Clinical outcome of low-grade central osteosarcoma and role of CDK4 and MDM2 immunohistochemistry as a diagnostic adjunct.
BACKGROUND
Low-grade osteosarcoma encompasses parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LCOS), with LCOS more rare than POS. LCOS is also more likely to be misdiagnosed and inappropriately treated with an intralesional procedure, due to its misleading radiological features and the overlap of its pathological characteristics with those of benign bone tumors. Therefore, as a diagnostic adjunct for LCOS, immunohistochemical assay with murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) have been tried with controversial results. We investigated (1) the clinical course and surgical outcome of LCOS, and (2) the diagnostic role of immune-histochemical markers (CDK4, MDM2) and their correlation with clinico-radiologic findings.


METHODS
We retrospectively reviewed 16 LCOS patients with regard to age, gender, tumor location, plain radiographic pattern, tumor volume, extraosseous extension, initial diagnosis, initial treatment, definitive diagnosis, definitive treatment, surgical margins, histochemical markers, and oncological outcome.


RESULTS
Final survival status was continuous disease-free in 14, alive with disease in 1, and remaining 1 patient died of other cancer. Except for 1 patient who had not undergone excision of their primary lesion, no patients developed a local recurrence. Eight tumors (50%) showed diffuse immunostaining for CDK4. Three of 8 tumors labeled for CDK4 were also positive for MDM2. Six (75%) of 8 CDK4-positive tumors displayed lytic lesions on a plain radiograph; in contrast, 2 (33%) of 6 tumors showing a sclerotic pattern on a plain radiograph were positive for CDK4.


CONCLUSIONS
The diagnosis of LCOS is challenging; however, if it is properly diagnosed, there is a high chance of a cure with wide excision alone. Positive immunostaining for CDK4 or MDM2 may be used as a diagnostic adjunct, although negative immunostaining cannot rule out this tumor. The clinical, radiological, and typical pathological findings are vital in raising the suspicion of this rare tumor.
Department of Orthopedic Surgery, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul, 139-706, Korea, dgjeon@kcch.re.kr.
Dae-Geun
DG
Jeon
Jae Soo
JS
Koh
Wan Hyeong
WH
Cho
Won Seok
WS
Song
Chang-Bae
CB
Kong
Sang Hyun
SH
Cho
Seung Yong
SY
Lee
Soo-Yong
SY
Lee
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D002648:Child; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012516:Osteosarcoma / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4