Extrathoracic Metastases in Pleural Mesothelioma

Abstract

Introduction: Guidelines recommend obtaining a computed tomography scan of the chest for the staging of pleural mesothelioma and for assessing response to treatment. Consensus is lacking regarding the necessity of serial imaging of distant extrathoracic sites. In this study, we determined the prevalence of extrathoracic metastases in patients with pleural mesothelioma.

Methods: We conducted a retrospective review of patients with pleural mesothelioma treated at Massachusetts General Hospital between 1999 and 2022 who were referred for extrathoracic imaging during their disease course. Imaging reports were reviewed to determine sites of metastasis and calculate the time to development of extrathoracic metastasis. Overall survival and prevalence of extrathoracic metastasis were compared for patients with epithelioid versus nonepithelioid mesothelioma.

Results: The study included 148 patients, 69 (47%) of whom had undergone cytoreductive surgery. Histologic types included epithelioid (n = 82, 55%), biphasic (n = 49, 33%), and sarcomatoid (n = 10, 7%) mesothelioma. The median overall survival for the cohort was 24.0 months, specifically 34.7 months and 16.7 months for patients with epithelioid and nonepithelioid tumors, respectively (p < 0.001). There were 65 (44%) patients who developed extrathoracic metastases, with a median time to extrathoracic metastasis of 11.5 months. The most common sites of involvement were extrathoracic nodes (22%), peritoneum (20%), bone (11%), and liver (11%). Of the 76 patients referred for brain imaging, seven (9%) had brain metastases. The frequency of extrathoracic metastasis was identical for epithelioid and nonepithelioid mesothelioma (44%). Overall survival was shorter for patients who developed extrathoracic metastases (hazard ratio 5.9, p < 0.001).

Conclusions: Patients with pleural mesothelioma often develop extrathoracic metastases, providing a rationale for routinely obtaining imaging that encompasses sites outside of the thoracic cavity.

Keywords: Bone metastases; Brain metastases; Mesothelioma; Metastases.

Figure 1

Study population. The study population is presented in the schema. ∗There were 27 patients who only had CT of the head (n = 8 without contrast). CT, computed tomography.

Figure 2

Multisite extrathoracic involvement in a patient with biphasic mesothelioma. At diagnosis, the CT scan reveals right pleural effusion and pleural thickening (arrow, A) associated with low-level uptake on fused positron emission tomography and CT scan (B). At 3.5 years after diagnosis, the patient developed new liver metastases (arrow, C) and bone metastases (arrows, D and E), as captured on abdominal CT and sagittal views of spine magnetic resonance imaging. CT, computed tomography.

Figure 3

Abdominal and brain involvement of epithelioid mesothelioma. At diagnosis, coronal views of the computed tomography (CT) scan revealed pleural thickening and nodularity (arrow, A) with high-level uptake on fused positron emission tomography and CT scan (B). Scans 1 year after diagnosis reveal new lung metastases (arrows, C), brain metastases (arrows, D), and multiple new extrathoracic nodal metastases. CT, computed tomography.

Figure 4

Brain metastasis in a patient with biphasic pleural mesothelioma. A biphasic mesothelioma exhibiting an epithelioid component (A) characterized by nests or solid sheets of epithelioid cells with abundant eosinophilic cytoplasm and centrally located, large nuclei with nucleoli, and a sarcomatoid component (B) characterized by a proliferation of pleomorphic polygonal or spindled cells. Abundant tumor-infiltrating lymphocytes are also noted. The tumor cells are immunoreactive to pan-keratin, keratin MNF116, and calretinin (C) and negative for claudin 4 (D) consistent with a mesothelial lineage.