J Clin Pathol 1983;36:1165-1170

Osteoclast-type giant cell tumour of the pancreasIONA JEFFREY, JULIE CROW, BW ELLIS*

From the Departments ofHistopathology and *Surgery, Northwick Park Hospital, Harrow

SUMMARY A case of osteoclast-type giant cell tumour of the pancreas is described and thefeatures of eight other previously reported patients are reviewed. Characteristically, these neo-plasms are large at presentation and show focal haemorrhage and necrosis, but seem slow to giverise to metastases. Histological examination reveals numerous osteoclast-like giant cells set in asarcomatous stroma, the appearances being similar to those seen in giant cell tumours of bone.They are distinct from pleomorphic giant cell carcinomas of the pancreas and may have a slightlybetter prognosis after resection than ordinary adenocarcinomas. The histogenesis of these raretumours is unknown.

Primary neoplasms containing numerousosteoclast-like giant cells and bearing a striking his-tological resemblance to giant cell tumours of bonehave been reported in various organs and tissuesother than the skeletal system, but they are rare.'I-IRosai'2 was the first to describe osteoclast-type giantcell tumours in the pancreas, (two cases), sincewhen, to our knowledge, only six other exampleshave been reported in the literature.'3-'7 Two of thestudies have included electron microscopical exami-nations'2 16 and these are contradictory in terms ofthe ultrastructural features observed and theinterpretation of the histogenesis. We present aninth case of this tumour which we also studied withthe electron microscope.

Case report

A 55-year-old Caucasian man presented with a twoweek history of fever and weight loss followed byobstructive jaundice. Ultrasound examinationrevealed common bile duct obstruction which wasshown on endoscopic retrograde choledocho-pancreatography to be due to extrinsic compression.At laparotomy, a firm tumour was palpable in the

head of the pancreas and this was locally invasive. Aneedle biopsy was taken. No metastatic spread tothe peritoneum, liver or lymph nodes was discerned.Only bypass surgery was considered feasible and acholecystojejunostomy was fashioned.The patient remained well for four months when

he again developed obstructive jaundice withanorexia and anaemia. Palliative treatment was

Accepted for publication 16 May 1983

given including transfusion and insertion of a com-mon bile duct catheter. Five weeks later hedeveloped ascites, recurrent gastrointestinal bleed-ing and anaemia. He died seven months from thedate of presentation.At necropsy the head of the pancreas was found

to be replaced by a firm tumour 10 cm in diameterwhich was occluding the pancreatic duct andinfiltrating through the adjacent duodenal wall. Thecholecystojejunostomy was occluded by fibrosis butthe common bile duct catheter was patent.The liver showed several circumscribed depoAits

of metastatic tumour measuring up to 2 cm indiameter. No other evidence of metastatic spreadwas found on naked-eye examination.

Material and methods

The needle biopsy specimen and representative nec-ropsy blocks of the tumour and liver metastaseswere fixed in 10% formol saline and embedded byroutine techniques in paraffin wax. Sections werestained with haematoxylin and eosin and selectedsections with periodic acid Schiff (PAS), PAS/diastase, alcian blue, mucicarmine, phosphotungsticacid haematoxylin (PTAH) and Gordon and Sweet'sreticulin. Frozen sections of formalin-fixed tissuewere stained with Oil-Red-O.

For electron microscopy small pieces of thefonnalin-fixed necropsy blocks were post fixed inglutaraldehyde followed by osmium tetroxide andblock-stained with uranyl acetate. Dehydration wasperformed through graded acetones to propyleneoxide and the blocks embedded in Spurr resin. Sec-tions (1 gm) were stained with toluidine blue.

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Fig. 1 Photomicrograph ofpancreatic tumour showing osteoclast-typemultinucleated giant cells and pleomorphic stromal cells. Haematoxylin and eosinx300.

Ultrathin sections were collected on copper grids,stained with Reynold's lead citrate and carboncoated before being viewed in a Philips 300 electronmicroscope.

Results

LIGHT MICROSCOPYThe tumour was composed of multinucleate giantcells in a stroma of pleomorphic spindle cells (Fig.1). The giant cells had abundant eosinophilic cyto-plasm and between five and 40 nuclei.The nuclear chromatin was finely distributed and

one or' two prominent nucleoli were present. Nomitoses were found in these cells and they closelyresembled osteoclasts in appearance. A few of thestromal cells showed similar features to the giantcells except for the presence of a single nucleus butmany were oval or spindle-shaped with enlarged,hyperchromatic nuclei and occasional mitoticfigures. Prominent areas of necrosis and haemor-rhage were present within the tumour. Examinationof multiple blocks revealed no evidence ofadenocarcinoma anywhere in the neoplasm andthere were no foci of calcification nor bone forma-tion. The cytoplasm of the osteoclast-like giant cellsand of a few stromal cells showed weak, patchypositivity with PAS, PAS/diastase and alcian blue.

The stromal background was also slightly alcian bluepositive. Mucicarmine and PTAH were negative.The Oil-Red-O stain for neutral fat showed occa-sional positive droplets within the cytoplasm of afew giant cells. There was a rich reticulin network inthe tumour, with fine fibrils surrounding single andsmall groups of cells.Tumour was found in three small lymph nodes

adjacent to the head of the pancreas and thesemetastases and those in the liver were histologicallythe same as the primary tumour.The needle biopsy taken at laparotomy showed an

infiltrating malignant tumour which at the time hadproved impossible to classify. Review of the sectionsafter the necropsy showed the appearance to besimilar to the stromal component of the neoplasmand a few small osteoclast-like giant cells were alsofound.

ELECTRON MICROSCOPYAs expected from necropsy material, preservationwas very poor but it could be seen that the giant cellcytoplasm contained large. numbers of mitochon-dria, many of which exhibited dense granules intheir matrix, and moderate amounts of rough endo-plasmic reticulum (RER) (Fig. 2). Occasional dilatedcistemae of RER contained fluffy electron densematerial but no clearly defined granules were

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Fig. 2 Electron micrograph ofpart ofa multinucleate giant cell showing cytoplasmcontaining numerous mitochondria with dense matrix granules (large arrows). Smallprofiles ofRER are also seen (thin arrows). N = nuclei. x14 000.

identified. No microvilli or ruffled membranes were

seen but at the edge of one cell an amorphous zone

of cytoplasm was noted (Fig. 3). The stromal cells inthe area examined had similar ultrastructural cyto-plasmic appearances to the giant cells. No desmo-somes were found between the cells.

Discussion

Giant cell tumours of the pancreas in which the giantcells appear benign and resemble osteoclasts shouldbe distinguished from pleomorphic carcinomas con-

taining bizarre multinucleated giant cells.'4 "8 Thesetwo types of tumour have been somewhat confusedin the literature'3 1920 but it appears that there are

eight other well documented osteoclast-type giantcell tumours. The features of our case and of theseeight are summarised in Tables 1 and 2.

Microscopically all these tumours showed a

remarkable resemblance to giant cell tumours ofbone with the osteoclast-like giant cells being set ina pleomorphic sarcomatous stroma. Focal haemor-

rhage was noted in all the tumours and similarresults were obtained with special stains where thesewere performed. The giant cells showed weakpatchy staining with alcian blue, PAS and PAS/diastase but mucicarmine staining was negative.Occasional fat droplets were found in cells adjacentto areas of necrosis and there was a prominentreticulin network around the tumour cells.Cases 1 and 7 were studied with the electron

microscope.'2 16 In case 1 both the giant cells and thestromal cells showed plentiful RER with dilatedcisternae containing dense granules of protein.Microvilli were present on the surface of the giantcells and numerous desmosomes were seen betweenthe stromal cells. These features were interpreted asindicating that the tumour derived from pancreaticacinar cells.'2 In contrast, in case 7, the mostprominent feature in the giant cell cytoplasm was thepresence of numerous mitochondria. The RER wasmuch less conspicuous and the cell surfaces showedruffled membranes. Two types of stromal cells wereidentified; type A had a structure similar to the giant

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Fig. 3 Amorphous area ofcytoplasm at edge ofgiant cell (arrows). x22 000.

Table 1 Osteoclast-type giant cell tumours ofpancreas

Case Author Age (yr) Sex Site of tumour Presentng complaints1 Rosai (1968) 82 F Tail Fatigue; weight loss; abdominal mass2 Rosai (1968) 74 F Head Anorexia; weight loss; gastrointestinal

bleeding3 Freund (1973) 32 F Head Jaundice; abdomninal pain; vomiting4 Cubilia and Fitzgerald (1979) 45 M Head Not given5 Alguacil-Garcia and Weiland (1977) 49 M Head Abdominal pain; anorexia6 Alguacil-Garcia and Weiland (1977) 95 F Not given Not given7 Robinson, Damjenov and 63 M Not given Abdominal mass

Brezina (1977)8 Posen (1981) 45 F Body and tail Abdominal pain; vomiting9 This report 55 M Head Jaundice; weight loss

cells and type B resembled fibroblasts. Onlyoccasional desmosomal junctions were seen. Theseauthors note the similarities between theseultrastructural features and those described for giantcell tumours of bone.'6The EM findings in our case most closely resem-

ble those of Robinson et al,'6 with prominentmitochondria in both giant cells and stromal cells.Although no ruffled borders were identified thiscould be attributed to the late fixation of this auto-psy material. The amorphous zone (Fig. 3) noted inone cell could represent the homogeneous layer freeof organelles which is seen in osteoclasts and in thegiant cells of giant cell tumours of bone.2'

Extraskeletal osteoclast-type giant cell tumourshave been described in a number of other sitesincluding soft tissue,56 heart,4 orbit3 myometrium9 "and dermis2 as well as in several sites in whichepithelial tumours predominate including breast,'thyroid8 and colon.7 The histogenesis of suchtumours occurring in the pancreas, and in othersites, is unknown.Some authors have suggested that they derive

from epithelium,'2 1517 whilst others favour an originfrom some mesenchymal cell.'3 The EM featuresfound by Robinson et al'6 and ourselves certainlyresemble those of giant cell tumours of bone. How-ever, this does not preclude an epithelial origin for

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1169Osteoclast-type giant cell tumour of the pancreasTable 2 Osteoclast-type giant cell tumours ofpancreas

Case Size of tumour Extent of extrapancreatic T&,atment Clinical coursespread at laporotomy

1 10.5 x 12 x 13 cm Stomach, splenic and mesenteric Subtotal pancreatectomy, Alive and well 4 monthsveins. Microscopically, tumour splenectomy postoperativelyin 2 of 16 parapancreatic nodes

2 7.5 x 8 x 4 cm Duodenum Whipples Alive and well 10 monthspostoperatively

3 7 cm diam None Pancreatico-duodenectomy Died 17 months afterpresentation. Local recurrence atnecropsy. No lymph node, liver ordistant metastases

4 7 x 6 cm None Whipples Developed pulmonary metastases.Died arter 4 years. No necropsy.

5 8 cm diam None Total pancreatectomy Alive and well 15 yearspostoperatively

6 Large Not given Exploration and biopsy only Died 10 months afterpresentation. No necropsy

7 15 cm diam Posterior abdominal wall Biopsy then radiation Developed pulmonary metastases.therapy Died 42 months after

presentation. No necropsy8 Giant cell tumour Giant cell tumour component Resection of tumour Still alive at time of case

was a 4 cm diam was partially encapsulated report; length of follow upnodule within a and confined to pancreas not given14 cm diamcystadenocarcinoma

9 10 cm in diam Duodenum Palliative cholecysto- Died 7 months afterjejunostomy presentation. Large pancreatic

tumour extending intoduodenum. Microscopic tumourdeposits in parapancreaticlymph nodes and multipleliver metastases at necropsy.

the neoplasm since mesenchymal differentiation hasbeen shown in epithelial tumours such as spindle cellsquamous carcinomas.22 On the other hand, theultrastructural features observed by Rosai'2 cannotbe regarded as specific for epithelial tumours. Mic-rovilli have been observed in giant cell tumours ofbone23 24 and electron dense condensations in RERcisternae have been described in a number of situa-tions including the stromal cells of osteogenic sar-coma.25 Desmosome-like junctions have also beendescribed in a number of mesenchymal cell typesand tumours.26

In this case, only tissue fixed in formol saline wasavailable for study. This precluded the successful useof modern immunocytochemical techniques. In thefuture, however, investigation of osteoclast-typegiant cell tumours of the pancreas with a range ofmonoclonal antibodies may help to delineate theprecise cell of origin. At the present time of moreimportance is the identification of features whichdistinguish osteoclast-type giant cell tumours frompleomorphic and other adenocarcinomas of the pan-creas. Osteoclast-type giant cell tumours tend to belarge at initial presentation and have a predilectionfor local spread. Lymph node metastases areuncommon and blood-borne secondary spread tendsto be a late event. This is in contrast to pleomorphicgiant cell and ordinary carcinomas in which metasta-tic deposits, especially in lymph nodes, are a com-

mon early finding.2728 The small number of casesreported so far precludes accurate comment uponthe prognosis of osteoclast-type giant cell tumoursalthough the evidence to date (Table 2) suggeststhat the outcome after resection may be morefavourable than for pancreatic adenocarcinoma. T-helatter claims the lives of the majority of patientswithin six months of presentation and shows a fiveyear survival rate of less than 6% even after appar-ently successful resection.2931

We would like to thank Mr A Cox under whose carethe patient was admitted and Professor G Slavinunder whose supervision the pathological studieswere performed. We are also most grateful to MrsPam Bellinger and Miss Alison Hoyle who typed themanuscript, and to Mrs J Crosby who prepared thephotomicrographs.

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Jeffrey, Crow, Ellis

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Requests for reprints to: Dr I Jeffrey, Department ofPathology, Stopford Building, University of Manchester,Oxford Road, Manchester M13 9PT, England.

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