Chordoid Meningioma. Case Report and Review of the Literature.

Chordoid meningioma is an uncommon histopathological type of meningioma, frequently associated with Castleman's syndrome. Histologically, chordoid meningiomas are similar to chordomas. Because of their high proliferative index, they present aggressive biological behavior and high risk of postoperative recurrence. We report a case of chordoid meningioma in an adult patient without Castleman's syndrome manifestation. As its chordoid feature is related with a rapid recurrence after incomplete removal, meticulous histopathological examination is crucial for the adequate postoperative treatment plan.

Heterogeneity of histopathological presentation of pilocytic astrocytoma - diagnostic pitfalls. A review.

Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection. However, the behaviour and prognosis might also be related to tumour histology and location. Pilomyxoid astrocytoma (PMA) represents a variant of classical PA with more invasive growth and increased risk of recurrences and dissemination. Typically, PAs exhibit distinct histology with biphasic architecture of loose, microcystic and compact, fibrillary areas. However, some tumours arise in an uncommon location and display heterogeneous histopathological appearance. The morphological pattern of PA can mimic some other glial neoplasms, including oligodendroglioma, pleomorphic xanthoastrocytoma, ependymoma or diffuse astrocytoma. Not infrequently, the advanced degenerative changes, including vascular fibrosis, and recent and old haemorrhages, may mimic vascular pathology. Sometimes, the neoplastic piloid tissue can resemble reactive gliosis, related to long-standing non neoplastic lesions. Not infrequently, PA exhibits histological features typical for anaplasia, including necrosis, mitoses and glomeruloid vascular proliferation that can suggest a diffuse high-grade glioma. However, even those PAs that lack distinct histological features of anaplasia can behave unpredictably, in a more aggressive manner, with leptomeningeal spreading. Genetic alterations resulting in aberrant signalling of the mitogen-activated protein kinase (MAPK) pathway have been considered to underlie the development of PAs. The most commonly identified KIAA1549-BRAF fusion is important for appropriate tumour molecular diagnosis. In this paper we summarize the clinicopathological presentation of PAs, with emphasis on their heterogeneous morphology, based on our own experience in the field of surgical neuropathology and the literature data. Diagnosis of pilocytic tumours requires careful analysis of clinical, histopathological and molecular features to avoid misinterpretation of these benign neoplastic lesions.

Lack of Impact of Presence of Positive C4d Staining in Capillaries in Myocardial Biopsies on Long-term Survival of Heart Transplant Patients.

BACKGROUND: The long-term survival of 209 consecutive patients (mean age, 46 ± 15 years) from a single center with ≥1 diagnostic myocardial biopsy after heart transplantation was analyzed. METHODS: Patients were considered as C4d positive if a capillary staining (immunohistochemistry in paraffin samples) was observed in ≥1 myocardial biopsy. Data were analyzed according to pathologic consensus of antibody mediated rejection definition of C4d+ positivity: 2004 definition in group A and the 2013 definition in group B and compared with their respective controls, composed of patients who do not meet those criteria. Age, follow-up time, and number of biopsies were comparable between patients with C4d+ and controls in both groups. Follow-up was 100% complete with mean of observation time 2143 days. RESULTS: During the follow-up period, 62 patients died (group A: C4d+ 32% vs controls 29%; group B: C4d+ 36% vs controls 29% [P = NS]). There were no differences in survival between patients with positive staining and without C4d+ staining when Kaplan-Meier survival curves were compared. CONCLUSIONS: The presence of C4d positive staining in myocardial capillaries of heart biopsies of patients after heart transplantation, as an isolated finding, was not related to worse long-term survival.

Identification of a novel inherited ALK variant M1199L in the WNT type of medulloblastoma.

Rearrangements involving the ALK gene were identified in a variety of cancers, including paediatric tumour neuroblastoma where presence of ALK expression is also associated with adverse prognosis. Microarrays data indicate that ALK is expressed in another paediatric tumour - medulloblastoma. Therefore, we investigated if the ALK gene is mutated in medulloblastoma and performed simultaneously the molecular profiling of tumours. Tumours from sixty-four medulloblastoma patients were studied for detection of ALK alterations in exons 23 and 25 using Sanger method. The molecular subtypes of tumours were identified by detection of mutations in the CTNNB1 gene, monosomy 6 and by immunohistochemistry using a panel of representative antibodies. Among three ALK variants detected two resulted in intron variants (rs3738867, rs113866835) and the third one was a novel heterozygous variant c.3595A>T in exon 23 identified in the WNT type of tumour. It resulted in methionine to leucine substitution at codon position 1199 (M1199L) of the kinase domain of ALK protein. Results of analysis using three in silico algorithms confirmed the pathogenicity of this single nucleotide variation. The same gene alteration was detected in both patient and maternal peripheral blood leukocytes indicating an inherited type of the detected variant. Presence of ALK expression in tumour tissue was confirmed by immunohistochemistry. The tumour was diagnosed as classic medulloblastoma, however with visible areas of focal anaplastic features. The patient has been disease free for 6 years since diagnosis. This is the first evidence of an inherited ALK variant in the WNT type of medulloblastoma, what altogether with presence of ALK expression may point towards involvement of the ALK gene in this type of tumours.

Erk activation as a possible mechanism of transformation of subependymal nodule into subependymal giant cell astrocytoma.

INTRODUCTION: Subependymal nodule (SEN) and subependymal giant cell astrocytoma (SEGA) are brain lesions frequently found in tuberous sclerosis (TS). As about 10-15% of SENs enlarge and transform into SEGAs, we examined here the possible mechanism of the phenomenon. MATERIAL AND METHODS: Using Western blot we studied 1 SEN and 3 SEGA samples; SEN and 1 SEGA came from the same TS patient. We evaluated e.g. the activation of the phosphorylated forms of proteins belonging to Akt, Erk and mTOR pathways. RESULTS: Differences in Erk pathway activation between SEN and SEGA were found. There was no upregulation of p-Erk, p-Mek or p-RSK1 in the SEN specimen, whilst we found these proteins to be significantly uptriggered in SEGA samples. Also, for the first time, we found p-Akt, p-GSK3 and p-PDK1 upregulated in both SEN and SEGA from the same TS patient. CONCLUSIONS: Our current study shows for the first time the possible mechanism of SEN/SEGA transformation, where Erk pathway hyperactivation seems to be significant. We hypothesize that SEN/SEGA transformation may depend on Erk potentiation.

Pathologic diagnosis of antibody-mediated rejection in endomyocardial biopsy after heart transplantation based on renewed International Society for Heart and Lung Transplantation criteria.

Heart transplantation is a well-established life-saving treatment for patients presenting with end-stage cardiac failure. Despite improved efficacy of the procedure, allograft rejection continues to be a major cause of mortality and morbidity in cardiact allograft patients. Although acute cellular rejection (ACR) is quite unusual nowadays, acute antibody-mediated rejection (AMR) remains a significant problem. The role of pathologists in detection of AMR is very important, especially in sub-clinical cases. In 1990, histologic hallmarks of AMR were first stated by International Society for Heart and Lung Transplantation (ISHLT) and detailed histopathologic features and immunopathologic criteria were established in 2005. Recently (2013) ISHLT revised nomenclature and classification of AMR. Aim of this paper was to present practical changes coming from new criteria as well as to highlight difficulties concerning AMR assessment in endomyocardial biopsies (EMB).

Ovarian small cell carcinoma of hypercalcemic type - evidence of germline origin and SMARCA4 gene inactivation. a pilot study.

Ovarian tumors from two patients, compatible by histological and immunohistochemical criteria with small cell carcinoma of hypercalcemic type (SCCHT) (WT1+, EMA dispersed+, synaptophysin+ or dispersed+), were extensively sampled in order to find clues to their histogenesis. Subsequently, small foci of immature teratoma were found in both of them (in 1/122 and in 3/80 tumor sections). In one case, microfoci of yolk sac tumor were also present within the teratoma area as well as in the background of the small cell tumor population - in the primary tumor and in omental metastasis. We found a resemblance of the microscopic patterns of SCCHT and atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, and this prompted us to evaluate INI-1 and SMARCA4 immunohistochemical expression, because their alternative loss is regarded as a molecular hallmark of AT/RT. INI-1 expression was retained, while that of SMARCA4 was lost. We therefore analyzed tumor DNA by PCR amplification and sequencing for mutations in the SMARCA4 gene (NG_011556.1), which were identified in both tumors (c.2184_2206del; nonsense c.3277C>T - both in one tumor; nonsense c.3760G>T in another tumor). These data suggest that SCCHT is most likely an embryonal tumor originating from immature teratoma and related to malignant rhabdoid tumor. Further analyses are necessary to determine whether the tumors diagnosed as SCCHT constitute a homogeneous group or represent more than one entity.

Atypical teratoid/rhabdoid tumor: short clinical description and insight into possible mechanism of the disease.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor typically appearing in childhood. Differentiation of AT/RT from other brain tumors is extremely important because of grim prognosis and necessity of more aggressive treatment. On the other hand, investigation is essential for new therapeutic agents based on continuously developing knowledge of AT/RT development mechanisms. Most AT/RT tumors have been demonstrated to harbor a chromosome 22 mutation in the region of hSNF5/INI1 gene, whose protein product participates in chromatin remodeling. Although the presence of this mutation is rather undisputable, additional molecular pathways underlying AT/RT development are poorly understood. Current paper discusses current views on molecular pathophysiology of the tumor.

Necrotic rhabdoid meningiomas with aggressive clinical behavior.

Rhabdoid meningioma (RM) is a rare, aggressive variant of meningioma classified as a WHO Grade III malignancy. RM exhibits a striking histological resemblance to other rhabdoid tumors and strong tendency towards local recurrences, CSF dissemination, and/or remote metastasis. The majority of reported cases are of secondary rhabdoid transformation in recurrent meningiomas. We present two unusual cases of rhabdoid meningiomas diagnosed as a primary intracranial lesion in adults that were associated with extensive necrosis and an aggressive clinical course. On histological examination, the majority of the tumor mass was composed of necrotic tissue with focal clusters of neoplastic cells, often localized around blood vessels. Most tumor cells exhibited typical rhabdoid morphology with large, vesicular, often eccentrically located nuclei with distinct nucleoli and abundant cytoplasm containing eosinophilic hyaline inclusions. Classical meningothelial features with focal whorl formation were scarce and seen only in one case; in the second case the tumor was entirely rhabdoid. The differential diagnosis with atypical teratoid/rhabdoid tumors (AT/RTs) and other neoplasms, particularly metastatic carcinoma, was considered. Immunohistochemical and electron microscopic study were critical for the accurate diagnosis of the rhabdoid subtype of meningiomas. Rhabdoid cells stained diffusely positive for vimentin and S-100 protein and showed focal but strong expression of epithelial membrane antigen and cytokeratins. The rhabdoid areas of the tumors exhibited high mitotic activity with a MIB-1 labeling index of 80 - 90%. The diagnosis of rhabdoid meningioma was supported by evidence of SNF5 (INI1) protein expression. Ultrastructural examination demonstrated the presence of interdigitating cell processes joined by numerous desmosomes and paranuclear whorls of intermediate filaments typical of the rhabdoid phenotype. Our two cases of rhabdoid meningiomas were associated with lethal outcome within a few months of initial diagnosis. Extensive necrosis in rhabdoid meningioma might be considered an additional predictor of aggressive clinical behavior.

Apoptotic proteins and markers of differentiation in childhood pineal parenchymal tumors: relationships and prognostic value.

Pineal parenchymal tumors (PPTs) in children and adolescents are uncommon and more data on their biological activity and behavior are still needed. The aim of our study was to estimate the expression and prognostic value of some proteins regulating apoptosis and cell cycle as well as being markers of cellular differentiation in PPTs. Tumor specimens obtained from 27 patients who underwent surgical treatment for PPTs were evaluated in immuno-histochemical analysis. The expression of Bcl-2, Bax, p53, NSE (neuron specific enolase), GFAP (glial fibrillary acidic protein), beta-III tubulin and nestin were studied. Co-localization of two chosen antibodies (e.g. Bcl-2/Bax, BCl-2/NSE, p53/NSE, etc.) was also made with a scanning confocal microscope. Histopathological examination revealed: 15 pineocytomas, 1 intermediately differentiated PPT and 11 pineoblastomas. For further analysis two groups were created: Group I: patients with pineocytoma or intermediately differentiated PPTs (16 cases) Group II: patients with pineoblastoma (11 cases). A statistically significant positive correlation between patients' survival time and tubulin and NSE expression was found. Bcl-2, p53 and nestin correlated negatively with survival time.

Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease.

AIMS: Leigh syndrome (LS) is characterised by almost identical brain changes despite considerable causal heterogeneity. SURF1 gene mutations are among the most frequent causes of LS. Although deficiency of cytochrome c oxidase (COX) is a typical feature of the muscle in SURF1-deficient LS, other abnormalities have been rarely described. The aim of the present work is to assess the skeletal muscle morphology coexisting with SURF1 mutations from our own research and in the literature. METHODS: Muscle samples from 21 patients who fulfilled the criteria of LS and SURF1 mutations (14 homozygotes and 7 heterozygotes of c.841delCT) were examined by light and electron microscopy. RESULTS: Diffuse decreased activity or total deficit of COX was revealed histochemically in all examined muscles. No ragged red fibres (RRFs) were seen. Lipid accumulation and fibre size variability were found in 14 and 9 specimens, respectively. Ultrastructural assessment showed several mitochondrial abnormalities, lipid deposits, myofibrillar disorganisation and other minor changes. In five cases no ultrastructural changes were found. Apart from slight correlation between lipid accumulation shown by histochemical and ultrastructural techniques, no other correlations were revealed between parameters investigated, especially between severity of morphological changes and the patient's age at the biopsy. CONCLUSION: Histological and histochemical features of muscle of genetically homogenous SURF1-deficient LS were reproducible in detection of COX deficit. Minor muscle changes were not commonly present. Also, ultrastructural abnormalities were not a consistent feature. It should be emphasised that SURF1-deficient muscle assessed in the light and electron microscopy panel may be interpreted as normal if COX staining is not employed.

[Tests for loss of heterozygosity in tuberous sclerosis]. / Badania nad utrata heterozygotycznosci w stwardnieniu guzowatym.

The authors assessed loss of heterozygosity in TSC1 and TSC2 genes in three patients undergoing resection of TSC hamartomas: two sub-ependymal giant cell astrocytomas and one kidney angiomyolipoma. Loss with heterozygosity was found only in the patient with kidney angiomyolipoma. A germline mutation, TSC2 E35 645 > A 1549Y > N missense mutation was identified by DHPLC and direct genome sequencing in the blood and loss of the normal allele was demonstrated in the tumor. In one of the patients with brain tumors no germline mutation was identified in the blood, but a heterozygous TSC2 E14 1516C > T 505R > X nonsense mutation was found in the SEGA. Another patient demonstrated germline mutation in TSC2 E38 5116C > T 1706R > C, but tumor DNA indicated that there was retention of heterozygosity for this mutation. The presence of LOH in internal organ tumors is consistent with the Knudson's two-hit model in TS. The frequency of LOH depends on the type of tumor and type of mutation (TSC1 or TSC2).

[Prenatal diagnosis of a brain tumour--an example of diagnostic and therapeutical algorithm].

The authors describe their cooperation in the diagnosis and treatment of a newborn with malignant brain tumour (rare case of carcinoma of the choroid plexus) recognised by means of prenatal sonography and magnetic resonance. The case history is an example of modern algorithm of diagnostic and therapeutic procedures in perinatal medicine and the necessary multicentre collaboration.

[Rasmussen syndrome--indications for surgical treatment of refractory epilepsy: report of two cases]. / Zespól rasmussena--wskazanie do operacyjnego leczenia lekoopornej padaczki. Opis dwóch przypadków.

AIM: Presentation of two cases of children with Rasmussen's encephalitis, treated by functional hemispherectomy. Two boys aged 4 and 6, with a typical clinical course, typical findings in CT and MRI scans and characteristic pathologic changes in brain specimens. In both cases was performed functional hemispherectomy. RESULTS: Immediate cessation of seizures in the immediate postoperative period (Engel class I and II). Later, in a 4-months' follow-up period, a worthwhile improvement in psychomotor development and social functioning was noted. Up-to date opinions published in available literature, related to pathogenesis and treatment modalities of Rasmussen's encephalitis are presented. CONCLUSIONS: 1) Rasmussen's encephalitis is a definite nosologic entity, leading to drug-resistant epilepsy and a progressive psychomotor deterioration; 2) functional hemispherectomy is a viable alternative, which should be considered in the treatment of Rasmussen's encephalitis; 3) Functional; hemispherectomy, in spite of it's aggressiveness, is a relatively safe procedure; 4) in the follow-up time of 4 months, the results are promising.

[Surgical treatment of GnRH secretory hypothalamic hamartomas causing precocious puberty]. / Leczenie chirurgiczne GnRH wydzielniczej postaci hamartoma podwzgórga wywolujacej przedwczesne pokwitanie plciowe.

Hypothalamic hamartomas (HHs) are benign lesions often associated with central precocious puberty. Resection of HHs has been recommended as a treatment option for selected cases, however recent reports stressed the role of effective medical management with a long-acting GnRH agonist. This paper describes incomplete response to the initial GnRH therapy and results of total resection of HHs. Five children two boys and three girls with physical signs of puberty at a mean age of 20.2 months (range 5-36 months) have been treated at our institution. All children had a pedunculated mass below the tuber cinereum. Two children were initially treated with GnRH agonist and had received follow-up care for 11 and 12 months respectively. These patients had incomplete regression of endocrinological disturbances to prepubertal level. Both patients were subsequently operated on. All five children underwent total surgical removal of HHs. The hamartomas were excised through pterional approach. Postoperatively two children showed transient third nerve palsy and one diabetes incipidus. There was no permanent disability due to surgical intervention. The clinical and biochemical symptoms and signs of precocious puberty completely regressed postoperatively including two cases treated initially with GnRH analog. The children have been followed for 1 to 6 years and no recurrence of puberty was observed. Surgical excision of pedunculated HHs is still a valuable option in the treatment of precocious puberty in small children. This alternative should be considered if the initial GnRH therapy failed to suppress++ puberty and reduce bone age advancement.

[Immunohistochemical and ultrastructural studies of subependymal giant cell astrocytomas in children with tuberous sclerosis]. / Badania immunohistochemiczne i ultrastrukturalne podwysciólkowych gwiazdziaków olbrzymiokomórkowych wystepujacych u dzieci ze stwardnieniem guzowatym.

Ten cases of subependymal giant cell astrocytoma associated with sclerosis tuberosa were reevaluated in order to assess their phenotyping and biologic features. All tumours were multifocal, located within lateral ventricles, often overlying the head of the caudate nucleus or protruding into the third ventricle. The phenotype of SGCA disclosed a complex pattern: giant cells were GFAP positive, some of them were stained with antibodies against neurofilament and NSE. Ultrastructurally, the cells of SGCA contained frequent dense bodies, numerous intermediate filaments and microtubules. Biologically SGCA is not malignant, although its appearance may suggest otherwise. No patient had an apparent recurrence within 3-5 years of observation.

[A case of gigantic orbital meningoencephalocele in a newborn]. / Przypadek olbrzymiej przepukliny oponowo-mózgowej w obrebie oczodolu u noworodka.

A case of a gigantic orbital meningoencephalocele in a neonate treated successfully by staged correction is presented. Correction of this congenital malformation enabled a more normal further development of brain and face, and also resulted in a much more acceptable cosmetic appearance. All this had a positive influence on psychomotor development of this child. An overview of pertinent literature is included.

[Craniopharyngioma in childhood. Significance of the extent of surgical resection and adjuvant megavoltage irradiation for event: free survival]. / Czaszkogardlaki wieku dzieciecego. Wplyw rozleglosci resekcji chirurgicznej oraz radioterapii na czas przezycia wolny od wznowy guza.

A series of 81 children with craniopharyngiomas is presented. All patients were operated on between 1981 and 1992. According to the applied treatment the presented group was divided into three distinct categories. 28 patients underwent what was considered by the surgeon to be total excision of their tumour, 27 bad partial excision, in the rest 26 children partial excision of the tumour was followed by local rtgtherapy. The impact on the outcome, the statistically estimated probability of event-free survival, following different type of applied treatment was the main aim of this study. The 5- and 10-year actuarial recurrence free survival rate were 78% and 52% respectively, for total removal group, versus 46% and 28% for partial removal, and 49% and 18% for partial removal followed by megavoltage irradiation. The study show a statistically significant advantage for radial surgical removal of childhood craniopharyngioma in event free survival. It is emphasized that total resection using modern diagnostic and surgical methods is the mainstay for childhood carniopharyngioma. Nearly 87% of pediatric craniopharyngiomas can be totally resected.

[Multiple pleomorphic xanthoastrocytoma tumors in a 12-year-old girl]. / Przypadek mnogich guzów xanthoastrocytoma pleomorphicum u 12-letniej dziewczynki.

This report presents a case of multiple bilateral hemispheric tumours (pleomorphic xanthoastrocytoma) in a practically asymptomatic 12-years-old girl. The tumours were removed radically in a staged procedure, with a favorable clinical outcome. Clinical history and neuropathologic findings are described. A review of pertinent literature is included.

[Results of combined treatment of cerebellar medulloblastomas in children with chemotherapy preceding radiotherapy]. / Wyniki leczenia skojarzonego rdzeniaka mózku u dzieci z zastosowaniem chemioterapii przed rozpoczeciem naswietlan.

153 patients presenting with medulloblastoma between 1980-1992 were treated at the Department of Pediatric Neurosurgery, Child's Health Centre in Warszawa. This group was studied retrospectively and assessed for clinical presentation, histology, treatment regimen and survival. 44 cases treated between 1980 and 1986 underwent surgical resection, postoperative staging evaluation, and craniospinal irradiation, additionally patients assigned to "high risk" group received post-irradiation chemotherapy. Beginning 1986-86 patients with "standard risk" medulloblastoma were treated with preirradiation--"sandwich" chemotherapy consisting of either procarbazine, vincristine and CCNU or "eight drugs a day", followed by megavoltage irradiation, while "high risk" group received also postirradiation chemotherapy. The 5-year actuarial survival rate for all patients was 43%. There were no statistically significant differences in 5-year survival rate between the group treated with preirradiation chemotherapy--52%, and without--54%. The presented group was studied to identify variables of prognostic significance. The extent of disease at the time of diagnosis, as measured by M staging criteria was significantly associated with outcome. The extent of tumour resection, histological subtype of the tumour, postoperative complications, T-staging, and age did not influence the prognosis in the present study.