Primary frontal sinus squamous cell carcinoma in a dog treated with surgical excision

Abstract

An 8-year-old castrated male mixed breed dog was presented for a squamous cell carcinoma of the left frontal sinus. A partial craniectomy was performed and polytetrafluoroethylene mesh was placed over the craniectomy site. The dog recovered well with a good cosmetic outcome. Histopathology confirmed primary frontal sinus squamous cell carcinoma.

Frontal sinus squamous cell carcinoma (FS-SCC) is extremely rare as a primary condition, with only 3 cases reported in the veterinary literature (1). Squamous cell carcinoma of the frontal sinus is more commonly seen as an extension of nasal SCC (2). In humans, primary FS-SCC is also rare, comprising 0.009% to 0.03% of head/neck cancers and 0.3% of all paranasal sinus cancers with case reports predominating (3,4). Principal treatments for humans with primary FS-SCC include surgery, radiation therapy, chemotherapy, or combinations thereof, with surgery being the mainstay option in most cases (5–7). Three cases reported in the veterinary literature were treated with chemotherapy alone with survival times ranging from 6 mo to 3 y (1). There are no reports of surgery as a component of treatment for primary FS-SCC in the veterinary literature.

Case description

An 8-year-old castrated male mixed breed dog was presented for SCC of the left frontal sinus. The dog was taken to the primary care veterinarian for sensitivity over the left frontal sinus. A mass was detected and skull radiographs revealed a bony defect over the frontal sinus. Biopsy was performed and it was noted that a soft tissue mass was attached to the rim of bone overlying the left frontal sinus and a portion of the external table of the frontal sinus had presumably been eroded by the tumor. After removal of this soft tissue mass, the tumor was noted to extend caudolaterally within the sinus. No bone was taken during this incisional biopsy. The mass was diagnosed by histopathology as SCC. The patient was referred to the Louisiana State University Veterinary Teaching Hospital for further evaluation.

A computed tomography (CT) scan revealed a defect within the left frontal bone overlying the left frontal sinus with extension of disease, seen as sclerosis and thickening of the bone, into the left frontal and parietal bones that crossed the midline caudally, extending into the right parietal bone (Figure 1). A complete blood (cell) count (CBC) and serum chemistry performed at this visit were unremarkable. Treatment options discussed with the owner included surgical excision with partial craniectomy, radiation therapy, or chemotherapy. The owners elected surgical excision, which was performed 1 wk later. The extent of the tumor was measured on CT images and a 1-cm margin was obtained around the biopsy scar and the visible extent of the tumor on the CT images. The skin and subcutaneous tissue were dissected down to the underlying bone rostrally and the dorsal sagittal crest caudally. The temporalis muscle was elevated from the underlying bone bilaterally. The extent of the excision was measured and marked and a 4-mm burr was used to drill holes into the frontal and parietal bones to form an outline of the planned excision. Once outlined, the bone between these holes was removed with a 4-mm burr until only the endosteum was visible ventrally. The excised skin from the biopsy tract was transected at the caudal extent of the frontal sinus and the underlying bone was drilled with the burr, which allowed removal of the external table of the frontal sinus and 7the septum. The caudolateral portion of the left frontal sinus was noted to have a plaque of abnormal tissue. Rongeurs were used to break through the internal table of the frontal sinus to connect the previously drilled lines in the cranium. Elevation of this bone from rostral to caudal proceeded with ease and the dorsal calvarium was removed without incident. The bone at the edges of the excision appeared grossly and palpably normal. The left temporal muscle was elevated and released caudally to allow for rotation rostrally to cover the defect. The left and right temporal muscles were sutured together to cover the defect. At the rostral most aspect, a temporalis muscle fascia flap from the left side was used to separate the frontal sinus from the brain. The dog recovered well from surgery.

Figure 1.

Sagittal reconstruction of CT images. The defect in the frontal sinus is indicated by the asterisk. The sclerosis of the parietal bone is indicated by the arrow. H — rostral; F — caudal.

The morning following surgery, the dog was bright, alert, and responsive and ambulating normally. Two hours later, the dog became comatose with normal vital signs and serum chemistry values. A CT scan was performed and revealed left-sided cerebral compression and displacement to the right from the swollen left temporalis muscle (Figure 2). The dog was returned to surgery where the compression was immediately relieved by releasing the left temporalis muscle. Polytetrafluoroethylene mesh was cut to size to cover the defect. A 1.1-mm drill bit was used to drill holes into the cranium surrounding the defect. The mesh was sutured to the calvarium using 2-0 polypropylene, resulting in a domed shape over the defect. A second temporalis muscle fascia flap was elevated from the left temporalis muscle and used to close the defect overlying the mesh. Post-operative radiographs confirmed appropriate placement of the mesh (Figure 3). The dog recovered well from anesthesia and was significantly more alert post-surgery compared to the comatose state that morning. The following morning, the dog was bright, alert, and responsive with an absent menace bilaterally and significant vestibular ataxia with a left-sided head tilt. All other cranial nerves were normal. Two days later, menace had returned and the vestibular ataxia was significantly improved. The dog was discharged to the owners. Histopathology confirmed SCC. Margins were free of disease except for an area of the rostral portion of the internal table of the frontal sinus.

Figure 2.

Transverse CT image showing left-sided cerebral compression and displacement to the right from the swollen left temporalis muscle. P — dorsal; R — right side; A — ventral; L — side.

Figure 3.

Post-operative oblique lateral radiograph showing appropriate placement of the polytetrafluoroethylene mesh over the craniectomy defect.

The dog was seen 2 wk after surgery for suture removal and was reported to be doing well at home with a good cosmetic outcome (Figure 4). The vestibular ataxia was markedly improved with the only neurologic abnormality being a mild residual head tilt to the left. Four weeks after surgery, the dog was again presented for discussion of adjuvant therapy with the owner. At this time, the dog was neurologically normal. Radiation therapy was not strongly recommended due to the location with underlying brain and previous reports showing that SCCs are not generally responsive to radiation (8). Chemotherapy was recommended based on 3 canine cases of primary FS-SCC treated with chemotherapy and a recent report in humans (1,9). A combination protocol with carboplatin and 5-flurouracil was chosen to be given every 21 d for a total of 4 to 6 doses and was started 7 wk after surgery. The protocol was modified from that reported in humans as carboplatin was substituted for cisplatin to decrease nephrotoxicity and standard canine doses were used (9).

Figure 4.

Photograph of the dog 48 days after surgery showing a good cosmetic outcome.

The patient was administered 1 mg/kg body weight (BW) maropitant citrate (Cerenia; Zoetis, Kalamazoo, Michigan, USA) subcutaneously 30 min prior to treatment with 5-flurouracil (Adrucil; Teva Pharmaceuticals, Haarlem, Netherlands), 150 mg/m², administered over 10 min. Thirty minutes later, carboplatin (Carboplatin; Teva Pharmaceuticals Industries, Haarlem, The Netherlands), 200 mg/m² was administered over 20 min. Complete blood cell counts were evaluated before treatment and every week after therapy until the next dose. Treatment was delayed if the neutrophil count was < 3000/μL and/or the platelet count was < 150 000/μL. A renal panel and urinalysis/urine specific gravity were used to assess renal function.

After the initial dose of chemotherapy, the patient had a double nadir with a grade I neutropenia at week 1 (2700 neutrophils) and week 3 (2400 neutrophils). No adverse events occurred due to the neutropenia. Treatment was delayed 1 wk and the interval of subsequent treatments extended to every 28 d. No gastrointestinal side-effects were reported. The patient received 6 total cycles of chemotherapy and a CT scan was performed 6 mo after surgery. Significant findings on the CT scan included a healing left dorsal craniectomy with a metal mesh implant and no evidence of recurrence of disease. The dog continues to do well 16 mo after surgery with no signs of recurrence.

Discussion

This is the first report in veterinary medicine of treatment of a primary FS-SCC with surgery. The only previous report of primary FS-SCC described 3 dogs that were treated with chemotherapy consisting of piroxicam and carboplatin and piroxicam and toceranib (1). Survival times were 6.5 mo, 11.5 mo, and 1 dog was still alive 3 y after diagnosis. Surgery was not used as a component of treatment in these cases due to extension of the tumor. Radiation therapy was not pursued due to risk of side-effects to adjacent structures (eye, brain). Surgery is often the chief treatment for primary FS-SCC in humans, with chemotherapy and radiation therapy used as adjuvant treatments (6,7). Chemotherapy for human paranasal sinus carcinomas using combination therapy including cisplatin has been shown to have an 82% response rate in previously untreated patients (10). Radiation therapy alone or combined with surgery for paranasal sinus carcinomas has not proven to significantly improve local control, with only 37% of patients remaining disease-free and 54% overall survival at 2 y (11). Use of chemotherapy induction followed with chemoradiation in patients with paranasal sinus undifferentiated carcinomas resulted in slight improvement with 43% progression-free survival and 64% overall survival at 2 y (12).

Squamous cell carcinoma is locally invasive but typically slow to metastasize. When located in the nasal cavity, SCC is typically treated with radiation therapy, as surgical treatment is unlikely to result in a cure due to early bone invasion (5,8). When confined to the nasal planum, surgery can result in a cure if adequate margins are obtained, although cosmesis is significantly affected (13). Based on pre-surgical imaging, it was believed that margins could be obtained with an aggressive surgical approach and acceptable cosmesis. The owners elected surgical treatment because of the chance of complete removal, and a concern that the cost and risks of radiation therapy were undesirable. More advanced imaging, such as positron emission tomography-computed tomography (PET-CT), may have been able to provide a more definitive margin assessment before surgery, but is not available in our practice.

After the initial surgery, the dog became comatose. On CT scan, the left temporal muscle was swollen, causing left-sided compression and rightward deviation of the brain. Neurological abnormalities were not seen initially and this delayed onset was most likely due to progressive swelling of the left temporal muscle until the brain could no longer compensate. It is likely that this compression and deviation affected the brainstem and cerebellum, resulting in coma and central vestibular signs in this patient. The dog’s condition immediately improved after a second surgery to relieve the compression. With time, the vestibular signs completely resolved, further supporting the theory that the temporary compression was the cause of the vestibular signs. Magnetic resonance imaging (MRI) was not performed, thus detail of the cerebral and cerebellar parenchyma were not available.

Primary FS-SCC is extremely rare in dogs. Chemotherapy has been shown to provide reasonable survival (1). Radiation therapy has not been evaluated for use in treatment of this condition. This report documents, for the first time, that surgery can be used as a primary treatment in some cases. In cases in which surgical margins cannot be achieved, surgical debulking may allow for better control by adjuvant therapies.