Primary osteogenic sarcoma of the skull: Report of two cases with review of literatureR Singh1, K Jha1, I Pant1, D Satti2
1 Department of Pathology, Institute of Human Behaviour and Allied Sciences, New Delhi, India
2 Department of Neurosurgery, Guru Teg Bahadur Hospital, New Delhi, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.JPGM_706_17
Source of Support: None, Conflict of Interest: None
Keywords: Craniofacial, primary osteosarcoma, skull
Only about 6% osteosarcomas arise in the craniofacial bones, 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, 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.
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 1]a and [Figure 1]b.
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 1]c and [Figure 1]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 1]e and [Figure 1]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.
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 2]a. A frontal craniotomy for gross total resection was performed and tumor tissue was sent for histopathology [Figure 2]b. Clinicoradiological diagnoses considered were aggressive vascular neoplasm and a metastatic lesion.
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 2]c and [Figure 2]d. A provisional diagnosis of malignant appendageal tumor was made. However, tumor cells stained negative for markers of epithelial differentiation [cytokeratin, [Figure 2]f. On re-evaluating histopathology, at places fibrillar eosinophilic material resembling osteoid was seen [Figure 2]e. For confirmation, immunohistochemistry for SATB2, a marker of osteoblastic differentiation, was carried out. SATB2 was diffusely immunopositive in the nuclei of tumor cells [Figure 2]f. 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.
Calvarial osteosarcomas peak in the third decade and, mostly, arise secondary to underlying bone disorders such as radiation exposure, fibrous dysplasia, and Paget disease.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. 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].
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. 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.
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. 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.
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. 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. 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., 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.,, Consensus on optimal regimen does not exist, and no regimen has been found prognostically superior.
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., Distant metastasis can be seen occasionally as a late event.
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.
Declaration of patient consent
The authors certify that appropriate patient consent was obtained.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]