Endobronchial metastasis as an uncommon pattern of metastatic dissemination from small cell osteosarcoma

Abstract

Endobronchial metastasis (EBM) from extrapulmonary primary malignancy is a rare entity. Although the most common site of metastasis of osteosarcoma is the lungs, EBM remains a rare occurrence. Cough and dyspnea are the most common symptoms. A significant number of patients are asymptomatic, making the diagnosis without any radiographic imaging challenging. CT scan of the lung, along with bronchoscopy and biopsy, is the mainstay of diagnosis and staging. A 36-year-old man presented with small cell osteosarcoma of the left maxillary region and was treated with surgery and adjuvant chemotherapy. The patient presented 8 years later with axillary metastasis and was found to have lung metastasis on further workup. Bronchoscopy and biopsy proved an EBM that was debulked by hot snare technique. The patient was then started on chemotherapy for recurrent small cell osteosarcoma.

Background

The lungs are the most common sites of osteosarcoma metastases. Most cases present as parenchymal metastases. Out of the patients treated with surgery alone or surgery with adjuvant chemotherapy, 80% relapse and develop lung metastasis some associated with unusual endobronchial involvement.¹ Extrapulmonary endobronchial metastasis (EEM) is a clinical entity in itself and refers to non-pulmonary tumours that are bronchoscopically visible with involvement of the sub-segmental or more proximal central bronchus.²

Case presentation

The patient is a 36-year-old man who was initially seen for a mass on the left side of his face. A CT scan of the sinuses revealed a soft tissue density in the left maxillary sinus with destruction of the walls of the sinus and the adjacent bone that was later confirmed by MRI. The epicentre of the lesion was in the left maxillary sinus. The patient underwent a left total maxillectomy with orbit preservation and a split thickness skin graft from the thigh that was placed into the mouth followed by a dacryocystorhinostomy. The biopsy from the left maxilla revealed small cell osteosarcoma without involvement of the left mandible, pterygoid plate or ethmoid tissue. Margins of the resection were free of tumour. Postoperatively, the patient received radiation along with cisplatin and adriamycin. Chemotherapy was stopped after two cycles secondary to severe mucositis and infection with the patient being lost to follow-up afterwards. After 8 years, the patient presented to the primary care physician after he noticed a self-palpated mass in the right axilla. He was subsequently referred to a surgeon who performed a right axillary soft tissue mass excisional biopsy with pathology showing high-grade sarcoma consistent with metastasis from the patient’s previously diagnosed small cell osteosarcoma. The patient had imaging for staging including a full body positron emission tomography (PET) and CT scan of the thorax, abdomen and pelvis.

Investigations

The CT scan of the chest with contrast showed multiple calcified pulmonary nodules that were felt to be radiologically consistent with metastatic osteosarcoma. The largest nodule seen was found near the hilum in the superior segment of the left lower lobe, which measured 3.9 cm. The nodule was calcified and consistent with osteosarcoma (figure 1). PET scan showed very low-grade metabolic activity at the partly calcified mass at the inferior aspect of the left hilum. Based on the radiological findings, the patient underwent an endobronchial ultrasound (EBUS). During airway evaluation by bronchoscopy, an endobronchial lesion was seen in the superior segment of the left lower lobe (figure 2A). The lesion was debulked using cryoprobe biopsies and cautery snare with subsequent application of argon plasma coagulation (APC) at the base of the lesion (figure 2B). EBUS confirmed deep extension of the lesion into the pulmonary parenchyma (figure 2C,D). The cryobiopsy showed small cell osteosarcoma (figure 3).

Figure 1.

Transverse cuts of a CT scan showing the largest nodule found in the superior segment of the left lower lobe (white arrow) measuring 3.9 cm with demonstration of calcifications.

Figure 2.

Bronchoscopic images of (A) endobronchial lesion seen in the superior segment of left lower lobe, (B) area of previous lesion post cryoprobe biopsies, cautery snare and APC application, and (C,D) EBUS images of lesion with confirmation of deep extension into the pulmonary parenchyma. APC, argon plasma coagulation; EBUS, endobronchial  ultrasound.

Figure 3.

Microscopic view of the crypobiopsy with findings consistent with small cell osteosarcoma.

Differential diagnosis

The differential diagnosis of the lung mass includes endobronchial metastasis (EBM) and primary lung cancer. It is often difficult to differentiate between EEM and primary lung cancers as the symptoms and imaging findings are similar for both.³ In this case, the history of osteosarcoma and presence of partially calcified lesions along with positive biopsy helped conclude that the patient had EBM from an extrapulmonary primary osteosarcoma.

Treatment

After the lesion was debulked using cryoprobe biopsies and cautery snare with the application of APC, the patient was started on systemic treatment with ifosfamide, carboplatin and etoposide for recurrent metastatic osteosarcoma. Due to the extension of disease into the pulmonary parenchyma, there was no further bronchoscopy performed while awaiting the response to systemic therapy.

Outcome and follow-up

The patient’s respiratory symptoms improved following chemotherapy and there was mild reduction in the size of the pulmonary metastasis. Immune markers were studied and patient was found to have a HEY1–NCOA2 fusion, which had no further implication in management.

Discussion

EBM usually presents secondary to pulmonary neoplasms. Extrapulmonary metastases presenting as endobronchial metastases are rare.¹ The widely accepted definition of EBM is that which defines it as non-pulmonary tumours that are bronchoscopically visible and is metastatic into the subsegmental or more proximal central bronchus.² The frequency of EBM varies according to definitions and ranges from 2% to 28%.⁴ If the definition includes invasion by parenchymal or lymph node masses, then the prevalence was high as EBM is not uncommon if secondary to pulmonary neoplasms. If we limit this to metastasis from extrapulmonary tumours, then the prevalence is much lower. Breast, colon and renal carcinomas are the primary tumours most associated with EEM.¹

There are four developmental modalities of EBM that were described by Kiryu et al.⁵ Type I is described as direct metastasis to the bronchus with type II described as bronchial invasion by a parenchymal lesion. Type III is bronchial invasion by lymph node metastasis (hilar or mediastinal), while type IV is when peripheral lesions extend along the proximal bronchus.^{1 2} According to Kiryu et al, type IV was the most common, however, many authors found it difficult to differentiate between type II and IV leading to no clear consensus on this.^4–6

Lee et al described the most common symptoms of patients with EBM were cough and dyspnea, which account for 79.1% of presenting symptoms together.⁶ Close to 28% of these patients were asymptomatic.⁶ In a series, Marchioni et al reported 176 patients who had shown dyspnea (23%) and cough (15%) as the most common symptoms, followed by hemoptysis (12%) with 26% being asymptomatic.⁷ CT is a valuable tool in the evaluation of EBM, and while it cannot always demonstrate luminal lesions, it can show mediastinal or hilar lymphadenopathy and other pulmonary metastatic lesions.⁸ Subsequent bronchoscopy and biopsy are still required for confirmation. Bronchoscopic studies are still not done in every patient with pulmonary metastasis, so there is a possibility that EBM may be under-reported.⁴

Endobronchial metastases, on average, are diagnosed about 4 years after the primary tumour.⁶ There are two approaches to management, which are treatment and palliation. Treatment comprises of chemotherapy, radiotherapy and surgery. Palliation comprises of intrabronchial stent insertion, brachytherapy, and laser evaporation.⁶ Lee et al report that the mean survival time in those who were treated was 17.4 months, whereas the mean survival time in patients who were given supportive treatment was 12.4 months.⁶ Of note, certain malignancies are more aggressive than others, so prognosis is greatly dependent on the type of primary tumour.⁶ Different treatment modalities are available for alleviating the airway symptoms caused by metastases including brachytherapy, photodynamic therapy and laser evaporation, which have shown to positively impact survival in a selected group of patients.⁹ Stenting and laser evaporation are newer modalities and have been reported in the literature much less than other modalities.¹⁰ Surgery and mechanical removal by rigid bronchoscopy can also be considered. In some cases, a combination of these modalities is used. Intraluminal radiotherapy (ILT) is a safe and effective way of alleviating symptoms from obstruction. Sørensen et al found that around two-thirds of patients benefited symptomatically from ILT.¹⁰ This offers a distinct advantage over external beam therapy as it can deliver high-dose radiation to a localised area with significantly less side effects, especially when the patient already has a decreased cardiac or pulmonary functional status.¹¹

Learning points.

• Endobronchial metastases from extrapulmonary tumours are rare with only a handful of cases arising from osteosarcoma.

• CT scans are valuable tools in diagnosis, but bronchoscopy and biopsy are required for confirmation.

• Intraluminal radiotherapy is a safe and effective method of treatment, especially in patients with cardiac or pulmonary comorbidities.