The Role of von Willebrand Factor, ADAMTS13, and Cerebral Artery Thrombus Composition in Patient Outcome Following Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND The aim of the study was to investigate the role of von Willebrand factor (vWF), the vWF-cleaving protease, ADAMTS13, the composition of thrombus, and patient outcome following mechanical cerebral artery thrombectomy in patients with acute ischemic stroke. MATERIAL AND METHODS A prospective cohort study included 131 patients with ischemic stroke (<6 hours) with or without intravenous thrombolysis. Interventional procedure parameters, hemocoagulation markers, vWF, ADAMTS13, and histological examination of the extracted thrombi were performed. The National Institutes of Health Stroke Scale (NIHSS) score was used on hospital admission, after 24 hours, at day 7; the three-month modified Rankin Scale score was used. RESULTS Mechanical thrombectomy resulted in a Treatment in Cerebral Ischemia (TICI) score of 2-3, with recanalization in 89% of patients. Intravenous thrombolysis was used in 101 (78%). Patients with and without intravenous thrombolysis therapy had a good clinical outcome (score 0-2) in 47% of cases (P=0.459) using the three-month modified Rankin Scale. Patients with a National Institutes of Health Stroke Scale (NIHSS) score ≥15 had significantly increased vWF levels (P=0.003), and a significantly increased vWF: ADAMTS13 ratio (P=0.038) on hospital admission. Significant correlation coefficients were found for plasma vWF and thrombo-embolus vWF (r=0.32), platelet (r=0.24), and fibrin (r=0.26) levels. In the removed thrombus, vWF levels were significantly correlated with platelet count (r=0.53), CD31-positive cells (r=0.38), and fibrin (r=0.48). CONCLUSIONS In patients with acute ischemic stroke, mechanical cerebral artery thrombectomy resulted in a good clinical outcome in 47% of cases, with and without intravenous thrombolysis therapy.

Are goblet cell carcinoids a group of heterogeneous tumors?

BACKGROUND: Goblet cell carcinoids belong to neuroendocrine tumors, according to the WHO classification. The tumors are diagnosed based on a typical histological pattern and using neuroendocrine markers. However, some tumors do not react with these markers and yet expression of proliferative markers is high. Do these tumors belong to G1 and G2 neuroendocrine tumors? METHODS: The sample comprised nine cases of tumors of the appendix identified by immunohistological methods as goblet cell carcinoids or adenocarcinoma ex goblet cell carcinoid. RESULTS: In six cases, hematoxylin and eosin staining revealed tumors completely or 90% made of characteristic large tumor cells observed in typical goblet cell carcinoids. The remaining three cases were identified as adenocarcinomas arising ex goblet cell carcinoids. Immunohistological examination revealed that in four cases of typical goblet cell carcinoids, expression of neuroendocrine markers was low or completely negative. Yet in two cases, the Ki-67 proliferative index exceeded the 20% cut-off for inclusion in the G1 and G2 category. CONCLUSIONS: Goblet cell carcinoids are a heterogeneous group of tumors that may express neuroendocrine markers in a small number of tumor cells or are negative to these markers. However, high expression of the proliferative marker Ki-67 exceeds the criteria for G1 and G2 neuroendocrine tumors. It is our opinion that these tumors may be classified as a specific type of carcinoma.

[Hypoglycemia in a solitary fibrous tumor of the liver]. / Hypoglykémie u solitárního fibrózního tumoru jater.

A 64-year-old patient developed sudden hypoglycemia leading to unconsciousness. Hypoglycemic episodes recurred on several occasions but were not accompanied by unconsciousness. Magnetic resonance imaging revealed a liver tumor in the right lobe sized 20.0 × 14.6 × 19.0 cm. No other masses were detected. Right hemihepatectomy was indicated but could not be performed due to heavy bleeding near the tumor. Histological examination showed a relatively cellular tumor made of elongated bland cells. The mitotic index was fewer than 4 mitoses per 10 HPF. The tumor was without necrosis or hemorrhage. The excised tumor was not encapsulated and showed no signs of invasive growth. On immunohistological examination, the tumor expressed NSE, CD34, CD99, Bcl2 and STAT6; Ki-67 was positive in approximately 20% of the cells. Both the histological pattern and immunophenotype were suggestive of solitary fibrous tumor of the liver. Given its size, cellularity and relatively high expression of the proliferation marker Ki-67, the tumor was classified as potentially malignant. The patient underwent embolization of arteries supplying the tumor with blood. The effect of the procedure on the tumor will only be assessed later. Hypoglycemia has resolved and the patient feels well.

An isolated metastasis to the heart from a malignant phyllodes tumor with osteosarcomatous differentiation.

A 74-year-old woman was admitted in a serious condition due to the failing right heart. A CT scan revealed a tumor infiltration through the interventricular septum in the right heart, spreading from the apex as far as under the tricuspid valve. The tumor penetrated into the conus of the pulmonary artery, bulging and markedly narrowing the lumen. As a result of the tumor infiltration, the patient died from cardiac failure. Histological examination of the tumor revealed atypical elongated cells and areas of large cells with significantly enlarged hyperchromatic and lobulated nuclei. In some portions, the tumors had a biphasic appearance. The tumor cells resembled epithelial tissue but immunohistological analyses to detect cytokeratins yielded negative results. The elongated cells expressed desmin and smooth muscle actin. A vast majority of the tumor was solid or hard, histologically corresponding to osteosarcoma. Later, it was found that the patient undergone right-sided mastectomy for a malignant phyllodes tumor with osteosarcomatous differentiation three years previously. The metastasis to the heart was the only metastasis detected by the autopsy.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT). Report of a case with lymph node metastasis.

UNLABELLED: Uterine tumors resembling ovarian sex cord tumors (UTROSCT) have an uncertain histogenesis. Although generally considered to be benign, they metastasize in some cases. We report the case of a 53-year-old woman who presented with vaginal bleeding. Clinical examination revealed a tumor sized 1.5 cm in diameter localized in the subendometrial region of the uterine wall. Histologically, the tumor consisted of epithelioid oval cells arranged in solid nests, trabeculae and ribbons. Immunohistochemically, approximately 1% of tumor cells expressed strong desmin positivity, calponin in 10% of cells, WT1 in 80% cells, and Ki-67 was positive in about 5 % of tumor cells. All the other immunohistochemical reactions applied including anti-cytokeratin antibodies were negative. The RT-PCR method for identification of the JAZF1-JJAZ1 fusion transcript was negative. In one lymph node in the right iliac artery region, a metastasis of UTROSCT was found. This finding adds to the previously reported UTROSCT cases with metastatic spread. KEYWORDS: uterine tumors resembling ovarian sex cord tumors - UTROSCT - metastasis - lymph node.

[Primary large cell neuroendocrine carcinoma of the urinary bladder]. / Primární velkobunecný neuroendokrinní karcinom mocového mechýre.

Large cell neuroendocrine carcinoma of the urinary bladder is rare. In the last five years, we have had the opportunity to see this type of cancer in an 88-year-old and in a 66-year-old males. In both cases, transurethral resection of carcinoma of the bladder was carried out. In the first case, urothelial carcinoma was detected and deeper in the bladder wall, large cell neuroendocrine carcinoma structures were found. In the second case, the bladder was only infiltrated with large cell neuroendocrine carcinoma. Both tumors expressed NSE, CD56 and synaptophysin. Other markers, such as those against calcitonin, chromogranin, PP, VIP, serotonin, gastrin, glucagon and somatostatin did not react with the tumor. In the first case, no tumor dissemination was found; in the second case, clinical methods confirmed dissemination into the liver, left adrenal gland, spleen and paracaval lymph nodes. Given his age, the first patient only received symptomatic therapy. The other patient underwent chemotherapy and his condition is stable. Paraneoplastic manifestations of the tumors were not clinically found. Histogenetic origin of neuroendocrine tumors is not fully clarified. In some cases, tumor development is thought to be associated with Brunns nests, cystitis cystica and urothelial carcinoma stem cells.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: case report and review of literature.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is a rare condition affecting mostly women in the fifth and sixth decades of life. Here we present a case of its accidental finding in the lung parenchyma of a 56-year-old non-smoker female. In the periphery of the right middle lobe, linear and nodular proliferations were detected in the wall of the small bronchi and terminal and respiratory bronchioles. Under the pleura, several tumorlets were located. Immunohistologically, neuroendocrine cells were positive with antibodies against chromogranin A, synaptophysin, CD56, serotonin (weak positivity of some cells only), calcitonin, GRP/bombesin, cytokeratin 7 and TTF-1.

[Nanopathology as a new scientific discipline. Minireview]. / Nanopatologie - nový vedecký obor. Minireview.

The detection of metal particles in the pathologically altered tissues (eg. in inflammatory lesions or tumors) led to the idea that they might be associated with emergence of some idiopathic diseases. To understand the etiopathogenesis of diseases associated with the presence of nanoparticles in the tissue there is a new area of pathology - nanopathology. Numerous studies have shown that nanoparticles can enter the human body through inhalation or ingestion. Through the pulmonary alveoli, skin and intestinal mucosa, the nanoparticles may reach the blood and lymphatic system, which subsequently distributes them to other target organs. Epithelial surfaces of conjunctiva and skin represent another potential way of penetration of nanoparticles into the body. There is a number of studies, which described the adverse effects of ultrafine particles on respiratory and cardiovascular system. Recent studies have also shown that some nanoparticles are able to pass through the pores of the nuclear membrane, where they may pose a risk of damage to cells and genetic information and they are also potentially capable to cross the placental and hematoencephalic barriers. Further, their role in the induction of oxidative stress is significant in relation to the mutagenesis. Scanning electron microscopy with energy disperse spectroscopy (SEM-EDS) represents a suitable tool for identification of metal-based particles in tissues and body fluids. Importance of nanopathology can be seen in the elucidation of the etiopathogenesis of many diseases, not only of respiratory and cardiovascular systems, but also of many other organ systems.

Primary neuroendocrine carcinoma of the kidney.

BACKGROUND: The objective of the study was to report a rare case of primary neuroendocrine carcinoma of the right kidney in a 36 year old male. METHODS: The patient was clinically assessed; CT and OctreoScan scintigraphy were performed and levels of 5-HIAA, vanillylmandelic acid and NSE were determined. The tumor and metastases were histologically and immunohistochemically examined. RESULTS: The imaging methods showed a cystic tumor in the lower pole of the right kidney. Macroscopically, the entire tumor was sized 8x8x7 cm. Histologically, it was made up of ribbon-line or trabecular patterns of tumor cells. Occasional adenomatoid and cystic structures were present. The tumor cell nuclei were round or oval, with no irregularities and fine lumpy chromatin. The mitotic count was < 1 /10HPF and the proliferation marker Ki-67 was < 1 % of tumor cells. Immunohistochemically, the tumor cells were positive with antibodies against chromogranin A, synaptophysin, CD56 (focally), cytokeratins AE1-AE3 (focally), vimentin (most cells), glucagon (focally), and pancreatic polypeptide (PP; focally). Antibodies against serotonin, somatostatin, gastrin, vasoactive intestinal polypeptide (VIP) and calcitonin did not react with the tumor. The results of biochemical markers (5-HIAA, vanillylmandelic acid and NSE) did not correlate with development or treatment of the tumor. CONCLUSIONS: Primary neuroendocrine carcinoma of the kidney was diagnosed both histologically and immunohistochemically. The patient was clinically investigated using CT and OctreoScan scintigraphy. Within two years from nephrectomy, metastases were found in the right humerus and retrocaval lymph nodes. The metastatic lesions were surgically removed. Currently, the patient's condition is good, with no tumor progression detected.