paget s disease of bone ( pdb ) is a disease of elderly characterized by disorganized bone remodeling . development of giant cell tumor in pdb ( gct - pdb ) is extremely rare , and little is known about its etiopathogenesis and management . we present a case report of such a development with a review of the literature and the role of various new modalities of treatment available in the management of this rare condition . a 40-year - old gentleman presented with back pain and on evaluation was diagnosed as a case of polyostotic pdb . after an asymptomatic period of 3-year , he presented with a gluteal mass involving ilium and sacrum which was confirmed as gct on biopsy . serial angioembolization was attempted but mass progressed , so surgery performed with excision and curettage of the lesion . he presented with a local recurrence 2 years later with a large soft tissue component . he was started on denosumab , rankl inhibitor , with the aim to downstage the lesion . the patient showed a good response after 6 doses with reduction in soft tissue mass followed by which he underwent surgery with partial t-1 internal hemipelvectomy and curettage of sacrum . gct - pdb is a rare phenomenon occurring mainly in polyostotic pdb and is associated with more severe manifestations of the disease . although surgery is the mainstay of treatment for gct , other modalities of treatment such as rank ligand inhibitors ( denosumab ) , selective arterial embolization , or radiation therapy has to be used for inoperable cases or where surgery would be functionally too morbid , especially in cases of gct - pdb where the disease affects more commonly the axial skeleton . paget s disease is a disease of elderly seen commonly after the fifth decade of life characterized by remodeling of bone in a disorganized manner . development of primary bone neoplasm is a rare but is known complication of paget s disease of bone ( pdb ) . long - term evolution of paget s disease increases the risk of various malignant tumors such as osteosarcoma , fibrosarcoma , chondrosarcoma , malignant fibrous histiocytoma , and very rarely locally aggressive tumor - like giant cell tumor ( gct ) . the reported cases of gct complicating paget s occur mainly in polyostotic disease . in view of its rarity , there is only modest information available about the etiology and management of gct - pdb . in addition , newer developments in the management of both these disorders have enabled new avenues for combined multimodal management in this rare coexistence . we also discuss the mechanism of development and multimodality treatment available for the management in such an uncommon situation . bone scan revealed multiple site involvement ( skull , sternum , dorsal and lumbar , pelvis , ribs , femur , and tibia ) ( fig . 1 , 2 , 3 , 4 ) . bone biopsy from the iliac region revealed numerous multinucleated giant cells with the haphazard new bone formation and diagnosis of polyostotic paget s disease was confirmed . the patient was treated with intravenous ( iv ) bisphosphonate every 3 weeks ( pamidronate 60 mg iv infusion ) with vitamin d and calcium supplement at another institution . he was apparently alright for 3 years when he noticed a lump in the right gluteal region . radiographs revealed a lytic lesion in right posterior ilium and a magnetic resonance imaging ( mri ) of the pelvis showed a large lesion with an extraosseous soft tissue component involving the iliac bone and adjacent sacral ala . blood investigations showed an elevated serum alkaline phosphatase . computed tomography - guided trucut biopsy from gluteal mass 5 ) were attempted with intent to control the disease without surgery owing to the complex anatomy and associated morbidity of surgery , but the mass progressed in size . excision of soft tissue mass with curettage and cementation of the right sacroiliac component of the lesion was done . 2 years after the surgery , he presented with a large local recurrence involving the posterior ilium and sacral ala . he was started on denosumab , a monoclonal rank ligand inhibitor in an attempt to downstage the lesion and thus reduce the morbidity of surgery . denosumab was administered at a dose of 120 mg subcutaneously at monthly intervals with loading doses at day 1 , 8 , and 15 . a repeat mri evaluation , after 6 injections of denosumab , revealed a good response with shrinkage of the soft tissue mass . he then underwent partial type-1 internal hemipelvectomy and curettage of the sacral lesion ( fig . 6 , 7 , 8 , 9 , 10 ) . at a 15 months follow - up ( a ) initial biopsy showing classical features of a giant cell tumor , including uniform sprinkling of osteoclast - like giant cells with intervening mononuclear stromal cells . hematoxylin and eosin ( h and e ) staining 200 , ( b ) sections from post denosumab - treated specimen displaying replacement by foamy histiocytes and lymphocytes . h and e staining 400 , ( c ) section from host bone displaying  jigsaw puzzle- like or mosaic pattern of lamellar bone , pathognomonic of paget s disease . h and e staining 200 , ( d ) disorganized collagen fibers arranged in several directions rather than uniform ( arrowhead ) , seen under polarized light . inspite of a reported increased incidence of gct of bone in the asian population , most of the cases of gct - pbd have been reported in caucasians . this may be explained by the fact that the incidence of pdb is higher in western population as compared to asians . available data also suggested a significant prevalence of familial gct occurring in pdb in italy region . a systematic review   was conducted to identify cases of cgt occurring in pdb patients ( prospero database registration number : crd42014007030 ) . the majority of ethnicity in this study was caucasians of european ancestry 82% and around 8% were asian . pdb : paget s disease of bone , gct : giant cell tumor gct in pdb more commonly involves the craniofacial bones followed by pelvis and spine as compared to gct which commonly occurs at an epiphyseal location . the understanding of genetics and pathophysiology of gct has considerably increased since the discovery of rank / rank - l ( receptor activator of nuclear factor - kappa b ligand ) pathway which is an important osteoclastic differentiating factor . osteoblasts and stromal stem cells express rankl , which binds to its receptor rank , on the surface of osteoclasts and their precursors . these stromal cells are the neoplastic mononuclear cells in gct , and it is postulated that the molecular signals from these stromal cells promote the formation of multinucleated osteoclast - like cells . the pathogenesis of pdb involves mutations / polymorphisms identified in genes tnfrsf11a encoding rank , tnfrsf11b encoding osteoprotegerin , valosin - containing protein encoding p97 , and sqstm1 encoding p62 play a role in the rank - nfkb signaling pathway [ 4 , 5 ] . thus , rank / rankl pathway seems to be an interlinking pathway in the development of gct in paget s disease . gct - pdb cases should be treated on the same principles as that of gct . surgery is the standard of treatment in gct , which may be either function preserving curettage or more morbid procedure like resection . traditionally , bisphosphonates have been used in the management of surgically nonresectable gct either alone or in combination with angioembolization . this leads to induction of osteoclasts apoptosis leading to decreased bone restoration and bone healing . similarly , bisphosphonates have also been used as a drug of choice for the management of and are also the treatment of choice in pdb . introduction of newer agents such as denosumab [ 6 , 7 ] , a human monoclonal antibody , has shown early promising results in managing the gct at difficult sites . denosumab inhibits the development of osteoclasts and their activity thereby reducing bone resorption and increase bone density and shrinks the tumor mass . although its use has been popularized in reducing the skeletal - related events in some carcinomas such as breast and prostrate carcinoma , it is proving to be effective in controlling the growth of axial gct where resection may be really morbid . literature search has shown cases where denosumab is used as a therapeutic agent targeting the pathophysiology in pdb . although currently not included as a standard of care in pdb , expected to become one of the potential therapeutic agents in the future . the duration of denosumab therapy is still a matter of debate , but complete cessation of therapy has seen resurgence of disease in most of the cases . histopathological studies have shown complete apoptosis of multinucleate giant cells , but stromal cells do show resistance to its treatment and are considered responsible for the recurrence of the disease . this modality may be combined with arterial embolization   to have effective disease control at axial sites . for refractive cases , radiotherapy gct - pdb cases should be treated on the same principles as that of gct . surgery is the standard of treatment in gct , which may be either function preserving curettage or more morbid procedure like resection . traditionally , bisphosphonates have been used in the management of surgically nonresectable gct either alone or in combination with angioembolization . this leads to induction of osteoclasts apoptosis leading to decreased bone restoration and bone healing . similarly , bisphosphonates have also been used as a drug of choice for the management of and are also the treatment of choice in pdb . introduction of newer agents such as denosumab [ 6 , 7 ] , a human monoclonal antibody , has shown early promising results in managing the gct at difficult sites . denosumab inhibits the development of osteoclasts and their activity thereby reducing bone resorption and increase bone density and shrinks the tumor mass . although its use has been popularized in reducing the skeletal - related events in some carcinomas such as breast and prostrate carcinoma , it is proving to be effective in controlling the growth of axial gct where resection may be really morbid . literature search has shown cases where denosumab is used as a therapeutic agent targeting the pathophysiology in pdb . although currently not included as a standard of care in pdb , expected to become one of the potential therapeutic agents in the future . the duration of denosumab therapy is still a matter of debate , but complete cessation of therapy has seen resurgence of disease in most of the cases . histopathological studies have shown complete apoptosis of multinucleate giant cells , but stromal cells do show resistance to its treatment and are considered responsible for the recurrence of the disease . this modality may be combined with arterial embolization   to have effective disease control at axial sites . for refractive cases , radiotherapy gct developing in the background of paget s disease is a rare occurrence which is commonly seen in polyostotic pdb . gct - pdb is associated with more severe manifestations of the disease with reduced life expectancy . pharmacological agents include the use of bisphosphonates and rank ligand inhibitors . although surgery is the mainstay of treatment for gct , denosumab , selective arterial embolization , or radiation therapy has to be used for inoperable cases or where surgery would be functionally too morbid , especially in cases of gct - pdb where the disease affects more commonly the axial skeleton . surgery is the mainstay of treatment , but one should be aware of all the armamentarium available like bisphosphonates , rank ligand inhibitor , angioembolization , and radiation therapy to downstage the lesion facilitating surgery or as a definitive modality of treatment in inoperable cases . the recent advances have led to successful cure and lesser morbidity in the treatment of this rare condition .
introduction : paget s disease of bone ( pdb ) is a disease of elderly characterized by disorganized bone remodeling . development of secondary neoplasm in pdb is a known but rare phenomenon . 
 development of giant cell tumor in pdb ( gct - pdb ) is extremely rare , and little is known about its etiopathogenesis and management . 
 we present a case report of such a development with a review of the literature and the role of various new modalities of treatment available in the management of this rare condition.case report : a 40-year - old gentleman presented with back pain and on evaluation was diagnosed as a case of polyostotic pdb . 
 he was treated with intravenous bisphosphonates , calcium , and vitamin d supplements . 
 after an asymptomatic period of 3-year , he presented with a gluteal mass involving ilium and sacrum which was confirmed as gct on biopsy . 
 serial angioembolization was attempted but mass progressed , so surgery performed with excision and curettage of the lesion . 
 he presented with a local recurrence 2 years later with a large soft tissue component . 
 he was started on denosumab , rankl inhibitor , with the aim to downstage the lesion . 
 the patient showed a good response after 6 doses with reduction in soft tissue mass followed by which he underwent surgery with partial t-1 internal hemipelvectomy and curettage of sacrum . 
 currently , the patient is asymptomatic at a follow - up of 15 months.conclusion:gct-pdb is a rare phenomenon occurring mainly in polyostotic pdb and is associated with more severe manifestations of the disease . 
 the management is challenging and requires multimodality management . 
 pharmacological agents include use of bisphosphonates and rank ligand inhibitor - denosumab . 
 although surgery is the mainstay of treatment for gct , other modalities of treatment such as rank ligand inhibitors ( denosumab ) , selective arterial embolization , or radiation therapy has to be used for inoperable cases or where surgery would be functionally too morbid , especially in cases of gct - pdb where the disease affects more commonly the axial skeleton .