Background

Tumors of the brain and spinal cord may present with devastating signs and symptoms. Even benign tumors may present with a medical emergency. The skull and vertebral column protect the vital organs but also provide very little room for expansion. Thus, any mass lesion may lead to compressive symptoms, leading to herniation of the brain and loss of function for many vital body systems.

Acoustic Neuroma (Schwannoma)
Astrocytoma and Glioblastoma Multiforme (GBM)
Atypical Teratoid/Rhabdoid Tumor of the Brain (AT/RT)
Chordoid Glioma
Chordoma
Craniopharyngioma
Desmoplastic Astrocytoma (of Infancy)
Desmoplastic Infantile Ganglioglioma
Dysembryoplastic Neuroepithelial Tumor-Like Neoplasm (DNT)
Ependymoma
Hemangioblastoma
Medulloblastoma
Meningioma
Myelomeningocele
Neurocytoma
Oligodendroglioma
Pituitary Adenoma
Pituicytoma
Tuberous Sclerosis

OUTLINE

Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Commonly Used Terms
Internet Links

RADIOLOGY/ LABORATORY	CHARACTERIZATION
RADIOLOGY
Current techniques used for the radiologic assessment of intracranial neoplasms. Debnam JM, Ketonen L, Hamberg LM, Hunter GJ. Department of Radiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.	Arch Pathol Lab Med. 2007 Feb;131(2):252-60. Abstract quote CONTEXT: Radiologic studies are obtained for diagnostic and treatment planning purposes in the evaluation of patients with intracranial neoplasms. These studies are discussed at radiology/pathology working conferences and are often beneficial in the analysis of pathologic specimens for tissue diagnosis. Therefore, clinical pathologists should be aware of the current and evolving imaging techniques that are used in the radiologic assessment of intracranial neoplasms. OBJECTIVE: To describe the imaging techniques used in the assessment of intracranial neoplasms and provide current references. DATA SOURCES: We searched PubMed for articles published between 1995 and 2006 and also reviewed several textbooks on intracranial neoplasms, to prepare a discussion of basic modalities such as computed tomography (CT) and magnetic resonance (MR) imaging as well as advanced imaging techniques such as CT and MR angiography and venography, CT and MR perfusion, MR spectroscopy, functional MR imaging, and positron emission tomography. CONCLUSIONS: Knowledge of currently used imaging techniques for the assessment of intracranial neoplasms will assist the clinical pathologist in communications with neuroradiologists, surgeons, and referring clinicians. This review will also aid the pathologist in understanding the new and rapidly evolving imaging techniques that will likely become the standard of care in the future.
MOLECULAR DIAGNOSTICS
Molecular diagnostics in central nervous system tumors. Fuller CE, Perry A. Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, and Division of Neuropathology, Washington University School of Medicine, St. Louis, MO, USA.	Adv Anat Pathol. 2005 Jul;12(4):180-94. Abstract quote   Central nervous system (CNS) neoplasms can be diagnostically challenging, due to remarkably wide ranges in histologic appearance, biologic behavior, and therapeutic approach. Nevertheless, accurate diagnosis is the critical first step in providing optimal patient care. As with other oncology-based specialties, there is a rapidly expanding interest and enthusiasm for identifying and utilizing new biomarkers to enhance the day-to-day practice of surgical neuropathology. In this regard, the field is primed by recent advances in basic research, elucidating the molecular mechanisms of tumorigenesis and progression in the most common adult and pediatric brain tumors. Thus far, few have made the transition into routine clinical practice, the most notable example being 1p and 19q testing in oligodendroglial tumors. However, the field is rapidly evolving and many other biomarkers are likely to emerge as useful ancillary diagnostic, prognostic, or therapeutic aids. The goal of this article is to highlight the most common genetic alterations currently implicated in CNS tumors, focusing most on those that are either already in common use in ancillary molecular diagnostics testing or are likely to become so in the near future.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
DURAL METASTASES
Dural Metastases A Retrospective Surgical and Autopsy Series B. K. Kleinschmidt-DeMasters, MD From the Departments of Pathology and Neurology, The University of Colorado Health Sciences Center, Denver, Colo.	Arch Pathol Lab Med 2001;125, No. 7:880–887. Abstract quote Background.—Metastases to dura constitute one of the least frequent and least studied patterns of neoplastic spread to the craniospinal axis. Older reports cited breast cancer as accounting for the largest number of dural metastases, often as a manifestation of end-stage disease. Since the early 1980s we have noted an increasing number and diversity of cancer types in patients with dural metastases in our surgical and autopsy neuropathology experience. Some surgical patients have experienced prolonged postoperative survival. Methods.—Review of autopsy records from 1982 to 1999 and surgical pathology records from 1990 to 2000 at a large university teaching hospital, including consultation files. Results.—Dural metastases removed at surgery (n = 33) were usually single, cranial, subdural lesions; coexistence with brain parenchymal or skull metastases varied according to tumor type. Unusual tumor types included carcinomas of colon, endometrium, cervix, and stomach. One well-documented patient developed postsurgical implantation metastases, and 2 patients had co-associated acute subdural hematomas. Surgical patients showed widely varying postoperative survival times, but in several of these patients survival times were in excess of 2 years. Dural metastases seen at autopsy (n = 27) could also be solitary and nodular, but more examples were extensive, diffuse, and both subdural and epidural in location. The expected cases of breast cancer (n = 5) occurred, but more examples of prostate cancer (n = 7) or unusual malignant neoplasms (cervical = 3, laryngeal = 1, gallbladder = 1, Ewing sarcoma = 1, intravascular lymphomatosis = 1, ocular melanoma = 1) were identified. Conclusions.—This combined surgical and autopsy series shows a different distribution of tumor types causing dural metastases than older series. Postoperative outcome may be favorable in select, surgically treated patients.

 

HISTOPATHOLOGICAL VARIANTS	CHARACTERIZATION
GENERAL
Clinical-histopathologic concordance of tumors of the nervous system at the manuel velasco suarez national institute of neurology and neurosurgery in Mexico city. Velasquez-Perez L, Jimenez-Marcial ME. Department of Neuroepidemiology, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico City, Mexico.	Arch Pathol Lab Med 2003 Feb;127(2):187-92 Abstract quote Context.-When making a diagnosis, the main purpose of clinicians should not be to achieve certainty, but to decrease diagnostic uncertainty in order to make optimal therapeutic decisions. Diagnostic concordance is an essential characteristic if a measurement is to be considered scientific. In the case of tumors of the nervous system (TNS), one of the most accurate diagnostic tests is magnetic resonance imaging. However, histopathologic analyses are essential, because they refine the diagnosis, benefit the patient, and improve our understanding of the disease. By determining the clinical-histopathologic correlation of TNS in one of the main neurologic centers in Mexico, we sought to project reliable morbidity and/or mortality statistics. Objective.-To assess clinical and histopathologic diagnostic agreement in cases involving TNS admitted to the Manuel Velasco Suarez National Institute of Neurology and Neurosurgery between 1990 and 1999. Design.-Cross-sectional diagnostic concordance study, including all clinical hospital records of patients with histopathologically diagnosed TNS, classified according to World Health Organization criteria. Results.-Among 2041 TNS cases, the 3 most frequent types were those affecting the neuroepithelial tissue (32.9%), tumors of the sellar region (29.2%), and tumors of the meninges (25.6%). We found that, overall, clinical-histopathologic concordance for these 3 categories was substantial and statistically significant. Conclusions.-Tumors of the nervous system constitute a heterogeneous group of neoplasms. In the present study, clinical diagnoses substantially agreed with pathologic diagnoses. The a priori clinical diagnosis allowed prompt treatment even before diagnostic confirmation by histopathologic analysis, which is the best way to confirm, clarify, and correct a diagnosis.
CHOROID PLEXUS TUMORS
Identification of Novel Diagnostic Markers for Choroid Plexus Tumors: A Microarray-Based Approach. Hasselblatt M, Bohm C, Tatenhorst L, Dinh V, Newrzella D, Keyvani K, Jeibmann A, Buerger H, Rickert CH, Paulus W. From the *Institute of Neuropathology and double daggerGerhard Domagk Institute of Pathology, University Hospital Munster, Munster, Germany; and daggerAxaron Bioscience, Heidelberg, Germany.	Am J Surg Pathol. 2006 Jan;30(1):66-74. Abstract quote   To identify specific markers for the diagnosis of choroid plexus tumors, gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays. Protein expression of genes overexpressed in choroid plexus was evaluated in normal choroid plexus, choroid plexus papilloma, choroid plexus carcinoma, other primary brain tumors, and cerebral metastases. Forty-six genes found to be overexpressed in normal choroid plexus epithelial cells were also present in choroid plexus papilloma. Among those, 11 were further analyzed by immunohistochemistry. Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases. Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases. Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower. Antibodies directed against coagulation factor V, glutathione peroxidase 3, pigment epithelium derived factor, serotonin receptor 5-HTR2C, lumican, fibulin-1, plastin-1, and cytokeratin 18 revealed varying degrees of specificity and sensitivity. Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors.
PAPILLARY TUMOR OF THE PINEAL REGION
Papillary tumor of the pineal region. Jouvet A, Fauchon F, Liberski P, Saint-Pierre G, Didier-Bazes M, Heitzmann A, Delisle MB, Biassette HA, Vincent S, Mikol J, Streichenberger N, Ahboucha S, Brisson C, Belin MF, Fevre-Montange M.	Am J Surg Pathol 2003 Apr;27(4):505-12 Abstract quote Primary papillary tumors of the central nervous system are rare. We have encountered a series of six papillary tumors of the pineal region with distinctive features that appear to represent a clinicopathologic entity. The tumors occurred in four women and two men, ranging in age from 19 to 53 years. Imaging studies showed a large well-circumscribed mass in the pineal region. The tumors were characterized by an epithelial-like growth pattern, in which the vessels were covered by a layer of tumoral cells. In papillary areas, the neoplastic cells were large, columnar or cuboidal, with a clear cytoplasm. Nuclei, round or infolded, were found generally at the basal pole of tumoral cells. Immunohistochemically, the tumor cells showed strong staining for cytokeratin, S-100 protein, neuron-specific enolase, and vimentin but only weak or no staining for epithelial membrane antigen and glial fibrillary acid protein. Ultrastructural examination of two cases revealed abundant rough endoplasmic reticulum with distended cisternae filled with secretory product, microvilli, and perinuclear intermediate filaments. The morphofunctional features of these papillary tumors of the pineal region, remarkably uniform within this series, are similar to those described for ependymal cells of the subcommissural organ, and the papillary tumors of the pineal region may be derived from these specialized ependymocytes.
TEXTILOMA
Textiloma (gossypiboma) mimicking recurrent intracranial tumor. Ribalta T, McCutcheon IE, Neto AG, Gupta D, Kumar AJ, Biddle DA, Langford LA, Bruner JM, Leeds NE, Fuller GN. Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Suner (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.	Arch Pathol Lab Med. 2004 Jul;128(7):749-58. Abstract quote   CONTEXT: Resorbable substances used to achieve hemostasis during neurosurgical procedures comprise 3 principal classes based on chemical composition: (1) gelatin sponge, (2) oxidized cellulose, and (3) microfibrillar collagen. Nonresorbable hemostatic aides include various forms of cotton and rayon-based hemostats (cottonoids and kites). Resorbable and nonresorbable hemostatic agents have been reported to cause symptomatic mass lesions, most commonly following intra-abdominal surgery. Histologic examination typically shows a core of degenerating hemostatic agent surrounded by an inflammatory reaction. Each agent exhibits distinctive morphologic features that often permit specific identification. Hemostat-associated mass lesions have been variously referred to as textilomas, gossypibomas, gauzomas, or muslinomas. OBJECTIVES: The aims of this study were to (1) identify cases of histologically proven cases of textiloma in neurosurgical operations, (2) characterize the specific hemostatic agent associated with textiloma formation, and (3) characterize the preoperative magnetic resonance imaging appearance of textiloma. DESIGN: Cases in which a textiloma constituted the sole finding on repeat surgery for recurrent brain tumor, or was a clinically significant component of a radiologically identified mass lesion together with residual tumor, constituted the study set. RESULTS: Five textilomas were identified and evaluated. The primary neoplasm was different in each case and included pituitary adenoma, tanycytic ependymoma, anaplastic astrocytoma, gliosarcoma, and oligodendroglioma. In all cases, preoperative magnetic resonance imaging suggested recurrent tumor. Textilomas included all categories of resorbable hemostatic agent. Other foreign bodies were present in some cases; the origin of these foreign bodies was traced to fibers shed from nonresorbable hemostatic material placed temporarily during surgery and removed before closure (cottonoids and kites). Inflammatory reactions included giant cells, granulomas, and fibroblastic proliferation. Microfibrillar collagen (Avitene) textilomas were associated with a striking eosinophil infiltration that was not seen with any other hemostatic agent. CONCLUSIONS: Hemostatic agents may produce clinically symptomatic, radiologically apparent mass lesions. When considering a mass lesion arising after intracranial surgery, the differential diagnosis should include textiloma along with recurrent tumor and radiation necrosis.

 

SPECIAL STAINS/ IMMUNO-HISTOCHEMISTRY	CHARACTERIZATION
GENERAL
New immunohistochemical markers in the evaluation of central nervous system tumors: a review of 7 selected adult and pediatric brain tumors. Takei H, Bhattacharjee MB, Rivera A, Dancer Y, Powell SZ. Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Suite 286A, Houston, TX 77030-3498, USA.	Arch Pathol Lab Med. 2007 Feb;131(2):234-41. Abstract quote CONTEXT: Immunohistochemistry (IHC) has become an important tool in the diagnosis of brain tumors. OBJECTIVE: To review the latest advances in IHC in the diagnostic neuro-oncologic pathology. DATA SOURCES: Original research and review articles and the authors' personal experiences. DATA SYNTHESIS: We review the features of new, useful or potentially applicable marker antibodies as well as the new uses of already established antibodies in the area of diagnostic neuro-oncologic pathology, focusing on the use of IHC for differential diagnosis and prognosis. We discuss (1) placental alkaline phosphatase, c-Kit, and OCT4 for germinoma, (2) alpha-inhibin and D2-40 for capillary hemangioblastoma, (3) phosphohistone-H3 (PHH3), MIB-1/Ki-67, and claudin-1 for meningioma, (4) PHH3, MIB-1/Ki-67, and p53 for astrocytoma, (5) synaptophysin, microtubule-associated protein 2, neurofilament protein, and neuronal nuclei for medulloblastoma, (6) INI1 for atypical teratoid/rhabdoid tumor, and (7) epithelial membrane antigen for ependymoma. All the markers presented here are used mainly for supporting or confirming the diagnosis, with the exception of the proliferation markers (MIB-1/Ki-67 and PHH3), which are primarily used to support grading and are reportedly associated with prognosis in certain categories of brain tumors. CONCLUSIONS: Although conventional hematoxylin-eosin staining is the mainstay for pathologic diagnosis, IHC has played a major role in differential diagnosis and in improving diagnostic accuracy not only in general surgical pathology but also in neuro-oncologic pathology. The judicious use of a panel of selected immunostains is unquestionably helpful in diagnostically challenging cases. In addition, IHC is also of great help in predicting the prognosis for certain brain tumors.
SPECIFIC MARKERS
alpha-v-beta-3 INTEGRIN
alphavbeta3 Integrin in central nervous system tumors. Lim M, Guccione S, Haddix T, Sims L, Cheshier S, Chu P, Vogel H, Harsh G.	Hum Pathol. 2005 Jun;36(6):665-9 Abstract quote.   Summary alpha v beta 3 is an integrin specifically expressed in endothelial cells of newly forming blood vessels. Integrin-mediated angiogenesis is hypothesized to play a central role in the development and the progression of central nervous system neoplasms. Accordingly, it is considered a potential target for antiangiogenic therapy. In the current study, we compare the expression of alpha v beta 3 in ependymomas, oligodendrogliomas, pilocytic astrocytomas, medulloblastomas, and vestibular schwannomas (acoustic neuromas). Samples of 5 tumors of each of the 5 tumor types were harvested surgically and frozen. After the pathological diagnosis was confirmed, immunohistochemistry was performed using an anti- alpha v beta 3 monoclonal antibody (LM609). The expression of alpha v beta 3 was assessed using a 4-tiered (0-3) grading scheme reflecting the percentage of positively staining vessels. All vestibular schwannomas demonstrated strong (grade 3) alpha v beta 3 expression. The expression was uniformly prominent in Antoni B regions of the tumors. Of 5 ependymomas, 4 demonstrated uniformly strong alpha v beta 3 expression. Oligodendrogliomas, medulloblastomas, and pilocytic astrocytomas demonstrated more variable alpha v beta 3 expression. alpha v beta 3 may contribute significantly to angiogenesis in vestibular schwannomas and ependymomas. Despite the high vascular density of oligodendrogliomas, pilocytic astrocytomas, and medulloblastomas, these tumors had variable moderate alpha v beta 3 expression. This discrepancy suggests temporal and/or regional variability in the angiogenesis in these types of tumor. This study provides the first demonstration of alpha v beta 3 expression in vestibular schwannomas, medulloblastomas, and pilocytic astrocytomas.
MIB-1/Ki-67
The Utility of MIB-1/Ki-67 Immunostaining in the Evaluation of Central Nervous System Neoplasms. Prayson RA. From the Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio.	Adv Anat Pathol. 2005 May;12(3):144-8. Abstract quote   The diagnosis and assignment of grade in neoplasms of the central nervous system (CNS), for the most part, are morphologically based and predicated on the interpretation of descriptions of what the phenotypic findings are for a particular tumor type. Not surprisingly, the application of various grading systems in CNS neoplasia has been limited somewhat by interobserver variability. Since assignment of grade and tumor type is the basis upon which therapeutic intervention is grounded, investigators have been searching for ancillary means by which morphologically based systems can be improved. Utilization of cell proliferation markers in the evaluation of tumors can be potentially useful in this endeavor. This review focuses on issues surrounding the utilization of MIB-1 or Ki-67 antibody in the evaluation of CNS neoplasms.
TTF-1
Immunohistochemical staining for thyroid transcription factor-1: A helpful aid in discerning primary site of tumor origin in patients with brain metastases. Srodon M, Westra WH. Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD.	Hum Pathol 2002 Jun;33(6):642-5 Abstract quote Metastatic carcinoma of unknown primary origin is a perplexing but common problem, accounting for up to 10% to 15% of all solid tumors at presentation. Many of these metastases presumably arise from primary lung carcinomas, but the morphologic features and immunohistochemical profile of lung cancer is often too nonspecific to permit unequivocal confirmation. Thyroid transcription factor-1 (TTF-1) is expressed in lung adenocarcinomas and thyroid carcinomas but not in adenocarcinomas arising from other sites. For patients with adenocarcinomas in the lung, TTF-1 staining is now routinely used to distinguish a primary lung cancer from a lung metastasis. Along these same lines, TTF-1 staining might prove useful in localizing the tumor origin of adenocarcinomas encountered outside of the lung. The archival surgical pathology files of The Johns Hopkins Hospital were searched for cases of brain metastases biopsied between 1990 and 2000. Tissue blocks were obtained and immunoperoxidase staining was performed using the TTF-1 antibody. The medical records were reviewed independent of the staining results to determine site of tumor origin. Seventy-five patients underwent biopsies of carcinomas metastatic to the brain. At the time of brain biopsy, the primary site of tumor origin was known in 45 cases and unknown in 30 cases. Ultimately, the primary site was established on clinical and radiographic grounds in 71 cases (95%). These included 40 (56%) metastases from a primary lung carcinoma and 31 (44%) metastases from some nonpulmonary carcinoma. TTF-1 staining was present in 31 of the 40 (78%) metastatic lung carcinomas, but in only 1 of the 31 (3%) metastatic nonpulmonary carcinomas (a small-cell carcinoma of the sinonasal tract). When the metastatic lung carcinomas were subtyped, TTF-1 staining was noted in 11 of 11 (100%) adenocarcinomas, in 6 of 7 (86%) small-cell carcinomas, in 15 of 19 (79%) large-cell carcinomas, and in none of 3 (0%) squamous cell carcinomas. TTF-1 staining is very reliable in discerning whether a brain metastasis has arisen from a pulmonary or nonpulmonary site, particularly when dealing with adenocarcinomas and large-cell carcinomas. TTF-1 immunohistochemistry could focus the search for the primary tumor for patients presenting with brain metastasis as the initial manifestation.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
CLEAR CELL NEOPLASMS
Clear cell neoplasms and pseudoneoplastic lesions of the central nervous system. Gokden M, Roth KA, Carroll SL, Wick MR, Schmidt RE. Department of Pathology, Washington University School of Medicine, St Louis, MO 63110-0193, USA.	Semin Diagn Pathol 1997 Nov;14(4):253-69 Abstract quote Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.
METASTATIC TUMORS
Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Department of Epidemiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.	Cancer 2002 May 15;94(10):2698-705 Abstract quote BACKGROUND: The objective of this study was to report on the incidence of and factors related to the occurrence of central nervous system metastases in a cohort of patients who were diagnosed with colorectal, lung, breast, or kidney carcinoma or melanoma. METHODS: Using the population-based Maastricht Cancer Registry (MCR), a cohort was created of patients with colorectal carcinoma (n = 720 patients), lung carcinoma (n = 938 patients), breast carcinoma (n = 802 patients), renal carcinoma (n = 114 patients), and melanoma (n = 150 patients). The patients had to live in the catchment area of the University Hospital Maastricht (UHM) and had to have been diagnosed at the UHM during the period 1986-1995. Patients with brain metastases were searched for by linking the MCR to the Neuro-Oncology Registry of the UHM. Radiology files were checked as well. Follow-up lasted until December 31, 1998. RESULTS: Brain metastases were diagnosed in 232 patients (8.5%) in the cohort (n = 2724 patients). Of these patients, 84 patients were diagnosed with brain metastases within 1 month after their primary diagnosis, 82 patients were diagnosed with brain metastases within 1 year of their primary diagnosis, and 66 patients were diagnosed with brain metastases more than 1 year after their primary diagnosis. The cumulative incidence after 5 years was estimated at 16.3% in patients with lung carcinoma, 9.8% in patients with renal carcinoma, 7.4% in patients with melanoma, 5.0% in patients with breast carcinoma, and 1.2% in patients with colorectal carcinoma. The incidence was lower in patients age > or = 70 years compared with younger patients (breast and lung carcinoma), lower in patients who were diagnosed before 1991 compared with patients who were diagnosed after 1991 (breast and lung carcinoma), and lower in patients who had nonsmall cell lung carcinoma compared with patients who had small cell lung carcinoma. CONCLUSIONS: The frequency of brain metastases in this cohort was highest in patients with lung carcinoma, followed by patients with renal carcinoma. There was no evidence of an increasing incidence of brain metastasis in patients with carcinoma of the breast or lung.
TUMORS IN THE AGED
Neoplasms involving the central nervous system in the older old. Kleinschmidt-DeMasters BK, Lillehei KO, Breeze RE. Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.	Hum Pathol. 2003 Nov;34(11):1137-47 Abstract quote.   Geriatric cancer patients present special challenges for clinicians. Few large series have been published in the last 20 years on the types of neoplasms that involve the central nervous system (CNS) in older individuals. To review types of neoplasms involving the central CNS that are currently being encountered by pathologists and neurosurgeons, we identified from our databases for the years 1992-2002, inclusive, patients 75 years or older who had symptomatic lesions requiring neurosurgical interventions. Retrospective characterization of tumors by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization was performed whenever possible and relevant to tumor type. Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients were diagnosed as having neoplasms, with clot evacuation or infections being the most frequent non-neoplastic conditions necessitating surgery. Tumor types included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12), lymphomas or other hematological malignancies (8), anaplastic gliomas (5), metastases (6), head and neck malignancies with direct intracranial extension (3), and other miscellaneous tumor types (4). Compared with older literature series, we encountered a larger number of elderly patients with CNS lymphomas and fewer who came to surgery for CNS metastatic disease. In the "older old", glioblastomas are the most frequent symptomatic tumors necessitating surgical intervention. Glioblastomas in this aged cohort display the signature features of the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1-labeling index=25.1%), and either amplification of epidermal growth factor receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of assessable cases).

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Alzheimer type II astrocyte-These special astrocytes are found in the gray matter. They are characterized by nuclei which are 2-3 times the size of a normal astrocyte. Unlike the name it shares, it is not a characteristic change of Alzheimer's disease. Instead, it is often found in conditions of metabolic disturbance, such as liver failure.

Astrocytes-This is found in both white and gray matter and are primarily responsible for repair and scar formation or gliosis.

Corpora amylacea-These are round lamellated structures found with increasing age. They represent degenerative changes within astrocytes.

Ependyma-These are the lining cells of the brain's ventricular system.

Glial cells-These are supporting cells of the nervous system. They support the neurons, play important roles in cellular metabolism, and initiate repair. They are composed of astrocytes, oligodendrocytes, ependyma, and microglia.

Gliosis-This is scarring in the brain, formed by proliferation of astrocytes.

Gray and white matter-The brain is broadly divided into these two types of tissues. Gray matter contains the neurons while the white matter contains the myelinated nerves.

Oligodendrocytes-These are mainly found in white matter. They produce the myelin that surrounds nerve fibers insulating them and allowing for rapid neural transmission.

Microglial cells-These are the scavenger cells of the CNS, functioning as macrophages.

Rosenthal fibers-These are thick, elongated, brightly eosinophilic structures. They are found in conditions of long standing gliosis, occasional tumors, and rare metabolic degenerative disorders.

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