Age / Sex : 35 / M

Age / Sex :  35/M
Chief complaint : left pelvic pain

1) What is your impression?

Two weeks later, you can see the final diagnosis with a brief discussion of this case.

* Send Application Answers to In Sook Lee, MD ([email protected])

Courtesy : Gyung Kyu Lee, MD , Hallym University College of Medicine, Hangang Sacred Heart Hospital

Giant cell tumor (with secondary ABC)

Discussion

Findings:

(a) Anteroposterior radiograph of the pelvis shows an expansile, lytic lesion in the left iliac wing.

(b) Bone scintigram reveals increased radionuclide uptake peripherally and photopenia centrally (“donut sign”)

(c, d) Unenhanced axial and reformatted coronal CT scan show an expansile, lytic lesion in the left iliac wing. A thin, expanded cortical rim is noted around the lesion. There is no mineralization within the mass.

(e) Coronal T1-weighted spin-echo MR image shows an expansile, low signal intensity mass.

(f, g) Axial and coronal T2-weighted turbo spin-echo MR images demonstrate predominantly low to intermediate signal intensity mass with several high signal intensity foci corresponding to secondary ABC regions.

(h) Gadolinium-enhanced coronal T1-weighted spin-echo MR image obtained with fat saturation reveals diffuse enhancement of solid portions of the mass and peripheral enhancement about the ABC regions

Differential Diagnosis: GCT, plasmacytoma, solitary metastasis (especially thyroid, RCC), lymphoma, desmoplastic fibroma etc

Diagnosis: Giant cell tumor (with secondary ABC)

Discussion: Giant cell tumor

1) Incidence : relatively common skeletal tumor

  a) all primary osseous neoplasm : 4 - 9.5%

  b) all primary benign bone tumor : 18 - 23%

  c) malignant GCT : 5 – 10 % of all GCT

2) Age and Sex distribution :
 a) age : 20 – 40 years (skeletally mature patient) (under 14 years old : 1-3% of GCT)

 b) sex : benign : F > M (1.5: 1),  malignant : M > F (3 : 1)

3) Symptoms and Signs : nonspecific
 a) localized pain of an aching nature : several month duration, reduced by rest

 b) restricted movement of the involved joint

 c) neurologic symptom : associated with spine lesion

4) Location : most important features
a) skeletally mature patient : arise on the metaphyseal side of epiphyseal plate
                        and subsequently extend to subarticular location

b) skeletally immature patient : in metadiaphyseal rather than metaepiphyseal
                         (open epiphyseal plate : barrier to tumor growth)

5) Location : decreasing order of incidence
 a) distal femur : 23 - 30%

 b) proximal tibia : 20 - 25%

 c) distal radius : 10 - 12%   

 d) proximal humerus : 4 - 8%

 e) spine : sacrum (4 – 9%) > vertebral body (3-6%)

 f) other site : ilium, calcaneus, rib, carpal bone, epiphyseal equivalent

          (patella, greater trochanter)

6) Pathologic features : Gross
a) relatively large lesions eccentricaly located in metaepiphyseal bone and extending to

   the articular surface
b) cortical beone : usually expaned

c) GCT tissue : soft, friable, and fleshy, with a variable appearance
  - fibrosis : white, - hemorrhage : red to brown, - xanthomatous regions : yellow

7) Pathologic features : Histologic
  highly vascular lesion is composed of stromal cells and giant cells
a) stromal cells :
  - mononuclear, spindle or ovoid shape
  - nuclei : abundant mitotic figures in women with increased hormone (preg, oral contracep)
 - stroma of most GCT : thin walled capillaries, often with small areas of hemorrhage(associated secondary ABC) and solid areas(DDx from primary ABC)
b) giant cells :

- multinucleated (> 10)
- pathologic DDX : GCRG, NOF, ABC, chondroblastoma, osteoblastoma, brown tumor,
  osteosarcoma with abundant giant cells, foreign body reaction, etc

8) Plain radiography :    

 a) metaphyseal – epiphyseal, b) eccentric location, c) subarticular extension,

 d) thin cortex with expansion, e) purely lytic(60%) and soap bubble pattern(40%)

9) Bone scan : static imaging  

  a) increased uptake

  b) donut sign : increased uptake peripherally with photopenia centrally (57%)

  c) contiguous bone activity : extended pattern of uptake (62%)
   - increased uptake in bone across an articulation and in adjacent joints
   - related to increased blood flow and disuse osteoporosis

10) Angiography :  

a) infrequently performed

b) vascularity : hypervascular lesion (60-65%), hypovascular lesion (26-30%), 

            avascular lesion (10%)

c) transcatheter arterial embolization : used to reduce blood loss during OP

11) CT :

a) improved detection : cortical thinning, pathologic fracture, periosteal reaction,

  and degree of osseous expansile romodeling

b) confirm absence of mineralization

c) solid portion of GCT : attenuation similar to that of muscle

e) soft tissue extension : 33-44%, MRI > CT

 - typically occur at metaphyseal end of the lesion

 - cartilage at epiphyseal margin : barrier to tumor extension
 => explain why joint involvement is unusual despite the subarticular spread of GCT

 * exception to this general rule : relatively common involvement of the SI joint and

   extension into the iliac bone by sacral GCT (38%)

12) MRI :

a) soft tissue extension : superior to CT
- typically occur at metaphyseal end (cartilage at epiphyseal margin : barrier to tumor extension)

b) solid components of GCT :

- low to intermediate SI at T1- and T2-WI : reported as hemosiderin deposition
   (more likely related to increased cellularity or high collagen content)
- exclude other subarticular lesions such as large subchondral cyst, intraosseous ganglion, Brodie’s abscess, chondroblastoma, clear cell chondrosarcoma : high SI at T2-WI

c) ABC components of GCT : 14% of lesions
- most common lesion a/w secondary ABC (39%)
- low or high SI at T1-WI and markedly high SI at T2-WI
- prominent ABC element : more aggressive radiographic appearance reflecting the expansile cystic component

d) distinction between cystic(ABC) and solid areas of GCT :
- to prevent misdiagnosis of lesion as a primary ABC(only cystic)
- to allow biopsy to be directed at the solid portions of lesions
e) contrast-enhanced CT or MRI :
 - cystic(ABC) areas : thin and delicate peripheral & septal pattern
 - solid regions : diffuse enhancement reflecting hypervascular tissue

13) Differential diagnosis : long bone 

a) chondroblastoma : young age, epiphyseal location, sclerotic rim,

chondroid tumor matrix(50%), metaphyseal periostitis, BM and soft tissue edema on MRI

b) clear cell chondrosarcoma : old age, usually occur in proximal femur & humerus,
   not typically aneurysmal

c) aneurysmal bone cyst : young age(5-20), marked expansile metaphyseal lesion,

no tumor matrix, multiple fine septa, periostel buttressing effect, fluid-fluid level on MRI

d) Brodie’s abscess : heavy reactive sclerosis

e) intraosseous ganglion : medial malleolus, carpal bone

14) Differential diagnosis : sacrum 

a) metastatic disease (RCC or thyroid ca) : old age, presence of other lesion, “cold” on delayed phase of bone scan d/t hypervascularity

b) solitary myeloma (plasmacytoma) : old age, calcification(may be present)

c) chordoma : old age(40-70), majority central location, calcification(50%), hyperintense T2 signal

d) chondrosarcoma : old age, chondroid tumor matrix(2/3), very bright T2 signal  

e) aneurysmal bone cyst : neural arch, fluid-fluid level on MRI

f) brown tumor : concomitant evidence or history of hyperparathyroidism

15) Staging : 
a) stage 1 : indolent radiographic appearance, indolent histologic appearance

b) stage 2 : more aggressive radiographic appearance with expansile remodeling of bone, but intact periosteum, benign histologic pattern

c) stage 3 : aggressive growth and extension into adjacent soft tissue, benign histological pattern (although distant meta)

16) Treatment, recurrence and prognosis :
 a) treatment :
 - surgical curettage combined with liquid nitrogen freezing, bone packing or graft
 - large and highly destructive GCT : wide resection & reconstruction with allografts or metal prostheses
 - inoperable lesion (spine or pelvis) : RT

b) recurrence : 2 – 25%

  curettage and filling of void with polymethylmethacrylate(PMMA)

c) prognosis : benign : excellent, malignant : 10% survive(5yr)

17) Recurrent GCT : Bone
a) recur within the first 3 years : 80 - 90%
   evaluation : 4-month intervals for first 2 years
             6-month intervals thereafter up to 5 years
b) Imaging findings : plain radiography
  - new areas of bone destruction at previous resection margin

   or resorption of intralesional bone graft material

DDX : normal radiolucent zone (usually < 2mm)
- around PMMA d/t retraction and cytotoxic effect of exothermic reaction on surrounding tissue at bone-cement interface
- does not progress after 6-8 months postoperatively
- usually smooth and symmetric(rather than lobular or focal)

c) imaging findings : CT and MRI
 - focal nodular masslike areas of marrow replacement
 - MRI : low to intermediate SI at T1-and T2-WI vs dark SI of PMMA,
   usually lobular or focal mass (rather than smooth and symmetric)

18) Recurrent GCT : Soft tissue
a) rarely recur in the soft tissue : 2%
- related to either surgical implantation or tumor spread secondary to pathologic fracture
b) imaging findings : peripheral ossificaton
DDX : from myositis ossificans
 - continued slow growth
 - occurrence more than 2 months after surgery
 - absence of subsequent maturation to bone centrally  

19) Multiple GCT and Malignant GCT

- Multiple GCTs, although rare, do occur and may be associated with Paget disease.

- Malignant GCT accounts for 5%–10% of all GCTs and is usually secondary to

 previous irradiation of benign GCT.

References :

1) Murphey MD, Nomikos GC, Flemming DJ, Gannon FH, Temple HT, Kransdorf MJ. Imaging of giant cell tumor and giant cell reparative granuloma of bone: radiologic-pathologic correlation. Radiographics. 2001;21:1283-1309