Cauda equina neuroendocrine tumors show biological features distinct from other paragangliomas and visceral neuroendocrine tumors.

Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.

Calcifying pseudoneoplasm of neuroaxis (CAPNON): a comprehensive immunohistochemical and morphological characterization of five cases.

Calcifying pseudoneoplasm of neuroaxis (CAPNON) is a rare lesion of the central nervous system with uncertain histogenesis. We further explored phenotypic spectrum of the entity with respect to possible histogenesis. We collected 5 cases of CAPNONs, performed a detailed morphological assessment, and performed an extensive immunohistochemical analysis (EMA, progesterone receptors, MUC4, SSTR2A, cytokeratin AE1/3, cytokeratin 18, GFAP, neurofilaments, desmin, nestin, synaptophysin, S100 protein, SOX10, CD56, Podoplanin, SATB2, ERG, CD45, and CD163) to elucidate the histogenesis. Furthermore, we performed NGS analysis of one case. The clinical course was benign in all cases. All lesions showed extensively calcified matrix in multilobular arrangement, with a palisade of osteoblast-like cells. Characteristic fibrohyaline matrix was notable in 4/5 cases, while one case was myxoid with rod-like calcifications. Metaplastic lamellar bone was present in 4/5 cases and psammoma bodies were present in 2/5 cases. In 4/5 cases, areas of entrapped glial tissue were present. Expression of EMA was focally present in 3/5 cases, SSTR2A and nestin in 2/5 cases, and progesterone receptor in 2/5 cases in rare cells. We did not observe concomitant expression of EMA, SSTR2A, and progesterone receptor in the same cellular subsets. In one case, NGS showed multiple chromosomal alterations and missense mutation in PIK3CA, attributable to the admixed meningothelial population compatible with meningioma. In another case, biphasic proliferation with myoepithelial phenotype was present. The lesions showed no lineage-specific immunoprofile. Additional pathology was identified in two cases, furthermore suggestive of a possible reactive origin of the lesion.

Evaluation of expression of somatostatin receptor 1, 2, 3, 5 and dopamine D2 receptor in spindle cell oncocytomas of posterior pituitary.

PURPOSE: Spindle cell oncocytomas (SCOs) are very rare tumors of the posterior pituitary with potential for locally aggressive behaviour. Their treatment includes surgery and possibly radiotherapy, however other options are lacking. Somatostatin receptors (SSTs) are a possible therapeutic target for somatostatin analogues and their expression has been demonstrated recently in closely related pituicytomas, but there are no data about their presence in SCOs. METHODS: We collected five cases of SCO from four patients including one recurrent case. Immunohistochemical detection of TTF1, GFAP, CD68, SST1, SST2, SST3, SST5 and D2 dopamine receptor (D2DR) was performed. Intensity, percentage of positive cells and pattern of expression was evaluated in semiquantitative fashion. Protein expression of SST1-5 and D2DR was further evaluated by western blot. RESULTS: Mean patient age was 61.8 years (range 47-71 years) with male to female ratio 1:1. In one patient, samples from the original tumor and its recurrence 16 years later were assessed. TTF1 was positive in all five cases, no expression of GFAP and CD68 was seen. Immunohistochemical expression of SST1 was noted in 1/5 cases, SST2 in 2/5 cases, including recurrent case but not the original case. SST3 was expressed in 3/5 tumors and D2 dopamine receptor in 4/5 cases. Western blot was successfully performed in four samples. SST2, SST3 and D2DR expression was identified in all the samples, including two cases originally negative for SST2 and one case negative for SST3 by immunohistochemistry. The number of positive cells and level of expression varied among different areas of the same tumors. No expression of SST5 was observed. In the patient with the recurrent tumor, intensity of SST2, SST3 and D2DR expression varied between original tumor and its recurrence. CONCLUSIONS: We demonstrated presence of different SST subtypes and D2DR in spindle cell oncocytomas. The most commonly expressed subtype was SST2 and SST3, while no expression of SST5 was observed. Expression showed spatial heterogeneity and temporal changes as seen in the recurrent case. The biological meaning of SSTs expression in SCOs is unclear as well as whether it may be exploited in treatment of selected cases.

Inhalation of molecular hydrogen prevents ischemia-reperfusion liver damage during major liver resection.

BACKGROUND: Liver resection is a surgical procedure associated with a high risk of hepatic failure that can be fatal. One of the key mechanisms involves ischemia-reperfusion damage. Building on the well-known positive effects of hydrogen at mitigating this damage, the goal of this work was to demonstrate the antioxidant, anti-inflammatory, and anti-apoptotic effects of inhaled hydrogen in domestic pigs during major liver resection. METHODS: The study used a total of 12 domestic pigs, 6 animals underwent resection with inhaled hydrogen during general anesthesia, and 6 animals underwent the same procedure using conventional, unsupplemented, general anesthesia. Intraoperative preparation of the left branch of the hepatic portal vein and the left hepatic artery was performed, and a tourniquet was applied. Warm ischemia was induced for 120 minutes and then followed by liver reperfusion for another 120 minutes. Samples from the ischemic and non-ischemic halves of the liver were then removed for histological and biochemical examinations. RESULTS: An evaluation of histological changes was based on a numerical expression of damage based on the Suzuki score. Liver samples in the group with inhaled hydrogen showed a statistically significant reduction in histological changes compared to the control group. Biochemical test scores showed no statistically significant difference in hepatic transaminases, alkaline phosphatase (ALP), lactate dehydrogenase (LD), and lactate. However, a surprising result was a statistically significant difference in gamma-glutamyl-transferase (GMT). Marker levels of oxidative damage varied noticeably in plasma samples. CONCLUSIONS: In this experimental study, we showed that inhaled hydrogen during major liver resection unquestionably reduced the level of oxidative stress associated with ischemia-reperfusion damage. We confirmed this phenomenon both histologically and by direct measurement of oxidative stress in the organism.

[Melanocytic matricoma--a case report]. / Melanocytární matrikom--kazuistika.

A rare skin tumor (melanocytic matricoma), 6 mm in diameter, was diagnosed on the skin of the back in a 66-year-old man. It was composed of two cellular types: 1. epithelial cells with hair follicle differentiation and 2. dendritic melanocytes. After two years of follow-up there are no signs of a relapse or generalisation of the tumor.

Rare case of a localized radial nerve amyloid neuropathy.

We report the case of a 55-year-old woman with a 6-month history of progressive paresis of the right radial nerve. Perioperative imaging detected a spindle-shaped expansion of the radial nerve caused by an isolated local deposit of amyloid (amyloidoma). The deposit was resected in 2 phases and the resulting defect was bridged by a sural nerve autograft. Overall internal and hematological examination did not reveal systemic amyloidosis or lymphoproliferative disorder. The reason for our report is that localized forms of amyloid neuropathy are very rare.

Histological assessment of tissue from large human bone defects repaired with ß-tricalcium phosphate.

This report describes the histological characteristics of large human bone defects that were implanted with ß-tricalcium phosphate (ß-TCP). Samples were obtained longer after the primary operation than in the earlier studies. We assessed a total of nine biopsies taken 33-208 weeks after implantation. The tissue sections were stained with hematoxylin-eosin for general observation, with Gomori stain to visualize the reticulin fibers, and with an antibody against tartrate-resistant alkaline phosphatase (TRAP) to characterize the cells. Ongoing bone remodeling was observed even 208 weeks after implantation as determined by the presence of osteoclasts and active osteoblasts and new woven and lamellar bone. We observed multinuclear giant cells phagocytosing the biomaterial and the attachment of osteoclasts to the ß-TCP. The osteoclasts showed intense TRAP positivity, while the giant cells showed variable TRAP positivity. There was a zonal pattern in the original defects: The central regions showed granules and fibrous septa, while peripheral areas showed a layer of new bone formation. These data demonstrate ongoing bone remodeling long after implantation in the peripheral regions of the original defects as well as fibrous changes in the central regions and phagocytosis of biomaterial by multinuclear giant cells.

The combination of mesenchymal stem cells and a bone scaffold in the treatment of vertebral body defects.

PURPOSE: Vertebral body defects represent one of the most common orthopedic challenges. In order to advance the transfer of stem cell therapies into orthopedic clinical practice, we performed this study to evaluate the safety and efficacy of a composite bioartificial graft based on a hydroxyapatite bone scaffold (CEM-OSTETIC(®)) combined with human mesenchymal stem cells (MSCs) in a rat model of vertebral body defects. METHODS: Under general isoflurane anesthesia, a defect in the body of the L2 vertebra was prepared and left to heal spontaneously (group 1), implanted with scaffold material alone (group 2), or implanted with a scaffold together with 0.5 million MSCs (group 3) or 5 million MSCs (group 4). The rats were killed 8 weeks after surgery. Histological and histomorphometrical evaluation of the implant as well as micro-CT imaging of the vertebrae were performed. RESULTS: We observed a significant effect on the formation of new bone tissue in the defect in group 4 when compared to the other groups and a reduced inflammatory reaction in both groups receiving a scaffold and MSCs. We did not detect any substantial pathological changes or tumor formation after graft implantation. CONCLUSIONS: MSCs in combination with a hydroxyapatite scaffold improved the repair of a model bone defect and might represent a safe and effective alternative in the treatment of vertebral bone defects.

Atypical lipomatous tumors of the tongue: report of six cases.

The occurrence of liposarcoma in the tongue is rare with only 34 cases published so far. We report six new cases of atypical lipomatous tumor (ALT) of the tongue, and detection of mdm-2 and CDK4 expression by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, was performed. The series comprised three males and three females, aged 11-78 years. The tumors arose at the lateral side of the tongue, and in one case, multiple tumor nodules were noted. Follow-up information in five cases (range from 4 to 159 months) revealed one local recurrence at 6 months. Microscopically, four cases had features of lipoma-like ALT, whereas two cases displayed patterns of sclerosing ALT. Immunohistochemically, tumor cells revealed expression of vimentin (five of five), S100 (five of five), mdm-2 (three of five), and CDK4 (four of five). Two cases were also examined by FISH; amplification of mdm-2 gene was found in both cases, whereas amplification of CDK4 gene was present in one case only. To the best of our knowledge, this is the third largest series reporting occurrence of ALT in the tongue and the first one where analysis of mdm-2 and CDK4 proteins/genes expression/amplification was performed. Both these markers may be of help in the differential diagnosis of ALT versus lipoma. Although most ALTs of the tongue behave in the nonaggressive fashion, they may recur locally. Based on current data, the term ALT is strongly recommended for tumors occurring in the tongue to prevent inadequate treatment.

Bone formation in cardiac valves: a histopathological study of 128 cases.

In a series of 1,177 patients with surgical valve resection, there were 128 (10.9%) patients with the histological finding of bone and/or cartilage formation (bony metaplasia; heterotopic ossification) in the excised valve (119 aortic, 9 mitral). The incidence was higher in men (12.8%) than in women (8.5%). The bony metaplasia was always associated with valvular calcification. The metaplastic changes were encountered in all types of calcific aortic valve disease (senile, bicuspid valve, post-rheumatic). The marrow of the heterotopic lamellar bone was mostly composed of adipose tissue. Frequently, it showed chronic inflammation with polyclonal plasmocytic infiltration. Complete haematopoiesis was present only rarely.

The sinus lift with phycogenic bone substitute. A histomorphometric study.

OBJECTIVES: The aim of this histomorphometric prospective study was to ascertain the efficacy of phycogenic bone substitute in an augmented sinus. The process of graft healing, bone remodeling, and biomaterial replacement was examined. MATERIAL AND METHODS: The phycogenic material (fluorohydroxyapatite) made from calcium-encrusted sea algae was used for the sinus lifts. Twenty-four procedures were carried out (one-stage and two-stage equally) and 45 titanium stepped-screw implants were placed. The patients were followed for 12-23 months. In intervals of 6, 9, 12, or 15 months after the sinus lift, 24 graft specimens were taken with a trephine bur. These specimens were examined histomorphometrically. RESULTS: The grafting material was gradually resorbed and replaced by newly formed bone. Between the sixth and 15th month after the sinus lift, the percentage of newly formed bone grew linearly (from 15.5+/-9.6% to 40.8+/-15.3%) and the percentage of bone substitute decreased linearly (from 34.5+/-8.6% to 13+/-9.6%). After 15 months, the density of trabeculae in grafted bone corresponded to cancellous bone of good quality; however, the bone substitute was not completely resorbed during this period. No significant difference between the quality of the newly formed bone in the cases of the one- and two-stage sinus lifts was found. CONCLUSION: Sinus lift carried out with phycogenic bone substitute was shown to be an effective method with limited invasiveness and a high survival rate of implants (97.8%).