Giant Cell Tumour of Bone

Giant cell tumour of bone is a locally aggressive primary bone neoplasm composed of neoplastic stromal cells and numerous osteoclast like giant cells.

It most commonly affects skeletally mature young adults.

Typical sites are the epiphysis and metaphysis of long bones, particularly:

Distal femur
Proximal tibia
Distal radius

The lesion usually extends to the subchondral bone.

Although conventionally classified as intermediate or locally aggressive rather than a conventional high grade sarcoma, it can:

Destroy bone extensively
Recur locally
Metastasise to lung
Rarely undergo malignant transformation

Campanacci classification

This is the main useful radiographic severity classification.

Grade I

Well defined lesion with intact cortex.

Grade II

Well defined lesion with cortical thinning and expansion but no major cortical breakthrough.

Grade III

Aggressive lesion with cortical destruction and soft tissue extension.

The grade assists operative planning but should not be used as the sole determinant of treatment.

Plain radiographs: classically demonstrate an eccentric expansile lytic epiphyseal lesion extending toward the articular surface.

A mature GCT generally has little surrounding sclerosis.

MRI: define:

Subchondral involvement
Soft tissue extension
Neurovascular relationships
Joint involvement

CT chest: obtain for pulmonary staging in aggressive or confirmed disease.

Biopsy is required before definitive treatment.

H3.3 G34W immunohistochemistry can support the diagnosis in appropriate lesions.

Intralesional surgery

For most Campanacci I and II lesions, and selected III lesions in which the joint can be preserved, perform extended intralesional curettage.

The quality of curettage determines recurrence risk.

Technique should include:

Large cortical window providing full visual access
Removal of all gross tumour
High speed burr extending treatment into cavity margins
Careful inspection for residual tumour in recesses

Local adjuncts can include:

Hydrogen peroxide
Phenol in selected practice
Argon beam
Cryotherapy

The evidence does not establish one universally superior local adjunct.

Defect reconstruction

Fill the cavity with:

PMMA bone cement
Autologous bone graft
Allograft
Bone substitute

PMMA provides immediate structural support and allows recurrent lysis at the cement interface to be recognised relatively easily.

In lesions immediately beneath articular cartilage, a layer of cancellous graft beneath the subchondral plate can reduce direct thermal or mechanical stress from cement.

Add plate fixation when curettage leaves the bone mechanically weak or pathological fracture risk is high.

Wide resection

Consider en bloc resection when there is:

Massive cortical destruction
Nonreconstructible joint surface
Extensive soft tissue extension
Repeated local recurrence
Pathological fracture with gross contamination that prevents reliable curettage
Anatomical location where recurrence would be catastrophic

Reconstruction can require:

Endoprosthesis
Osteoarticular allograft
Arthrodesis
Structural graft

Wide resection lowers local recurrence but sacrifices more normal tissue and joint function.

Denosumab

Denosumab blocks RANKL and profoundly suppresses giant cell mediated bone resorption.

Use primarily for:

Unresectable disease
Sacral or spinal lesions where surgery would cause major neurological morbidity
Tumours where initial resection would require highly morbid surgery

A standard regimen is:

Denosumab 120 mg subcutaneously every 4 weeks

with additional doses on:

Days 8 and 15 during the first month.

Provide:

Calcium supplementation
Vitamin D supplementation

unless hypercalcaemia is present.

Before treatment:

Correct hypocalcaemia
Assess dental health
Address significant dental infection

Monitor for:

Hypocalcaemia
Osteonecrosis of the jaw
Atypical femoral fracture with prolonged therapy
Rebound hypercalcaemia after discontinuation, particularly in younger patients

Denosumab does not eliminate the neoplastic stromal cells. It can produce a thick sclerotic shell that makes later tumour boundaries difficult to identify during curettage.

Therefore, routine preoperative denosumab before an otherwise straightforward joint preserving curettage should not be automatic. Its role is most valuable when it meaningfully reduces surgical morbidity.

Pulmonary metastases

Small stable pulmonary metastases may behave indolently.

Resect progressing or technically suitable pulmonary disease when appropriate.

Denosumab can be used for unresectable metastatic GCT.

Surveillance

Local recurrence occurs most frequently during the first several years.

Follow with:

Local radiographs
Clinical examination
Chest imaging according to disease severity

Rapid destructive progression during or after denosumab warrants reassessment and repeat biopsy because malignant transformation or an initially missed sarcoma must be considered.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Cholangiocarcinoma

Also known as: Bile duct cancer

Malignancy arising from the bile duct epithelium, classified by anatomical location as intrahepatic (arising within the liver parenchyma, increasingly grouped and managed alongside hepatocellular carcinoma given overlapping presentation), perihilar (Klatskin tumor, at the confluence of the right and left hepatic ducts, the most common location), and distal (extrahepatic, closer to the pancreatic head, sharing much of its clinical presentation and management pathway with pancreatic cancer).

Risk factors include primary sclerosing cholangitis (a major and well recognized association, see Ulcerative Colitis entry), liver fluke infection (Clostorchis sinensis and Opisthorchis viverrini, endemic in parts of Southeast Asia), choledochal cysts, hepatolithiasis, and chronic viral hepatitis.

Perihilar and distal tumors present similarly to pancreatic head cancer: painless, progressive obstructive jaundice, pale stools and dark urine, pruritus from cholestasis, and weight loss. Intrahepatic cholangiocarcinoma more often presents with nonspecific abdominal pain, weight loss, and a hepatic mass detected on imaging, since jaundice only occurs late once major ducts are compressed. Fever suggests superimposed cholangitis from biliary obstruction, and should be actively assessed for given the need for urgent drainage if present (see Cholangitis entry).

LFTs show a cholestatic pattern. CA19-9 is used as a tumor marker to support diagnosis and monitor treatment response, though it lacks the sensitivity and specificity to be diagnostic alone, and can be markedly elevated by biliary obstruction of any cause including benign disease. Cross sectional imaging with contrast enhanced CT or MRI with MRCP characterizes the tumor, its relationship to the biliary tree and vasculature, and assists staging. ERCP or percutaneous transhepatic cholangiography allows tissue sampling (brushings or biopsy, though sensitivity is limited given the typically desmoplastic, hypocellular nature of these tumors) and, importantly, therapeutic biliary drainage. PET CT and staging laparoscopy assess for occult metastatic or peritoneal disease prior to considering resection.

Differentials include pancreatic cancer (for distal tumors), benign biliary stricture (particularly in the context of primary sclerosing cholangitis, where distinguishing benign dominant stricture from malignant transformation can be genuinely difficult and requires close surveillance), hepatocellular carcinoma (for intrahepatic tumors), and other periampullary malignancy.

Resectable disease is treated with surgical resection tailored to tumor location: major hepatectomy with extrahepatic bile duct resection for perihilar tumors, pancreaticoduodenectomy for distal tumors (following the same principles as for pancreatic cancer), and hepatic resection for intrahepatic tumors, followed by adjuvant chemotherapy (commonly capecitabine). Liver transplantation, combined with neoadjuvant chemoradiotherapy under a strict protocol, is an option for carefully selected perihilar cholangiocarcinoma at specialist centers. Unresectable or metastatic disease is managed with palliative chemotherapy (gemcitabine and cisplatin is the standard first-line combination), with targeted therapy increasingly available for tumors harboring specific molecular alterations (FGFR2 fusions, IDH1 mutations) identified on molecular profiling. Biliary decompression, whether by ERCP stenting or percutaneous transhepatic drainage, is a central component of management at every stage, both to relieve symptomatic jaundice and pruritus and to permit safe delivery of chemotherapy in patients with obstructive jaundice.

Referral: hepatobiliary surgery and oncology multidisciplinary team for all confirmed or suspected cases; gastroenterology for biliary drainage and tissue sampling.

Giant Cell Tumour of Bone

Overview

Clinical Features

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management