including intraoperative video). CASE DESCRIPTION: A 49-year-old female with a 4-year history of tingling in the left lower extremity presented with vomiting, stepwise worsening of bilateral scapular pain, new upper motor neuron signs, and severe sensory loss bilaterally below C4 on the left and T4 on the right. The magnetic resonance imaging demonstrated a well-circumscribed, uniformly enhancing intramedullary tumor at the C2 level with hyperintensity on the T2 study consistent with acute hemorrhage and cord edema. An urgent C2 laminectomy was performed for gross total tumor resection. Intraoperatively, intramedullary hemorrhage was identified anterior to the tumor mass and was confirmed histopathologically. Postoperatively, the patient had no new sensorimotor deficits and fully recovered within two postoperative months. CONCLUSIONS: Patients presenting with acute intramedullary hemorrhage within hemangioblastomas of the spinal cord may demonstrate significant postoperative neurological recovery.

Gastric neuroendocrine carcinoma with positive staining for prostate cancer markers including prostate-specific antigen and alpha-methylacyl-CoA racemase.

We report a case with prostate cancer and gastric neuroendocrine carcinoma. A 72-year old male presented with a gastric lesion 5 months after radical prostatectomy. The lesion was immunohistochemically positive for PSA, alpha-methylacyl-CoA racemase, synaptophysin, and chromogranin A, but negative for androgen receptor (AR). Differentiating gastric neuroendocrine carcinoma from gastric metastasis of prostate cancer is difficult, as both lesions exhibit similar acinar cell proliferation with prominent nucleoli.1 We discuss the diagnostic process of this case and how AR was a useful specific marker for diagnosing primary gastric neuroendocrine carcinoma.

Expression of keratinocyte growth factor receptor (KGFR/FGFR2 IIIb) in human uterine cervical cancer.

Keratinocyte growth factor receptor (KGFR), also known as FGFR2 IIIb, is a splice variant of FGFR-2. KGFR is expressed in many types of epithelial cell and is activated with four known ligands [FGF-1, FGF-3, FGF-7 (also known as KGF) and FGF-10] that are predominantly synthesized by mesenchymal cells. KGFR is highly expressed in the late-proliferative phase of a normal endometrium and in endometrial adenocarcinoma. In the present study, we attempted to determine the expression and localization of KGFR in human cervical cancer cell lines and cervical cancer tissues. The KGFR protein was detected in CaSki and HeLa cells, but not in ME-180 cells of cervical cancer cell lines. In non-cancer cervical tissues, KGFR immunoreactivity was weakly expressed in the surface of squamous epithelial cells and vascular smooth muscle cells. Immunohistochemically, the KGFR protein was detected in squamous cell carcinoma in 36 of 42 (86%) cervical cancer patients. In cervical cancer tissues, KGFR was detected in 17 of 18 (94%) of patients with the keratinizing type and 19 of 24 (79%) of patients with the non-keratinizing type of cervical cancer. Furthermore, KGFR was prominently localized in proliferating reserve cells and squamous metaplastic reserve cells adjacent to cancer cells. In contrast, KGFR was not detected in cervical ductal cells in cancer or non-cancer cervical tissues. These findings may indicate that KGFR mediates the growth and differentiation of reserve cells and squamous cell carcinoma in the cervix.

Fine needle aspiration cytology of primary epithelioid sarcoma. A report of 2 cases.

BACKGROUND: Epithelioid sarcoma is a rare soft part tumor, the cytologic features of which have not been fully elucidated to date. We describe the cytologic features in 2 cases of primary epithelioid sarcoma with samples obtained by fine needle aspiration (FNA). CASES: Case 1 was a 50-year-old male who complained of a small mass in his left palm. Case 2 was a 56-year-old female who presented with a mass on the medial aspect of her right forearm. Preoperative FNA smears in both cases showed loose, aggregated and isolated tumor cells that were round to polygonal, with eccentrically located nuclei, against a background of inflammation and necrosis. The tumor cells showed moderate atypia, irregularity in size and many mitoses. In case 1 a presumptive diagnosis of epithelioid sarcoma was made by FNA cytology, while in case 2, FNA cytology revealed a high grade sarcoma with abundant matrix mimicking osteoids, difficult to differentiate from an extraskeletal osteosarcoma. CONCLUSION: Epithelioid sarcoma may be difficult to differentiate from an extraskeletal osteosarcoma in cases with abundant hyalinized collagen on FNA cytology.

External whole-body image of EGFP gene expression.

Whole-body optical imaging is an external and noninvasive procedure that enables the continuous visual monitoring of malignant growth and spread within intact animals. The human colon adenocarcinoma cell-line HCT-15 was transfected with a pIRES 2-EGFP vector, and stable enhanced green fluorescence protein (EGFP) expression was established (Fig.1). Approximately 10(6) HCT-15 EGFP stable transfectant cells were subcutaneously injected into the left flank of six-week-old male Balb/c-nu/nu mice. On post-injection day 78, the size of the subcutaneous tumor was 13.1 mm x 15.4 mm in diameter, as observed using an ORCA-C 7780-20 three-chip cooled color charge-coupled-device camera (Hamamatsu Photonics Systems, Hamamatsu City, Japan). An external fluorescent image of the tumor was acquired through the skin (Fig.2B). The tumor could be seen more clearly once the skin was removed (Fig.2D). Furthermore, in the peritoneal metastasis (Fig.3B) and liver metastasis models (Fig.3D), metastasis could also be seen through the skin. This new technology is a useful method for investigating tumor growth in vivo. In the future, this method could be applied to the detection of peritoneal, liver and lung metastasis in living animals.

Pathogenesis and protection of ischemia and reperfusion injury in myocardium.

The important factors that influence the progress of ischemic cardiac lesion are blood flow condition and abnormal cardiac metabolism. Myocardial ischemia is promoted by either an increase in oxygen demand or a shortage of oxygen supply. The Na(+)-Ca(++) ion exchange mechanism is very important for myocardial contraction and cell damage. Na(+)-K(+)ATPase and Ca(++)ATPase are enzyme histochemically localized in subsarcolemmal cisterns, sarcolemmal reticulum and capillary endothelium, and keep myocardial function. These ATPases are impaired by anoxia, superoxides and free radicals. The reduction of O(2) results in the production of superoxides as well as hydrogen peroxide (H(2)O(2)). H(2)O(2) is highly diffusible and induces cell damage. H(2)O(2) appears to affect not only lipids but also intramembranous proteins embedded in the cell membrane. The hydroxyl radical (OH) also participates in lipid hyperoxidation. In the pathogenesis of ischemic and/or reperfused heart disease, ischemia induces rapid or gradual changes in all membrane systems and causes reversible or irreversible injury including necrotic and apoptotic cell death. Advanced glycation end products (AGEs) accumulation induced by diabetic conditioning is an etiologic factor inducing cardiomyopathy. The AGEs protein affects cell changes such as increased number, transformation, functional disturbance and cytokine elimination. In coronary arteries, the migration of smooth muscle cells caused by the taking up of AGEs proteins through the receptor (RAGE), and cytokine discharge are suggested. AGEs accumulation may induce diabetic macroangiopathy through RAGE, and the increase in the level of RAGE expression by endothelial cells could be a reason that diabetes mellitus accelerates atherosclerosis. On the other hand, we also reported that hyperglycemia was a promoting factor of ischemic heart injury in diabetic animals. Ischemic preconditioning is a useful phenomenon that limits myocardial damage. We foused on protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and mitochondrial ATP-dependent potassium (mitoK(ATP)) channel as mediator or end which effector are necessary for adaptation. The opening of the mitoK(ATP) channel induces the depolarization of mitochondria, reducing Ca(++)overload during reperfusion. The regeneration of myocardial cells is confirmed using embryonic stem cells. Myocardial cells that exhibit self-pulsation are generated from mesenchymal stem cells in mesodermal tissues of the bone marrow.

Expression of E-cadherin catenin and C-erbB-2 gene products in invasive ductal-type breast carcinomas.

Special attention has focused on E-cadherin and the invasiveness of breast carcinoma because E-cadherin was suggested to be the major cell adhesion molecule in the mammary gland. In the cytoplasm, E-cadherin is linked to beta-catenin and alpha-catenin which mediate the connection of the cytoskeleton. In addition, c-erbB-2 oncoprotein causes disruption of this cell adhesion system through beta-catenin phosphorylation. We investigated the expression of E-cadherin, alpha-catenin and c-erbB-2 gene products in 66 invasive ductal carcinomas by immuno-histochemistry to examine the relation between the E-cadherin mediated cell adhesion system and histological subtypes used in Japan as well as histological grading. The series included 21 papillotubular carcinomas, 16 solid-tubular carcinomas and 29 scirrhous carcinoma. There were 33 cases of grade I, 20 cases of grade II and 13 cases of grade III. We defined P&P&N as E-cadherin positive and alpha-catenin positive and c-erbB-2 negative cases to evaluate the preservation of the E-cadherin mediated cell adhesion system. There were only 13 cases (19.7%) of P&P&N in total. As for the frequency of E-cadherin/alpha-catenin/c-erbB-2 expression and P&P&N, no significant difference between histological subtypes was found. However, those in the grade I group tended to be higher than in the other two grade groups. Regarding the rates of alpha-catenin positive cases and P&P&N cases, there were significant differences between the grade I group and a combination group consisting of the grade II and grade III groups. These results suggest that the E-cadherin-mediated cell adhesion system is frequently lost in invasive ductal-type breast cancers by random loss of E-cadherin/catenins or c-erbB-2 overexpression, and that the preservation of this system correlates with well differentiated morphological features.

Cavernous sinus angioleiomyoma: case report and review of the literature.

Cavernous sinus angioleiomyoma (ALM) is extremely rare. Only three cases have been reported to be cavernous sinus ALM, and very few reports described characteristic findings for intracranial ALMs in detail. We report a new case of cavernous sinus ALM, with detailed information on the clinical presentation, radiology, pathology, and surgical approach. A 52-year-old woman had a 6-month history of right eye discomfort. Magnetic resonance imaging showed a right cavernous sinus tumor with heterogenous blush enhancement. Enhanced computed tomography scans and angiography showed small nodular enhancement in the tumor. Complete tumor resection was achieved via an extradural temporopolar approach. ALM was identified based on histologic examination. Intracranial ALMs are different from the ALMs that occur in the extremities based on our review of the literature. Intracranial ALMs appear more frequently in men than women. The cavernous type was the most common pathologically, and they occur often in the epiperidural location. Because cavernous sinus ALM occurs in the interdural space, an epidural approach should be selected. Therefore, it is important to include cavernous sinus ALM into a differential diagnosis of a cavernous sinus tumor. The blush enhancement and nodular enhancement within this lesion may be useful to distinguish cavernous sinus ALM from other differential diagnoses.

Treatment strategy for reducing the risk of rituximab-induced cytokine release syndrome in patients with intravascular large B-cell lymphoma: a case report and review of the literature.

INTRODUCTION: Intravascular large B-cell lymphoma is a rare aggressive disseminated disease characterized by the presence of lymphoma cells in small vessels without lymphadenopathy. Rituximab, a novel monoclonal antibody against the CD20 B-cell antigen, has been reported to be effective in treating intravascular large B-cell lymphoma. However, adverse events have been reported in association with rituximab infusion. CASE PRESENTATION: We report the case of a 54-year-old Japanese man diagnosed with Asian variant intravascular large B-cell lymphoma who died within five hours of the initiation of a first course of chemotherapy including rituximab. Autopsy results suggested that the patient died of severe systemic inflammatory response syndrome. A literature review revealed that rituximab administered during the second course of chemotherapy (instead of during the first course) appears to reduce the incidence of infusion reactions (from 48% to 15%) without altering the frequency of complete remission outcomes. CONCLUSIONS: Our data indicate that the incidence of adverse reactions to rituximab can be markedly decreased if the tumor load is first reduced with an initial course of chemotherapy excluding rituximab. Future prospective studies of the timing of rituximab administration are warranted.

Chronic expanding hematoma extending over multiple gluteal muscles associated with piriformis syndrome.

We report on a patient with an unusual, slowly enlarging hematoma of the left buttock. A 62-year-old man presented with a 6-year history of an enlarging mass of the left buttock. He had first noted the mass 6 years earlier and had had sciatica of the left lower limb for the last 2 months. He denied any history of antecedent trauma. The lesion extended over 3 gluteal muscles (the gluteus medius, gluteus minimus, and piriformis). On microscopic examination, the lesion showed typical signs of chronic expanding hematoma. The sciatica was relieved after surgical removal of the lesion. The lesion had not recurred at the last follow-up 4 years after the operation. The present case suggested that chronic expanding hematoma can extend into multiple muscles due, perhaps, to long-term growth and the anatomical and functional conditions of the affected muscles. Our case also suggests that chronic expanding hematoma can be a cause of piriformis syndrome.