Case Study 64

1. Case Study 64 Kenneth Clark, MD

2. Question 1 • This is a 32-year-old woman with a history of a skull-base tumor, status-post resection 2 years ago. She has recently developed multiple cranial nerve palsies. MRI and CT scans of the head revealed recurrent tumor. • Describe the MRI and CT findings.

3. Axial T1 Axial T1 + Contrast Axial T2 FLAIR Axial CT Scan

4. Answer • MRI shows a large expansile skullbase mass centered within the right aspect of the clivus and crossing the midline. There is also extensive involvement of the petrous and mastoid portions of the right temporal bone and extension into the dorsum sellae. It shows variegated isointensity/hypointensity on T1-weighting, mild heterogeneous contrast enhancement and diffuse hypointensity in T2 FLAIR. • CT scan shows similar features although better highlights the lobulated quality of the lesion. It also reveals ring-like structures most compatible with cartilaginous matrix production.

5. Question 2 • What is the differential diagnosis of a destructive expansile skull base lesion?

6. Answer • Osteoma • Chordoma • Chondroma • Plasmacytoma • Ossifying and Non-Ossifying fibromas • Fibrous Histiocytoma • Chondrosarcoma • Chondroblastoma • Meningioma • Metastatic Lesions

7. Question 3 • The lesion was biopsied and submitted for intra-operative examination. The specimen was firm and heavily mineralized, making the smear difficult. Describe the findings. How would you report to the surgeon? • Click here to view the smear

8. Answer • The smear shows a dense, cohesive, highly cellular neoplasm that is extensively mineralized. The cells appear large, with ovoid nuclei and fine, evenly dispersed chromatin. The cells are arranged in sheets and interweaving streams. No mitotic activity is seen. Very rare multinucleated giant cells are seen. Within the background are moderate numbers of inflammatory cells and extensive hemosiderin deposition. • A. Neoplastic • B. Large spindle cells and giant cells seen

9. Question 4 • The specimen was then resected and submitted for pathologic examination. It was heavily mineralized and had to undergo decalcification prior to processing. • How would you describe the findings? • Click here to view the H&E slide

10. Answer • The tissue show a mildly polymorphic neoplasm comprised predominantly of spindle cells with smaller regions of epithelioid cells as well as multinucleate giant cells. The majority of cells have round-to-ovoid nuclei with evenly distributed chromatin, mildly irregular nuclear contours and distinct nucleoli. Some cells show hyperlobulated nuclei with prominent nuclear grooves. No mitotic activity is seen. Many of the cells show homogeneous amphiphilic-to-light eosinophilic cytoplasm, with a lesser number displaying dense eosinophilic cytoplasm. The tumor cells show infiltrative and solid growth patterns. The majority of background tissue consists of distinct appearing fibrillary and mineralized osteo-chondroid matrix with multifocal calcification. Some regions appear fibrous, with thick-walled sclerotic blood vessels scattered throughout. Variably dense lymphoplasmacytic infiltrates are seen throughout the lesion.

11. Question 5 • What is your differential diagnosis based on this histology (abundant osteochondroid matrix production)?

12. Answer • Chondroblastoma • Although chordoma, chondroma, and chondrosarcoma are theoretically still in the differential, the lack of physaliferous cells (chordoma), well-differentiated chondrocytes (chondroma) and extensive mineralization and fibrosis (not a consistent feature of any of these entities) essentially excludes these as diagnostic possibilities.

13. Question 6 • What immunohistochemical stains would you order to confirm the diagnosis of chondroblastoma?

14. Answer • S100 • Vimentin • Low molecular weight keratin, PAS with diastase (glycogen) • Reticulin (surrounds each cell) • Neuron specific enolase (NSE) • Click to see S100, NSE

15. Question 7 • The patient has a reported history of recurrent chondroblastoma, which is now confirmed by H&E and immunohistochemical examination. • How aggressive are these tumors?

16. Answer • Chondroblastomas usually behave in a benign fashion, although local recurrence is common. Sometimes they behave more aggressively, invading surrounding tissues and in some cases resulting in metastases. Metastases, however, usually occur following surgical manipulation of the primary lesion.

17. Question 8 • Is the skull base an unusual location for this tumor?

18. Answer • Yes. Most cases of chondroblastoma occur in the distal femur, proximal humerus, proximal tibia, and sometimes the pelvis. Approximately 60 cases of skull base chondroblastoma have been reported worldwide.

19. Question 9 • Where do chondroblastomas most often occur in the head?

20. Answer • They most commonly occur in the temporal bone.

21. Question 10 • What age group is most commonly affected?

22. Answer • Chondroblastomas of the lone bones are almost exclusively found in patients (usually males) in the second decade of life. Skull base chondroblastomas are almost exclusively found in patients over the age of 30.

23. Question 11 • What cytogenetic abnormalities are associated with chondroblastoma?

24. Answer • Recurrent cytogenetic abnormalities on chromosome 6 have been found. • Recent studies have also shown LOH on 5q, 9p, 11p, 13q, and 19q. • Loss of heterozygosity of 17p (p53) has also been reported in greater than 50% of chondroblastomas

25. References • Kutz JW, Verma S, Tan H, Lo W, Slattery W, Friedman R. Surgical Management of Skull Base Chondroblastoma (2007). Laryngoscope. 117:848-853. • Rosai J. Rosai and Ackerman’s Surgical Pathology, Ninth Edition (2004). Elsevier, Inc. • Blaauw G, Prick J and Versteege C. Chondroblastoma of the temporal bone (1988). Neurosurgery, 22:1102–1107. • Goga D, Fassio E, Fetissof F, Jan M. Chondroblastoma of the temporomandibular region (1999). J Oral Maxillofac Surg. 57:1270-1272. • Papachristou D, Goodman M, Cieply K, Hunt J, Rao U. Comparison of allelic losses in chondroblastoma and primary chondrosarcoma of bone and correlation with fluorescence in situ hybridization analysis (2006). Hum Pathol. 37(7):890-898.