the subject of tumors of the nervous system is often looked upon with apprehension by medical students and practitioners , with some justification . the plethora of terminologies and systems of grading and classification , the bewildering numbers of separately named lesions , and their apparently endless histologic variations provide ample basis for their perception . central nervous system ( cns ) tumors are the neoplasms constituting 1 - 2% of all the neoplasms . gliomas constitute 38.7% of cns tumors in which high - grade gliomas are 59.5% and low - grade gliomas are 33.1% . the incidence of metastasis from lung carcinoma is 18 - 60% , breast carcinoma 5 - 21% , melanoma 4 - 16% , genitourinary 310% , while gastrointestinal malignancies constitute 5 - 12% . immunohistochemistry ( ihc ) has become an important tool in the diagnosis of brain tumors . although conventional hematoxylin and eosin ( h and e ) 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 . ihc using monoclonal or polyclonal antibodies has greatly influenced the diagnosis of various neurological disorders . using this technique , the presence of characteristic antigen can be precisely defined in a sensitive and reproducible manner , thereby providing a better tool for making an accurate diagnosis of brain tumors . glial fibrillary acidic protein ( gfap ) was first isolated from old multiple sclerosis plaques by roy and sarkar . it is normally present in the astrocytes ( mature and developing ) , ependymal cells , and radial glia of developing the brain . positive reaction to gfap has been demonstrated in astrocytomas , ependymoma , and astrocytic cells of mixed gliomas , subependymal giant cell astrocytoma , pleomorphic xanthoastrocytoma , astroblastoma , and gliosarcoma . cytokeratins ( cks ) monoclonal antibodies are useful in identification of the epithelial nature of the neoplasm . these antibodies are most useful in the differentiation of poorly differentiated epithelial malignancies from those other nonepithelial neoplasm . group a ( acidic ) and group b ( basic ) keratins are separated into 19 members by molecular weight , charge specificities , and immunoreactivity with monoclonal antibodies with restricted specificities . it has been shown to react with one group a keratin ( molecular weight 50 kd ) and two group b keratins ( molecular weight 43 kd and 39 kd ) . high - grade gliomas are difficult to differentiate from metastatic tumors on the basis of light microscopy alone . the role of cam5.2 being highly specific is emerging as a specific marker to diagnose metastatic carcinoma . hence , this study is planned to differentiate glial tumors from metastatic tumors with the help of ihc ( cam5.2 and gfap ) . the present study was conducted over a period of 2 years , from december 2010 to december 2012 in department of pathology , pandit b.d . sharma pgims , rohtak and comprised of total 80 cases of cns tumors including metastatic tumors to the cns . special ihc markers ( gfap and cam5.2 ) were used to differentiate high - grade gliomas from metastatic tumors . sections of the human brain were run with each batch of ihc stains to act as a positive control for gfap and skin biopsy as a positive control for cam5.2 . a negative control was obtained by substituting the primary antibody with an antibody of unrelated specificity . over a period of 2 years , we examined total 80 cases of cns tumors including metastatic tumors to the cns [ figure 1 ] . in our study , the average age for the glial tumor was 35 years and for the metastatic tumor was 55 years . among glial tumors , 71% were male , and 29% were female in a ratio of 2.5:1 , whereas in metastatic tumors male to female ratio was 2:1 showing male preponderance . radiological findings based on contrast - enhanced computer tomography ( ct ) revealed that the maximum cases of glial tumors were nonenhancing as compared to metastasis , which were enhancing and hypodense . frequency of various histologic subtypes of glial and metastatic tumors in the present study , glial tumors were widely reactive for gfap [ figures 2 and 3a  b ] except few oligodendrogliomas [ figure 3c and d ] and mixed glial tumors and metastatic tumors were negative for gfap and reactive for cam5.2 [ figures 46 ] . gfap expression in glial tumors was statistically significant ( sensitivity 81.1% and specificity 100% ) as compared to metastatic tumors . cam5.2 expression in metastatic tumors was also statistically significant ( sensitivity 100% and 100% specificity ) [ table 1 ] . grade i astrocytoma ( a ; h and e , 200 ) and gemistiocytic astrocytoma ( c ; h and e , 200 ) . glial fibrillary acidic protein was positive in both the tumors ( b ; immunohistochemistry , 100 ) ( d ; immunohistochemistry , 200 ) glioblastoma multiforme ( a ; h and e , 40 ) revealing glial fibrillary acidic protein positivity ( b ; immunohistochemistry , 100 ) . however , oligodendroglioma ( c ; h and e , 100 ) did not show positivity for glial fibrillary acidic protein ( d ; immunohistochemistry , 400 ) metastatic adenocarcinoma ( a ; h and e , 100 ) revealing cam5.2 positivity ( b ; immunohistochemistry , 200 ) metastatic renal carcinoma ( a ; h and e , 200 ) revealing cam5.2 positivity ( b ; immunohistochemistry , 200 ) and glial fibrillary acidic protein negativity ( c ; immunohistochemistry , 200 ) photomicrograph showing cam5.2 positivity ( a;ihc;200 ) and gfap negativity ( b;ihc;200 ) in metastatic follicular carcinoma thyroid correlation of gfap and cam5.2 staining in glial and metastatic tumors some of the ihc markers are relatively sensitive and specific for some tumors ( e.g. , gfap for astrocytomas ) . gfap is currently used as a routine antigenic marker for normal developing and mature astroglial cells and for pathologically altered astrocytes . this protein is typically absent in primitive or neoplastic neuroepithelial cells , ganglion cells , oligodendrocytes , vascular endothelium , meningeal cells , fibroblasts , and other mesenchymal elements . the value of immunoperoxidase stain for gfap is relevant in documenting astrocytic differentiation in the tumor growing outside the cns parenchyma . the false negative reaction may occur as a consequence of delayed or improper fixation , presumably because much of the gfap is in the soluble form and that can leach from the tissue before it is processed appropriately . gfap found to be highly specific and sensitive marker when compared with other special stains and markers . it was found of particular importance in demonstration of astrocytic cellular differentiation in primitive or highly anaplastic cns tumors , in study of mixed glial tumors , demonstration of glial nature of tumors , and diagnosing glial tumors invading meninges and extraneural sites . glial filament immunoreactivity had been observed in tumor cells of glial origin and in tumor cells with foci of glial differentiation arising within cns . the value of the immunoperoxidase stain for gfap is particularly relevant in documenting astrocytic differentiation in tumors growing outside the cns . it is , therefore , required for each center to determine the sensitivity and specificity of gfap staining under their own conditions . cam5.2 is an igg2a murine monoclonal immunoglobulin composed of lower molecular weight ck proteins ( 50,000 , 43,000 , and 39,000 daltons ) . comparison of cam5.2 with other epithelial markers showed that it was most effective in discriminating between benign and malignant lesions . it is critical to keep this point in mind when faced with the differential diagnosis of high - grade gliomas versus metastatic tumors in brain biopsies . it would be appropriate to go with highly specific low molecular weight ck ( cam5.2 ) , which are positive in metastatic tumors and do not stain glial tumors . the wide variation in different series as shown in table 1 may be due to various factors such as difference in source of material that is surgical or autopsy , the type of the concerned hospital that is neurological or surgical and the hospital concerned may serve a selective population of older patients . it also depends on the tendency of a neurosurgeon to avoid a biopsy if a primary site is known and multiple lesions are seen in the brain in ct scan . high - grade astrocytic malignant neoplasms are difficult to distinguish from poorly differentiated metastatic carcinomas , particularly on small open biopsies . metastatic tumors seen in cns may occasionally be difficult to distinguish histologically from high - grade gliomas . glioblastoma multiforme ( gbm ) is characterized histologically by the presence of nuclear atypia , high mitotic rate and presence of necrosis , all characteristics often encountered in poorly differentiated metastatic carcinoma . the absence of well differentiated foci of metastatic carcinoma may make a diagnosis of metastatic carcinoma versus gbm difficult by light microscopic examination alone . early detection of cancer and effective treatment increases the longevity of cancer patients . in the present study , astrocytomas , as expected , besides helping in the origin of histopathologically difficult cases of anaplastic astrocytoma , gfap immunostain helped in the objective assessment of the degree of differentiation in these neoplasms . astrocytic nature of the tumor cells was confirmed by demonstration of gfap in less anaplastic areas . positive gfap immunostaining helped to overcome histopathological diagnostic problems in some undifferentiated tumors and to categorize these tumors as gbm . use of gfap and cam5.2 immunomarker easily distinguished these two lesions in the occasional cases where light microscopic evaluation proven insufficient . gfap is a superior marker to s-100 and vimentin as observed by few authors based on immunostaining pattern of gfap , vimentin , and s-100 using ihc techniques in human glial tumors . perry et al . studied the diagnosis of metastatic adenocarcinomas to the brain of unknown primary . sixty - eight cases of metastatic adenocarcinomas to the brain with known primaries were immunostained with antibodies to ck 7 , ck 20 , and cam5.2 . cam5.2 is a useful confirmatory stain in suspected metastatic adenocarcinoma to the brain . unlike nonspecific ae1/3 ae1/3 antibody should be avoided in the brain because of the common staining of both normal and neoplastic astrocytes , but cam5.2 does not suffer this drawback and it is expressed in metastatic tumors to the brain . concluded that normal and malignant astrocytes can be positive with nonspecific cks ae1/3 along with gfap but not with monoclonal antibody cam5.2 . an understanding of the pathology of cns tumors plays a vital role in the management of patients and in clinical and biological research . although ct and magnetic resonance imaging allow accurate localization of intracranial and spinal lesions , and often serve as a very good guide to the nature of the lesion , the final diagnosis of a tumor relies almost exclusively on histological evaluation of tissue taken at biopsy or autopsy . pathology , radiology , and clinical evaluation all play a key role in the diagnosis and prognosis of tumors of the nervous system . an accurate diagnosis of brain tumors is usually possible after a careful assessment of routine microscopic features with sufficient clinical and radiological information . high - grade gliomas such as gbm are fairly encountered in routine surgical neuropathology and it is crucial to differentiate them from metastatic tumors . categorization is more problematic in such cases due to various parameters including the presence of necrosis and small sample size due to stereotactic biopsies . from the present study , it is concluded that ihc is a valuable technique and the best effective combination in differentiating high - grade gliomas from metastatic tumors of cns are gfap and cam5.2 .