Management of stage IVa thymoma with coexistence of Lambert-Eaton myasthenic syndrome and myasthenia gravis in a postpartum female case report

Introduction

Background

Thymomas are rare malignant neoplasms (<2% cancer diagnoses) (1) arising from thymic epithelial cells, which play a crucial role in T-cell maturation. They are typically indolent and rarely metastasize beyond the thorax. As lymphatic spread is uncommon, staging follows the Masaoka system, which is based on the extent of local invasion. Advanced thymoma stages involving neighboring organs are managed with neoadjuvant chemotherapy or chemoradiotherapy and surgery when possible (2). Unresectable cases are treated with systemic and/or radiation therapy (2).

Rationale and knowledge gap

While thymomas are commonly associated with myasthenia gravis (MG) (3), their association with Lambert-Eaton myasthenic syndrome (LEMS) is rare (4,5). LEMS, an autoimmune condition targeting the presynaptic neuromuscular junction, is more often associated with small cell lung carcinoma seen in 40–62% of LEMS cases (6,7). Even more rare, thymoma has been linked to overlapping presentations of LEMS and MG; of 55 cases reviewed, only 5 involved thymoma (8). In such cases, patients demonstrate oculo-bulbar muscle weakness, acetylcholine receptor (AChR) antibody positivity, limb weakness, and about a 50% positive rate for voltage-gated calcium channel (VGCC) antibody (8). Given the rarity, the optimal treatment strategy remains undefined. Further, there is no standardized treatment for stage IVa thymomas, though complete surgical resection is key in survival prognosis (9).

Objective

This case highlights a young, postpartum Asian woman with stage IVa type B2 thymoma who underwent successful aggressive multimodal treatment. Her presentation, marked by AChR antibody positivity, bulbar and autonomic symptoms, raises the possibility of a paraneoplastic overlap syndrome with features of both LEMS and MG. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-114/rc).

Case presentation

A 36-year-old Asian woman presented to the emergency department with dyspnea on exertion and right-sided pleuritic chest pain, 2.5 weeks postpartum following a normal spontaneous vaginal delivery. Her past medical history was significant for gestational diabetes mellitus, with no prior surgical history and no active medications. She was an active, healthy, non-smoker. The clinical timeline and granular details are summarized in Table 1, but key diagnostic and treatment events are described here to highlight critical clinical decision points.

On presentation, a computed tomography (CT) Chest revealed a large (>20 cm), heterogeneous mass occupying the right pleural space, a right pleural effusion, and a separate large (10 cm) anterior upper mediastinal mass with suspected invasion into the innominate vein (Figure 1).

Figure 1 Initial computed tomography of chest with evidence of a large anterior mediastinal mass, with extension into the right chest and with associated pleural effusion. (A) Axial view; (B) coronal view.

A CT-guided biopsy of the anterior mediastinal mass confirmed thymic epithelioid neoplasm consistent with thymoma, favoring World Health Organization (WHO) Classification B1/B2. The Multidisciplinary Thoracic Tumor Board recommended four cycles of neoadjuvant chemotherapy due to invasion of the innominate vein/superior vena cava (SVC) junction, followed by possible surgical resection. Shortly after this recommendation, however, she developed worsening shortness of breath, new-onset diplopia, dysphagia, and generalized extremity weakness, with an elevated AChR blocking antibody level of 57 nmol/L. Given the autonomic features, paraneoplastic context, AChR positivity, and bulbar symptoms, she was diagnosed with suspected overlapping LEMS-MG. She was started on Mestinon (pyridostigmine) 30 mg three times daily (TID), leading to symptomatic improvement, supporting the likelihood of a mixed paraneoplastic neuromuscular process.

Surgical details

After completion of neoadjuvant chemotherapy, a restaging CT showed a minimal response with progression of the tumor. She underwent a right extrapleural pneumonectomy (EPP) (right pneumonectomy, visceral/parietal pleurectomy, pericardial resection, diaphragm resection) and mediastinal lymph node (MLND) dissection of levels 4–11, with preservation of the right phrenic nerve. Reconstruction of diaphragm was performed using a 20 cm × 20 cm firm Strattice^TM mesh and 1-0 vicryl suture; the pericardium was reconstructed with bovine pericardium mesh using 2-vicryl. Gross macroscopic resection was achieved in the right chest (Figure 2). A median sternotomy with cardiopulmonary bypass (CPB) was employed for resection of the mediastinal portion of the tumor invading the SVC and innominate vein, and pericardium (Figure 3). The tumor was resected along with the pericardium around the right ventricle towards the left chest, with preservation of the left phrenic nerve. The SVC was repaired with bovine pericardial patch and 5-0 prolene, and the innominate vein was ligated. The pericardium was further reconstructed with a bovine patch. The tumor was resected, with a small sliver infiltrating into the posterior SVC and left atrium/pulmonary vein orifice remaining, clipped for radiation therapy.

Figure 2 Gross specimens of extrapleural pneumonectomy with right lung, diaphragm and pericardial segments.

Figure 3 Gross pathology of resected thymoma (WHO type B2). WHO, World Health Organization.

Postoperatively the patient’s course was uncomplicated and she was discharged on post-operative day (POD) 7. Pathology confirmed diffuse thymoma type B2 with R1 resection. She recovered uneventfully and underwent radiation therapy. She discontinued use of Mestinon less than 1 week after surgery, and her most recent CT chest does not depict evidence of recurrent disease, 2 years later.

The patient shared the following reflection on her experience: “Going through surgery and chemotherapy was one of the hardest things I’ve ever faced, both physically and emotionally. There were days I felt completely drained. But I’m incredibly grateful for the care I received. As a mom to a 2-year-old, being able to recover and keep up with them means everything to me. I’m also hopeful now that I can continue to grow my family in the future.”

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 presentation of advanced malignant thymoma in a young and otherwise healthy postpartum Asian woman, complicated by the development of a paraneoplastic neuromuscular syndrome with overlapping features of LEMS and MG, treated with EPP, thymectomy and SVC reconstruction necessitating CPB, after minimal response to chemotherapy.

Strengths and limitations

In this case, our patient presented with a large tumor with invasion into the SVC and innominate vein with compressive symptoms and neuromuscular decline. The patient developed bulbar symptoms, generalized extremity weakness, and respiratory compromise, with evidence of positive AChR blocking antibody level. These features supported a clinical diagnosis of LEMS and concurrent MG, given the antibody positivity and symptomatic improvement with pyridostigmine. While confirmatory electrophysiologic or VGCC antibody was not available or performed, the clinical context of these symptoms occurring in the presence of a thymoma (10), supported the coexistence of both syndromes.

There are limited data regarding first line treatment of an invasive thymoma with LEMS-MG, therefore a multidisciplinary approach was crucial. Previous studies have shown that when feasible, initial surgery in thymoma provides better progression free and overall survival (OS) (11), with chemotherapy regimens and response rates being highly variable (12). This was demonstrated in our patient with minimal response, prompting surgical intervention.

Further, this case report highlights the development of a malignant thymoma in an otherwise healthy, nonsmoking, Asian woman, providing insight into the epidemiology of thymomas and associated malignancies. Currently, thymoma incidence is noted to be higher among Asians and Pacific Islanders (0.25 per 100,000 person-years) when compared to non-Hispanic whites (0.10 per 100,000), though the reasons remain unknown (1). Within Asian subgroups, Japanese individuals exhibit the highest incidence at 0.30 per 100,000, followed by Vietnamese (0.26), Filipinos (0.18), and Chinese and Koreans (0.17) (1). Possible genetic predispositions with specific HLA alleles, and environmental or infectious factors such as Epstein- Barr virus exposure have been speculated as potential causes for the development of thymomas in Asian populations, though larger multicenter case-control studies are needed to formally evaluate environmental and genetic risk factors (1,13,14).

Intraoperatively, this case is notable given the extent of disease and the surgical techniques employed in order to perform aggressive debulking. However, not all cases with vascular invasion are equal, and must be approached on a case-by-case basis. This report highlights the techniques and tools available to attempt complete resection, rather than stating that all tumors invading the SVC are resectable.

Important to note, part of her treatment also included ovarian suppression to preserve fertility and delay premature menopause. A study at the University of California, San Francisco (UCSF), noted that the current estimates of the impact of chemotherapy on women’s reproductive health have been understated, and reported a correlation between acute ovarian failure and age at diagnosis, as well as a rate of infertility of at least 40% at age 35 in those who had received chemotherapy. This reinforces the need for multidisciplinary care in the treatment of women with thymomas and of reproductive age (15).

Comparison with similar research

There are few cases of thymoma associated with LEMS (4,5,16), and even fewer involve LEMS-MG overlap syndromes (8). Given that association with thymic epithelial tumors is rare, there are no specific guidelines on management when it is diagnosed. Morimoto et al., described a stage II thymoma associated LEMS case that showed neurologic improvement after resection, without the need for advanced vascular reconstruction or CPB (4). Similarly, other studies have shown similar resolution of LEMS symptoms after surgical resection of follicular thymic hyperplasia (17,18). Soma et al reported a case of LEMS in thymic marginal zone B-cell lymphoma, where medical management alone alleviated symptoms (19). In a case with LEMS-MG, Tabbaa et al., demonstrated near complete remission of symptoms after complete resection of thymoma and splenic metastasis in 1986 (20). Subsequent treatment approaches have varied widely and often combined modalities. In the largest review of LEMS-MG overlap syndrome confirmed in 39 patients, 82% were found to be AChR antibody positive, and 53% VGCC antibody positive (8). Thymectomy was performed in 10 patients, and anti-cholinesterase therapy led to “good and dramatic improvement” in 4 patients, moderate in 16, and no response in 2 (8). Diaminopyridine (DAP), a medication commonly used in LEMS, was effective in 4 of 5 patients treated, and guanidine showed a good response in 6 patients. Corticosteroids were also used with neurologic improvement in several patients (8). These findings demonstrate that medications traditionally used in either MG or LEMS can be effective in LEMS-MG overlap symptoms. However, given lack of standardization, an individualized approach remains essential. Our case adds to the growing body of evidence in this topic, demonstrating clinical improvement after pyridostigmine.

Regarding surgical management in thymoma, complete resection remains a critical determinant of survival, including for select stage IVa patients (9). A large retrospective study involving 1,320 patients showed improved long-term survival when resection was attempted, even in advanced cases (21). Studies have also shown that debulking surgery can improve survival in stage III and IVa due to improved efficacy of radiotherapy (22). A study comparing 5 and 10 years OS between patients who were surgically managed vs. non-surgically, showed 5-year OS 79% vs. 52% and 10-year OS 54% vs. 36% (23). Surgery for disseminated pleural involvement however, is not well defined (24). A multicentric analysis of the European Society of Thoracic Surgery (ESTS) thymic working group of 152 patients with pleural involvement highlighted the benefit of specific procedures including EPP, total pleurectomy (TP) and local pleurectomy (LP) on OS. Study populations treated with EPP, TP and LP had similar survival and found to be equally effective procedures, with procedural choice dependent on extent of tumor distribution (25). Case reports and studies have demonstrated success with such procedures on achieving complete local control and improving survival with the use of multimodal therapy, in select stage IVa patients (26-28).

Historically, tumors invading the great vessels have been considered unresectable due to the high surgical risk and poor survival outcomes (29). With the availability of better prosthetics, multi-disciplinary care and perioperative monitoring, several case reports have demonstrated success in achieving complete resection in stage III and IVa thymomas, even with the use of aggressive surgery and invasive techniques such as CPB (29-32).

Lastly, reports of thymoma in the immediate postpartum woman are rare. The earliest case of thymoma in pregnancy was reported in 1959, and since then, about 20 more cases have been reported (33,34). Even rarer, are reports of cases of thymoma with LEMS-MG overlap in the postpartum state. Anggrena et al. reported a case of thymoma with MG during pregnancy but without postpartum exacerbation (33). To our knowledge, there are no reported cases of thymoma with LEMS-MG overlap in the immediate postpartum state. It has been shown that 40% of patients with thymomas experience exacerbation of symptoms during pregnancy, 31% remain stable, and 29% have disease improvement (35). In the case of our patient, symptoms were not apparent until the postpartum state. It is plausible that during her pregnancy she did not experience myasthenic symptoms due to elevated levels of alpha-fetoprotein (AFP) that inhibit binding of AChR antibodies to AChRs. Levels drop in the postpartum state, causing more obvious symptoms (33). Furthermore, her dyspnea may have been overlooked during pregnancy, as it was likely attributed to normal physiological changes of gestation. This case highlights the importance of maintaining a broad differential diagnosis, including thymoma, even in pregnant patients where symptoms may mimic normal physiological changes.

Explanations of findings

This case demonstrates successful medical treatment of LEMS-MG symptoms with the use of acetylcholinesterase inhibitors during a patient’s treatment course for a malignant thymoma. This case also demonstrates that aggressive surgical debulking of stage IVa Type B2 thymomas can be safely performed even when more extensive and invasive techniques are required, with successful outcomes in select, healthy patients. Lastly, this case underscores the potential for rapidly progressing thymoma in a previously healthy young postpartum Asian patient.

Implications and actions needed

It is important to note that treatment of advanced thymomas is successful when a multidisciplinary team drives care, and when surgical intervention is performed at high volume centers with experience in aggressive surgical debulking. By utilizing this approach, treatment of patients with aggressive thymomas has higher likelihood of success.

Conclusions

This rare case of stage IVa type B2 thymoma with LEMS-MG overlap in a postpartum Asian woman highlights the role of acetylcholinesterase inhibitors for symptom management, the limited efficacy of chemotherapy, and the role of aggressive radical debulking surgery with CPB, in treatment of select, young, otherwise healthy nonsmoking patients. This case contributes to the limited body of literature regarding the coexistence of LEMS-MG overlap with advanced (stage IVa) thymoma.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-114/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-114/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-114/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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