Skull Base Primary Extracranial Meningioma with Hyperostosis in a Small Mixed-Breed Dog

Introduction

Meningioma is a mesenchymal neoplasm of the central nervous system originating from arachnoid cells, typically within arachnoid villi, that undergo mesenchymal and epithelial differentiation.^1–3 They may also arise from the dura or pia matter.^2,4 Primary extracranial meningioma (ECM) is uncommonly described in the veterinary literature; however, there are multiple theories in the human literature as to how they occur. This includes arising from arachnoidal cells located along neurovascular sheaths where they exit the skull, displaced pacchionian bodies during embryogenesis, trauma or cerebral hypertension displacing arachnoid islets, and/or from undifferentiated or multipotential mesenchymal cells.^3,5 Meningioma is the most common primary tumor of the central nervous system in canines, with ˜80% reported as primary intracranial meningioma (ICM).³ The remaining ˜20% are ECM reported in the spinal cord (˜15%), along with the retrobulbar region, para-nasal sinuses, and eyelid.^2,3,6,7 Although ECM has been reported in humans along the ear and temporal bone, ECM originating from along the skull base has not been previously reported in the veterinary literature.⁵ Hyperostosis associated with ECM in canines has also not been previously reported.

Case Report

A 7 yr old 5.2 kg female spayed Chihuahua-terrier mix was presented to the surgery department for a progressive dry, hacking cough with increasing frequency of nonproductive retching, stridor, and panting. Coughing had been noted the patient’s entire life and was unresponsive to multiple courses of antibiotics, steroids, and antitussives. For 9 mo before presentation, the coughing had increased in frequency with excitement or when drinking water. There was a marked amount of referred upper airway noise on thoracic auscultation with normal bronchovesicular sounds. Oral exam revealed right-lateral lingual deviation, with the left half of the tongue atrophied relative to the right half. Review of previous skull radiographs identified a mineralized mass on the base of the skull at the level of the left tympanic bulla.

A computed tomography (CT)^a scan of the head/neck/chest with pre- and postcontrast enhancement after administration of iohexol^b (2 mL/kg IV) was performed the following day. At the time of intubation, a large, firm, left-sided intraoral swelling pushing the soft palate ventrally was appreciated, causing severe narrowing of the oropharynx. Normal bilateral laryngeal function was noted. Contiguous images (slice thickness, 2.0 mm) of the head/neck/chest as well as three-dimensional volume reconstruction of the images were obtained and reviewed (Figures 1A, B; Supplementary Videos I, II).

View Figure

• Download as Powerpoint
• Download Figure

The CT scan revealed a large-mass lesion (3.0 cm (H) × 2.2 cm (W) × 2.3 cm (L)) with a stippled mineral attenuating pattern in the periphery and a soft-tissue attenuating center, located medial to the left tympanic bulla. There was tumor invasion in the left side of the base of skull, left petrous temporal bone and occipital bones, and left tympanic bulla/inner ear resulting in severe secondary compression/obstruction of the nasopharynx and oropharynx. The nasopharyngeal lumen could not be visualized. The caudal fossa had rough inner margins due to the bony changes of the base of the skull. The left carotid artery was displaced lateroventrally without significant compression or tumor invasion in the lumen. There were pulmonary osteoma lesions in the thoracic cavity, but no evidence of metastatic disease was observed. The trachea and bronchi were unremarkable. An intraoral aspirate of the mass was attempted, but cells could not be aspirated because of poor exfoliation. The patient recovered uneventfully from anesthesia.

Worsening respiratory signs, including intermittent cyanosis, were reported upon presentation to the surgical oncologist the following week. Differential diagnoses discussed for a skull base extracranial tumor included ossifying neoplasia (multilobular osteochondrosarcoma, chondrosarcoma, osteosarcoma, etc.), ectopic soft-tissue ossification, or ossifying soft-tissue tumor. The best treatment option for immediate palliation of clinical signs and obtaining histopathology, based on the CT, included marginal surgical excision followed by adjuvant intensity-modulated radiation therapy (IMRT) if histopathology revealed neoplasia. Other options discussed included stereotactic radiation therapy if incisional biopsy revealed neoplasia, palliative radiation therapy, and palliative medical management.

When the patient was presented for surgery, she was cyanotic and dyspneic. She was placed in an oxygen cage at 40% O₂ and administered butorphanol^c (0.2 mg/kg IV) with acepromazine^d (0.02 mg/kg IV) for sedation. A preoperative complete blood count and serum chemistry panel revealed no significant abnormalities. Dexamethasone sodium phosphate^e (0.15 mg/kg IV) was administered preoperatively because of concern for postoperative oropharyngeal inflammation.

The patient was positioned in dorsal recumbency, and a modified hypophysectomy approach⁸ was performed by making an incision ventrally through the left intermandibular space. The incision was advanced dorsally through the base of the tongue and the soft palate until the mass medial to the left ventral bulla was visualized (Figures 2A, B). Approximately 90% of the mass was excised via use of a high-speed pneumatic surgitome^f with varying burr sizes while the surgical site was periodically lavaged with sterile saline. The majority of the mass was composed of firm mineral, with a smaller softer core. The mass was placed in formalin^g and submitted for histopathology. Postoperatively, a left intraoral swelling could no longer be palpated.

View Figure

• Download as Powerpoint
• Download Figure

The patient was maintained on a ventilator throughout surgery and recovered from anesthesia without complication. Postoperatively, the patient was maintained on Norm-R^h (52 mL/kg/d) + metoclopramideⁱ (2 mg/kg/d) + 20 mEq KCl/L^j, a fentanyl (4 mcg/kg/hr)^k/lidocaine (1.5 mg/kg/hr)^l constant rate infusion, ampicillin and sublactam^m (30.7 mg/kg IV q 8 hr), dexamethasone sodium phosphate (0.15 mg/kg IV q 24 hr), famotidineⁿ (1 mg/kg IV q 12 hr), and acepromazine (0.02 mg/kg IV q 6 hr). The patient was placed in an oxygen cage at 40% O₂ and monitored for dyspnea, with orders to ice the incision every 4 hr. Five hours postoperatively, left perilingual edema was noted with a mildly increased inspiratory effort, stertorous breathing, and mild right-sided foamy epistaxis. This progressed to cyanosis within 2 hr because of worsening oropharyngeal inflammation and development of a large left-sided pseudoranula. A 4.5 mm internal diametertemporary tracheostomy tube^o was placed between the fourth and fifth tracheal rings in a routine fashion under general anesthesia. The patient was returned to 40% O₂, and tracheostomy tube maintenance was started q 6hr.

The following morning, the intraoral swelling was significantly reduced. Over the first 2 days after the operation, the patient was transitioned to tramadol^p (5.6 mg/kg per os [PO] q 8 hr for 10 days), prednisone^q (1 mg/kg PO q 24 hr tapered over 1 mo), gabapentin^r (11.2 mg/kg PO q 8 hr for 10 days), amoxicillin/clavulonic acid^s (14 mg/kg PO q 12 hr for 14 days), and acepromazine^t (0.56 mg/kg [0.26 mg/lb] PO as a slurry q 8 hr for 10 days). Syringe feeding of various canned canine diets every 6 hr was started as well. The tracheostomy tube was removed 3 days after the operation because the appreciable intraoral swelling had resolved completely. The patient also started drinking and eating small amounts of boiled chicken and baby food on her own, although with a pronounced swallow. She was discharged 5 days after the operation with instructions for activity restriction, chest harness use when out to void, and being kept near a cool air humidifier.

On histopathological examination, the mass was composed of large coalescing spicules of reactive membranous bone that housed osteocytes lacking atypia in lacunae (Figures 3A, B). Between the spicules, there was extensive reactive fibrosis with distinct abutting to coalescing nests of epithelioid cells that resulted in hyperostosis. These cells had abundant cytoplasm with distinct cell borders, occasionally separated by modest mucinous material with a hint of intercellular bridging. Anisocytosis observed ranged from round and discrete to plump and spindeloid cells containing ovoid nuclei, finely stippled regularly distributed chromatin, and a single small distinct nucleolus. The mitotic index was low (<2/10 400× fields). The tumor cells were strongly positive for vimentin and negative for pancytokeratin with immunohistochemical staining, supporting a diagnosis of ECM (compared with metastatic carcinoma). Adjuvant IMRT was recommended but declined by the owner.

View Figure

• Download as Powerpoint
• Download Figure

An upper airway exam under general anesthesia performed at the 1 wk postoperation recheck revealed left arytenoid paralysis with a normal right arytenoid, suspected to be from transient inflammation of the left recurrent laryngeal nerve. A small portion of the caudal soft palate incision had dehisced, confirmed by flushing saline through the nostrils. The edges of the dehisced soft palate were debrided and reapposed under general anesthesia. To prevent further dehiscence, a 14-French red rubber catheter^u was placed percutaneously into the left lateral neck as an esophagostomy tube (E-tube). The patient was discharged that evening.

Two weeks after E-tube placement, the left ventral mandibular, dorsal lingual, and soft palate incisions were completely healed. The E-tube was removed 3 wk after placement. The only abnormality noted at subsequent rechecks was intermittent left-sided hypersalivation. At the 9 mo recheck, the owner reported that the patient was coughing and hacking up thick, viscous saliva. Sedated oral exam revealed recurrence of the firm swelling along the left aspect of the hard palate in the same area as the surgical site, half the size relative to when it was initially observed. The left arytenoid paralysis had resolved. The owner elected to monitor for quality of life at that time. Eleven months after the operation, the patient was presented for euthanasia because of a decreased quality of life, with recurrence of dysphagia and panting. A necropsy was not performed.

Discussion

Although ECM has been reported in humans along the ear and temporal bone, the ECM located at the base of the skull along the tympanic bulla identified in the present report is, to the authors’ knowledge, the first report of ECM in dogs in this location.⁵ This manuscript is also the first to report hyperostosis in canine ECM. Macroscopic hyperostosis occurs in up to 73% of feline ICM and 4.5–25% of human ICM, whereas macroscopic hyperostosis associated with canine meningioma is uncommon.^9–11 Extracranial osseous masses in dogs are more commonly due to etiologies such as osteosarcoma or multilobular osteochondrosarcoma.¹² ECM with no direct communication with the intracranial region is extremely rare; however, there was no evidence of direct communication on the CT scan or in surgery.¹³

Histopathology of the left skull base mass was consistent with an ECM. Several reports have identified that similar to humans, canine meningioma stains positive for vimentin and has variable yet typically negative immunostaining for cytokeratin.^1–3 In humans, meningiomas are more positive for vimentin and have variable immunostaining with cytokeratin, typically with less expression relative to carcinoma.¹⁴ The tumor core in this patient immunostained positive for vimentin and negative for pancytokeratin, consistent with what has previously been reported in dogs.^1–3

The patient in the current report was younger than the average age reported for canine meningiomas and was not a mix of breeds commonly associated with the disease. Meningioma typically occur in patients with a mean age of 9–10 yr, with a predisposition for boxers, golden retrievers, and German shepherd dogs.^2,15,16 There is still disagreement in the literature about whether a sex predilection exists in dogs toward females, with the current thought being that there is not one.^15,16 Based on primary location or location of metastases, meningioma typically results in progressive insidious clinical signs.¹² The location of the ECM along the left skull base near the tympanic bulla in the current case report resulted in lingual deviation and laryngeal compression, leading to a chronic progressive cough, intermittent dysphagia, and intermittent dyspnea. Chronic compression of cranial nerve XII exiting through the left jugular foramen is thought to have caused the lingual deviation at the time of presentation.

Although macroscopic hyperostosis associated with canine meningioma is uncommon, psammoma bodies (mineralized concentrically laminated structures), chondroid metaplasia, and osseous metaplasia have been observed on histopathology in some meningiomas.^2,3 Typically, hyperostosis appears as a diffuse bone thickening with skull invasion, adjacent to ICM.^9,10 The hyperostosis observed in our patient involved a sphere of new bone noted focally, medial to the tympanic bulla, expanding outward from the central meningioma tissue. This is similar to two other reports of canine ICM with macroscopic hyperostosis, in which new bone appeared as a focal area of proliferation.^17,18 The precise mechanism of hyperostosis secondary to meningioma is still unknown at this time.

Once diagnosed, the gold standard of treatment for meningioma is surgical excision, ideally of the entire tumor. Anatomic location, absence of a clear demarcation between neoplastic and healthy brain tissue, local infiltration into the dura mater or leptomeninges, and tumor friability can make complete excision of a canine ICM difficult.¹⁶ This differs from feline and human ICM, which are encapsulated and shell out easily during surgical excision.^9,19 A transoral approach was considered for our patient, but given the size of the mass and the limited intraoral working space, a ventral paramedian approach along the medial aspect of the ramus was used to approach the base of the skull.⁸

Surgical risks discussed included death from airway swelling, hemorrhage due to proximity of the mass to the maxillary artery, mass recurrence, thromboembolism, need for a temporary tracheostomy tube, and cranial nerve deficits. When careful surgical technique is used, the most common causes for postoperative complications include location and size of the tumor.²⁰ Intraoperatively, a stretched nerve coursing along the ventral surface of the hyperostotic shell was transected to allow for better surgical access. Cranial nerves run IX, X, and XI are along the medial aspect of the tympanic bulla.²¹ The postoperative hypersalivation and intermittent dysphagia may indicate that one of those cranial nerves was transected.

The reported median survival time (MST) with surgical excision of ICM alone is up to 7 mo, with a longer MSTof 42 mo in dogs who underwent resection with an ultrasonic aspirator.^4,16 The location of the tumor and degree of hyperostosis in our patient prevented complete excision of the mass. Adjuvant IMRT is recommended in patients with residual or recurrent ICM following primary excision, with improved MST of up to 16 mo when adjuvant radiation therapy was used.⁴ Chemotherapy has not been shown to be effective for treating canine meningioma and was not discussed with the owner.⁴

Conclusion

Earlier detection of the ECM in this patient may have facilitated easier and more complete excision, and adjuvant IMRT may have improved the disease-free interval. Marginal excision of the mass resulted in good quality of life for 11 mo, until tumor recurrence diminished quality of life leading to humane euthanasia. Meningioma should be considered as a differential diagnosis for primary ECMs associated with the skull, even with evidence of hyperostosis.