Mr B. is a 69 year-old man with no significant past medical history. He presented to our Institute with a left pre-tragus mass that appeared a few weeks ago. His general practitioner ordered a Computed Tomography (CT) scan then a Magnetic Resonance Imaging (MRI) that revealed a bifocal parotid mass. The first nodule extended into the superficial lobe of the parotid and the second through the angle of the mandible with a marked osteolysis. A nodule was also seen at the upper front of the maxillary left sinus without continuity with previous one. Clinically no mucosal lesion was identified. The fine needle aspiration biopsy of the parotid lesion exhibited glandular epithelial cells suspicious of malignancy. The biopsy then demonstrated a papillary adenocarcinoma suggesting a cystadenocarcinoma. Immunohistochemical assessment of HER2 showed grade 2+ overexpression but no HER2 gene amplification by FISH (fluorescence in-situ hybridization). Positron Emission Tomography (PET) staging showed distant metastases. Multiple bone hyperfixations were localized in C3 right costal arch, C6 with posterior wall destruction, L4 pedunculate, left femur and pelvis.
A chemotherapy was initiated on July 2011. Three cycles of cisplatin 100 mg/m2 and 5-fluorouracil 1000 mg/m2/d (J1-J4) were delivered with good tolerance. The CT scan evaluation revealed a stabilization of the mass developed at the expense of the superficial lobe of the parotid but a marked progression of bone localizations of the malar mass (33 mm versus 14 mm) and of mandible osteolysis with pathological fracture. Distant bone metastases progressed too on the MRI with an epidural extension of C6 damage and appearance of T8 and L5 lesions.
In October 2011, palliative radiation therapy was administered on the primary parotid mass, the adjacent mandible lesion and on symptomatic distant bone localizations (C6 and L4). The dose delivered was 30 Gy in 10 fractions.
The April 2012 CT scan evaluation reported a discrete regression of the irradiated parotid mass but a further progression of the malar mass measured at 53 mm. Moreover, enlarged mediastinal lymph nodes appeared in 2R, 4R and 7 as well as multiple osseous sites throughout the pelvis and spine.
Given the aggressiveness and resistance of this disease to radio-chemotherapy, an additional molecular analysis was requested to attempt to identify mutations on EGFR, KRAS and BRAF genes. No mutations were found except for BRAF. A polymerase chain reaction followed by an allele specific oligonucleotide revealed a V600E mutation of BRAF.
A compassionate treatment with a BRAF inhibitor (Vemurafenib) was started at a dose of 240 mg bid for 2 months after approval of internal ethic committee. The patient reported a great improvement in clinical condition from the first month. His fatigue declined allowing him to enjoy activities such as gardening. His vision improved with ptosis regression. Clinical examination found a clear regression of the malar mass. The CT scan obtained after 2 months of treatment confirmed the good clinical impression. The malar mass regressed by 42% (60 × 47 × 53 mm versus 46 × 42 × 45 mm) (Figure 1A,B). Mediastinal lymph nodes showed a complete response (Figure 1B,E). Bone regeneration was seen on pelvis (Figure 1C,F) and spine.