bromochloroacetic-acid and Brain-Neoplasms

Papillary tumor of the pineal region (PTPR) was introduced to the WHO classification in 2007. This rare tumor of little known natural history and unpredictable behavior was described in fewer than 100 cases. Its optimal treatment is not established yet. We report another two cases of PTPR in whom tumors were totally removed via supracerebellar infratentorial approach and both were treated with radiotherapy. In a 37-year-old man the operation was delayed 6 years after the first tumor diagnosis and subsequent shunt placement. He has no complaints 10 years after the onset of the disease. A 45-year-old woman has no complaints 24 months after surgery. Our experience and the data from literature indicate that a total tumor removal is the major prognostic factor.

Topics: Aged; Brain Neoplasms; Carcinoma, Papillary; Female; Humans; Keratins; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Middle Aged; Phosphopyruvate Hydratase; Pineal Gland

Papillary tumour of the pineal region (PTRR) is one of the new tumour entities to be included in the latest World Health Organization classification of central nervous system tumours. We report two illustrative patients, a 25-year-old female who presented following a head injury sustained from a fall due to gait disturbances, and a 42-year-old man who presented with headaches. Histology of both cases showed distinct papillary growth patterns with lining of the papillae by multi-layered cuboidal to columnar cells, prominent perivascular rosette and focal true rosette formation. Immunohistochemistry exhibited strong cytokeratin immunoreactivity in addition to CD56, focal S100, glial fibrillary acidic protein and neuron specific enolase positivity which supported a diagnosis of PTPR in both patients. Postoperatively, both patients underwent courses of adjuvant radiation therapy. One patient reported local recurrence of the tumour 23 months after surgery. While PTPR may have been misdiagnosed in the past, clear and consistent characteristics are beginning to be elucidated in the published reports and literature, which have been reviewed. As a relatively new distinct clinicopathological entity, prognostic data are limited and guidelines for treatment protocols are still being investigated in view of its propensity for local recurrence.

Topics: Actins; Adult; Brain Neoplasms; Carcinoma, Papillary; Female; Humans; Keratins; Magnetic Resonance Imaging; Male; Nerve Tissue Proteins; Pineal Gland; Vision Disorders

Papillary tumor of the pineal region (PTPR) is a newly recognized distinct entity in the 2007 World Health Organization nomenclature. This tumor is characterized by epithelial-appearing areas with papillary features and more densely cellular areas that often display ependymal-like differentiation. Ultrastructurally, this rare neuroepithelial tumor possesses neuroendocrine, secretory, and ependymal organelles that likely originate from the subcommissural organ (SCO) near the aqueduct of Sylvius. To date, approximately fifty-seven described cases worldwide have been recognized, with ages ranging from 5 years to 66 years (mean age=32 years). Clinical presentation most often includes headache and obstructive hydrocephalus. The tumor, which is well circumscribed, may be cystic and radiographically is often considered to be consistent with the findings of a pineocytoma. Microscopic evaluation often demonstrates a lesion with papillary areas lined by epithelioid tumor cells with eosinophilic cytoplasm and more cellular areas with cells exhibiting clear or vacuolated cytoplasm. Perivascular and true rosettes may be identified. Distinctive immunohistochemical features including reactivity for keratins (AE1/AE3, CAM 5.2, CK18) and only focal GFAP staining help distinguish this neoplasm from an ependymoma. The relative paucity of data compiled for this tumor makes giving an accurate diagnosis and prognosis a daunting task. We discuss two additional cases of PTPR that presented to us within a three-month span in order to more fully elucidate the possible presentations of this rare entity. Furthermore, we examine now 59 reported cases of PTPR in order to review the current diagnostic and treatment modalities in addition to exploring emerging research encompassing this unusual neoplasm.

Topics: Adult; Biomarkers; Brain Neoplasms; Carcinoma, Papillary; Female; Humans; Keratins; Male; Middle Aged; Pineal Gland

Epidermoids occurring within the lateral ventricles are rare. At one time, they were regarded as anatomical curiosities. The lesions are of developmental aetiology, due to migration of epiblast inclusion at the time of formation of the cerebral vesicle. They are slow growing, and presentation is non-specific in the form of deteriorating mental functions. Generally seen in the fifth decade, but they have also been observed in the paediatric age group. MRI is suggestive of a cystic lesion, and is confirmed to be a typical epidermoid within the lateral ventricle at operation, often having a connection to the midline through the choroidal fissure. The cysts should be excised with no additional morbidity. Histopathology reveals typical stratified squamous epithelium.

Topics: Brain Neoplasms; Cerebrospinal Fluid Pressure; Cerebrospinal Fluid Shunts; Cholesterol; Cognition Disorders; Disease Progression; Epidermal Cyst; Epithelial Cells; Headache; Humans; Keratins; Lateral Ventricles; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Telencephalon; Treatment Outcome

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cytogenetic Analysis; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Mesothelioma; Neoplasm Metastasis; Neoplasms, Unknown Primary; Peritoneal Neoplasms; Positron-Emission Tomography; Prognosis; Rhabdomyosarcoma; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

A cutaneous meningioma of the external auditory canal occurred in a 48-year-old Filipino woman who had undergone subtotal resection of a dural-based intracranial meningioma at the ipsilateral cerebellopontine angle 36 months previously. Radiologic findings demonstrated a recurrence of intracranial meningioma with surface erosion and heterogeneous densities of the mastoid bone, without extension to the area of the external auditory canal. Meningioma in the external ear canal is extremely rare. To our knowledge, there have been only two previously reported cases, both without intracranial lesion. In this case, the auditory canal lesion may represent either an ectopic meningioma arising from an arachnoid cell rest or an occult direct extension from intracranial menigioma.

Topics: Actins; Brain Neoplasms; Chromogranins; Ear Canal; Female; Humans; Immunohistochemistry; Keratins; Meningioma; Middle Aged; Mucin-1; Neoplasms, Unknown Primary; Skin Neoplasms; Synaptophysin; Tomography, X-Ray Computed

Mesenchymal chondrosarcomas arising in the central nervous system are extremely rare. Morphologic features have not been found to correlate reliably with prognosis.. Eight intracranial and five intraspinal mesenchymal chondrosarcomas were reviewed with regard to location, treatment, and long term follow-up data. The histopathologic and immunohistochemical results, including Ki-67 nuclear staining frequency, were critically reviewed, and deoxyribonucleic acid content was analyzed by flow cytometry.. Microscopically, all 13 cases were remarkably similar. Immunoreactivity in the small cell component included vimentin in 100% and cytokeratin and glial fibrillary acidic protein in 25% of cases. S-100 immunoreactivity was noted in the cartilaginous component of 100% of cases, and in rare cells in the small cell component along the interface. Flow cytometry of the eight tumors studied revealed a diploid pattern in six, aneuploidy in two, and a wide range of S-phase fractions (0-36.5%).. Review of the literature and the findings of the current series indicates that mesenchymal chondrosarcomas presenting in the brain and spinal cord pursue a progressive course that correlates most reliably with extent of surgical resection. This limited retrospective study also suggests that survival may be shorter for those patients with a high S-phase fraction and a high Ki-67 staining frequency.

Topics: Adolescent; Adult; Aged; Aneuploidy; Antigens, Neoplasm; Brain Neoplasms; Child; Chondrosarcoma, Mesenchymal; Diploidy; DNA, Neoplasm; Female; Flow Cytometry; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Neoplasm Proteins; Nuclear Proteins; Prognosis; Retrospective Studies; S Phase; S100 Proteins; Spinal Cord Neoplasms; Survival Rate; Vimentin

The maturation process of basal cells in craniopharyngiomas was studied using a panel of lectins, and antibodies against cytokeratin 13 and bcl-2 protein, using oral mucosa for comparison. Seven lectins were employed: peanut (Arachis hypogaea) agglutinin, Dolichos biflorus agglutinin (DBA), Ulex europaeus agglutinin-I (UEA-I), soybean agglutinin, Ricinus communis agglutinin-I, succinyl wheat germ agglutinin, and Pisum sativum agglutinin. DBA and cytokeratin 13 stainings of the suprabasal cells in craniopharyngiomas were comparable to those of the oral mucosa, but not to those of the skin. Staining patterns of the basal cells in the oral mucosa and craniopharyngiomas were generally similar, but UEA-I binding and bcl-2 protein expression in suprabasal cells differed. The difference appeared to be due to a disturbance in the differentiation of the basal cells, because only a small fraction of the basal cells followed a normal maturation process in craniopharyngiomas in comparison to the oral mucosa. The expression of bcl-2 protein may be involved in the pathogenesis of craniopharyngiomas.

Topics: Binding Sites; Brain; Brain Neoplasms; Craniopharyngioma; Humans; Keratins; Lectins; Mouth Mucosa; Protein Binding

Thymomas are cytologically benign epithelial neoplasms of the thymus gland. They compose 10% of mediastinal tumors, and are most common in the anterosuperior compartment. Seven to 36% of thymomas are malignant, as determined by tissue invasion, yet they metastasize in less than 3% of cases. Distinguishing lymphoma from lymphocyte-predominant thymoma is imprecise due to their histologic similarities. We present a 45-year-old man with intracranial metastatic thymoma. The lesion was interpreted radiographically as meningioma, and as possible lymphoma by frozen section. Flow cytometry proved this neoplasma to be a metastatic thymoma. Sixteen monoclonal antibodies were used to immunophenotype the CD45+ component of this tumor. Coexpression of CD4 and CD8 along with CD1 demonstrated lymphocytes of late cortical thymocyte origin; a second component was cytokeratin positive. This is the first reported case of extrathoracic metastases of thymoma diagnosed using flow cytometry. We propose this method as an invaluable technique to diagnose these histologically difficult neoplasms.

Topics: Aneuploidy; Antibodies, Monoclonal; Antigens, CD; Antigens, Neoplasm; Biomarkers, Tumor; Brain Neoplasms; Combined Modality Therapy; Diagnosis, Differential; DNA, Neoplasm; Flow Cytometry; Frozen Sections; Humans; Immunophenotyping; Keratins; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Male; Meningioma; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Parietal Lobe; T-Lymphocyte Subsets; Thymectomy; Thymoma; Thymus Neoplasms

We report three cases of brain metastases from malignant pleural mesothelioma that were seen at autopsy. We present a summarized review of 15 similar reports that were previously published. Our study included three aged male patients with a long occupational history of heavy asbestos exposure. In two patients, the metastases were discovered incidentally at autopsy, and there were no neurologic symptoms referred to before death. In the other patient, who had clinically occult mesothelioma, the intracranial tumor was discovered ante mortem: in this patient, the clinical features, as well as a computed tomographic scan, suggested a primary tumor of the brain. Interestingly, the histologic features of the latter case that were seen at autopsy depicted a spindle cell tumor that focally exhibited pseudopalisading, necrosis, vascular buds, which deceptively recalled a glioblastoma. All the three cases shared a basic sarcomatous pattern of malignant pleural mesothelioma in both primary and metastatic tumors. The immunohistochemical profile was consistent with such interpretation. It was concluded that metastases to the brain from malignant pleural mesothelioma, although rare, are not exceptional even if their clinical relevance is not prominent. They are seen concomitantly with high-grade tumors, and by mimicking a primary tumor on a clinical, instrumental, and histologic ground, they may occasionally represent a potential source of diagnostic pitfall.

Topics: Adult; Aged; Asbestos; Brain Neoplasms; Female; Humans; Keratins; Male; Mesothelioma; Middle Aged; Neoplasm Metastasis; Pleural Neoplasms; Vimentin

Topics: Brain Neoplasms; Chondroma; Chondrosarcoma; Chordoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mucin-1; S100 Proteins

During the last few years, methods have been developed which permit practical use of biochemical research on the nervous system. In the central nervous system, proteins have been identified for astrocytes (glial fibrillary acidic protein and vimentin) and oligodendroglia (myelin basic protein and other glycoproteins). For certain classes of nerve cells, the neurofilament proteins and neuron-specific enolase (a glycolytic isoenzyme) have been identified. Detection of some of these substances in body fluids is possible via radioimmunoassays (RIA) and in tissue sections using the peroxidase-antiperoxidase immunohistochemical method.

Topics: alpha-Fetoproteins; Animals; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Avidin; Biotin; Body Fluids; Brain Neoplasms; Chorionic Gonadotropin; Desmin; Factor VIII; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Gonadotropin-Releasing Hormone; Humans; Immunoenzyme Techniques; Immunoglobulins; Intermediate Filament Proteins; Isoenzymes; Keratins; Melanins; Myoglobin; Nerve Tissue Proteins; Neurofilament Proteins; Phosphopyruvate Hydratase; Polyamines; Radioimmunoassay; S100 Proteins; Vimentin; von Willebrand Factor

Topics: Brain Neoplasms; Breast Neoplasms; Female; Humans; Immunoassay; Keratins; ROC Curve

Despite potential clinical implications, the complexity of breast cancer (BC) brain metastases (BM) immune microenvironment is poorly understood. Through multiplex immunofluorescence, we here describe the main features of BCBM immune microenvironment (density and spatial distribution) and evaluate its prognostic impact.. Sixty BCBM from patients undergoing neurosurgery at three institutions (2003-2018) were comprehensively assessed using two multiplex immunofluorescence panels (CD4, CD8, Granzyme B, FoxP3, CD68, pan-cytokeratin, DAPI; CD3, PD-1, PD-L1, LAG-3, TIM-3, CD163, pan-cytokeratin, DAPI). The prognostic impact of immune subpopulations and cell-to-cell spatial interactions was evaluated.. Subtype-related differences in BCBM immune microenvironment and its prognostic impact were observed. While in HR-/HER2- BM and HER2+ BM, higher densities of intra-tumoral CD8+ lymphocytes were associated with significantly longer OS (HR 0.16 and 0.20, respectively), in HR+/HER2- BCBMs a higher CD4+FoxP3+/CD8+ cell ratio in the stroma was associated with worse OS (HR 5.4). Moreover, a higher density of intra-tumoral CD163+ M2-polarized microglia/macrophages in BCBMs was significantly associated with worse OS in HR-/HER2- and HR+/HER2- BCBMs (HR 6.56 and 4.68, respectively), but not in HER2+ BCBMs. In HER2+ BCBMs, multiplex immunofluorescence highlighted a negative prognostic role of PD-1/PD-L1 interaction: patients with a higher percentage of PD-L1+ cells spatially interacting with (within a 20 µm radius) PD-1+ cells presented a significantly worse OS (HR 4.60).. Our results highlight subtype-related differences in BCBM immune microenvironment and identify two potential therapeutic targets, M2 microglia/macrophage polarization in HER2- and PD-1/PD-L1 interaction in HER2+ BCBMs, which warrant future exploration in clinical trials.

Topics: B7-H1 Antigen; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Female; Forkhead Transcription Factors; Humans; Keratins; Lymphocytes, Tumor-Infiltrating; Prognosis; Programmed Cell Death 1 Receptor; Tumor Microenvironment

Gamma-glutamyltransferase (GGT) and keratins (KRT) are key factors in regulating tumor progression rely on emerging evidence. However, the prognostic values of GGT and KRT isoforms and their regulation patterns at transcriptional and post-transcriptional levels have been rarely studied. In this study, we aimed to identify cooperative prognostic biomarker signature conducted by GGT and KRT genes for overall survival prediction and discrimination in patients with low-grade glioma (LGG) and glioblastoma multiforme (GBM). To this end, we employed a differential expression network analysis on LGG-NORMAL, GBM-NORMAL, and LGG-GBM datasets. Then, all the differentially expressed genes related to a GO term "GGT activity" were excluded. After that, for obtained potential biomarkers genes, differentially expressed lncRNAs were used to detect cis-regulatory elements (CREs) and trans-regulatory elements (TREs). To scrutinize the regulation on the cytoplasm, potential interactions between these biomarker genes and DElncRNAs were predicted. Our analysis, for the first time, revealed that GGT6, KRT33B, and KRT75 in LGG, GGT2, and KRT75 in GBM and KRT75 for LGG to GBM transformation tumors can be novel cooperative prognostic biomarkers that may be applicable for early detection of LGG, GBM, and LGG to GBM transformation tumors. Consequently, KRT75 was the most important gene being regulated at both transcriptional and post-transcriptional levels significantly. Furthermore, CREs and their relative genes were coordinative up-regulated or down-regulated suggesting CREs as regulation points of these genes. In the end, up-regulation of most DElncRNAs that had physical interaction with target genes pints out that the transcripted genes may have obstacles for translation process.

Topics: Biomarkers, Tumor; Brain Neoplasms; gamma-Glutamyltransferase; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioma; Humans; Keratins; Protein Isoforms

We describe a cytokeratin positive interstitial reticulum cell tumor (CPIRCT) as the cause of a large and defacing scalp tumor. Clinically these tumors manifest as progressive, painless swelling. Treatment usually consists of surgery with or without irradiation; chemotherapy is applied in metastatic disease.. A patient was referred after attempted removal of a large bump on the head. The tumor was initially noted about 12 months earlier. Assuming a benign lipoma, resection without prior imaging was attempted. During surgery, the underlying bone was found to be profoundly destroyed. Cranial magnetic resonance imaging revealed a large mass with an extracranial and intracranial component. Subsequent extensive resection finally led to the diagnosis of CPIRCT.. Most CPIRCTs manifest as progressive palpable or visible masses. Radical excision is usually the mainstay of treatment, although there is no generally accepted treatment strategy. A needle biopsy might not be diagnostic and can complicate future curative surgery. Especially in fast-growing lesions, imaging studies should be considered before surgery. Their potential recurrence and metastatic spread render CPIRCTs an interdisciplinary challenge and highlight the need for long-term follow-up.

Topics: Adult; Brain Neoplasms; Diagnostic Errors; Head and Neck Neoplasms; Humans; Keratins; Lipoma; Magnetic Resonance Imaging; Male; Scalp; Skull Neoplasms

Currently used glioblastoma cultures have many disadvantages and are being replaced by short-term cultures. However, these may include normal brain cells.. A comparative model of normal and glioma cultures is lacking. A significant contributory factor is because cultures from adult human brain contain small amounts of cells with glial phenotypes. The predominant population of flat or spindle shaped cells does not express glial markers and are often termed as "glia-like".. Cryopreserved glioblastoma cultures from 28 bioptic samples were examined by immunofluorescence using antibodies to intermediate filaments (IF): glial fibrillary acidic protein (GFAP), cytokeratins (CK), nestin (Nes), vimentin (Vim) and neurofilaments (NF).. In short-term glioblastoma cultures GFAP-positive cells occured at higher percentages in 3/28 cultures and in lower percentages in further 5 cultures. Subpopulation of nestin positive cells were observed in all cultures and CK-positive cells were found in 25/28 cultures. All cells in all cultures were positively stained only for vimentin and negatively for NF. Cells grew slowly in 5 cultures which showed early proliferation arrest between passages 7 to 8. A further 23 cultures showed growth arrest by passages 10 to 15.. The presence of normal cells in short-term glioblastoma cultures may be caused by the infiltrative growth of these tumors. Our comparative analysis of morphological, growth and cytoskeletal properties revealed similarities between glioblastoma and normal brain cultures. In this study, the majority (28/30) of short-term glioblastoma showed limited life spans, similar to normal cells lacking spontaneous immortalization. The use of short-term glioblastoma cultures has two main problematic areas: cultures may contain a major subpopulation of normal "glia-like" cells; or they may contain the inital phases of spontaneously immortalized glioblastoma cells bearing properties of permanent cell lines (Tab. 1, Fig. 2, Ref. 19).

Topics: Brain Neoplasms; Glial Fibrillary Acidic Protein; Glioblastoma; Glioma; Humans; Intermediate Filaments; Keratins; Nestin; Neuroglia; Tumor Cells, Cultured; Vimentin

Astroblastoma is a rare neuroepithelial neoplasm of unknown origin, usually occurring in children and young adults. Here we report a case of astroblastoma with uncommon features in an 18-year-old female. The tumor was a well-circumscribed cystic and solid mass with marked gadolinium enhancement in the right frontal lobe. Cytological examination showed polarized monopolar cells with diminished cohesiveness. Tumor cells possessed eccentric round to oval nuclei with abundant eosinophilic cytoplasm, sometimes having cytoplasmic processes. Histopathologically, the tumor showed perivascular pseudorosettes with prominent vascular sclerosis. Foam cells were frequently infiltrated around blood vessels and among tumor cells. In some areas, a solid growth pattern of plump tumor cells with abundant inclusion-like eosinophilic cytoplasm showing rhabdoid appearance was observed. The immunohistochemical study revealed strong and diffuse positivity for vimentin and epithelial membrane antigen. Tumor cells were focally positive for glial fibrillary acidic protein and cytokeratin AE1/AE3. Nuclear immunoreactivity for INI1 protein was evident. The Ki-67 labeling index was 10.8%. This tumor was finally diagnosed as low-grade astroblastoma and the patient had no evidence of recurrence without postoperative radiotherapy or chemotherapy during the last 6 months of follow-up. This report describes novel cytological, histopathological, and immunohistochemical features of the rare tumor.

Topics: Adolescent; Biomarkers, Tumor; Brain Neoplasms; Female; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Keratins; Ki-67 Antigen; Mucin-1; Neoplasm Grading; Neoplasms, Neuroepithelial; Rhabdoid Tumor; Treatment Outcome; Vimentin

Atypical teratoid/rhabdoid tumors are rare malignant pediatric brain tumors. This study was performed to characterize the clinicopathologic and neuroradiologic characteristics of atypical teratoid/rhabdoid tumors from 8 patients, including 5 male and 3 female infants (median age, 67 months). Neuroimaging revealed bulky masses of heterogeneous intensity with inhomogeneous enhancement. Three cases were infratentorial and 5 were supratentorial. Histopathologically, the tumors were predominantly composed of rhabdoid cells and undifferentiated small cells, mixed with some spindle or epithelial components. The tumors displayed striking polyphenotypic immunoreactivity, including varying degrees of positivity for vimentin, epithelial membrane antigen, smooth-muscle actin, cytokeratin, glial fibrillary acidic protein, neurofilament protein, synaptophysin, and CD99, and immunonegativity for desmin, placental alkaline phosphatase, and INI-1. The median survival duration was 9.5 months (range, 1-15 months) despite aggressive therapy. These results suggest that atypical teratoid/rhabdoid tumors display distinct clinicopathologic characteristics and indicate a poor prognosis. Immunohistochemistry facilitates the appropriate diagnosis of these tumors.

Topics: 12E7 Antigen; Adolescent; Antigens, CD; Brain Neoplasms; Cell Adhesion Molecules; Child; Child, Preschool; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Female; Humans; Infant; Keratins; Male; Mucin-1; Retrospective Studies; Rhabdoid Tumor; SMARCB1 Protein; Teratoma; Tomography, X-Ray Computed; Transcription Factors; Young Adult

Glioblastoma multiforme (GBM), one of the most aggressive tumors in humans, is highly angiogenic. However, treatment with the angiogenesis inhibitor bevacizumab has not significantly prolonged overall patient survival times. GBM resistance to angiogenesis inhibitors is attributed to multiple interacting mechanisms. Although mesenchymal transition via glioma stem-like cells has attracted attention, it is considered a poor biomarker. There is no simple method for differentiating tumor-derived and reactive vascular cells from normal cells. The authors attempted to detect the mesenchymal transition of tumor cells by means of p53 and isocitrate dehydrogenase 1 (IDH1) immunohistochemistry.. Using antibody against p53 and IDH1 R132H, the authors immunohistochemically analyzed GBM tissue from patients who had undergone surgery at the University of Miyazaki Hospital during August 2005-December 2011. They focused on microvascular proliferation with a p53-positive ratio exceeding 50%. They compared TP53 mutations in original tumor tissues and in p53-positive and p53-negative microvascular proliferation cells collected by laser microdissection.. Among 61 enrolled GBM patients, the first screening step (immunostaining) identified 46 GBMs as p53 positive, 3 of which manifested areas of prominent p53-positive microvascular proliferation (>50%). Histologically, areas of p53-positive microvascular proliferation tended to be clustered, and they coexisted with areas of p53-negative microvascular proliferation. Both types of microvascular proliferation cells were clearly separated from original tumor cells by glial fibrillary acidic protein, epidermal growth factor receptor, and low-/high-molecular-weight cytokeratin. DNA sequencing analysis disclosed that p53-positive microvascular proliferation cells exhibited TP53 mutations identical to those observed in the original tumor; p53-negative microvascular proliferation cells contained a normal allele. Although immunostaining indicated that 3 (2 primary and 1 secondary) of the 61 GBMs were positive for IDH1, no tumors contained microvascular proliferation cells positive for IDH1 R132H.. Some microvascular proliferation clusters in GBM result from mesenchymal transition. The identification of useful markers might reveal this phenomenon as an infrequent event in GBMs.

Topics: Biomarkers, Tumor; Blood Vessels; Brain Neoplasms; Cell Proliferation; Epithelial-Mesenchymal Transition; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Isocitrate Dehydrogenase; Keratins; Male; Middle Aged; Mutation; Retrospective Studies; Tumor Suppressor Protein p53

Topics: Adamantinoma; Brain Neoplasms; Female; Humans; Keratins; Magnetic Resonance Imaging; Membrane Glycoproteins; Membrane Proteins; Middle Aged; Tibia

Little is known about the cytokeratin (CK) expressions in glioblastoma multiforme (GBM). The aim is to explore the CK expression in GM using immunohistochemistry (IHC). IHC study in 30 cases (median = 68 years, SE = 12.6) of GBM in brain. CK expression using AE1/3 antidody was seen in 29/30 (97 %) cases. There were no expressions of CK34BE12, CK5, CK6, CK7, CK8, CK14, CK 18, CK19, and CK20. Expression of p53 and glial fibrillary acidic protein (GFAP) were recognized in all 30 cases (100 %). All cases showed Ki-67 antigen labeling, index of which ranged from 6 to 43 % (m ± SD = 24 + 16). The IHC using CKAE1/3 in GBM very frequently shows positive reaction. The expression may cause difficulty in pathologic diagnosis in GBM, particularly in discrimination between GBM and metastatic carcinoma. The CK positivity in GM may be due to CK molecules other than CK34BE12, CK5, CK6, CK7, CK8, CK14, CK18, CK19 and CK20. GBM frequently expression p53 and high Ki-67 labeling.

Topics: Aged; Biomarkers, Tumor; Brain Neoplasms; Female; Follow-Up Studies; Glioblastoma; Humans; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Male; Neoplasm Grading; Prognosis

Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear-cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient's recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation.

Topics: Biomarkers, Tumor; Brain Neoplasms; Carcinoma in Situ; Cell Differentiation; Diagnosis, Differential; Epithelial Cells; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Keratins; Male; Middle Aged; Mucin-1; Neuroglia; Radiography; Temporal Lobe

Papillary tumors of the pineal region (PTPR) are recognized as a distinct entity in the World Health Organization classification of CNS tumors. Papillary tumors of the pineal region frequently show loss of chromosome 10, but no studies have investigated possible target genes on this chromosome. Chromosome 10 harbors the PTEN (phosphatase and tensin homolog) gene, the inactivation of which, by mutation or epigenetic silencing, has been observed in different brain tumors, including high-grade gliomas. In this study, we investigated copy number changes by molecular inversion probe (MIP) analysis and the mutational status of PTEN in 13 PTPR by direct sequencing. MIP analysis of 5 PTPR showed chromosome 10 loss in all cases. In addition, there were losses of chromosomes 3, 14, 22, and X, and gains of whole chromosomes 8, 9, and 12 in more than 1 case. One case had a homozygous PTEN deletion; and 2 point mutations in exon 7 of PTEN (G251D and Q261stop) were found. Immunohistochemistry revealed decrease or loss of the PTEN protein and increased expression of p-Akt and p-S6. These results indicated that PTEN mutations and activation of the PI3K/Akt/mTOR signaling pathway may play a role in the biology of PTPR. This evidence may lead to the possible use of PI3K/Akt/mTOR inhibitors in therapy for patients with PTPR.

Topics: Adolescent; Adult; Brain Neoplasms; Female; Humans; Keratins; Male; Microtubule-Associated Proteins; Middle Aged; Mucin-1; Mutation; Neoplasms, Neuroepithelial; Nerve Tissue Proteins; Pineal Gland; Pinealoma; PTEN Phosphohydrolase; S100 Proteins; Signal Transduction; Young Adult

To study the clinicopathologic features of papillary tumor of the pineal region (PTPR).. Three hundred and eighty six cases of pineal region and posterior third ventricle tumors, two newborn and two adult pineal glands were analyzed by HE, PAS and immunohistochemistry of 16 antibodies (EnVision method).. Five cases of PTPR were diagnosed with mixed papillary features and densely cellular areas, and included one recurrent case. In the papillary areas, the vessels were lined by one or several layers of cuboidal/columnar cells; the vessel wall was hyalinized. In the densely cellular areas, sheets or nests of tumor cells were seen. The tumor cells of these five cases were immunoreactive to CK, CK8/18, synaptophysin, MAP2, nestin, S-100, and vimentin. Four cases were immunoreactive to NSE and CgA; and 2 cases were immunoreactive to NF. All five cases were negative for EMA, CK5/6, CEA, and NeuN. Ki-67 labeling index ranged from 1% to 6%.Three patients were alive, and the recurrent one died.. PTPR occurs in patients with over a wide age range, from children to adults, and is more commonly found in male than female. PTPR is composed of both papillary and solid areas, characterized by epithelial cytology, and needs to be differentiated from ependymoma. PTPR may originate from the specialized ependymocytes of the subcommissural organ. The prognostic factors are early diagnosis, complete surgical resection and radiotherapy.

Topics: Adolescent; Adult; Brain Neoplasms; Carcinoma, Papillary; Child; Diagnosis, Differential; Ependymoma; Female; Humans; Immunohistochemistry; Keratin-18; Keratin-8; Keratins; Male; Microtubule-Associated Proteins; Nestin; Pineal Gland; Pinealoma; S100 Proteins; Synaptophysin; Tomography, X-Ray Computed; Vimentin; Young Adult

Spindle cell carcinoma (SpCC) is a rare tumor consisting of spindle cells which express cytokeratin. Despite recent advances in immunohistochemical and genetic studies, precise histogenesis of SpCC is still controversial and this tumor had been referred to with a wide range of names (in the past): carcinosarcoma, pseudosarcoma, sarcomatoid carcinoma, pseudosarcomatous carcinoma, and collision tumor. Recently, the authors experienced an extremely rare case of SpCC arising from the stomach. A 64-year-old male presented with unintended weight loss and hematochezia. Endoscopic examination revealed a fistulous tract between the stomach and the transverse colon which was made by direct invasion of SpCC of the stomach to the colon. Histologically, the tumor was positive for both vimentin and cytokeratin but negative for CD117, CD34, actin, and desmin. Herein, we report a case of SpCC arising from the stomach that formed a fistulous tract with the colon which was diagnosed during evaluation of hematochezia and weight loss.

Topics: Antineoplastic Agents; Brain Neoplasms; Carcinoma; Colon, Transverse; Endoscopy, Digestive System; Fistula; Gastrointestinal Hemorrhage; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Stomach Neoplasms; Tomography, X-Ray Computed; Weight Loss

To study the clinicopathologic features, immunohistochemical findings, diagnosis and differential diagnosis of atypical teratoid/rhabdoid tumors (AT/RT) of central nervous system in childhood.. The clinicopathologic data, morphologic features and immunophenotypes were reviewed in 6 cases of AT/RT. EnVision method was applied. Antibodies include cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, smooth muscle actin (SMA), muscle specific actin (MSA), glial fibrinary acid protein (GFAP), desmin, placental alkaline phosphatase (PLAP) and INI1.. Five of the six cases of AT/RT occurred in infancy and early childhood. Histologically, the predominant component was rhabdoid cells. Cytoplasmic inclusions were present in all cases. Primitive neuroectodermal tumor (PNET) component was also identified in 5 of the 6 cases studied. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin. The staining for INI1, desmin and PLAP was negative. Smooth muscle actin was expressed in 2 cases and glial fibrillary acidic protein in 5 cases. The proliferative index as demonstrated by Ki-67 staining was high.. AT/RT is not a particularly uncommon malignancy in childhood. The histologic hallmark is the presence of rhabdoid cells with cytoplasmic inclusions. The tumor cells are positive for cytokeratin, epithelial membrane antigen and vimentin, and negative for INI1. Differential diagnosis includes PNET, medulloblastoma and medullomyoblastoma.

Topics: Brain Neoplasms; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Keratins; Male; Medulloblastoma; Mucin-1; Neuroectodermal Tumors, Primitive; Rhabdoid Tumor; Teratoma; Vimentin

Pineal parenchymal tumors comprise a rare group of primary neoplasms of the pineal gland. We describe a case involving a 29-year-old woman who presented with signs and symptoms of hydrocephalus secondary to a pineal region tumor obstructing the third ventricle. Surgical resection was performed and pathological analysis revealed a novel diagnosis consistent with a pineal parenchymal tumor of intermediate differentiation (PPTID) with transition to a papillary tumor of the pineal region (PTPR). To our knowledge, this particular pineal region tumor pathology has not yet been reported in the literature and highlights the continuum with which primary pineal tumors exist. We provide a review of the existing literature on pineal region tumors, specifically PTPR and PPTID, and offer insight into the management of these rare neoplasms.

Topics: Adult; Brain Neoplasms; Cell Differentiation; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Magnetic Resonance Imaging; Pineal Gland; Pinealoma; Synaptophysin

Angiogenesis is believed to be essential for the growth of metastatic tumors in the brain. We analyzed the vascularization of tumors formed by 4 epithelial cell lines (C38, ZR75, HT25, and H1650) and a fibrosarcoma (HT1080) cell line injected into the brains of mice. No peritumoral angiogenesis was observed. Tumors apparently acquired their vasculature by incorporation of native vessels. Vessel density was lower, but vessel diameter and vascular cell proliferation were higher within all tumors versus those in the peritumoral tissue. There was an inverse correlation between the number of incorporated vessels and vascular cell proliferation. Epithelial tumors with pushing growth patterns had lower vessel density and elevated vascular cell proliferation compared with invasive tumors. The incorporated vessels retained their normal structure, with the exception of astrocyte foot processes that were replaced by tumor cells. Attachment to the vascular basement membrane led to the differentiation of the ZR75 breast cancer cells. In the HT1080 metastases, there was intussusceptive angiogenesis, that is, the fibrosarcoma cells that were attached to the vessel caused lumen splitting and filled the developing pillars. Branching angiogenesis was not observed either in the tumors or in control cerebral wounds. These data suggest that sprouting angiogenesis is not needed for the incipient growth of cerebral metastases and that tumor growth in this model is a result of incorporation of host vessels.

Topics: Angiopoietin-1; Animals; Brain Neoplasms; Breast Neoplasms; Bromodeoxyuridine; Carcinoma; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Disease Models, Animal; DNA-Binding Proteins; Electron Microscope Tomography; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Lamins; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Quinolines; Receptor, Platelet-Derived Growth Factor beta; Thiazoles; Vascular Endothelial Growth Factor A

Occasional reports indicated cytokeratin (CK) protein expression (mainly by immunohistochemistry) in malignant melanoma (MM) and suggested an association with unfavorable clinical parameters. However, the mRNA expression of CK and its clinicopathologic significance in MM has not been specifically evaluated. We investigated the mRNA and protein expression of nine CKs in melanoma cell lines and tissues, in particular the prognostic significance of CK18 mRNA expression. Reverse transcription (RT)-PCR (CK6-10, 14 and 18-20), in-situ hybridization (ISH) (CK18), and western blotting (CK18 and pan-cytokeratin AE1/AE3) were performed on MM cell lines A375, A875, M14, and SK-MEL-1. Eighty MM tissue samples were analyzed by ISH and immunohistochemistry for CK18 expression. The mRNA of CK6-8, 10, 14, 18, and 19 (but not CK9 and 20) was detected in one to four of the melanoma cell lines by RT-PCR. CK18 was detected in all four cell lines by RT-PCR, ISH, and western blotting. CK18 mRNA ISH was positive in three of 30 (10.0%), 10 of 25 (40.0%), and 12 of 25 (48.0%) of primary cutaneous, primary mucosal, and metastatic melanomas, respectively (overall positivity: 25 of 80, 31.3%). CK18 immunostaining was only observed focally in eight of 80 (10.0%) of MM tissue samples, and AE1/AE3 immunostaining was altogether negative. Significantly, CK18 mRNA ISH positivity (but not protein immunohistochemistry) was associated with poorer prognosis by both univariate analysis (P<0.001) and multivariate analysis (relative risk=5.430, 95% confidence interval 2.246-13.128, P<0.001). CK18 mRNA could be identified in one-third of melanoma tissue samples and is an adverse prognostic factor. ISH is superior to immunohistochemistry for analyzing CK18 expression in MM.

Topics: Blotting, Western; Bone Neoplasms; Brain Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; In Situ Hybridization; Kaplan-Meier Estimate; Keratin-18; Keratins; Lymphatic Metastasis; Melanoma; Neoplasm Proteins; Prognosis; Proportional Hazards Models; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Skin Neoplasms

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive infantile neoplasm of uncertain origin. This study was performed to assess the clinicopathologic and immunohistochemical features of four AT/RT cases.. Two cases were male and two were female, and their ages ranged from 8 to 103 months. Tumors were located in the cerebellum (two cases), frontoparietal lobe (one case), and third ventricle (one case). Histopathologically, the tumors were composed of rhabdoid cells and undifferentiated small cells mixed with epithelial or mesenchymal components. However, one of the tumors was composed predominantly of a mesenchymal component mimicking a sarcoma. Immunohistochemically, vimentin (4/4), epithelial membrane antigen (4/4), cytokeratin (3/4), smooth muscle actin (4/4), glial fibrillary acidic protein (4/4), S-100 (4/4), and synaptophysin (1/4) were positive in varying proportions, while desmin and INI-1 were negative in all the cases. All of the patients died within a mean of 14 months due to tumor progression despite the chemotherapy. Only one of our patients lived for 40 months after the diagnosis. In conclusion, AT/RTs are aggressive tumors. They can occur in a variety of locations, such as the third ventricle. Morphologically, a large spectrum can be seen, like predominantly sarcoma in appearance, but immunohistochemistry is helpful in the correct diagnosis.

Topics: Actins; Brain; Brain Chemistry; Brain Neoplasms; Child; Child, Preschool; Chromosomal Proteins, Non-Histone; Desmin; Diagnosis, Differential; DNA-Binding Proteins; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Infant; Keratins; Male; Mucin-1; Rhabdoid Tumor; S100 Proteins; SMARCB1 Protein; Synaptophysin; Teratoma; Transcription Factors; Vimentin

The aim of present study is to explore the immunohistochemical profiles of brain metastases from breast cancer. We retrospectively performed immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2/neu), and cytokeratin (CK) 5/6 in 29 patients with resected tumor specimens of brain metastases. Immunohistochemical staining for ER, PgR and HER2/neu was performed in 24 patients with primary tumors. The positive frequency of immunohistochemical profiles of ER, PgR, HER2/neu, and CK5/6, in the brain metastases were 13.8%, 6.9%, 37.9%, and 24.1%, respectively. The immunohistochemical profiles including ER, PgR, and HER2/neu of the primary tumor and the brain metastasis differed in seven patients (29.2%, N = 7/24). Interestingly, the biological characteristics of brain metastasis sometimes changed which were represented by immunohistochemical staining. Therefore, the changes in the biological features of breast cancer should be taken into account when developing treatment strategies, including new molecular-targeted drugs, for brain metastases.

Topics: Adult; Aged; Brain; Brain Neoplasms; Breast Neoplasms; Chi-Square Distribution; Epidermal Growth Factor; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies

Distinguishing hemangioblastomas from metastatic clear-cell renal cell carcinomas (CCRCCs) in the brain is a diagnostic challenge owing to similar clinical and morphologic presentations. Inhibin-alpha and aquaporin1 were shown as positive markers of hemangioblastoma, but are not totally reliable distinguishing hemangioblastoma from metastatic CCRCC. This study shows that the diagnosis can be achieved using a combination of markers. To identify the panel of markers useful for this differential, 67 hemangioblastomas and 34 metastatic CCRCCs were analyzed using a panel of antibodies including aquaporin1, inhibin-alpha, D2-40, cytokeratin AE1/AE3, epithelial membrane antigen, and CD10. The study confirms the usefulness of aquaporin1 (97% sensitivity, 83% specificity) and inhibin-alpha (88% sensitivity, 79% specificity) as positive markers of hemangioblastoma and shows that aquaporin1 is a superior positive marker versus inhibin-alpha for the differential. Positivity of tumor cells with cytokeratin AE1/AE3 is the signature of a metastatic CCRCC (100% specificity, 88% sensitivity) and CD10 expression as well (100% specificity, 79% sensitivity). The combined use of aquaporin1 and AE1/AE3 yields a high degree of sensitivity and specificity to differentiate between hemangioblastoma and metastatic CCRCC. All tumors but one aquaporin1 positive and cytokeratin AE1/AE3 negative (65/66) correspond to hemangioblastomas (97% sensitivity, 97% specificity, 98.5% diagnostic positive predictive value). Tumors with the opposite profile, aquaporin1 negative, and cytokeratin AE1/AE3 positive, (25/25), correspond to metastatic CCRCC (74% sensitivity, 100% specificity, 100% diagnostic positive predictive value). In summary, aquaporin1 is the most sensitive positive marker of hemangioblastoma. Despite its moderate specificity, when used in combination with epithelial marker AE1/AE3, it allowed to reliably distinguish hemangioblastoma from metastatic CCRCC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aquaporin 1; Biomarkers, Tumor; Brain Neoplasms; Carcinoma, Renal Cell; Child; Diagnosis, Differential; Female; Hemangioblastoma; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged

Metastatic carcinoma, which is a common malignant tumor seen in the central nervous system is often difficult to distinguish from glioblastoma multiforme. In general, neoplastic cells maintain fidelity in the expression of parent cell intermediate filament and immunohistochemistry remains the mainstay in diagnosis. A panel consisting of GFAP (usually positive for astrocytic tumors) and cytokeratin (usually positive for metastatic carcinomas) is most commonly used for this purpose. However, co-expression of two or more classes of intermediate filament proteins by neoplasms is a widespread phenomenon and there are reports of glial neoplasms expressing keratin markers. Our aims and objectives were to analyse the expression of both cytokeratin and GFAP in different glial tumors and metastatic carcinomas. Cases were collected for a period of two years. All the cases were diagnosed as primary or metastatic intracranial tumors. Formalin-fixed paraffin-embedded thin sections were taken on egg-albumin coated slides and immunostaining with GFAP and polyclonal cytokeratin was done. Forty-five tumors were analysed, including 35 glial neoplasms and 10 metastatic carcinomas of which 7 of the 32 astrocytic neoplasms (22%) showed focal immunoreactivity with pancytokeratin. All of the glial tumors but none of the metastatic carcinomas were positive with GFAP. So our conclusion was that co-expression of GFAP and CK is a fairly common phenomenon, especially in case of undifferentiated and high grade gliomas and this must be kept in mind while differentiating these cases from metastatic carcinoma, as CK positivity does not rule out the diagnosis of a glial neoplasm. Further studies with an expanded panel of CK is most useful for this.

Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Carcinoma; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Glioblastoma; Glioma; Humans; Immunohistochemistry; Keratins; Oligodendroglioma

Topics: Aged; Brain Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Meningioma; Mucin-1; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Telencephalon

Craniopharyngioma is a rare, benign epithelial brain tumor of the suprasellar region with a high rate of recurrence. Clinical and histopathological features that might be predictors of recurrence/regrowth have not been clearly delineated.. We compared recurrence/regrowth of the tumors with the clinico-pathological characteristics, vascular density, cell proliferation index, and immunohistochemical profile (cytokeratins, epithelial membrane antigen [EMA], carcinoembrionary antigen [CEA], and laminin) of 47 patients with craniopharyngioma followed for more than 5 years.. Tumors were adamantinomatous in 42 cases (89%) and papillary squamous in 5 cases (11%). Immunoreactivity for cytokeratin 8/18/19 was positive in 64%; cytokeratin 5 in 42%; laminin 8 in 62%; and CEA in 21%. The cell proliferation index and vascular density were greater in adamantinomatous than in papillary tumors (22+/-6 versus 17+/-3, p=0.05; and 21+/-3 versus 17+/-3, p=0.037, respectively); they were neither related to recurrence nor to regrowth. No significant differences were found between adamantinomatous and papillary tumors regarding the presence of cytokeratin, laminin, CEA or glial fibrillary acidic protein (GFAP). Recurrence rate at 5 years was 59%. No relation was found between recurrence and adjuvant radiotherapy (AR). Residual tumor after surgery, whorl-like arrays (p=0.04) and immunoreactivity for p53 (p=0.022) were significantly related to recurrence/regrowth.. Residual tumor after surgery, immunoreactivity to p53 and presence of whorl-like arrays are associated to recurrence/regrowth of craniopharyngioma.

Topics: Adult; Biomarkers, Tumor; Brain Neoplasms; Carcinoembryonic Antigen; Cell Proliferation; Craniopharyngioma; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Laminin; Male; Mucin-1; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Predictive Value of Tests; Prognosis; Radiotherapy; Tumor Suppressor Protein p53

Brain metastases (BM) from breast cancer are associated with significant morbidity and mortality. In the current study, we have examined a cohort of breast cancer patients who went on to develop BM for clinical-pathologic features and predictive markers that identify this high-risk subgroup of patients at the time of diagnosis. The primary tumors from 55 patients who developed BM were used to construct a tissue microarray. The clinical and pathologic features were recorded and the tissue microarray was stained for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, and epidermal growth factor receptor by immunohistochemistry. This cohort of patients was compared against a group of 254 patients who remain free of metastases (67 mo mean follow-up), and another cohort of 40 patients who developed mixed visceral and bone metastatic disease without brain recurrence over a similar period of time. Breast cancer patients who went on to develop BM were more likely to be <50 years old (P<0.001), and the primary tumors were more likely to be estrogen receptor negative (P<0.001) and high grade (P=0.002). The primary tumors were also more likely to express cytokeratin 5/6 (P<0.001) and epidermal growth factor receptor (P=0.001), and to overexpress human epidermal growth factor receptor 2 (P=0.001). The data presented above suggest a profile for breast cancer patients at increased risk for developing BM. Predictive factors to help identify patients with metastatic breast cancer who are at an increased risk for developing central nervous system recurrence might allow for screening of this population for early detection and treatment or for the development of targeted strategies for prevention.

Topics: Brain Neoplasms; Breast Neoplasms; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Middle Aged; Receptor, ErbB-2; Receptors, Estrogen

To study the clinicopathologic features and differential diagnosis of atypical teratoid/rhabdoid tumor (AT/RT) occurring in the central nervous system.. Two cases of AT/RT were studied by hematoxylin-eosin, reticulin and immunohistochemical staining. The clinical and pathologic features were analyzed and the literatures reviewed.. Histologically, AT/RT was characterized by the presence of rhabdoid cells associated with various degrees of primitive neuroectodermal, epithelial or mesenchymal differentiation. Abundant reticulin fibers and a complex immunophenotype were observed. The tumor cells were positive for vimentin, CD99, epithelial membrane antigen, cytokeratin, glial fibrillary acidic protein, S-100 protein, neurofilament, desmin and smooth muscle actin. They were negative for synaptophysin, MyoD1, placental alkaline phosphatase and HMB45.. AT/RT is a highly malignant tumor occurring in the central nervous system. It manifests mainly in children and occasionally in adults. The tumor is characterized by a heterogeneous histologic and immunohistochemical phenotype. It needs to be distinguished from a number of central nervous system tumors, including medulloblastoma, primitive neuroectodermal tumor, germ cell neoplasm and rhabdoid meningioma.

Topics: 12E7 Antigen; Actins; Adult; Antigens, CD; Brain Neoplasms; Cell Adhesion Molecules; Child, Preschool; Desmin; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Muscle, Smooth; Neurofilament Proteins; Rhabdoid Tumor; S100 Proteins; Teratoma; Vimentin

A case of a histologically unclassified brain tumor in a 32-month-old boy is reported. He presented with vomiting, appetite loss, and right motor weakness. MR images revealed a huge mass in the left frontoparietal region that was enhanced after the administration of Gd-DTPA. The mass was removed three times because of its recurrence.. Histologically, the tumor was composed largely of small-undifferentiated round cells without any patterns of differentiation. Immunohistochemically, the tumor cells were positive for cytokeratin and focally for epithelial membrane antigen (EMA). Glial fibrillary acidic protein (GFAP), S-100 protein and neuronal markers were negative. Electron microscopic investigations demonstrated no evidence of specific differentiation. MIB-1 staining index was 10-40%. The origin of the tumor was not detected. Expression of the hSNF5/INI1 of this tumor was not detected by reverse transcription-polymerase chain reaction (RT-PCR). The patient has been in a good condition for 7 years after the first operation.. Based on the immunohistochemical findings, the tumor was descriptively diagnosed as an embryonal tumor with an epithelial immunophenotype. The hSNF5/INI1 gene has recently been reported to act as a tumor suppressor in atypical teratoid/rhabdoid tumors. The hSNF5/INI1 gene may lead to tumorigenesis in this case.

Topics: Biomarkers; Brain Neoplasms; Child, Preschool; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Gadolinium DTPA; Gene Expression Regulation, Neoplastic; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Mucin-1; Parietal Lobe; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; SMARCB1 Protein; Tomography, X-Ray Computed; Transcription Factors

Few reported cases of gliosarcomas or glioblastomas with epithelial-like areas exist. Most cases were originally diagnosed as metastatic carcinoma. Focal expression of glial fibrillary acidic protein has helped characterize these tumors as having a glial origin. We report a case of gliosarcoma with multifocal, extensive areas of well-differentiated carcinoma; demonstrating squamous and glandular differentiation. The expression of glial fibrillary acidic protein and epithelial phenotype were mutually exclusive. We performed extensive immunohistochemical analyses and comparative genotypic analysis using microdissection to secure representative glial and epithelial components. Loss of heterozygosity was analyzed with a panel of 12 polymorphic microsatellite markers designed to indicate allelic loss and situated in proximity to known tumor suppressor genes located on chromosomes 1p, 9p, 10q, 17p and 19q. We found comparable patterns of acquired allelic loss between the glial and carcinomatous components, strongly supporting the monoclonal origin of this neoplasm. This case represents an extreme form of phenotypic divergence in a malignant glioma, and constitutes a difficult diagnostic challenge. This heterogeneity reflects the potential for a range of phenotypic expression in malignant gliomas that needs to be recognized. We suggest microdissection genotyping as a molecular technique to better characterize these tumors.

Topics: Aged; Biomarkers; Brain Neoplasms; Cell Differentiation; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 9; Epithelial Cells; Genotype; Glial Fibrillary Acidic Protein; Gliosarcoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-67 Antigen; Loss of Heterozygosity; Male; Review Literature as Topic; Tumor Suppressor Protein p53

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain; Brain Neoplasms; Cerebrospinal Fluid; Diagnosis, Differential; Facial Nerve; Humans; Keratin-7; Keratins; Lateral Ventricles; Lung; Lung Neoplasms; Male; Meningeal Neoplasms; Middle Aged; Miller Fisher Syndrome; Oculomotor Nerve

Astroblastoma is one of the very unusual type of tumors, whose histogenesis has not been clarified. It occurs mainly among children or young adults. Astroblastoma is grossly well-demarcated, and shows histologically characteristic perivascular pseudorosettes with frequent vascular hyalinization. Perivascular pseudorosettes in astroblastoma have short and thick cytoplasmic processes and blunt-ended foot plates. A 15-yr-old girl presented with headache and diplopia for one and a half year. A well-demarcated mass, 9.7 cm in diameter, was found in the right frontal lobe in brain MRI, and it was a well-enhanced inhomogenous mass. Cystic changes of various sizes were observed inside the tumor mass as well as in the posterior part of the mass, but no peritumoral edema was found. Histologically, this mass belongs to a typical astroblastoma, and no sign of anaplastic astrocytoma, gemistocytic astrocytoma or glioblastoma was found in any part of the tumor. Immunohistochemically, the tumor cells showed diffuse strong positivity for glial fibrillary acidic protein, S-100 protein, vimentin and neuron specific enolase, and focal positivity for epithelial membrane antigen and CAM 5.2, while showing negativity for synaptophysin, neurofilament protein, pan-cytokeratin and high molecular weight keratin.

Topics: Adolescent; Biomarkers; Brain Neoplasms; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Magnetic Resonance Imaging; Neoplasms, Neuroepithelial; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

Two metachronous glioblastomas with different cerebral locations in a 53-year-old long-term survival patient were analyzed by multiple genetic approaches. Using comparative genomic hybridization a different pattern of chromosomal aberrations was observed, with 19 imbalances in the first tumor and only 2 imbalances in the second. Sequence analysis revealed a distinct mutation profile in each tumor, with amino acid substitutions in the p53 and PTEN genes only in the first tumor, ie, p53 in codon 273 (CGT-->TGT, Arg-->Cys) and PTEN in codon 336 (TAC-->TTC, Tyr-->Phe). A splicing acceptor site PTEN mutation (IVS8-2A>G) was observed only in the second GBM. EGFR amplification, mutations of p16INK4a/CDKN2A or p14ARF were not observed. According to the results of p53 mutational analysis and EGFR amplification studies, the first tumor is classified as a type 1 GBM, whereas the alterations in the second one are different from those typically encountered in type 1 or type 2 tumors. In conclusion, our data strongly suggest that the metachronous tumors in this patient are exceptional in that they developed independently from each other. Whether the molecular features of the first glioblastoma are associated with the notably extended recurrence-free period of 5 years remains to be elucidated.

Topics: Brain Neoplasms; Chromosome Mapping; Chromosomes, Human, Pair 10; Cyclin-Dependent Kinase Inhibitor p16; DNA Mutational Analysis; DNA-Binding Proteins; Genes, erbB-1; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Loss of Heterozygosity; Magnetic Resonance Imaging; Male; Middle Aged; MutS Homolog 2 Protein; Neoplasms, Second Primary; Nerve Tissue Proteins; Phosphoric Monoester Hydrolases; Polymerase Chain Reaction; Proto-Oncogene Proteins; PTEN Phosphohydrolase; S100 Proteins; Sequence Analysis, DNA; Staining and Labeling; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Vimentin

Cytokeratin (CK)7 and CK20, the low molecular weight cytokeratins, have been found to have a benefit in the differential diagnosis of some epithelial neoplasms. In the present study, the actual role of these markers in the search of primary tumors in 32 patients with craniospinal metastasis of an unknown primary site at presentation, is evaluated. A series of 36 patients with a known primary tumor were presented for comparison. In the first group, two CK7 and CK20 expression profiles were observed; 87% of metastatic tumors were CK7+/CK20- and 13% CK7-/CK20-. The lung was the major source (82%) of CK7+/CK20- metastatic tumors, whereas it represented only 38% of primary tumor in the second group of a known primary site (P=0.006). Given the fact that metastatic tumors to the craniospinal axis of an unknown primary site are frequently CK7+/CK20-, and they have commonly metastasized from the lung, it is doubtful that immunohistochemistry is really helpful. However, CT scan and MRI of the chest still play an important role. Many patients in the present study had to undertake these imaging studies, regardless of the CK7/CK20 result. The immunostains may be useful in cases with other expression profiles, but such examples constituted only a minority in the present study.

Topics: Biomarkers, Tumor; Brain Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasms, Unknown Primary; Spinal Neoplasms

We report a case of astroblastoma with unusual signet-ring-like cell components. A 33-year-old-woman presented with occasional partial seizures of the face. Radiological studies revealed an enhanced frontal mass lesion. At surgery, a gray, soft, well-circumscribed mass was seen and shelled out. Histologically, the tumor showed a perivascular arrangement and papillary-like patterns with compact cellularity. The tumor cells radiating from the hyalinized vessels showed broader, shorter, less tapered processes. A part of each tumor cell displayed prominent islands of signet-ring-like cells. Glial fibrillary acidic protein reaction revealed strongly positive staining of tumor cells and signet-ring-like cells. Eight years after the operation the patient remains well with no tumor recurrence. It remains to be determined whether, in this astroblastoma, the unusual signet-ring-like cell components were related to benign biological characteristics or to the tumor's low-grade form with incidental signet-ring-like cell appearance.

Topics: Adult; Brain Neoplasms; CD57 Antigens; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Ki-67 Antigen; Mucin-1; Neoplasms, Neuroepithelial; S100 Proteins; Vimentin

This study examined immunohistochemical staining patterns for several meningioma variants involving either the brain or spinal cord of dogs. Formalin-fixed, paraffin-embedded tissue from 15 tumors was obtained. The selected tumor group included seven meningothelial, three transitional, two malignant (anaplastic), one myxoid, one papillary, and one osteomatous meningiomas. Tumors were evaluated for reactivity to the following six immunohistochemical markers: vimentin, pancytokeratin, glial fibrillary acidic protein (GFAP), S100, neuron-specific enolase (NSE), and synaptophysin. Vimentin expression was detected in all meningiomas, and 14 of 15 tumors demonstrated intense vimentin staining in more than 50% of the neoplastic cells. Pancytokeratin expression was present in 11 of 15 neoplasms; however, positive staining frequently was focal and often involved a small percentage of the neoplastic cells. GFAP expression was detected in a single, anaplastic meningioma. Although expression of NSE and S100 was detected in 12 of 25 meningiomas, the intensity of the staining and the percentage of positive neoplastic cells was highly variable. Synaptophysin was uniformly negative. These results will help to establish immunohistochemical profiles for meningiomas that will improve our ability to correctly differentiate these neoplasms of meningeal origin from central nervous system tumors originating from other sites.

Topics: Animals; Brain Neoplasms; Central Nervous System Neoplasms; Dog Diseases; Dogs; Female; Glial Fibrillary Acidic Protein; Immunohistochemistry; Immunophenotyping; Keratins; Male; Meningioma; Phosphopyruvate Hydratase; S100 Proteins; Synaptophysin; Vimentin

histological features of metastasis are not always specific of the origin. The usefulness of cytokeratin 7 and 20 (CK7 and CK20) in cerebral metastases from an adenocarcinoma was studied in a series of 78 patients.. metastases from lung adenocarcinoma showed a CK7+/CK20- pattern in 79% of cases, CK7+/CK20+ in 19% and CK7-/CK20- in 2%. When observed, positivity for cytokeratin 20 was generally focal or weak. Breast adenocarcinoma metastases were CK7+/CK20- in 71% of cases and CK7-/CK20- in 29%. Less differentiated tumours were usually negative for both cytokeratins. Metastases by colonic adenocarcinoma were CK7-/CK20+ in 100% of cases. Cytokeratins 7 and 20 are useful to distinguish lung from colonic metastatic carcinoma. In case of double positivity, a more intense CK7 expression is rather suggestive of a lung origin.. these results might modify paraclinic investigations in search of the primitive tumor.

Topics: Adenocarcinoma; Brain Neoplasms; Breast Neoplasms; Colonic Neoplasms; Diagnosis, Differential; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms

Although craniopharyngiomas have been examined in several microscopical studies to date, immunohistochemical analysis has not been sufficient.. In addition to the routine haematoxylin and eosin staining, 38 cases of intra- and/or supra-sellar craniopharyngioma, including 34 adamatinomatous and 4 squamous papillary types, were studied using immunohistochemistry for expression of four types of cytokeratin.. Histological examination found epithelial cells in 26 of 38 (68.40%) cases. However, cytokeratins were demonstrated in 35 of 38 (92.1%) cases. The remaining 3 cases without demonstration of epithelial cell nests were supposed to be adamantinomatous craniopharyngiomas based on the findings in the stroma. In 31 of 34 adamantinomatous craniopharyngioma cases, the epithelium was detected by immunostaining for cytokeratins. The epithlieum expressed 56 kDa (KL-1) and 40 kDa (cytokeratin 19) cytokeratins with similar staining patterns and intensities. The staining intensity of 54 kDa cytokeratin (cytokeratin 7) was similar to that of the high molecular weight cytokeratin (keratin M-903). However, in many cases (15 of 27), immunoreactivity of cytokeratin 7 was not demonstrated in an outer palisaded basal layer. In all 4 squamous papillary craniopharyngiomas, moderate staining with cytokeratin 7 appeared in the superficial layer, whereas basal or mid-zone epithelial cells were negative for cytokeratin 7. The basal layer stained negatively for KL-1, as well as cytokeratin 7.. Immunostaining for cytokeratin is valuable in the investigation of craniopharyngioma, especially when specimens contain only a small or questionable part of epithelium. Most notably, KL-1 or cytokeratin 7 stainings are suitable for analyzing these tumours, with special reference to histological subtypes.

Topics: Adolescent; Adult; Brain Neoplasms; Child; Craniopharyngioma; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged

Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.

Topics: Adrenal Gland Neoplasms; Aged; Bone Neoplasms; Brain Neoplasms; Carcinoma, Renal Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Survival Rate; Vimentin

Here we report tumor-to-tumor metastases identified in two patients with von Hippel-Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis.

Topics: Biomarkers, Tumor; Brain Neoplasms; Carcinoma, Renal Cell; Female; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Middle Aged; Mucin-1; Neoplasms, Second Primary; Stromal Cells; von Hippel-Lindau Disease

High-grade invasive ductal carcinomas (IDCs) of the breast with large, central acellular zones on their cut surfaces are usually associated with the myoepithelial immunophenotype of carcinoma cells, which includes the expression of S-100 protein, alpha-smooth muscle actin, and keratin 14. To clarify the clinical significance of these features of IDCs, the authors compared the incidence of the myoepithelial immunophenotype immunohistochemically, patient prognosis, and metastatic sites of the tumor between 20 high-grade IDCs with large, central acellular zones and 40 control high-grade IDCs without these zones. The myoepithelial immunophenotype was detected in 16 IDCs (80%) with large, central acellular zones but in only seven IDCs (18%) without. The risk ratio of metastasis, especially in the brain and lung, and death from cancer were significantly higher (p = 0.0096 and p = 0.030) for the 20 IDCs with large, central acellular zones than for those without by Cox's univariate analysis. Using Cox's multivariate analysis, large, central acellular zones in IDCs were an indicator of high risk of brain and lung metastases and of death by cancer independent of nodal status and tumor size. Examination of large, central acellular zones and myoepithelial immunophenotype in high-grade IDCs appears helpful in predicting patient prognosis and preferential metastatic sites of the tumors.

Topics: Actins; Adult; Aged; Brain Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Cell Differentiation; Female; Follow-Up Studies; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Lung Neoplasms; Middle Aged; Myoepithelioma; Prognosis; S100 Proteins; Survival Rate

Topics: Adolescent; Antibodies, Monoclonal; Brain; Brain Neoplasms; Germinoma; Granuloma; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Mucin-1

Metastases to the oral mucosa are rare, representing less than 1% of the tumors at this site. Most of these metastatic neoplasms originate in the lungs, kidneys, and liver.. The clinicopathologic features of an occult hepatocellular carcinoma, metastatic to the oral mucosa, are reported. The patient, a 70-year-old male, complained of 3 distinct polypoid, reddish lesions of the antero-inferior alveolar crest and both the right and left postero-superior attached gingiva, without bone involvement. The lesions were excised, with the clinical diagnosis of multiple vascular tumors, formalin-fixed, paraffin-embedded, cut and stained with hematoxylin and eosin. Consecutive sections were immunostained for alpha-1-antichymotrypsin, CEA, cytokeratins, EMA, hepatocyte antigen, PSA, S-100 protein, and thyroglobulin, using the alkaline phosphatase/anti-alkaline phosphatase technique.. The morphologic features of the lesions were consistent with the diagnosis of carcinoma with trabecular and glandular patterns and bile secretion; furthermore, immunohistochemical reactivity for alpha-1-antichymotrypsin, cytokeratins, CEA, EMA, and hepatocyte antigen was demonstrated and the hepatic origin of the tumor was postulated. Ultrasonography demonstrated a liver mass, which was biopsied and treated by chemoembolization. While no further complications occurred in the oral mucosa, the patient died 8 months after the diagnosis for widespread diffusion of the tumor to the lungs and brain.. This case emphasizes the need to include metastatic tumors in the differential diagnosis of atypical neoplasms of the oral mucosa and to evaluate the opportunity of surgical treatment in order to preserve the functions of the mouth, even if the prognosis of the primary tumors remains unfavorable.

Topics: Aged; alpha 1-Antichymotrypsin; Biomarkers, Tumor; Brain Neoplasms; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Diagnosis, Differential; Fatal Outcome; Gingival Neoplasms; Humans; Keratins; Liver Neoplasms; Lung Neoplasms; Male; Mucin-1; Polyps; Vascular Neoplasms

Carcinoma that has metastasized to the central nervous system (CNS) poses a particular clinical problem regarding confirmation of the diagnosis and subsequent management. Prior to excision, thorough evaluation for coexisting systemic disease is essential, but current imaging techniques are limited by their spatial resolution and under-stage many patients. We evaluated the potential utility of bone-marrow evaluation for micrometastatic cells in patients with CNS metastasis. Bone-marrow aspirates were examined for cytokeratin-positive cells in 12 consecutive patients who presented with symptomatic space-occupying lesions of the CNS. These patients had previously undergone surgical excision of either gastrointestinal or breast cancers. All twelve had micrometastases in their bone marrow at the time of presentation with the CNS disease and all had a fatal outcome within 13 months. In nine of the 12 patients, bone-marrow micrometastases were the only evidence for systemic spread. Three patients had elevated serum tumour markers and two of these had radiologically detectable recurrence elsewhere. Bone-marrow micrometastases indicate concurrent systemic involvement and a poor prognosis. The results suggest that bone-marrow evaluation for systemic spread is a useful diagnostic adjunct and should be performed before considering diagnostic biopsy or excision.

Topics: Adenocarcinoma; Biomarkers, Tumor; Bone Marrow Examination; Bone Marrow Neoplasms; Brain; Brain Neoplasms; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Female; Flow Cytometry; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Neoplasm Staging; Predictive Value of Tests; Prospective Studies; Tomography, X-Ray Computed

A diagnostic problem can occur at the time of intraoperative consultation of neurosurgical tumors as to whether the tumor is of neuroectodermal origin or whether it represents an epithelial metastasis from another site. Intraoperative diagnoses based on hematoxylin and eosin stained frozen sections are often later confirmed by immunocytochemical analysis of formalin-fixed, paraffin-embedded tissue sections that are not available at the time of surgery. The objective of the current study was to demonstrate that the application of direct immunofluorescence to the intraoperative diagnosis of neurosurgical tumors would provide unequivocal, and nearly immediate results. This report describes a new application of an existing technique for an optimized, rapid procedure utilizing direct immunocytochemistry with fluorescence-labeled primary antibodies to analyze surgical biopsies intraoperatively. The examination of five neurosurgical biopsies established a neuroectodermal origin of three tumors via immunolabeling for glial fibrillary acidic protein (GFAP) and lack of labeling with keratin markers, whereas several metastatic lung carcinomas were identified by immunostaining for keratin, but not GFAP, markers. The results of the direct immunolabeling method were unequivocal and required only minutes. The same diagnoses were confirmed by standard immunocytochemical labeling of formalin-fixed, paraffin-embedded sections, though it required several days to obtain the results. Direct immunofluorescence using fluorescently conjugated primary antibodies is a practical and rapid method for deciding whether a neurosurgical tumor is a primary glial or an epithelial metastatic tumor in origin. It is the first reported application of the technique for this aspect of rapid neurosurgical diagnosis.

Topics: Antibodies, Monoclonal; Astrocytoma; Brain Neoplasms; Fluorescent Antibody Technique, Direct; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Intraoperative Period; Keratins; Neurosurgery; Paraffin Embedding

Atypical teratoma/rhabdoid tumor (AT/RT) of the central nervous system is a highly malignant neoplasm in infants and early childhood. Approximately one third of patients develop intracranial dissemination with involvement of cerebral spinal fluid (CSF). The clinical, radiological, and pathological features have been described, but cytology of the tumor cells in CSF has not. Multiple CSF samples were examined in a case of AT/RT in a 2-yr-old girl. The most consistent cytologic features of AT/RT are the large size of the tumor cells, eccentricity of the nuclei, and prominent nucleoli. The differential diagnosis includes medulloblastoma/primitive neuroectodermal tumor (PNET) of the brain. Because AT/RT often contains PNET-like regions, the differential diagnosis mainly relies on the presence or absence of large rhabdoid tumor cells. Cytological examination of CSF from a patient with AT/RT is important in the early diagnosis, disease progression analysis, and therapy modulation.

Topics: Brain; Brain Chemistry; Brain Neoplasms; Child, Preschool; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mucin-1; Rhabdoid Tumor; Teratoma

Glial fibrillary acidic protein (GFAP), vimentin (Vi) and cytokeratin (CK) intermediate filament (IF) proteins were studied in glioblastoma cell line GL-15. The immunofluorescence staining revealed strong positive staining for vimentin in all cultured cells. Approximately 20% of analyzed cells showed strong and 50% moderate intensity of staining for GFAP. About 3% of all cells were positively stained with a mixture of anti-CK monoclonal antibodies. The expression of all IF was not in relation to the cell density or days in vitro after passage. The double immunofluoresce revealed that all CK-positive cells express GFAP and vimentin. This study demonstrates the heterogeneity of the clonal GL-15 glioma cell line which consists in three immunocytochemically distinct cell types: Vi+/GFAP-/CK-, Vi+/GFAP+/CK-, and Vi+/GFAP+/CK+. These findings give further evidence about the expression of non-glial IF in cultured glioma cells.

Topics: Brain Neoplasms; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Keratins; Microscopy, Fluorescence; Tumor Cells, Cultured; Vimentin

Poorly differentiated metastatic carcinoma may be difficult to distinguish histologically from high-grade astrocytic malignant neoplasms, particularly on small open or stereotactic biopsy specimens. Previous authors have reported that a subset of glioblastoma multiforme (GBM) variably stains with cytokeratin immunomarkers. The authors examined a panel of epithelial and keratin antibodies by paraffin immunohistochemistry to evaluate the immunophenotype of GBM for these markers and to determine what combination of immunostains would be optimal in distinguishing GBM from metastatic carcinoma.. Twenty-three patients with GBM (age range, 19-86 years; mean, 63.4 years; 14 men and 9 women) and 22 patients with metastatic carcinoma (age range, 26-77 years; mean, 58.1 years; 7 men and 15 women) to the brain were studied with a panel of immunostains, including glial fibrillary acid protein (GFAP), Ber-EP4, antikeratin monoclonal antibodies AE1/3, and antibodies to CAM 5.2 and cytokeratins 7 (CK7) and 20 (CK20). Sites of origin for the metastatic tumors included lung (n = 11), breast (n = 5), endometrium (n = 1), prostate (n = 1), colon (n = 1), presumed kidney (n = 1), and unknown (n = 2).. All GBMs stained positive for GFAP (100%), and all but 1 (95.7%) stained positive for cytokeratins AE1/3. Only rare focal immunoreactivity was observed in a single case of GBM with CAM 5.2 (4.3%), CK7 (4.3%), and CK20 (4.3%). Immunoreactivity with Ber-EP4 was not observed in any of the GBMs (0.0%). All cases of metastatic carcinoma stained positive with cytokeratins AE1/3 (100%) and CAM 5.2 (100%). Variable staining was observed in carcinomas with CK7 (17 of 22, 77.3%), Ber-EP4 (11 of 22, 50.0%), and CK20 (9 of 22, 40.9%). Three metastatic carcinomas showed rare GFAP-positive staining cells (13.6%).. Based on the aforementioned results, a combination of immunostains, including GFAP and cytokeratin CAM5.2, may be the most useful in differentiating poorly differentiated metastatic carcinoma from GBM. A significant number of GBMs stain with some cytokeratin markers, in particular cytokeratins AE1/3. Because of the poor specificity of cytokeratins AE1/3 in distinguishing metastatic carcinoma from GBM, it should not be used to differentiate the 2 entities.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Brain Neoplasms; Cell Adhesion Molecules; Female; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged

Keratin intermediate filaments (Ifs) are specific for epithelial cell differentiation. This study demonstrates the presence of keratin in two recently established human glioblastoma cell lines 8-MG-BA and 42-MG-BA. Immunofluorescence staining was performed on cells within passage 230 to 235 using monoclonal pan-cytokeratin antibodies. The cells were analyzed during several DIV at different cell density. Keratin-positive stained cells reached 5 to 7% in 8-MG-BA and less than 0.1% in 42-MG-BA cell line. The presence of keratin-positive cells was independent on cell density and days in vitro. Keratin-positive cells appeared unevenly distributed in both cell lines. They were observed as single or areas of keratin-positive cells. The morphological features of keratin-positive and keratin-negative cells were similar. The results are discussed with respect to previous studies on glial fibrillary acidic protein (GFAP) and vimentin to show the heterogeneity of IFs expression in glioma cell lines.

Topics: Brain Neoplasms; Fluorescent Antibody Technique; Genetic Heterogeneity; Glioma; Humans; Keratins; Tumor Cells, Cultured

We have encountered a series of 8 third ventricular neoplasms with a distinctive chordoid appearance that appear to represent a clinicopathologic entity. The tumors occurred in 7 females and 1 male, ranging in age from 31 to 70 years. In all cases, imaging studies showed a large well-circumscribed third ventricular mass; a cystic component was noted in 2. The tumors consisted of cords and clusters of cohesive, oval-to-polygonal epithelioid cells with abundant eosinophilic cytoplasm, relatively uniform round-to-oval nuclei, and inconspicuous nucleoli. Mitotic activity was absent. The stroma consisted of scant, coarse fibrillar processes, as well as prominent, slightly basophilic, extracellular mucin resembling that in chordomas. Throughout the tumor, and surrounding its well-defined borders, were infiltrates of mature lymphocytes and plasma cells. Russell bodies were prominent in the latter. Adjacent brain tissue showed reactive changes with gliosis and numerous Rosenthal fibers. Immunohistochemically, tumor cells were strongly reactive for GFAP and vimentin, but negative or only weakly staining for EMA. The MIB-1 labeling index was approximately 1%. Ultrastructural examination of 4 cases revealed focal microvilli, scattered "intermediate" junctions, and focal basal lamina formation. Neither desmosomes nor cilia were seen. Total resections were achieved in 2 cases; only subtotal removals were achieved in 6. Subsequent tumor enlargement was noted in 3 of the 6 patients with incomplete resection, and of these, two died at post-operative intervals of 8 months and 3 years. The other patient survives 4 years post-operatively with stable residual disease. Of the 2 patients with total resection, 1 was lost to follow-up; the other, during a brief follow-up period, did well without evidence of recurrence.

Topics: Adult; Aged; Antigens, Nuclear; Brain Neoplasms; Cerebral Ventricles; Diagnosis, Differential; Fatal Outcome; Female; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Middle Aged; Mucin-1; Nuclear Proteins; Vimentin

Intracranial nervous-system tumours were diagnosed in three of 1092 bovine necropsy specimens submitted to the Department of Veterinary Pathology, Obihiro University between April 1983 and March 1996. A fourth case was a referral from the Department of Veterinary Pathology, Rakuno Gakuen University. Histopathological examination revealed four types of tumour: intracranial malignant peripheral nerve sheath tumour (MPNST), choroid plexus papilloma, differentiated fibrillary astrocytoma and anaplastic (malignant) astrocytoma. Immunohistochemically, the intracranial MPNST was strongly positive for S-100 protein and vimentin, and in places weakly positive for glial fibrillary acid protein (GFAP). The choroid plexus papilloma was strongly positive for epithelial membrane antigen (EMA), keratin, S-100 protein and vimentin, and positive for GFAP in places. The cytoplasm and fibrous component in the differentiated fibrillary astrocytoma were strongly positive for S-100 protein and GFAP. The anaplastic (malignant) astrocytoma was strongly positive for vimentin, S-100 protein and keratin in the cytoplasm and fibrous processes, and weakly positive for GFAP and EMA in places. Myelin basic protein (MBP) and synaptophysin showed a weak positive reaction in the marginal areas of the tumour.

Topics: Animals; Astrocytoma; Brain Neoplasms; Cattle; Cattle Diseases; Glial Fibrillary Acidic Protein; Glioblastoma; Glioma; Immunohistochemistry; Keratins; Mucin-1; Myelin Basic Protein; Nerve Sheath Neoplasms; S100 Proteins; Vimentin

To investigate the epithelial features of intraspinal meningiomas, 25 intraspinal meningiomas and 25 intracranial meningiomas were examined for the presence of pseudopsammoma bodies with hematoxylin-eosin and periodic acid-Schiff staining. In addition, we investigated the expression of keratin and epithelial membrane antigen (EMA) by immunohistochemical methods. Pseudopsammoma bodies were found in 3 of 25 cases of intracranial meningiomas (12%), but no definitive pseudopsammoma bodies were observed the intraspinal meningiomas. Three cases (12%) of intraspinal meningiomas and 9 cases (36%) of intracranial meningiomas, including 3 cases with pseudopsammoma bodies, were immunoreactive for keratin. All 25 (100%) intracranial meningiomas and 20 of 25 (84%) intraspinal meningiomas were reactive for EMA. In the intraspinal meningiomas, 4 of 25 cases (16%) showed no reactivity for EMA. These findings suggest that the origin of certain cell components of meningiomas may be different according to the site of the tumor or that the nature of meningioma may be modified by the local environment.

Topics: Aged; Aged, 80 and over; Brain Neoplasms; Cell Differentiation; Eosine Yellowish-(YS); Epithelium; Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Mucin-1; Periodic Acid-Schiff Reaction; Spinal Cord Neoplasms; Staining and Labeling

Topics: Animals; Brain Neoplasms; Carcinoma, Squamous Cell; Cattle; Cattle Diseases; Diagnosis, Differential; Euthanasia; Eyelid Neoplasms; Female; Horner Syndrome; Keratins; Pituitary Gland; Pituitary Neoplasms; Vimentin

The diagnosis of metastatic adenocarcinoma to the brain of unknown primary is problematic, and the role of immunohistochemistry in identifying a source has not been fully characterized. Sixty-eight metastatic adenocarcinomas of the brain with known primaries were immunostained with antibodies to cytokeratin 7 (CK7), cytokeratin 20 (CK20), CAM 5.2, wide-spectrum keratin (WSK), gross cystic disease fluid protein-15 (GCDFP-15), glial fibrillary acidic protein (GFAP), estrogen receptor (ER), and progesterone receptor (PR). True positive staining was defined as CK7 in lung or breast; CK20 in gastrointestinal; and GCDFP-15, ER, and PR in breast carcinomas. CK7 immunoreactivity was present in all 27 lung carcinomas and 14 of 15 breast carcinomas with a sensitivity of 98% and specificity of 78%. CK20 stained 15 of 16 GI carcinomas with a sensitivity and specificity of 94%. None of the cytokeratins stained surrounding brain tissue. GCDFP-15, ER, and PR had sensitivities of 33%, 33%, and 87%, with specificities of 92%, 84%, and 28%, respectively. PR often stained nuclei of normal brain tissue and was accentuated in areas of necrosis or cautery artifact. CK7 and CK20 are highly sensitive and specific in patients with metastatic adenocarcinoma to the brain of unknown primary. GCDFP-15 and ER are relatively specific, but insensitive markers, and PR is nonspecific and difficult to interpret.

Topics: Adenocarcinoma; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Brain Neoplasms; Carrier Proteins; Glial Fibrillary Acidic Protein; Glycoproteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Membrane Transport Proteins; Neoplasms, Unknown Primary; Receptors, Estrogen; Receptors, Progesterone

Several studies have shown that immunoenzymatic staining of formalin-fixed, paraffin-embedded astrocytomas with keratin antibodies frequently yields positive labelling, but no biochemical evidence of keratin expression in astrocytomas has been reported. We have investigated the presence of keratin in astrocytoma and normal brain tissues both by immunofluorescence on frozen sections and by 1D and 2D immunoblotting using seven monoclonal antibodies that, collectively, recognize most keratin polypeptides. Four of these antibodies did not stain neural tissues by immunofluorescence and were also negative by immunoblotting. The remaining three keratin antibodies stained normal brain and/or a high proportion of astrocytomas. Two of these three antibodies only stained glial fibrillary acidic protein (GFAP)-positive cells, while the third only stained GFAP-negative cells. 1D and 2D immunoblotting analysis showed that positive immunofluorescence staining of normal brain and/or astrocytomas seen with these three keratin antibodies was due to cross-reactivity with non-keratin proteins, such as GFAP. These results demonstrate that, contrary to earlier suggestions, keratin polypeptides are not frequently expressed in astrocytomas. Our studies also emphasize that keratin antibodies should be used cautiously for the differential diagnosis of undifferentiated gliomas from tumours of non-glial origin.

Topics: Antibodies, Monoclonal; Astrocytoma; Brain; Brain Neoplasms; Cross Reactions; False Positive Reactions; Fluorescent Antibody Technique, Direct; Glial Fibrillary Acidic Protein; Humans; Immunoblotting; Keratins

We examined the expression of glial- and neuronal-specific mRNAs within human gliomas using in situ hybridization. We found that low-grade astrocytomas contained a high number of proteolipid protein (PLP) mRNA-positive cells and that the number of PLP-stained cells decreased markedly with increasing tumor grade. Interestingly, the ratio of PLP mRNA-stained cells:myelin basic protein (MBP) mRNA-stained cells in normal white matter and low-grade astrocytoma was about 2:1 but approached 1:1 with increasing tumor grade. This parameter appeared to be a good indicator of tumor infiltration in astrocytomas, so we tested this in the analysis of other gliomas. Unlike astrocytomas, oligodendrogliomas were found consistently to contain few PLP mRNA- or MBP mRNA-expressing cells. In contrast, gemistocytic astrocytomas, typically highly invasive tumors, contained high numbers of PLP-positive cells and a ratio of PLP mRNA:MBP mRNA-stained cells of about 1.5:1, similar to low-grade astrocytomas. Nonradioactive in situ hybridization also enabled the morphological identification of specific cells. For example, gemistocytic astrocytes, which were found to be strongly vimentin mRNA positive, contained little glial fibrillary acidic protein mRNA and did not stain for PLP or MBP mRNAs. Neuronal mRNAs, such as neurofilament 68, were observed in small numbers of entrapped neurons within gliomas but were uninformative with respect to predicting tumor grade. Our results suggest that oligodendrocytes survive low-grade tumor infiltration and that glial tumor cells, unlike cell lines derived from them, do not express oligodendrocyte or neuronal mRNAs. In addition, the expression of mRNAs for the two major myelin protein genes, PLP and MBP, could be used to predict the grade and extent of tumor infiltration in astrocytomas.

Topics: Astrocytoma; Brain Neoplasms; Gene Expression Regulation, Neoplastic; Glial Fibrillary Acidic Protein; Glioma; Humans; In Situ Hybridization; Keratins; Myelin Basic Protein; Myelin Proteolipid Protein; Neurofilament Proteins; Neuroglia; Neurons; Oligodendroglia; Oligodendroglioma; RNA, Messenger; RNA, Neoplasm; Vimentin

A case of epithelioid sarcoma in the tongue is reported. The patient, a 35 year old woman, presented with a non-ulcerated painful lesion of the tongue. Microscopically, the tumour was characterised by multiple coalescent nodules with central geographic necrosis infiltrating the lingual muscle. The tumour cells were epithelioid with abundant eosinophilic cytoplasm and atypical nuclei. Immunohistochemically, the tumour cells stained for vimentin, keratin, and epithelial membrane antigen. These morphological and immunohistochemical appearances led to the diagnosis of epithelioid sarcoma of the tongue. Seven years later, the patient died with metastatic dissemination to the scalp, lungs, and brain. No case of epithelioid sarcoma arising in the tongue has been described previously.

Topics: Adult; Brain Neoplasms; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Sarcoma; Scalp; Skin Neoplasms; Tongue Neoplasms

Topics: Adenocarcinoma; Aged; Autoantigens; Biomarkers; Brain Neoplasms; Carcinoembryonic Antigen; Cerebellum; DNA-Binding Proteins; Gynecomastia; Humans; Immunoglobulins, Intravenous; Immunohistochemistry; Keratins; Male; Neoplasm Proteins; Neoplasms, Unknown Primary; Nerve Tissue Proteins; Paraneoplastic Syndromes; Plasma Exchange; Purkinje Cells

We present the clinical findings, radiological aspects, operative results, and histopathological features of four typical primitive neuroectodermal tumors (PNET) located in the pontine region in children. All the tumors had an endophytic intra-axial growth pattern. All the children had a short history of severe neurological deficits with involvement of the cranial nerves and pyramidal tract. MRI did not reveal any common feature of malignancy. Compared to our successful experience in operations of intra-axial endophytic brainstem tumors in a total of 32 children, the outcome was poor: all 4 children died within 13 months. We conclude that PNET occurring in the pons is not as rare as was believed, and, compared to PNET in other areas the prognosis is worse.

Topics: Actins; Adolescent; Brain Neoplasms; Child, Preschool; Desmin; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Infant; Keratins; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Nerve Tissue Proteins; Neuroectodermal Tumors, Primitive; Neurofilament Proteins; Phosphopyruvate Hydratase; Pons; Radiography; Synaptophysin; Vimentin

Topics: Animals; Astrocytoma; Blindness; Brain; Brain Neoplasms; Glial Fibrillary Acidic Protein; Goat Diseases; Goats; Immunohistochemistry; Keratins; Motor Activity; Nerve Tissue Proteins; Neurofilament Proteins; Vimentin

From a human oligodendroglioma cell line cDNA library, ten intermediate filament (IF) cDNA clones were isolated. Five clones corresponded to vimentin mRNA, two corresponded to cytokeratin K7 mRNA, and two corresponded to cytokeratin K8 mRNA. One clone encoded a novel IF mRNA. The expression of these and other IF protein genes was examined in five cell lines derived from human oligodendroglioma, astrocytoma and neuroblastoma tumors. Vimentin mRNA and K18 mRNA were expressed in all the cell lines. The K7 and K8 genes were expressed only in the oligodendroglioma cell lines. Surprisingly, nestin mRNA was expressed in the astrocytoma lines and the neuroblastoma line, but was not expressed in the oligodendroglioma lines. These results indicate that oligodendroglioma cell lines express Types I and II cytokeratin genes. This pattern of IF gene expression was different from that of the astrocytoma and neuroblastoma cell lines, which expressed IF genes usually associated with the mature cell types or with differentiating fetal neural precursor cells, i.e. GFAP and neurofilament-L. The results also suggest that the oligodendroglioma cell lines are more epithelial in character and do not reflect the gene expression of mature oligodendrocytes.

Topics: Blotting, Northern; Brain Neoplasms; Cloning, Molecular; DNA, Complementary; Gene Expression; Glial Fibrillary Acidic Protein; Humans; Intermediate Filament Proteins; Keratins; Nerve Tissue Proteins; Nestin; Oligodendroglioma; RNA, Messenger; Tumor Cells, Cultured

A 39-year-old male presented with an exceedingly rare primary intracranial epithelioid angiosarcoma in the right parietal lobe manifesting as weakness of the left hand. Neuroimaging revealed a well-defined intensely enhanced lesion in the right parietal lobe with peripheral cerebral edema. The tumor was grossly totally removed. Light microscopy of the surgical specimens revealed features typical of an epithelioid vascular tumor. The tumor cells showed intense positive immunohistochemical staining for cytokeratin and vimentin and focally positive staining for both Ulex europaeus agglutinin and anti-human endothelial cells, CD31. Tumor regrowth required two further operations. This progressive growth was consistent with an angiosarcoma. The tumor was diagnosed as an epithelioid angiosarcoma based on the histological and clinical characteristics. He became progressively obtunded and finally died. This is the first intracranial epithelioid angiosarcoma which expressed epithelial markers detectable by immunohistochemical methods.

Topics: Adult; Biomarkers, Tumor; Brain Neoplasms; Fatal Outcome; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Parietal Lobe; Reoperation; Vimentin

A rare case of cutaneous skin metastasis from an intracranial chordoma is presented. A large nodule developed in the left thigh of a 22-year-old woman who had been previously diagnosed to have a chordoma at the base of her skull. Sections from the biopsied specimens of the nodule showed proliferations of physaliphorous cells and stellate cells in cords and in nests in a myxoid stroma. Immunohistochemically, neoplastic cells were stained positively with antibodies to S-100 protein and cytokeratin. The results of the histopathological and immunohistochemical studies of the nodule were interpreted as pointing to a diagnosis of metastatic chordoma based on their similarity to the results of studies of the primary neoplasm in the cranial region. Based on the number of cases of skin metastasis from chordoma reported in the literature, skin should be kept in mind as one of the target organs, although such metastases are still rare.

Topics: Adult; Brain Neoplasms; Cell Nucleus; Chordoma; Cytoplasm; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Recurrence, Local; S100 Proteins; Skin Neoplasms; Thigh; Vacuoles

Immunohistochemical and electron microscopic studies were carried out on 9 cases of intracranial chordomas. Three of them were typical chordomas and 6 were chondroid chordomas. Immunohistochemically, both typical chordomas and chondroid chordomas were positively stained for cytokeratin and epithelial membrane antigen. Chondroid chordomas were stained for vimentin with moderate intensity whereas typical chordomas were only slightly stained. In comparison to typical chordomas, the chondroid chordomas had relatively few desmosomes and intermediate filaments. These findings suggest that intracranial chordomas are of mixed epithelial-mesenchymal nature, and that chondroid chordomas have a predominant mesenchymal character as compared to typical chordomas.

Topics: Adult; Aged; Brain; Brain Neoplasms; Chordoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Vimentin

We report on a primary cutaneous rhabdoid tumour in a 14-month-old child, to the best of our knowledge, the second case in the literature. The tumour showed a multipolypoid gross appearance and classical histological features. The neoplastic cells were positive for keratin and vimentin and most were positive for proliferating cell nuclear antigen. The ultrastructural examination revealed typical intracytoplasmic aggregates of intermediate filaments. The tumour showed a very aggressive course, and the child died 5 months after the diagnosis of cerebral metastasis.

Topics: Brain Neoplasms; Cell Nucleolus; Cell Nucleus; Cytoplasm; Fatal Outcome; Humans; Hyalin; Immunohistochemistry; Inclusion Bodies; Infant; Intermediate Filaments; Keratins; Male; Organelles; Rhabdoid Tumor; Skin Neoplasms; Vimentin

Hepatocellular carcinoma rarely metastasizes to the brain or orbit. We report 3 clinically manifest examples, one of which occurred in a 13-yr-old boy. In 2 cases the intracranial metastasis was the initial presenting lesion. The 2 cases of brain metastasis both presented with intracerebral hemorrhage. Light microscopic examination of these tumors revealed a trabecular hepatocellular carcinoma of Edmondson grade II with focal hemorrhage and necrosis. Their immunohistochemical profile was identical to that described for primary hepatocellular carcinoma. The differential diagnosis from other intracranial metastatic tumors is discussed.

Topics: Adolescent; Adult; Aged; alpha 1-Antitrypsin; alpha-Fetoproteins; Brain Neoplasms; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Orbital Neoplasms

Clinical and immunophenotypic (IP) data are presented on three children with choroid plexus (CP) tumors. Two children ages 0.2 and 2 years old with histologically proven malignant tumors had subtotal tumor resections and were treated with ten monthly cycles of eight-drugs-in-1-day chemotherapy without radiation therapy (XRT). Both are free of tumor 4 and 7 years later. The literature on survival of children with CP carcinomas after chemotherapy and XRT is reviewed. Monoclonal antibodies to 17 neuroectodermal, neuronal, glial, and leukocytic markers on frozen sections were used to IP the two malignant tumors and a CP papilloma. All tumors expressed two neuroectodermal markers (PI-153/3 and UJ 223.8), cytokeratin 19, and a neural and leukocyte marker (Thy-1). Two of three expressed neurofilament protein (NF-H) and glial fibrillary acidic protein (GFAP) and one expressed NF-M and common leukocyte antigen. None had strong expression for the panneuroectodermal antigen UJ13/A. There was variable expression of the other markers. The most common IP profile for CP tumors (cytokeratin 18+, PI-153/3+, Thy-1+, UJ 223.8+, and GFAP+ and UJ13A-, UJ 127.11-, and NF-L-) is discussed in the context of the current knowledge of the ontogenetic origin of the CP. It was concluded that chemotherapy for malignant CP tumors can be associated with long-term survival in young children and that the unique IP profile of CP tumors with coexpression of three intermediate filaments suggests new and provocative evidence of their cellular complexity and heterogeneity.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Child; Child, Preschool; Choroid Plexus Neoplasms; Female; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Immunophenotyping; Keratins; Male; Neurofilament Proteins; Tomography, X-Ray Computed

To determine the possible histogenesis of the intracranial variant of olfactory neuroblastoma.. Four specimens from three cases of intracranial olfactory neuroblastoma were studied by light microscopy and immuno-histochemistry, and electron microscopy in two cases.. Light microscopical examination showed small cell tumour with additional features of epithelioid cells in one case and ganglion cells in another. Olfactory and Homer-Wright rosettes were present. All the specimens showed a uniform positive reaction to neurone specific enolase, S-100, and cytokeratin antibodies. Glial fibrillary acidic protein was absent. The salient electron microscopic features were the presence of cell junctions, cytoplasmic intermediate filaments, basal bodies and cytolasmic processes. Dense cored vesicles were absent.. The results strongly support the view that intracranial olfactory neuroblastomas are of olfactory epithelial origin and differ from conventional neuroblastomas.

Topics: Adult; Brain Neoplasms; Cranial Fossa, Posterior; Humans; Immunoenzyme Techniques; Keratins; Male; Neuroectodermal Tumors, Primitive, Peripheral; Phosphopyruvate Hydratase; S100 Proteins

We report an unusual large, multicystic, posterior fossa neuroepithelial neoplasm involving the cerebellum, brain-stem, and quadrigeminal cistern of a 9-month-old girl. The neoplasm consisted of variably sized, sharply demarcated nests of small cells with a high nuclear-cytoplasmic ratio and moderately basophilic nuclei, embedded in a desmoplastic, immature-appearing, mesenchymal stroma. The nests contained mitoses but none were seen in the stroma. Glial fibrillary acidic protein (GFAP), neurofilament protein, synaptophysin, and cytokeratin (AE-1) were expressed in the nests. Mesenchymal cells were negative for neural markers but positive for vimentin and desmin. The neoplasm was interpreted as a mixed mesenchymal and primitive neuroectodermal tumor (PNET) with histologic features reminiscent of a recently described intraabdominal desmoplastic small cell tumor. The tumor responded poorly to chemotherapy and a second operation was performed 1 year later. The second specimen bore no resemblance to the original and consisted of epithelial-like nests and clusters of neoplastic cells frequently interrupted by sinusoidal vessels. Tumor cells had medium-sized vesicular nuclei with small nucleoli, and a granular cytoplasm. Occasional less cellular islands of neuropil-like tissue contained larger cells having eccentric, vesicular nuclei with prominent nucleoli and abundant pink cytoplasm. Mitoses were not conspicuous. Many cells expressed synaptophysin, neurofilament protein, and GFAP. Neurofilament protein was strongly positive in the larger, neuron-like cells and synaptophysin stained the neuropil-like areas strongly but was less prominent in the neuronal perikarya. Unexpectedly, the neuropil-like areas expressed epithelial membrane antigen, whereas the neuronal cells were negative for chromogranin A. The peculiar histologic picture, combination of phenotypic markers, and remarkable biologic behavior of this unusual tumor defies classification according to existing nomenclature and exemplifies the broad range of phenotypes expressed by primitive neuro-epithelial neoplasms.

Topics: Brain Neoplasms; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Desmin; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Infant; Karyotyping; Keratins; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Phenotype; Synaptophysin; Terminology as Topic; Vimentin

Adenomyoepitheliomas of the breast have been considered to have limited metastatic potential; axillary node metastasis has been reported, but there has been no report of distant metastasis. We report six cases, including two malignant adenomyoepitheliomas, one of which metastasized to the lung and brain. Patient age ranged from 26 to 63 years (mean 46). Primary tumors were solitary and measured 0.9-3.5 cm (mean 1.7). Five of six tumors presented as palpable masses. Two patients treated by local resection have no evidence of disease at 5 and 18 months' follow-up. Two patients treated by local resection had recurrences, one at 48 the other at 60 months. The fifth patient had a spindle-cell type adenomyoepithelioma diagnosed as malignant because of high mitotic rate and cytologic atypicality of the myoepithelial component. This patient was treated by mastectomy and has no evidence of disease at 18 months. The sixth patient, initially treated by local excision, had six local recurrences over 52 months treated by reexcisions, mastectomies, and radiation. A lung metastasis was resected at 54 months and brain metastases were identified at 60 months with death occurring at 64 months. Both malignant adenomyoepitheliomas had high mitotic rates [11-14/10 high-power fields (HPF)] diffusely throughout the tumors and foci of cytologically malignant cells. The malignant adenomyoepithelioma that metastasized had an infiltrative growth pattern that increased with successive local recurrences. The four other tumors had only isolated areas of mitotic activity (maximum 1-9/10 HPF) and minimal cytologic atypia. Immunohistochemistry performed on five of six cases confirmed dual epithelial/myoepithelial cell populations in all tumors examined, including the metastasis. Electron microscopic examination of the malignant adenomyoepithelioma that metastasized also confirmed dual epithelial/myoepithelial cell populations in a local recurrence and the lung metastasis. We conclude that there is a spectrum of behavior for breast adenomyoepitheliomas with potential for local recurrence and, rarely, distant metastasis.

Topics: Adult; Brain Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mitotic Index; Mucin-1; Myoepithelioma; Neoplasm Metastasis; Recurrence

Twenty-six cases of malignant soft tissue tumors with features similar to renal rhabdoid tumors were identified among approximately 3,000 childhood sarcomas entered on Intergroup Rhabdomyosarcoma Studies I-III. The tumors consisted of polygonal cells with vesicular nuclei and prominent nucleoli and cytoplasmic intermediate filament inclusions as identified by electron microscopy and immunohistochemistry. The growth pattern was predominantly solid or solid-trabecular. Immunohistochemistry showed vimentin, wide spectrum keratin, and epithelial membrane antigen to be the most consistent antigenic phenotypes. Eleven patients were infants less than 1 year of age. The tumors affected predominantly soft tissues of proximal extremities, trunk, and retroperitoneum/pelvis/abdomen. Nineteen patients died within 1 to 82 months (median, 6 months) from the start of treatment. Five patients have survived the disease for 2 to 13 years. When compared with the survival analysis of 991 Intergroup Rhabdomyosarcoma Study II patients, it was obvious that this group of tumors fares very poorly (P less than .001). The tumor belongs to the group of soft tissue neoplasms showing mesenchymal and subtle epithelial differentiation, similar to epithelioid sarcoma. Because of its identifiable histology, site and age distribution, and poor outcome, it warrants a status as an independent entity.

Topics: Adolescent; Antigens, Neoplasm; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Keratins; Kidney Neoplasms; Male; Membrane Glycoproteins; Mucin-1; Rhabdomyosarcoma; Soft Tissue Neoplasms; Vimentin

Immunoreactivities of 35 different monoclonal antibodies (MAbs) that detect intermediate filaments were studied systematically on serial cryostat sections of 14 well-defined human gliomas (five astrocytomas, three oligodendrogliomas, six glioblastomas) and on normal brain. Glial fibrillary acidic protein (GFAP), vimentin, desmin, neurofilaments, and broad-specificity keratin MAbs, as well as MAbs that recognize several or only single keratin polypeptides, were used. Unexpected reactivities were surprisingly frequent. As these may lead to diagnostic confusion and misinterpretation on this material, the authors investigated these phenomena more thoroughly. Four major sources of artifactual staining were found: 1) positive staining attributable to the rabbit gamma G immunoglobulins used in the alkaline phosphatase anti-alkaline phosphatase technique; 2) certain desmin and keratin MAbs cross-reacted with astrocytic glia and with other brain-specific epitopes; 3) technical difficulties; 4) some MAbs directed against neurofilaments and keratins showed unexpected reactivities only on individual anaplastic gliomas. The implications of these findings for intermediate filament typing of neuropathologic material are discussed.

Topics: Antibodies, Monoclonal; Brain; Brain Neoplasms; Cross Reactions; Desmin; False Positive Reactions; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Staining and Labeling

Nineteen primary intracranial sarcomas out of a total of about 25,000 brain tumour biopsies are reported. Subtypes included malignant fibrous histiocytoma (6 cases), leiomyosarcoma (3), rhabdomyosarcoma (2), angiosarcoma (2), and one case each of fibrosarcoma, low-grade fibromyxoid sarcoma, malignant ectomesenchymoma, mesenchymal chondrosarcoma, differentiated chondrosarcoma and Ewing's sarcoma. Histological and immunohistochemical features corresponded to those of extracranial sarcomas. Nests of pleomorphic astrocytes mimicking glioma were detected in the five storiform-pleomorphic malignant fibrous histiocytomas. Our results indicate that intracranial sarcomas can be classified like their extracranial counterparts. The low incidence compared with earlier series is related to changes in classification and progress in histogenetic clarification.

Topics: Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Child; Child, Preschool; Desmin; Female; Glial Fibrillary Acidic Protein; Hemangiosarcoma; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Infant; Keratins; Leiomyosarcoma; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Rhabdomyosarcoma; Sarcoma; Vimentin

We have studied paraffin-embedded specimens of 17 rat granular cell brain tumors (GCBT) from four long-term drug safety carcinogenicity studies by peroxidase-antiperoxidase (PAP) immunohistochemistry with either polyvalent or monoclonal antibodies against glial fibrillary acidic protein (GFAP), S-100 protein (S-100), Leu-7 epitopes, vimentin (VIM), keratin, desmin, and myelin basic protein. We have found that 9 of the 17 GCBT contained GFAP-positive, S-100-positive, and VIM-positive astrocytes, while GFAP-positive and VIM-positive granular cells were observed in 5 of these 9 tumors. Our findings indicate that astroglial cells are involved in rat GCBT and suggest that an astrocytic origin should be considered for these neoplasms.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Antigens, Differentiation; Brain Neoplasms; CD57 Antigens; Desmin; Female; Glial Fibrillary Acidic Protein; Granular Cell Tumor; Immunohistochemistry; Keratins; Male; Myelin Basic Protein; Rats; Rats, Inbred Strains; S100 Proteins; Vimentin

The authors add to the literature an account of four aggressive glial neoplasms characterized by diffuse cytoplasmic lipidization and a cohesive architectural disposition in epithelioid nests and sheets. These neoplasms arose in the cerebral hemispheres of adults and tended to a circumscribed neuroradiologic presentation that in two instances prompted an unrewarding preoperative search for an extracranial primary. One represented recurrent disease in a patient being followed for a biopsy-proven low-grade astrocytoma. Three cases were collected by way of consultation from pathologists uncertain as to their primary versus metastatic derivation. The apparent expression of cytokeratins and epithelial membrane antigen further conspired to obscure the glial lineage of these peculiar neoplasms, which are best regarded as tumors of the astrocytic series.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Immunohistochemistry; Keratins; Lipid Metabolism; Lipids; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Neoplasm Metastasis

The case of a woman who died from cerebral metastasis of adenocarcinoma of the uterine corpus, clinical stage IA at the time of first referral, is described. Three months after preoperative endocavitary radiotherapy followed by radical surgery followed by postoperative radiotherapy, the 59-year-old patient developed neurological symptoms. A cerebral tumor was diagnosed and subsequently excised. Histology showed metastasis of an adenocarcinoma. The patient died 3 weeks after cranial surgery. Meticulous postmortem examination failed to reveal any other tumor besides the endometrial neoplasm. Comparative immunohistochemical examination of the primary tumor and the cerebral process supported the assertion that the brain metastasis derived from the adenocarcinoma of the endometrium. Literature reports on cerebral metastasis of endometrial carcinoma are discussed.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Brain Neoplasms; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Uterine Neoplasms

Nineteen epithelial cysts in the central nervous system including six colloid cysts of the third ventricle, seven Rathke's cleft cysts in the sella, two enterogenous cysts in the posterior fossa, two epithelial cysts in the spinal canal and two neuroectodermal cysts in the cerebrum were examined immunohistochemically for expression of intermediate filament proteins-simple type, stratified type and skin type cytokeratins and GFAP. Colloid cysts of the third ventricle, Rathke's cleft cysts in the sella and epithelial cysts in the spinal canal expressed complex type cytokeratins while enterogenous cysts and neuro-ectodermal cysts showed only simple type cytokeratins. In addition, Rathke's cleft cysts expressed GFAP in occasional lining cells. The characteristic composition and distribution of cytokeratins in various kinds of epithelial cysts in the central nervous system are demonstrated and discussed with regard to their origins.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Diseases; Brain Neoplasms; Child; Child, Preschool; Choroid Plexus; Craniopharyngioma; Cysts; Ependyma; Epithelium; Female; Humans; Keratins; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Spinal Diseases; Spinal Neoplasms; Spine

Reported in this paper is a congenital ependymoma in an 23-week old foetus. The neoplasm was well vascularised and contained typical ependymal rosettes. The tumour cells did not react with GFAP-antiserum. They reacted weakly with neuron-specific enolase and vimentin and exhibited strong antigenicity with S-100-protein-antiserum. Cytokeratin antigen was recordable from some tumour cells. The tumour was sufficiently mature for classification as ependymoma. Immunohistochemical findings suggested possible ectodermal origin of the tumour cells.

Topics: Brain Neoplasms; Ependymoma; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Infant, Newborn; Infant, Premature; Keratins; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

Two cases of olfactory neuroblastoma which presented clinically as intracranial lesions are described. Prominent features of epithelial differentiation were present, which led to initial diagnoses of poorly differentiated carcinoma. The true nature of the lesions was only established subsequently by careful histological examination, immunohistochemistry and electron microscopy. The potential towards epithelial differentiation in such tumours was emphasized and certain new histological features were described, including a biphasic epithelial and stromal pattern, papillae formation and positive staining for cytokeratin. These two cases underline the importance of exhaustive examination of poorly differentiated epithelial-like lesions of the frontal lobes by conventional histology, immunohistochemistry and electron microscopy.

Topics: Brain Neoplasms; Cell Differentiation; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Neuroectodermal Tumors, Primitive, Peripheral

The successful application of immunostaining on smear preparations from 34 tumours of the central nervous system using the peroxidase-antiperoxidase technique and the avidin-biotin-peroxidase complex technique with commercially available antibodies is described. When combined with conventional smear preparations, the technique contributed to a rapid and accurate diagnosis in 79% of cases and is advocated to be a useful adjunct in neurosurgical diagnosis.

Topics: Antigens; Astrocytoma; Biopsy; Brain Neoplasms; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; In Vitro Techniques; Keratins; Membrane Glycoproteins; Meningioma; Mucin-1; S100 Proteins; Spinal Cord Neoplasms

Twenty-six intracranial germ cell tumours (11 germinomas, 10 teratomas, 2 endodermal sinus tumours, 1 teratocarcinoma, and 2 undifferentiated embryonal carcinomas) and 26 gonadal germ cell tumours (13 testicular seminomas, 2 ovarian dysgerminomas, 9 ovarian teratomas, and 2 myometrial choriocarcinomas) were studied by immunoperoxidase with monoclonal antibodies (MAbs) against epithelial membrane antigen (EMA), cytokeratin, and vimentin. Typical tumour cells in three of the 11 germinomas (two of the latter being situated in the posterior fossa) expressed both EMA and cytokeratin, whereas those in the seminomas and dysgerminomas did not. In one seminoma, a few multinucleated giant cells expressed cytokeratin. In three of seven germinomas, vimentin-positive tumour cells were found, but all seminomas and dysgerminomas were negative. In the other forms of intracranial and gonadal germ cell tumours, epithelial and mesenchymal elements displayed the expected patterns of immunoreactivity to the respective determinants. The immunoperoxidase differences between the intracranial germinomas and their gonadal equivalents indicate that, in the former, early epithelial or mesenchymal differentiation of the primordial germ cells may be present. The findings draw attention to the heterogeneous cellular composition of these otherwise morphologically homogeneous-appearing tumours and, especially in the posterior fossa, to their transitional links to the immature teratomas.

Topics: Adolescent; Adult; Antigens, Neoplasm; Brain Neoplasms; Child; Child, Preschool; Choriocarcinoma; Dysgerminoma; Epitopes; Female; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Membrane Glycoproteins; Mesonephroma; Middle Aged; Mucin-1; Ovarian Neoplasms; Teratoma; Testicular Neoplasms; Uterine Neoplasms; Vimentin

Intermediate filament keratin is regarded as a good marker for epithelial and mesothelial tumors. In the intracranial and intraspinal spaces keratin has been demonstrated only in the endocrine cells of the adenohypophysis, squamous epithelial islands in the pars tuberalis of the hypophysis and in the choroid plexus epithelium. Since gliomas and meningiomas do not express keratin, this marker provides an additional help for differentiating between primary and secondary CNS tumors. Indirect immunofluorescence using an anti-keratin serum was used in a retrospective search for keratin in 80 tumors of the cranium and intraspinal space. Of the primary CNS tumors keratin positivity occurred in craniopharyngiomas, epidermoid tumors, pituitary adenomas, chordomas, a plexus papilloma as well as in the majority of germ cell tumors. Only 3 renal cell carcinoma metastases of 21 metastatic epithelial cell tumors (7 bronchial carcinomas, 6 breast cancers, 6 renal carcinomas, 1 rectum carcinoma, 1 cervix carcinoma) were keratin-negative. Similar findings were made in two melanoma metastases which we examined, whereas in a seminoma metastasis a few keratin expressing cells were found. Primary CNS tumors such as myxopapillary ependymomas, medulloepitheliomas, malignant meningiomas and paragangliomas which are often difficult to distinguish from these metastases proved to be keratin negative.

Topics: Brain Neoplasms; Cell Differentiation; Epithelial Cells; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Neoplasm Metastasis; Spinal Cord Neoplasms

A cerebral neoplasm containing a well differentiated epidermoid cyst surrounded by islands of infiltrating squamous cell carcinoma and a pleomorphic spindle cell stroma was described. By immunoperoxidase staining all these components contained keratin. The lesion was therefore similar to malignant squamous cell lesions with sarcoma-like stroma occurring in other body sites.

Topics: Brain Neoplasms; Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged

Topics: Alopecia; Brain Neoplasms; Cobalt Radioisotopes; Facial Dermatoses; Forehead; Glioma; Hair Diseases; Humans; Keratins; Male; Middle Aged; Scalp Dermatoses; Skin Pigmentation

Topics: Brain Neoplasms; Calcium; Craniopharyngioma; Culture Techniques; Cytoplasm; Desmosomes; Esterases; Histocytochemistry; Humans; Keratins; Microscopy, Electron; Mitochondria; Organoids