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Table 3 Malignancies in giant tumor of bone

From: Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab

Patient no.a (age range)

Cohort

Site

Malignant histology

Radiation received, dose

Latency period

Duration of denosumab

Malignancy present prior to denosumab

Malignancy outcome

Primary malignancies

 1 (80–89 y)

Primary resectable

Femur

Initial diagnosis: appearance suspicious of sarcoma based on imaging atypical for GCTB and no lytic bone lesions

Diagnosis: Undifferentiated pleomorphic sarcoma

No

4 y, 3 mo

2 y, 5 mo

Likelyb

Death after postsurgical complications from femur replacement

 2 (50–59 y)

Recurrent unresectable

Femur

Giant cell tumor with pleiomorphic spindle cells, suspect malignant areas, extensive reactive changes due to fracture

Diagnosis: Undifferentiated spindle cell sarcoma

No

2 y

10 mo

Likelyb

Chemotherapy with complete response

 3 (20–29 y)

Primary resectable

Pelvis

Numerous cores, largest was 1.5 cm, consisting of brown, friable tissue; GCTB with atypical features and high expression of proliferation markers

Diagnosis: Osteogenic sarcoma

No

13 mo

6 mo

Likelyb

Lost to follow-up

 4 (70–79 y)

Primary resectable

Sacrum

Spindle cell proliferation and cellular atypia, no giant cells. Suggests malignant transformation characterized by aspects of pleomorphism and cellular atypia with mitotic index elevated

Diagnosis: Undifferentiated pleomorphic sarcoma

No

10 mo

8 mo

Yes

Death of primary disease 3 mo after malignancy diagnosis

 5 (30–39 y)

Primary resectable

Tibia

Malignant spindle cell sarcoma (no maturation due to denosumab)

Diagnosis: Undifferentiated pleomorphic sarcoma

No

2 y, 8 mo

2 y, 4 mo

Yes

Patient underwent planned amputation plus chemotherapy

SMGCTB

 6 (40–49 y)

Recurrent unresectable

Metatarsus

Diagnosis: High-grade sarcoma

Yes, 50 Gy

13 y

6 y, 3 mo

No

Amputation plus chemotherapy; deceased 12 mo after malignancy diagnosis

 7 (40–49 y)

Recurrent unresectable

Sacrum

At enrollment, lesion contained few giant cells. In foci, sheets of cells exhibiting epithelioid morphology with cytologic atypical and brisk mitotic activity, including atypical mitoses

Diagnosis: Undifferentiated pleomorphic sarcoma

No

25 y

4 mo

Likelyb

Deceased 6 mo after malignancy diagnosis

   8 (40–49 y)

Recurrent resectable

Tibia

Malignant spindle cell sarcoma (no maturation due to denosumab)

Diagnosis: Undifferentiated pleomorphic sarcoma

Yes, 56 Gy

7 y, 8 mo

1 mo

Yes

Amputation plus chemotherapy; alive at last follow-up

 9 (20–29 y)

Recurrent resectable

Femur

Areas of solid ABC and GCTB associated with epithelial and spindle cell proliferation.

Diagnosis: GCTB with suspect progression to sarcoma

Yes, 56 Gy

4 y, 8 mo

6 mo

Likelyb

Lung metastases diagnosed soon after femur malignancy; deceased 5 mo after malignancy diagnosis

10 (50–59 y)

Recurrent unresectable

Sacrum

Diagnosis: High grade undifferentiated spindle cell sarcoma, consistent with differentiation arising in malignant GCTB

Yes, 25 fractions

6 y, 7 mo

1 y, 8 mo

Yes

Surgery (resection and curettage, laminectomy); deceased 2 mo after malignancy diagnosis

Sarcomatous transformation

11 (30–39 y)

Recurrent unresectable

Distal femur

Diagnosis: Undifferentiated spindle cell sarcoma

No

11 y

6 y, 2 mo

No

Amputation and chemotherapy; alive at last follow-up

12 (60–69 y)

Primary resectable

Tibia

Diagnosis: High-grade osteosarcoma

No

2 y, 11 mo

2 y, 2 mo

No

Chemotherapy and amputation; deceased 7 mo after malignancy diagnosis

13 (30–39 y)

Recurrent resectable

Distal femur

Diagnosis: Undifferentiated spindle cell sarcoma

No

4 y, 9 mo

2 y, 5.5 mo

No

Tumor resection and prosthesis plus chemotherapy; alive, no evidence of disease at last follow-up

14 (50–59 y)

Primary resectable

Distal femur

Microscopic picture corresponds to chondroblastic/osteoblastic osteosarcoma high grade that probably developed from GCTB

Diagnosis: High-grade osteosarcoma

No

1 y, 5 mo

1 y, 2 mo; progression after only 3 mo of treatment

No

Amputation plus chemotherapy; alive at last follow-up

  1. ABC aneurysmal bone cyst, GCTB giant cell tumor of bone, Gy Gray unit, mo months, SMGCTB secondary malignant giant cell tumor of bone, y years
  2. aPatient numbers and age ranges (in brackets), instead of age at treatment, are identifiers for the purposes of this publication only and do not link to patients
  3. bMalignancy likely, but not definitively, present prior to denosumab due to lack of sufficient biopsies for expert review; opinion of expert reviewers based on available evidence (existing biopsy samples or local pathologist report) as noted in the “malignant histology” column)