Temporal Chondroblastoma with a Novel Chromosomal Translocation (2;5) (q33;q13).

The case of a 51-year-old man with a large temporal mass is presented. The mass eroded the floor of the middle fossa medially to the sphenoid sinus. A combined approach with neurosurgery and otolaryngology was performed to achieve maximal resection of the mass. Pathology was typical for chondroblastoma: a rare, benign but locally invasive chondroid tumor. Genetic testing revealed a translocation of (2;5) (q33;q13). This is a unique genetic mutation in all chondroid tumors to our knowledge. The diagnostic utility or role of this mutation in the pathobiology of this tumor remains to be determined.

Case Report

A 51-year-old man presented with a history of a mass on the right side of the face and had previously undergone an open biopsy at an outside facility; the mass was revealed to be a chondroblastoma. His primary complaints at the time of initial evaluation were headache, blurry vision, pain, and numbness on the right side of the face as well as generalized fatigue. Imaging revealed a destructive mass eroding from the infratemporal fossa into the middle fossa and medially into the sphenoid sinus (Fig. 1). The mass also displaced the lateral orbital wall medially. A combined surgical approach with neurosurgery and otolaryngology was recommended to resect as much of the tumor as possible. Preoperative exam and workup revealed severely decreased sensation in V1 and V2 (first and second trigeminal nerve divisions) distributions on the right as well as severe mixed hearing loss demonstrated by audiology. Ophthalmologic evaluation revealed right eye proptosis without vision loss.

Figure 1

(a) Noncontrasted, axial computed tomography scan through the skull base showing the erosive lesion in the floor of the right middle fossa. The mass is seen extending to the carotid canal and into the sphenoid sinus. (b) Postcontrast, T1-weighted coronal magnetic resonance imaging showing no significant enhancement of the lesion and its relationship to the infratemporal and middle fossae.

The patient was taken for resection of the lesion via a right frontal craniotomy, extended preauricularly into the cervical region. The zygoma was reflected inferiorly with the temporalis flap. A frontotemporal craniotomy was performed, revealing the tumor expanding and eroding the temporal bone and sphenoid wing. The dura was opened to inspect for intradural extension and found to be clear of tumor, so was reclosed in a watertight fashion. The otolaryngology team then dissected the mandibular head and temporomandibular joint (TMJ). This glenoid plane appeared to be the origin of the tumor. A thin layer of cortical bone and tumor was dissected away from the temporal dura as well as the lateral orbit all the way down the sphenoid bone to the superior orbital fissure and into the sphenoid sinus (Fig. 2). The V1 and V2 branches were isolated in floor of the middle fossa. The tumor encased these nerves but did not infiltrate into the cavernous sinus, and so the nerves were sacrificed and the tumor was removed from the lateral cavernous sinus wall. The tumor invaded the petrous temporal bone and was removed medially, exposing the petrous carotid artery and eustachian tube. After curetting out the petrous bone surrounding the carotid artery, no further gross tumor was seen. The skull base was reconstructed using two vascularized flaps. The sphenoid sinus was filled with an extended temporalis muscle flap and covered with DuraSeal (Coviden, Mansfield, MA). A vascularized periosteal graft was then laid across the exposed petrous air cells and covered with DuraSeal. A titanium mesh cranioplasty was secured in place.

Figure 2

Intraoperative photograph. The suction is pointing out the resection through the lateral wall of the sphenoid sinus. MH, mandibular head; TL, temporal lobe.

Gross examination of the lesion showed multiple, fragmented tissue types, with osseous as well as soft, reddish-purple necrotic portions. Microscopic examination showed a typical appearance of chondroblastoma, with many multinucleated giant cells against a chondroid background. There were portions of cortical bone that the tumor abutted and invaded (Fig. 3).

Figure 3

Representative section, hematoxylin and eosin, 200 × magnification. Typical multinucleated giant cells can be seen (white arrow) against a hemorrhagic chondroid background. Areas where the tumor abuts the osseous component can also be seen.

Karyotyping revealed a male chromosome complement with translocation t(2;5) was present in 9 of 20 cells analyzed (Fig. 4). Eleven cells had a male chromosome complement with no clonal abnormalities detected. Cytogenetic studies were performed on tumor cells using short-term unstimulated cultures set up on the same day of the surgery. Metaphases were Giemsa (G)-banded by conventional G-bands by trypsin using Wright stain–banding and at least 20 metaphases were analyzed.1

Figure 4

Karyotype 46,XY, t(2;5)(q33;q13)[9]/46,XY[11].

Literature Review

Temporal bone chondroblastoma is a rare tumor in the skull base with ~75 cases reported worldwide.2,3 Though generally considered benign,2 it can have locally aggressive features,3,4 and recurrence after resection is around 20%.5 Chondroblasts and multinucleated giant cells in a chondroid matrix are diagnostic.2 The squamous temporal bone, especially the glenoid region,6 embryologically has a cartilaginous origin, making this a potential site of growth. Reflecting this cartilaginous origin, the tumors typically stain for S-100 and vimentin.2,3,7,8,9 Fine-needle aspiration of these lesions can be misleading10; temporal bone chondroblastomas need to be distinguished from giant cell tumor of bone, chondromyxoid fibroma, and osteosarcoma. Petrous location,11,12 as well as mandibular13,14 and less commonly, other craniofacial locations, have also been reported.15,16,17,18 Radiographically and pathologically, cystic degeneration is common.3,17,19,20 Though small lesions occasionally are reported,3,21 extensive local invasion of the middle fossa, TMJ, and petrous bone is typical.21,22,23,24 A single report of intracranial hemorrhage related to skull chondroblastoma exists.25

Recommended treatment is surgical with total resection.3,5,6,26,27 The potential areas of difficulty with total resection have been pointed out to be at the TMJ as well as at the dural interface.3 Though true dural invasion is uncommon, it can occur, necessitating careful inspection.23 Familiarity with skull base approaches, techniques, and anatomy allows for safer resection, even when the tumor abuts structures such as the petrous carotid artery6 (as in our case). Familiarity with vascular variations of this region is also critical in planning resection.28 Overall recurrence is reported as 20 to 40%,5,29 though correlated with resection.30 Modern aggressive skull base resection techniques may improve this rate as noted in several small series. In four patients undergoing total resection, no recurrence was noted at 5 years.3 Another five patients treated aggressively showed good long-term control with gross total or near total resection.6 Four patients treated with an aggressive transzygomatic approach also showed no recurrence at mean follow-up of 9 years.31 In cases of recurrence, repeat resection may still offer acceptable control as well.4,17,32 Preoperative embolization has been reported29 but is generally not considered for particularly vascular tumors. Radiation is generally not recommended due to the potential for inducing malignant transformation3; however, proton beam therapy has been reported with good local control.11,33 Metastases for chondroblastoma in general are exceedingly rare and may involve lung or skin.34,35

Significance of Translocation of Previously Unreported t(2;5)(q33;q13) in Temporal Bone Chondroblastoma

A large series of cytogenetic abnormalities of chondroid tumors from the Chromosomes and Morphology (CHAMP) Collaborative Study Group36 includes four cases of chondroblastoma arising in extremities, all of which had a normal karyotype. Nonrandom karyotypic aberrations in chondroid tumors reported by CHAMP investigators and others include loss of distal 8q in osteochondroma; gain of chromosome 5 in chondroma; rearrangements of 6p and 6q in chondromyxoid fibroma36,37,38,39; gains of chromosome 7; losses of chromosomes 5q, 6q, and 9p40; and abnormalities in 12q and 17p in chondrosarcoma41,42 and the translocation (9;22)(q22;q12) in extraskeletal myxoid chondrosarcoma.43,44,45,46 Clonal abnormalities have been reported in typical epiphyseal chondroblastomas,47,48,49,50,51,52 but never to our knowledge in temporal bone chondroblastoma. Loss of chromosome 5q is a recurring alteration,47,48,49,51 and rearrangement of chromosome 8q was described in an aggressive or malignant chondroblastoma.49 More recently, chondroblastoma was associated with ring chromosome 4,50 and in a different report with a balanced translocation (5;17) (p15;q22–23).52

Conclusion

In summary, we present a novel clonal abnormality in temporal bone chondroblastoma. This finding opens the possibility to retrospective genomic analysis of previously reported cases to ascertain whether this clonal alteration is diagnostically useful and to understand its role in the pathobiology of this rare skull neoplasm.