Primary osteogenic sarcoma of the skull: Report of two cases with review of literature.

Primary calvarial (excluding jaw) osteosarcoma is rare. We report two cases highlighting their unusual presentation and histopathologic variability - a 30-year-old female who presented with progressively increasing headache and a rapidly growing frontal swelling and a 16-year-old girl who had a rapidly growing mass in the left frontoparietal region which had recurred thrice but was otherwise asymptomatic. The lesions were osteolytic on neuroimaging and histopathological examination confirmed osteosarcoma. These two unusual cases are discussed along with a brief review of literature.

Introduction

Only about 6% osteosarcomas arise in the craniofacial bones,[1] and those occurring in the skull bones (excluding the jaw bones) arise in a background of an underlying bone disorder and constitute less than 2% of all osteosarcomas,[2] making de novo tumors at this site even rarer. Moreover, at this site, chondroblastic osteosarcoma is the commonly reported subtype. In this report, we discuss two patients with primary osteogenic sarcoma of the skull with osteoblastic morphology and review the available literature.

Case Report

Case 1

A 30-year-old female presented with rapidly growing frontal mass associated with headache and episodes of dizziness for 6 months. Physical examination revealed a firm-to-hard mass beneath the scalp. No focal motor or sensory deficits were seen.

On magnetic resonance imaging (MRI) brain, an extra-axial, heterogenously enhancing lesion was seen eroding the outer and inner tables of frontal bone, with a large extra calvarial component in the frontal scalp soft tissue showing heterogeneous contrast enhancement [Figure 1a and b].

Figure 1

(a and b) Sagittal postcontrast T1 weighted and coronal T2 weighted MRI images showing a heterogenously enhancing extraaxial mass in the left frontal convexity with few hypointensities and midline shift towards right, also showing extra calvarial component; (c and d) Squash smears showing oval to spindly tumor cells and scattered fragments of bone in between (H and E ×400); (e and f) Histopathology showing a moderately cellular tumor with spindly cells present in sheets against a background of abundant lace like osteoid (H and E ×200)

On frontal craniotomy, the mass seemed to be attached to the dura at places and was found to be of mixed density; firm and gritty at places and bony hard at others. Gross total resection was performed and tumor tissue along with a piece of thickened pericranium over the tumor was sent for histopathology. Hematoxylin and eosin (H and E) stained intraoperative smears revealed [Figure 1c and d] oval-to-spindly tumor cells with scattered fragments of bone in between, and the perioperative clinical differentials included aggressive meningioma and bony tumor.

Routine histopathologic examination on H and E showed a moderately cellular tumor with spindly cells present in sheets against a background of abundant lace-like osteoid. Tumor cells were seen rimming the osteoid at many places. Individual cells were moderately pleomorphic, with abundant eosinophilic cytoplasm, round-to-spindly nuclei, granular-to-vesicular chromatin, and inconspicuous nucleoli. Interspersed osteoclastic giant cells were seen, and mitotic count was 1–2/HPF [Figure 1e and f]. A final diagnosis of primary osteosarcoma was made.

The postoperative period was uneventful. The patient was discharged after being advised adjuvant chemotherapy and radiotherapy. However, she refused adjuvant therapy, and as of now is on regular follow-up. No recurrence has been reported till the last follow-up 18 months post surgery.

Case 2

A 16-year-old girl presented with a rapidly growing mass in the left frontoparietal region which was otherwise asymptomatic. The mass had recurred at the same site for the third time within 6 months, and the patient had undergone surgeries twice before in another hospital. Physical examination revealed a firm-to-hard, exophytic, fungating mass.

MRI images and previous histopathology reports were unavailable, while non contrast CT (NCCT) head revealed an extracranial, left frontoparietal calvarial lesion, destroying underlying bone and showing intracranial extension [Figure 2a]. A frontal craniotomy for gross total resection was performed and tumor tissue was sent for histopathology [Figure 2b]. Clinicoradiological diagnoses considered were aggressive vascular neoplasm and a metastatic lesion.

Figure 2

(a) Noncontrast computed tomography brain showing a well defined iso to hyperdense extracranial calvarial lesion in the left frontoparietal area with bone destruction and intracranial extension into the left parietal lobe (b) Gross image showing tumor mass along with circumferentially attached scalp and underlying bone. (c and d) Histopathology showing tumor cells in large multi layered fronds, nests, and sheets. (H and E ×100) (e) Histopathology showing moderately pleomorphic tumor cells laying down lacy matrix of osteoid (H and E ×200) (f) Cells show nuclear immunopositivity for SATB2 and immunonegativity for cytokeratin (inset)

Histopathological evaluation of the surgical specimen revealed a highly cellular tumor forming large multi-layered fronds, nests, and sheets. Tumor cells were moderately pleomorphic with moderate eosinophilic cytoplasm and round-to-oval nuclei [Figure 2c and d]. A provisional diagnosis of malignant appendageal tumor was made. However, tumor cells stained negative for markers of epithelial differentiation [cytokeratin, Figure 2f]. On re-evaluating histopathology, at places fibrillar eosinophilic material resembling osteoid was seen [Figure 2e]. For confirmation, immunohistochemistry for SATB2, a marker of osteoblastic differentiation, was carried out. SATB2 was diffusely immunopositive in the nuclei of tumor cells [Figure 2f]. A final diagnosis of an osteoblastic osteosarcoma was made. The patient was advised chemo and radiotherapy and was discharged. She was subsequently lost to follow-up.

Discussion

Calvarial osteosarcomas peak in the third decade[3] and, mostly, arise secondary to underlying bone disorders such as radiation exposure, fibrous dysplasia, and Paget disease.[4] De novo primary tumors of the calvarial bones, as seen in both cases reported here, are rare, but should form a part of the differential diagnosis of calvarial lesions. Since 1945, around 150 cases of primary calvarial bone osteosarcomas have been reported.[5] A search of English language literature was done on PubMed Central (PMC) using the search “Osteosarcoma” [Majr] AND “primary” AND “skull” AND (Humans [Mesh]). The search revealed 13 primary cranial osteosarcomas reported in the last 20 years, out of which only 4 were from India [Table 1].

Table 1

Summary of primary osteosarcomas of skull (excluding jaw bones) reported in last 20 years

Author(s)	Year	Age/sex	Site	Clinical features	Radiology	Treatment	Follow up
Fernandes et al.	2017	14/female	Frontoparietal bone	Headache, mass	CT: Hyperintense mass with intra and extracranial involvement	Surgical excision only	NA
Wu et al.	2017	33/female	Frontal bone	Headache, mass	CT: Lytic lesion with intra and extracranial involvement	3 surgical excisions f/b adjuvant radiotherapy, chemotherapy	Disease free 4 years post surgery
Mathkour et al.*	2016	29/male	Clivus	Right frontal headache	CT: Lytic lesion extending to sphenoid sinus	Gross total excision	Disease free 2 years post surgery
Hadley et al.	2014	14/male	Parietal bone	Painful swelling after minor trauma	CT: Expansile mass with intra and extracranial extension	Surgical excision f/b adjuvant chemotherapy	Disease free 16 months after therapy
Mohindra et al.*	2014	55/male	Clivus	Nasal obstruction, headache	CT: Isodense, intra-osseous, expansile mass	Gross total excisions f/b adjuvant radiotherapy, chemotherapy	Numbness in right V2 distribution 1 year post surgery
Meel et al.*	2012	10/male	Greater wing sphenoid	TM joint pain, headache, vomiting, reduced vision right eye	CT: Expansile bony lesion extending into middle cranial fossa	Surgical excision f/b adjuvant chemotherapy	Disease free for 18 months after therapy
Oakley et al.	2011	15/male	Anterior skull base	Diplopia, mass left orbit	CT: Left fronto-ethmoid mass with bone erosion	Surgical excision only	NA
Kirby et al.	2011	16/male	Parieto-occipital bone	Painless mass	CT: Left parietal mass	Surgical resection f/b chemotherapy	Disease free 5 months after therapy
Patibandla et al.*	2011	30/female	Occipital bone	Headache, nausea, vomiting	CT: Lytic lesion with intra and extracranial involvement	Near total resection f/b radiotherapy, chemotherapy	Died 16 months post surgery
Chou et al.	2009	22/female	Parietal bone	Painful, progressively increasing mass	CT: Osteolytic lesion, total destruction of parietal bicortex	Gross total excisions f/b adjuvant chemotherapy	No recurrence 8 years posttreatment
Chennupati et al.	2008	14/female	Clivus	Dysphagia, voice changes, neck pain	MRI: Minimal irregularity of right basisphenoid	Radiotherapy, chemotherapy	Reduction in tumor size at 1 year follow up
Gadwal et al.	2001	9/male	Sphenoid	Headache and lethargy	CT: Erosion of the sella tursica and sphenoid sinus	Surgical excision f/b radiation therapy	Died 0.8 years post surgery
Hayashi et al.	2000	28/male	Sphenoid bone	Headache, TM joint pain, right exophthalmos	MRI: Multiple masses temporal lobe, orbit	Surgical excision f/b adjuvant radiotherapy, chemotherapy	Died 10 months post surgery

*Cases reported from India. TM: Temporomandibular, CT: Computed tomography, MRI: Magnetic resonance imaging, f/b: Followed by, NA: Not available

Clinical presentation depends upon the location of the tumor, with most patients presenting with mass lesions with or without pain while others have features of raised intracranial pressure. Plain skull radiographs reveal areas of bone destruction as well as formation, usually with a large soft tissue component. Sunburst pattern, typical of long bone osteosarcomas, is usually absent in calvarial osteosarcomas.[4] CT scan is helpful in detecting calcification in the tumor and intraosseous extent of the sarcoma. MRI evaluation is superior to other modalities in determining the soft tissue extension.[6]

Histologically, the key diagnostic features of osteosarcoma include pleomorphic spindle-shaped cells which are seen directly laying down lace-like osteoid. There is high mitotic activity, atypical mitotic figures, and permeation into the surrounding tissue. In head and neck, chondroblastic subtype has been reported to be the most frequent.[7] Both our cases had an osteoblastic appearance, which is rare at this site. Other variants of osteosarcoma, such as telengiectatic and parosteal, have not been described in the skull.[8]

Depending upon the microscopic patterns encountered in an osteosarcoma, a wide variety of benign and malignant lesions can be considered as differentials such as myositis ossificans, osteoblastoma, fibrous dysplasia, fibrosarcoma, chondrosarcoma, and osteochondroma. As with other bone neoplasms, clinical and radiological correlation is imperative for diagnosis. In case 1, with predominant osteoblastic morphology, aggressive osteoblastoma was a close differential. Osteoblastomas too are rare in skull, with very few case reports describing atypical cytological features and locally aggressive behavior at this site.[9] Osteoblastomas can be distinguished from osteosarcomas by lack of lace-like osteoid, presence of well-formed bony trabeculae at periphery (maturation), and absence of permeation of surrounding tissue.[10] For case 2, a differential of malignant adnexal tumor was considered due to areas of fronds and nest-like arrangement of tumor cells in a background of abundant eosinophilic material. However, close re-evaluation showed areas showing classical lace-like osteoid being laid down by tumor cells, which were negative for epithelial marker cytokeratin and immunopositive for a marker of osteoblastic differentiation (SATB2). This clinched the diagnosis in favor of an osteosarcoma.

Osteosarcomas of calvarium tend to have a better prognosis than those arising elsewhere in the body.[411] Treatment of craniofacial osteosarcomas follows the same principles as those in the extremities, consisting of complete surgical resection with wide tumor margins, supplemented by chemotherapy and radiotherapy in incomplete resection, aggressive, or recurrent cases.[478] Consensus on optimal regimen does not exist, and no regimen has been found prognostically superior.[8]

Local recurrence is the main cause of treatment failure in head and neck osteosarcomas and is seen in 25–50% cases, usually in the first year post treatment.[811] Distant metastasis can be seen occasionally as a late event.[8]

Conclusion

This report highlights the clinical, radiological, and pathologic features in two cases of primary osteosarcoma, occurring at a rare site, and describes the histopathologic variability that can be observed. While one of the cases was a relatively straightforward histological diagnosis, immunohistochemistry with SATB2 (a novel marker of osteoblastic differentiation) clinched the diagnosis in the other. Due to their rarity in skull bones, these tumors pose a radiological dilemma and histomorphology aided by immunohistochemistry remains the mainstay of diagnosis. Although head and neck osteosarcomas have been found to have better prognosis than those found elsewhere, treatment regimen followed is not standardized, which is an area to be worked upon.

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Conflicts of interest

There are no conflicts of interest.