they consist of spectrum of tumors ranging from benign tumors such as neurofibroma ( nf ) and schwannoma to malignant tumors , called malignant pnst ( mpnst ) . mpnst is a rare tumor with incidence of 0.001% and in patient of neurofibromatosis 1 ( nf1 ) , its incidence increases to 44.6% . initially , world health organization ( who ) has classified these tumors under 2007 who classification of tumors of the central nervous system under cranial and peripheral nerves , skin , head , and neck . now these tumors are classified under 2013 who classification of tumors of soft tissue and bone thus bringing all mesenchymal tumors under a single roof . benign pnsts ( bpnst ) are not studied much while morphological , immunohistochemical , and molecular studies on mpnst are available . in this communication , we describe morphological spectrum of 143 pnst from a single center of south india . this is a retrospective study conducted at a medical college and teaching hospital for 6 years from january 2010 to june 2015 . the demographic profiles of the patients such as age , sex , and site of tumor and gross findings such as size and other details were noted from the pathology case files . the hematoxylin and eosin ( h and e ) stained slides were retrieved from the archives and in cases where h and e slides are not available , paraffin block was removed and 35  thick sections were cut and stained by h and e. the slides were reassessed and the lesion were categorized and classified as per the who 2013 classifications . the tumors were assessed for morphological features such as ( a ) variants , ( b ) mitotic activity , ( c ) necrosis , ( d ) cystic change , ( e ) verocay body , ( f ) hemorrhage , ( h ) myxoid change , ( i ) pigment , and ( j ) calcification . necrosis was graded as 0 , 1 , and 2 representing 0% , < 50% , and > 50% , respectively . malignant tumors were graded as low grade and high grade , based on mitotic activity , tumors with mitotic count more than 5/hpf are considered as high grade . for the diagnosis of nf1 , the criteria given in 2007 who classification of tumors of the central nervous system were used . the present study comprised 143 cases of pnsts ranging in age from 5 to 75 years . these tumors were most commonly encountered in the age group of 2130 ( 52 [ 36.5% ] ) years followed by 3140 years ( 35 [ 24.5% ] ) . head and neck ( 47 [ 33% ] ) was the most common location followed by upper extremities ( 35 [ 24.5% ] ) and lower extremities ( 32 [ 22.5% ] ) . acoustic neuroma / vestibular schwannoma was not observed in the present study as this location requires neurosurgical approach for resection , same is not available in our center . the pnsts observed in the present study in the decreasing order of frequency are nf ( 87 [ 61.5% ] ) , schwannoma ( 52 [ 36% ] ) , mpnst ( 3 [ 2% ] ) , and granular cell tumor ( 1 [ 0.5% ] ) [ table 1 ] . age , sex and site distribution of peripheral nerve sheath tumors the gross features of peripheral nerve sheath tumors among nf , diffuse variant was most common ( 50 [ 57.5% ] ) followed by localized ( 25 [ 29% ] ) and plexiform ( 12 [ 14% ] ) . diffuse and localized variant are most commonly observed in second decade and head neck and extremities are most commonly involved sites . plexiform nf was more common in multiple locations and most common age of occurrence was in the first and second decade [ table 1 ] . diffuse nf had infiltrative type of growth and invades the surrounding structures while localized nf had localized type of growth . myxoid change was the most common secondary degeneration associated with nf followed by cystic change and lymphocytic infiltration [ figure 1a  i and table 2 ] . of 90 cases of nf , 9 ( 10% ) fulfilled the criteria for nf1 , of 9 cases 8 were plexiform nf and 1 was multiple nf ; the common associated finding was caf au spots , in addition , one case of plexiform nf had family history . ( a - c ) microphotograph of diffuse neurofibroma , note the infiltration of tumor to dermis and subcutaneous tissue . ( h and e , 40 ) , ( d ) diffuse neurofibroma showing myxoid change ( h and e , 40 ) , ( e ) diffuse neurofibroma with prominent lymphoid aggregates ( arrowhead ) ( h and e , 40 ) , ( f ) microphotograph of localized neurofibroma , note the well delineated tumor ( h and e , 40 ) , ( g ) localised neurofibroma with extensive myxoid change ( h and e , 40 ) , ( h ) lnf with areas of calcification ( h and e , 40 ) , ( i ) plexiform neurofibroma showing tortuous and expanded nerve bundles ( h and e , 40 ) like nf , schwannomas were also most commonly located in head and neck extremities and in contrast , they are observed a decade later . classic variant is most common ( 42 [ 81% ] ) followed by ancient ( 8 [ 15.5% ] ) and plexiform ( 2 [ 4% ] ) [ table 1 ] . classical schwannomas have both hypercellular ( antoni a ) and hypocellular ( antoni b ) areas in varying proportions . the characteristic verocay bodies are seen in 100% ( 2 cases ) of plexiform variant and 69% ( 25 cases ) of classical schwannoma . secondary degenerative changes were more evident in schwannomas more so in ancient variant [ table 3 and figure 2a  i ] . the morphological changes associated with peripheral nerve sheath tumors ( a ) microphotograph of conventional schwannoma showing hypercellular , antoni a areas ( black arrowhead ) and hypocellular antoni b areas ( red arrowhead ) . ( c - f ) microphotograph of  ancient  schwannoma showing degenerative nuclear atypia ( black arrowhead ) , hyalinized areas ( red arrowhead ) , cystic change ( blue arrow head ) , areas of hemorrhage ( * ) and myxoid change ( + ) ( h and e , 40 ) . ( g ) whole mount section of plexiform schwannoma note the subcutaneous multiple nodules ( h and e , 4 ) , ( h and i ) higher magnification of the same showing hypocellular and hypercellular areas with verocay body ( black arrow ) only one case of granular cell tumor has been observed in the present study in a 35-year - old lady , and the tumor was located in left breast . on periodic acid on immunohistochemistry ( ihc ) , tumor cells were positive for s-100 and vimentin [ figure 3a  f ] . ( a ) microphotograph of granular cell tumor showing tumor cells arranged in interlacing pattern with benign nuclei and granular cytoplasm ( h and e , 10 ) . ( b and c ) higher magnification of granular cell tumor ( h and e , 40 ) . ( e ) tumor cells showing intense cytoplasmic and nuclear positivity for s-100 ( immunohistochemistry , s-100 , 40 ) ( f ) tumor cells showing cytoplasmic positivity for vimentin ( immunohistochemistry vimentin , 40 ) three cases ( 2% ) of mpnst were observed in the present study . in contrast to bpnst , mpnst was seen in fourth to fifth decade . all the cases showed mitotic activity in the range of 05/hpf ( low grade ) , myxoid change , hemorrhage , and grade 1 necrosis [ table 1 ] . on ihc , two cases were positive for vimentin , s-100 and negative for sma while one case was s-100 negative , vimentin and epithelial membrane antigen positive [ figure 4a  d ] . ( a ) microphotograph of malignant peripheral nerve sheath tumors showing malignant tumor cells with hyperchromatic , pleomorphic nuclei with eosinophilic to clear cytoplasm ( h and e , 40 ) ( b ) tumor cells showing diffuse cytoplasmic and nuclear positivity for s-100 ( immunohistochemistry s-100 , 40 ) . ( c ) tumor cells showing cytoplasmic positivity for vimentin ( immunohistochemistry vimentin , 40 ) . ( d ) tumor cells showing nuclear positivity for ki 67 indicating proliferative activity ( black arrowhead ) ( immunohistochemistry ki 67 , 40 ) with the invention of ihc and molecular diagnostic methods , many tumors are now getting proven to be neural in origin , hence , the list of pnst are increasing . to the existing list of who classification , new variants , benign tumors which are added are granular cell tumor , dermal nerve sheath myxoma ( dnm ) , solitary circumscribed neuroma ( scn ) , ectopic meningioma / meningothelial hamartoma , nasal glial heterotopias , benign triton tumor ( btt ) , and hybrid nerve sheath tumors . malignant triton tumor , malignant granular cell tumor ( mgct ) , and ectomesenchymoma ( em ) are the malignant tumors now proven to be of neural origin . nf and schwannoma are the well - defined benign tumors of pnst . schwann cells are considered by many authors as the cell of origin for both the tumors ; however , dermal nf may arise from neural crest cell . an ultrastructural study by erlandson and woodruff on 23 schwannomas , 10 nfs , and 10 mpnst concluded that schwannoma to be consisting of well - differentiated schwann cells ; hence , the cell of origin is a schwann cell . the neoplastic cell in nf did not resemble schwann cell ; on contrary , in six cases , it resembled perineural cells . few authors believe that mpnst is the malignancy arising from schwannoma and designate them as malignant schwannoma . nf occurs commonly in the age group of 2030 years with head and neck being common site ( as observed in our study ) . among the variants of nf , localized is the most common followed by diffuse and plexiform ; however , in our study , we have observed diffuse variant as most common followed by localized and plexiform . diffuse variant presents as plaque - like enlargement of nerve while localized present as fusiform enlargement of nerve [ figure 5a ] . plexiform arise from major nerve or trunk and appearance called  bag of worms ,  [ figure 5b ] secondary degenerative changes are uncommon with nf . in a study by gabhane et al . , capsule was evident in 14% of cases , myxoid change was observed in 18% , and pigment in 5.5% . in the present study , 8% of nf was capsulated and secondary degenerative changes such as myxoid change ( 46% ) , cystic change ( 25% ) , and lymphocytic infiltration ( 17% ) were more evident in all variants . ( a ) gross photograph of localized neurofibroma showing fusiform growth with myxoid and cystic areas . ( b ) gross photograph of plexiform neurofibroma with thickened skin and gray - white tumor ( bag of worms ) like nf , schwannoma is also common in head and neck region but they are observed a decade later , i.e. , 2050 years ( as observed in our study ) . in contrast to nf , schwannomas are capsulated , secondary changes are more evident , and variants are well defined and practiced by a pathologist . conventional or classic schwannomas are most common followed by cellular , ancient , plexiform , and melanotic . to the existing list , who 2013 added microcystic / reticular schwannoma . classical schwannomas are easy to diagnose , and they have alternating areas of hypercellular areas , consisting of palisading arrangement of nuclei of spindle cells forming verocay body and hypocellular areas consisting of myxoid material , macrophages , and cystic change . hyalinized blood vessels are constant findings . cellular variant will have more hypercellular areas with minimal hypocellular areas but verocay bodies are absent . in ancient variant , the tumor usually occurs in subcutaneous tissue ; however , deep visceral sites are also reported . these tumors arise from nerve plexuses or fascicles , less circumscribed and unencapsulated ( as observed in our cases ) . melanotic schwannoma ( ms ) is a rare variant of schwannoma , and the tumor arises from cervical and thoracic spinal root . microscopically , they consist of areas of spindle and epithelioid cells with melanin pigment . sometime , in addition , they show calcification termed , microcystic / reticular schwannoma occurs in the visceral organs with gastrointestinal tract being the most common ; however , these tumors are reported in other sites . microscopically , they have microcyst - rich network of interconnected spindle cells . in the present study , secondary degenerative changes are common in schwannoma . in a study by gabhane et al . , observed secondary degenerative changes such as cystic change , hyalinization , necrosis , myxoid change , and verocay bodies were observed in 85.18% , 72.22% , 59.25% , 24.07% , and 70.37% cases , respectively . in the present study , we have observed cystic change , hyalinization , necrosis , myxoid change , and verocay bodies in 73% , 71% , 15% , 71% , and 60% cases , respectively , and our findings are in consistent with literature . unlike bpnst , mpnst is rare ( 0.001% ) and the age group observed ranged from 16 to 60 years with extremities being the most common site ( as observed in our study ) . like bpnst , even mpnst observed necrosis and hemorrhage in 75% of cases and cystic change in 50% of tumor . in the present study , myxoid change , necrosis , and hemorrhage the common differential diagnoses of mpnst include other mesenchymal tumors such as rhabdomyosarcoma , leiomyosarcoma , synovial sarcoma , fibrosarcoma , and malignant fibrous histiocytoma . the comparison of dimensions of bpnst and mpnst with the previous literature is shown in table 4 . the comparison mean size ( in cm ) of peripheral nerve sheath tumors published in the literature diagnosis of schwannoma and nf s-100 is found to be constantly expressed in schwannoma and nf . as the differential diagnoses of mpnst are wide , ihc is essential for confirmation . s-100 which is found to be constantly expressed in bpnst may not be positive in all cases of mpnst ( as observed in one of our case ) . it is negative or weakly expressed in leiomyoma , nf , schwannoma , synovial sarcoma , liposarcoma , carcinosarcoma , and malignant fibrous histiocytoma . in difficult cases of bpnst and mpnst , proliferating cell nuclear antigen and ki67 help in diagnosis . these tumors are most commonly seen in middle age with extremities being the most common site and are rarely associated with nf1 . granular cell tumor is now proved to be neuroectodermal in origin . these tumors are most common in head and neck region and are component of noonan syndrome . we have observed only one case of granular cell tumor in 35-year - old female in left breast . scn is most commonly observed in adult population and head and neck being the usual site of occurrence . in contrast to nf and schwannoma , in scn , schwann cells replete with axon which is neurofilament - positive . ectopic meningioma needs to be differentiated from hamartomatous condition which contains nonneoplastic proliferation of arachnoidal cells . nasal glial heterotopias are the presence of mature glial tissue outside the cranial cavity , most commonly observed in nasal cavity of children . btt is extremely rare , and they contain mature skeletal muscle with clusters of nerve fibers . the common combinations are nf - schwannoma , schwannoma - perineuroma , and nf - perineuroma . mgct is a high - grade sarcoma most commonly occurs in extremities and head and neck region . em is a variant of rhabdomyosarcoma with neural component . nf1 and nf2 , schwannomatosis , and noonan syndrome are genetic syndromes associated with pnst . nf1 is a neurocutaneous disease affecting 1 in 3000 people and transmitted as autosomal dominant disorder . all variants of nf can be seen in patients with nf1 but plexiform variant is most common . in the present study , 10% of nf is associated with nf1 and plexiform variant is the most common . nf2 also transmitted as autosomal dominant disorder occurs due to the germ line mutation of nf2 gene on chromosome no 22 . both conditions will have peripheral nerve and cranial nerve schwannomas ; in addition , nf2 will have other intracranial tumors . due to the modern diagnostic modalities , list of pnst is increasing . in the present study , we have described the gross and microscopic features of benign and mpnsts and their variants . as these tumors have varied biological behavior and few are associated with inherited tumors , pathologists must be aware of all these variants for accurate diagnosis .
introduction : peripheral nerve sheath tumors ( pnsts ) are neuroectodermal in origin . 
 now these tumors are classified under world health organization ( who ) classification of tumors of soft tissue and bone 2013.objective:to study the morphological spectrum of pnst and to study the secondary degenerative changes associated with it.materials and methods : this study was conducted from january 2010 to june 2015 . 
 the gross details of tumor and patient 's demographic profiles were reviewed . 
 the hematoxylin and eosin stained slides were reassessed and the lesions were categorized and classified as per the who 2013 classification . 
 the tumors were also assessed for secondary degenerative changes.results:our study comprised 143 cases of pnst . 
 age of the patients ranged from 5 to 75 years . 
 2130 years is the most common age of occurrence with head and neck being the most common site . 
 the pnsts observed in the present study were neurofibroma ( nf ) ( 61.5% ) , schwannoma ( 36% ) , malignant pnst ( 2% ) , and granular cell tumor ( 0.5% ) . 
 nearly 10% of nf fulfilled the criteria for neurofibromatosis 1 ( nf1 ) . 
 rare tumors such as plexiform schwannoma and granular cell tumor were also observed . 
 malignant tumors were larger in dimension than benign . 
 myxoid , cystic , and hyaline changes were commonly associated with benign tumors while necrosis , hemorrhage , and mitotic activity were seen with malignant tumors.conclusion:this series highlights the pathological variants of pnst along with their morphological changes and nf1 association . 
 it is essential to be familiar with all these variants of pnst for accurate diagnosis as they have varied biological behavior .