Calvarial TumorS

+ Presentation and clinical signs

Dogs presenting with tumors of the calvarium are typically older patients and may have a range of clinical signs depending on the location and size of the tumor. A mass effect on the head may be the only clinical sign, though neurologic signs including seizures, changes in mentation, or other neurologic deficits may be present depending on the location of the tumor and potential for secondary compression, invasion, or inflammation of the neural tissues.

+ Diagnosis and staging

Initial diagnostics include a general physical and neurologic/orthopedic examinations, survey three-view thoracic radiographs or CT scan, and full screening bloodwork (complete blood count/serum biochemistry panel). Abdominal imaging (ultrasound or CT) can also be considered for thorough systemic health screening. Fine-needle aspiration (ideally with sterile technique) of the mass and cytologic evaluation or an incisional biopsy may be performed for definitive diagnosis. The location for biopsy should always be considered along with potential future treatment to avoid creating a biopsy tract in a location that would complicate or alter the planned surgical excision or radiation therapy. Fine-needle aspiration of the locoregional lymph nodes could also be considered for staging and indirect lymphography may help to identify a sentinel lymph node for sampling, though lymphography has not yet been well documented for calvarial tumors and the most common calvarial tumor types predominantly metastasize hematogenously.

+ Imaging

Advanced imaging including CT scan and/or MRI are helpful tools to understand tumor extent and relationship to important anatomical structures as well as to aid in planning definitive treatment. MRI can be useful for evaluation of the soft tissue component of the mass, the brain (if there is an intracranial component of the tumor or neurologic signs are present), and the vasculature of the skull in relation to the tumor (most importantly, the transverse sinuses and the dorsal sagittal sinus). Skull radiographs generally lack detail needed for definitive local treatment planning.

+ Differential diagnosis

Differentials for calvarial tumors include both benign (osteoma) and malignant etiologies. Osteosarcoma (OSA), multilobular osteochondrosarcoma (MLO), chondrosarcoma, squamous cell carcinoma, hemangiosarcoma, and other sarcomas may occur in this location and each carry the potential for metastatic disease. MLO has a characteristic “popcorn” appearance on CT imaging with well-defined borders, limited osteolysis, and coarse granular mineral density.

+ Treatment

For localized disease and when feasible, en bloc surgical resection of calvarial tumors should be planned with excision of 1-2 cm of unaffected bone (based on CT or MRI) in all lateral directions. In general, craniectomy approaches are based on described craniotomy approaches but can be combined or modified based on tumor size and location relative to planned margins of excision. The soft tissues overlying the tumor as well as dura deep to the tumor may be preserved if they are uninvolved but should be excised if there is tumor invasion. Consideration must be given to the location of the two transverse sinuses and the dorsal sagittal sinus. Laceration of these sinuses can result in life-threatening hemorrhage, and occlusion can result in fatal cerebral edema. Acute ligation of one transverse sinus was well tolerated at least short-term in 13 dogs (Pluhar 1996, Bagley 1997), though ligation of two of these three sinuses has been demonstrated to result in increased intracranial pressure and herniation of the brain (Slatter 2003). It is possible that chronic gradual sinus occlusion by the tumor may allow for the development of collateral circulation, thereby permitting safe occlusion of two or three of the sinuses, though it is difficult to determine which patients may tolerate this (Slatter 2003). Surgical resection was safely accomplished in two cases of midline occipitotemporal MLO which had complete obstruction of the dorsal sagittal sinus flow into the transverse sinuses, presumptively due to the development of collateral circulation (Gallegos 2008). In addition, selective catheterization and gradual occlusion of the dorsal sagittal sinus-confluens sinuum has been performed in two dogs for lateralized occipital MLOs 24-48 hours prior to surgical resection of the mass to allow for collateral circulation development and safe ligation of the dorsal sagittal sinus (McAnulty 2019). Both of these dogs survived surgery without evidence of clinically significant increased intracranial pressure or cerebral edema (McAnulty 2019).

Radiation therapy (RT) can also be performed in an adjuvant setting following incomplete resection (though data on outcomes is limited) or alternatively as a sole local treatment modality for calvarial tumors. Multiple RT protocols for axial OSA have been described, and recently stereotactic radiation therapy (SRT) was described for treatment of MLO (Sweet 2020). Pending tumor type and grade as well as stage of disease, systemic chemotherapy can also be considered.

+ Cranioplasty considerations

Following craniectomy, reconstruction may be indicated. If dura was concurrently excised, the dura can be reconstructed with temporalis fascia or bovine or porcine small intestine submucosa. However, the necessity for dura reconstruction is unknown as anecdotally no complications have been observed following dura resection without reconstruction in dogs. In addition, if the frontal sinus is entered during craniectomy, then there may be a risk for infection or pneumocranium post-operatively. Porcine small intestine submucosa (PSIS) may be used to protect the brain from the frontal sinus, as well as to cover small calvarial defects (Sheahan 2008).

With regards to the calvarial defect, small defects may not need to be reconstructed if there is no significant risk for trauma to the brain or fibrosis that could result in brain compression. Hard external helmets may be fashioned for patients to wear to prevent head trauma. If the temporalis muscle can be preserved during tumor resection, then closure of this muscle over the craniectomy defect can provide an additional layer of protection. For larger defects that require reconstruction, polymethylmethacrylate (PMMA) with or without a polypropylene mesh has been used (Bryant 2003, Gallegos 2008, McAnulty 2019). The benefits of PMMA are low cost, wide availability, and its malleability to fit a defect as necessary. However, the variation in porosity may lead to an increased risk for infection and the thick material can result in pressure necrosis of adjacent soft tissues over time. Because it undergoes an exothermic reaction during preparation, PMMA must be prepared away from the surgical field to protect the nervous tissues and subsequently placed after being molded. An alternative option for reconstruction is a titanium mesh implant which can be cut to size and molded to the shape of the craniectomy defect (Bordelon 2007, Rosselli 2017). Benefits of this material include a relative radiolucency such that post-operative radiographic or CT imaging interpretation is not impaired by the implant during restaging diagnostics, the material is MRI compatible (non-ferrous), osteointegration may develop through the pores, and it can be trimmed relatively quickly intra-operatively to fit the defect. However, cost may be a limiting factor and it may not be as robust a protective material from trauma as PMMA. In a case series of five dogs with craniectomy reconstruction using titanium mesh, PSIS was placed on the brain over the dural defect followed by titanium mesh secured to the skull, and all patients did well without morbidity associated with the implants (Rosselli 2017). There was minimal artifact when performing radiographs, CT, or MRI post-operatively and tissue could be visualized within 2 mm of the implants, allowing for adequate evaluation for tumor recurrence (Rosselli 2017). Recently, 3D printed custom implants have been reported using a cutting guide followed by a custom printed titanium plate for reconstruction of the craniectomy defect (Hayes 2019). A report suggested a 2-3 week turnaround time from initial CT scan to custom implant generation, though difficulty in access to these technologies may limit availability of this technique (James 2020).

+ Prognosis

A recent study retrospectively evaluated the peri- and post-operative complications associated with craniectomy and craniotomy in 165 dogs and cats (Morton 2022). The mortality rate within 10 days of surgery was 14.5%. Complications were reported in 35.2% of cases within 24 hours and 52.1% of cases 1-10 days post-operatively. The most common complications reported included seizures, anemia, aspiration pneumonia, neurologic deficits, and hypotension. A blood transfusion was required in 9.7% of patients. Early enteral feeding within 24 hours was associated with reduced risk of complications and use of fentanyl post-operatively was associated with increased risk of complications, though both of these factors may be correlated with case complexity and systemic health rather than representing a causal relationship. Total IV anesthesia with propofol was associated with lower odds of developing complications. A rostrotentorial approach was associated with higher risk for complications compared to caudal tentorial approaches. Importantly however, intracranial tumors were the most common indication for surgery in this retrospective study and primary bone tumors represented only 8.6% of the included cases (Morton 2022).

Prognosis following surgical resection varies depending on tumor type, grade, and disease stage. MLO has a reported overall metastatic rate of approximately 50% (Dernell 1998, Lipsitz 2001), though the reported disease free interval was 542 days in the largest study on MLO that included 14 calvarial cases, suggesting a prolonged time to metastasis (Dernell 1998). Even with pulmonary metastatic disease patients may remain subclinical for a prolonged period of time; the reported median time to death was 239 days following detection of metastatic disease or recurrence, also supporting slow progression of disease (Dernell 1998). The overall median survival time for dogs in this study on MLO was 797 days (Dernell 1998). Tumor recurrence was associated with both the grade of the tumor and incomplete histologic resection (Dernell 1998). Tumors which were incompletely resected had an 11-fold increased chance of a shorter time to local recurrence (Dernell 1998). Adjuvant therapies may play a role following incomplete resection of MLO. Three dogs with grade 1 or 2 MLOs that underwent craniectomy and reconstruction (with titanium mesh +/- PMMA) had histopathologic diagnosis of incomplete or narrow margins of excision and subsequently received adjuvant radiotherapy (2.5 Gy x 22 fractions) (Holmes 2019). All three cases had mild acute and late radiation therapy toxicities (skin/ocular/oral) and survival times ranged from 387-730 days (Holmes 2019). In a recent report of eight dogs that underwent SRT (10 Gy x 3 fractions) as a primary treatment modality for MLO of the calvarium and mandible, the median survival time was 329 days (Sweet 2020). Five of these dogs had CT scans after treatment and tumor volume decreased by 26-87% in four patients (Sweet 2020). Tumor growth following SRT was noted in three dogs and metastatic disease occurred in two dogs (Sweet 2020).

OSA of the skull has a reported metastatic rate that ranges from 11-46% (Dickerson 2001, Heyman 1992, Hammer 1995, Selmic 2014). In a study including 43 dogs with calvarial OSA, 80% of dogs experienced local progression following treatment with surgery, SRT, finely fractionated RT, or surgery followed by adjuvant RT (Selmic 2014). The median survival time for all patients in this study, including cases of calvarial, maxillary, and mandibular OSA, was 329 days, and the progression free survival time was 239 days (Selmic 2014). Prognostic factors for overall survival time included surgical treatment, tumor-free histologic margins, and development of local recurrence (Selmic 2014). Telangietactic OSA had a higher recurrence rate than osteoblastic OSA (Selmic 2014).

+ References

Bagley RS, Harrington ML, Pluhar GE, et al. Acute, unilateral transverse sinus occlusion during craniectomy in seven dogs with space-occupying intracranial disease. Vet Surg 1997;26:195- 201.

Bordelon JT and Rochat MC. Use of a titanium mesh for cranioplasty following radical rostrotentorial craniectomy to remove an ossifying fibroma in a dog. JAVMA 2007;231:1692-1695.

Boston SE. Craniectomy and orbitectomy in dogs and cats. CVJ 2010;51:537-540.

Bryant KJ, Steinberg H, McAnulty JF. Cranioplasty by means of molded polymethylmethacrylate prosthetic reconstruction after radical excision of neoplasms of the skull in two dogs. JAVMA 2003;223:67-72.

Dernell WS, Straw RC, Cooper MF, et al. Multilobular osteochondrosarcoma in 39 dogs: 1979-1993. J Am Anim Hosp Assoc 1998;34:11-8.

Dickerson ME, Page RL, LaDue TA, et al. Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs. J Vet Intern Med 2001;15:120–124.

Gallegos J, Scwarz T, McAnulty JF. Massive midline occipitotemporal resection of the skull for treatment of multilobular osteochondrosarcoma in two dogs. JAVMA 2008;233:752-757.

Hammer AS, Weeren FR, Weisbrode SE, Padgett SL. Prognostic factors in dogs with osteosarcomas of the flat or irregular bones. J Am Anim Hosp Assoc 1995;31:321–326.

Hayes GM, Demeter EA, Choi E, Oblak M. Single-stage craniectomy and cranioplasty for multilobular osteochondrosarcoma managed with a custom additive manufactured titanium plate in a dog. Case Reports in Veterinary Medicine;2019.

Heyman SJ, Deifenderfer DL, Goldschmidt MH, Newton CD. Canine axial skeletal osteosarcoma. A retrospective study of 116 cases (1986 to 1989). Vet Surg 1992;21:304–310.

Holmes ME, Keyerleber MA, Faissler D. Prolonged survival after craniectomy with skull reconstruction and adjuvant definitive radiation therapy in three dogs with multilobular osteochondrosarcoma. Vet Radiol Ultrasound 2019;60:447-455.

James J, Oblak ML, zur Linden AR, et al. Schedule feasibility and workflow for additive manufacturing of titanium plates for cranioplasty in canine skull tumors. BMC Vet Res 2020;16:180.

Lipsitz, David, Robin E. Levitski, and Wayne L. Berry. Magnetic resonance imaging features of multilobular osteochondrosarcoma in 3 dogs. Vet Radiol Ultrasound 2001;42(1):14-19.

McAnulty JF, Budgeon, C, Waller KR. Catheter occlusion of the dorsal sagittal sinus–confluens sinuum to enable resection of lateral occipital multilobular osteochondrosarcoma in two dogs. JAVMA 2019;254:843-851.

Morton BA, Selmic LE, Vitale S, et al. Indications, complications, and mortality rate following craniotomy or craniectomy in dogs and cats: 165 cases (1995–2016). JAVMA 2022;260:1048-1056.

Pluhar, G. E., Bagley, R. S., Keegan, R. D., Baszler, T. V., & Moore, M. P. The effect of acute, unilateral transverse venous sinus occlusion on intracranial pressure in normal dogs. Vet Surg 1996;25(6):480-486.

Rosselli DD, Platt SR, Freeman C, et al. Cranioplasty Using Titanium Mesh After Skull Tumor Resection in Five Dogs. Vet Surg 2017;46:67-74.

Seguin B. Tumors of the mandible, maxilla and calvarium. In Slatter D, ed. Textbook of Small Animal Surgery. 3rd ed. Philadelphia, Pennsylvania: Saunders, 2003:2488–2515.

Selmic LE, Lafferty MH, Kamstock DA, et al. Outcome and prognostic factors for osteosarcoma of the maxilla, mandible, or calvarium in dogs: 183 cases (1986–2012). JAVMA 2014;245:930-938.

Sheahan DE and Gillian TD. Reconstructive cranioplasty using a porcine small intestinal submucosal graft. JSAP 2008;49:257-259.

Sweet KA, Nolan MW, Yoshikawa H, Gieger TL. Stereotactic radiation therapy for canine multilobular osteochondrosarcoma: eight cases. Vet Comp Oncol 2020;18:76-83.