Chest wall recurrence of epithelioid malignant pleural mesothelioma 16 years after pathologic complete response: a case report

Introduction

Background

Malignant pleural mesothelioma (MPM) remains a rare and aggressive malignancy with a median overall survival of 12–18 months despite aggressive multimodal therapy involving resection, chemotherapy, and radiotherapy (1). Epithelioid type offers slightly better prognosis than sarcomatoid variants (1). The latency between asbestos exposure and MPM diagnosis typically ranges between 20 and 40 years, and recurrence is frequent even after macroscopic complete resections such as extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (E/PD) (1,2).

Patterns of recurrence are usually intrathoracic (ipsilateral pleural cavity, lung parenchyma, mediastinum) in over 75% of cases (3). Chest wall or isolated costal recurrences are less common, but when they occur as solitary lesions, resection may be feasible (4). Burt et al. reported a series of 47 patients with isolated ipsilateral chest wall recurrence following initial cytoreduction; chest wall resection led to a median post-recurrence survival of 17.2 months in epithelioid type when the time to recurrence exceeded 24 months (versus 8.9 months for recurrence within 12 months) (5). Likewise, Bertoglio et al. described chest wall resection for a solitary epithelioid recurrence at 3 years post-EPP, resulting in symptom control and 6 months of disease-free survival (4). A systematic review by Bellini et al. noted that a second resection can yield survival benefits in selected patients with recurrent MPM (6).

Rationale and knowledge gap

Resection of recurrent tumours remains a reasonable treatment with a long disease-free interval (>12–24 months), in highly selected patients with epithelioid subtype or localised tumours, absence of distant metastases and good performance status. Tumour location, resection margins, prior therapies, and procedural morbidity may influence outcomes (2,3). Chest wall resections have demonstrated acceptable perioperative morbidity and no 30-day mortality in experienced centers, with hospital stays of 3 to 12 days (5). This case differs from previous reports in the 16-year disease-free interval and in the possibility to resect the recurrence after neoadjuvant chemotherapy. A systematic follow-up allowed the diagnosis of recurrence that could still be treated with curative intent.

Objective

The objective of this case report is to highlight the relevance of long follow-up of patients whose MPM have had pathologic complete response (pCR) and the importance of resections of localized recurrences in the context of multimodal therapies. We present this article in accordance with the CARE reporting checklist (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-29/rc).

Case presentation

A 56-year-old man with past medical history of hypertension, atrioventricular block and occupational exposure to asbestos was found to have a right pleural effusion on a X-ray of the chest ordered as part of his preoperative evaluation for inguinal hernioplasty. In November 2008, a computed tomography (CT) of the chest confirmed the presence of right-sided pleural effusion with collapse of the right lower lobe (Figure 1A,1B). Cytologic examination of the pleural fluid obtained by thoracentesis showed atypical mesothelial cells. A right single-port thoracoscopy was performed and a friable, granulomatous and infiltrative parietal pleural appearance was observed. Histopathologic study of the biopsies was diagnostic of MPM and compatible with epithelial subtype. A talc poudrage was performed. Definitive histopathologic study confirmed the intraoperative diagnosis epithelial mesothelioma (Figure 1C,1D). After multidisciplinary tumour board evaluation, systemic treatment was proposed. Our department does not routinely offer the surgical option for MPM because of the poor results usually observed and the morbidity associated with the procedures (7,8). In this particular case, the patient requested a surgical approach and this option was only accepted if, after systemic treatment, the disease remained without progression and a surgical re-staging ruled out mediastinal nodal and peritoneal involvement. The patient underwent 3 cycles of cisplatin (20 mg/m² every 3 weeks) and pemetrexed (75 mg/m² every 3 weeks) followed by tumour re-staging with a chest CT and positron emission tomography (PET) that did not show progressive disease (Figure 1E). A video-assisted mediastinoscopy to rule out mediastinal involvement and an exploratory laparoscopy with peritoneal and diaphragm biopsies were performed without evidence of malignancy. The patient underwent EPP with resection of the pericardium and right hemidiaphragm, and systematic nodal dissection. The resected diaphragm was replaced by Goretex mesh anchored with 2-0 unabsorbable sutures; and the resected pericardium was replaced by a perforated Marlex mesh fixed with the same sutures. The port of the previous thoracoscopy was not resected.

Figure 1 A graphical timeline of the case evolution. (A) Axial plane of CT where triangle indicates an area of pleural thickening. (B) PET-CT before neoadjuvant chemotherapy shows an area of suspicious hyperuptake at the posterior parietal pleura. (C) Optic microscopy of the tumour with H&E staining (×10, triangles indicate epithelioid mesothelioma area). (D) Arrows show calretinin positive staining (×10). (E) After systemic treatment, PET-CT shows reduced pathological uptake. (F) Optic microscopy of the tumour with H&E staining (×10); triangles indicate stromal reaction zone and fibrosis after systemic treatment; arrows show residual fibrosis (×20), histological changes attributable to pathologic complete response. (G) CT reveals cystic lesions with nodular component and another suspicious nodule. Circles indicate the chest wall lesions. (H) PET-CT confirmed hypermetabolic activity of each of both chest wall lesions. Circles indicate the chest wall lesions. (I) PET-CT after neoadjuvant chemotherapy shows near complete resolution of the primary anterior chest wall lesion, and stability of the hypermetabolic nodule of the chest wall at the level of the 10th costal arch. Circles indicate the chest wall lesions. (J) Optic microscopy of the tumour with H&E staining (×20); triangles indicate atypical mesothelial cells. (K) Cytokeratin 5/6 positive staining (×10); arrows mark positivity of immunohistochemistry staining. CT, computed tomography; EPP, extrapleural pneumonectomy; MPM, malignant pleural mesothelioma; pCR, pathologic complete response; PET-CT, positron emission tomography-computed tomography; H&E, hematoxylin and eosin; RT, radiotherapy.

The histopathologic study of the surgical specimen revealed a pCR to chemotherapy, with no evidence of residual tumour (Figure 1F). The patient received adjuvant radiotherapy (50 Gy in 25 sessions) to the right hemithorax and was subsequently followed with clinical examination and CT of the chest every 6 months for the first two years postoperatively, and every year thereafter. Surveillance imaging between 2009 and 2023 remained stable, showing only the expected post-surgical and post-radiotherapy changes without radiologic evidence of recurrence.

In July 2024, a CT revealed a predominantly cystic mass in the right lower chest wall. The lesion exhibited thickened walls and an internal nodular component, measuring approximately 10 cm in anteroposterior diameter and 7 cm craniocaudally. There were no signs of costal involvement. Additional CT findings in the residual right pleural space included apical calcified lesions (Figure 1G). Subsequent PET-CT confirmed hypermetabolic activity within the chest wall lesion, with additional FDG-avid nodularity identified posteriorly at the level of the 10th right costal arch suspicious of locoregional recurrence. The most superior chest wall lesion was located below the previous right thoracotomy. The lesion located at the level of the 10^th rib was in an area distant from thoracoscopy ports and thoracotomy from the EPP. Therefore, it is unlikely that these lesions were related to port- or thoracotomy-site seeding. No other hypermetabolic lesions were detected elsewhere in the body (Figure 1H).

An ultrasound-guided fine-needle aspiration (FNA) biopsy of the chest wall mass confirmed recurrence of epithelial mesothelioma. The case was presented at the multidisciplinary tumor board. Given the patient’s preserved functional status, long disease-free interval (after 16 years), and localized disease pattern, neoadjuvant chemotherapy followed by reassessment for surgical resection was planned.

The patient completed 5 cycles of carboplatin [area under the curve (AUC) 5 (425 mg) every 3 weeks] and pemetrexed (500 m/m² every 3 weeks) with partial tumour response. PET-CT showed near complete resolution of the primary anterior chest wall lesion and stability of the hypermetabolic nodule of the chest wall at the level of the 10th costal arch (Figure 1I). With documented partial response and no evidence of distance progression, the patient was deemed eligible for resection of his tumour recurrence. Ultrasonographic localization and wire marking of the residual fluorodeoxyglucose (FDG)-avid was performed. The patient underwent resection of the residual tumour: a spindle-shaped section of skin encompassing the previous thoracotomy scar was excised extending from the inferior scapular tip to the anterior chest wall, and the fibrotic tissue surrounding the hook-wire was removed en bloc. An additional incision was performed at the level of the 10^th costal arch to remove the well circumscribed nodule with wide margins. Redon drains were left in both operative fields and the incisions were closed in layers.

The patient had an uneventful postoperative course and was discharged home 24 hours postoperatively with both Redon drains in place and instructions for outpatient management. The patient was followed in the thoracic surgery outpatient clinic and the Redon drains were removed 16 days postoperatively with no complications.

Histopathologic study found less than 5% of viable tumor cells (Figure 1J,1K). The patient received postoperative radiotherapy (50 Gy in 28 sessions) and is well and disease-free 1 year after diagnosis of recurrence.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Key findings

This case highlights a rare late recurrence of MPM 16 years after the initial treatment that resulted in pCR. The patient, initially managed with multimodal therapy including chemotherapy, right EPP and adjuvant radiotherapy, remained disease-free until a follow-up CT identified localized chest wall recurrence. Neoadjuvant chemotherapy followed by image-guided surgical resection resulted in successful management of the lesion, without complications. Therefore, even long-term survivors of MPM can experience local recurrence. In selected cases, aggressive rescue treatment may be both feasible and beneficial.

Strengths and limitations

The primary strength of this case lies in its unique long-term disease-free interval (16 years), which is well beyond the typical recurrence timeframe for MPM. This extended latency challenges the prevailing assumption that long-term remission equates to cure in mesothelioma and emphasizes the need for continued close follow-up. Additionally, the successful use of multimodal treatment, including systemic chemotherapy, precise preoperative lesion localization and complete resection, demonstrates the clinical value of a personalized approach in late recurrences.

However, one of the limitations of this case is that it represents a single patient’s outcome, and generalizability remains limited. The absence of molecular or genomic profiling limits further understanding of potential predictors for such late recurrence. Moreover, long-term oncologic outcomes following resection of recurrent tumour remain uncertain and will require extended follow-up.

Comparison with similar researches

pCR is a rare occurrence in MPM and those reported patients in whom it was achieved were followed up for short periods of time. Kao et al. reported on a 57-year-old man with epithelioid MPM who was treated with 6 cycles of pemetrexed and carboplatin followed by EPP resulting in pCR. At 1 year follow-up the patient was free from recurrences (9). In the report by Pasello et al., a 75-year-old man with epithelioid MPM was administered 4 cycles of the same chemotherapeutic regimen followed by pleurectomy/decortication. Pathologic study of the resected specimen identified pCR. Radiotherapy was given to the surgical scar. After 4 years of follow-up, the patient remained free from disease (10). Three cycles of cisplatin and pemetrexed were given to a 59-year-old woman with epithelioid MPM reported by Bech et al. At the time of intended EPP, the operation was changed to pleurectomy because no macroscopic tumour was found. Pathologic examination of the resected specimen showed pCR. No postoperative radiotherapy was given and the patient remained free of disease 14 months postoperatively (11). In recent years immunotherapy has been added to treatment protocols. Tostes et al. reported on a 73-year-old female whose epithelioid MPM was programmed death-ligand 1 (PD-L1) positive in 80% of tumour cells. She was treated with 4 cycles of cisplatin, pemetrexed and pembrolizumab followed by pleural decortication and mediastinal lymph node dissection, with the result of pCR. At 18-month follow-up since the initiation of systematic therapy, there were no signs of recurrence (12). A 58-year-old man with biphasic (less than 5% component of spindle cells) MPM was treated with 5 cycles of nivolumab and ipilimumab followed by extended pleurectomy/decortication and mediastinal lymph node dissection with the result of pCR. The patient was free of disease at 6 months of follow-up (13). The patient reported by Jurić Čuljak et al. presented some distinctive features. A 67-year-old man had undergone EPP for his pathologic T3N2N0 epithelioid MPM and had recurrence at the chest wall three months after the operation. Two cycles of cisplatin and pemetrexed were administered but there was progressive disease that was treated with 15 cycles of gemcitabine and bevacizumab that achieved initial partial response followed by progressive disease. Because PD-L1 was positive in 2% of tumour cells, the patient was given 12 cycles of pembrolizumab that achieved complete radiological response maintained for 7 years of follow-up (14). Clinical complete response does not always correspond to pCR (10) but after this prolonged follow-up with no signs of recurrence, pCR is very likely to have occurred in this patient. The patient reported by Xie et al. had tumour mass involving the upper lobe of the left lung which was removed by wedge resection of the lung. It was an epithelioid MPM and cisplatin and pemetrexed were given postoperatively. Eighteen months later there was tumour relapse in the mediastinal lymph nodes that was treated with carboplatin and pemetrexed. However, the tumour progressed. Because the tumour had ROS-1 fusion, the patient was treated with crizotinib resulting in complete remission, and the patient was still alive 7.6 years after diagnosis (15).

Recurrence of MPM is common, with most studies reporting relapse within 12 to 24 months after initial treatment. Kindler et al. noted that over 70% of patients experience relapse within two years despite multimodal therapy (1,2,11). The report by Burt et al. involved 47 patients undergoing chest wall resection for local recurrence following surgical resection, of whom 21 had epithelioid histologic type and a time to recurrence >24 months. These patients had a median post-recurrence survival of 17.2 months, suggesting a potential benefit of resection in carefully selected patients (5).

Similarly, Bertoglio et al. described an epithelioid MPM recurrence 36 months after EPP managed with radical chest wall resection and reconstruction. The patient achieved 6 months of disease-free survival postoperatively (4). Both cases involved considerably shorter disease-free intervals compared with the current case.

In 2022, Bellini et al. conducted a systematic review and meta-analysis evaluating redo resection in recurrent MPM. They concluded that in patients with epithelioid histologic type, long disease-free intervals and localized recurrence, subsequent resections—especially chest wall resections—can yield meaningful survival and symptom control without significantly increased morbidity (6). These findings support the rationale behind surgical intervention in the present case.

Although very few studies report recurrence beyond 10 years, similar late relapses have been observed in other thoracic malignancies, such as thymoma and early-stage lung cancer, and are attributed to tumour dormancy, immune escape, or microenvironmental changes (16,17).

Explanations of findings

The extremely delayed recurrence observed in this case, despite a pCR in the initial diagnosis, may be attributable to tumor dormancy mechanisms, where unknown residual microscopic disease remains clinically undetectable for extended periods before reactivation. This phenomenon may result from changes in local immune surveillance, stromal remodeling, or altered angiogenic signaling, which are incompletely understood in MPM (18,19). The fact that the recurrence was not detected in the previous CT scan a year earlier may be due to its rapid development and to the small dimension of its two solid components. Figure 1 shows the timeline of relevant events in the patient’s history.

Epithelioid subtype is associated with a more indolent course and better response to treatment compared to biphasic or sarcomatoid variants (1). The patient’s initial pCR followed by 16 years of remission suggests an inherently favorable tumour biology. The localized nature of recurrence—limited to soft tissue and without bony invasion—also supports the possibility of late clonal reactivation rather than disseminated metastatic disease.

The use of systemic chemotherapy prior to surgical resection aligns with published recommendations favouring neoadjuvant chemotherapy to assess tumour biology and response before considering invasive interventions (2,5). In our case, significant response was achieved with chemotherapy, reducing the tumour burden and allowing for safer resection with minimal morbidity. Neoadjuvant immunotherapy was considered but not selected in this case. After multidisciplinary discussion, taking into account the patient’s age, his comorbidities and the good tumor response of the primary tumor with cisplatin and pemetrexed, the decision was to administer carboplatin and pemetrexed as neoadjuvant treatment for the recurrence.

Preoperative localization using ultrasound-guided hook-wire placement facilitated precise intraoperative identification of the lesion. This approach is well-established in thoracic surgery for pulmonary nodules but has not been widely reported for chest wall recurrence in MPM. Its successful use in this context demonstrates the applicability of this technique beyond lung parenchymal lesions (20).

Implications and actions needed

This case underscores the need for continued long-term surveillance in MPM survivors, even beyond the conventional 5-year period. Clinicians should maintain a high index of suspicion for late recurrence, especially when evaluating new chest wall symptoms or imaging findings in previously treated patients.

From a therapeutic standpoint, our case supports the role of aggressive, personalized strategies in patients with localized recurrence and favorable histologic type. Multidisciplinary evaluation, including input from thoracic surgeons, oncologists, radiologists, specialists in nuclear medicine and pathologists, is essential in selecting appropriate candidates for resection. In the resection of the recurrent tumor of this patient, it is important to highlight the usefulness of image-guided localization techniques to make sure the resection margins are negative; and the relevance of reoperations for resectable recurrences, as well as a careful selection of the surgical candidates.

Future directions should focus on identifying biomarkers predictive of late recurrence and dormancy reactivation in mesothelioma. Incorporating molecular profiling and circulating tumor DNA analysis may aid in risk stratification and earlier detection of recurrence (21-23). Additionally, prospective multicentre registries could help define the indications, outcomes, and cost-effectiveness of surgical resection in MPM.

Conclusions

This case report presents the unusual evolution of a patient diagnosed with a MPM whose tumour achieved pCR after multimodality therapy but recurred 16 years after diagnosis. The systematic, prolonged follow-up enabled the early diagnosis of a local recurrence and the possibility of new multimodality treatment that allowed the complete resection of the recurrent tumour.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-29/rc

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-29/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-29/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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