Spleen metastasis as rare systemic manifestation of thymoma: a case report

Introduction

Thymomas and thymic carcinomas are the most common primary tumors of the anterior mediastinum and these thymic epithelial tumors (TETs) have an incidence rate of 1.7 per million per year in Europe (1). Furthermore, thymomas grow slowly and rarely metastasize, whereas thymic carcinomas behave more aggressively and frequently develop metastases to the liver, lymph nodes or bones. Hence, to find extrathoracic metastatic disease from a thymoma, is extremely rare (1). Here we report the case of 73-year-old man of Caucasian origin with a splenic metastasis of a resected type B2/B3 thymoma.

Patient information

The patient was an asymptomatic 73-year-old man in whom an anterior mediastinal mass was found on a computed tomography (CT) scan of the chest during work-up for his planned radical prostatectomy for a Gleason 3+3 (cT1c) prostate carcinoma in June 2022. Apart from the prostate carcinoma there was no significant medical history: arterial hypertension and a groin operation as a child. There were no other relevant family, psychosocial or genetic antecedents.

Clinical findings

No relevant abnormalities in routine clinical examination including chest auscultation were encountered. We present this article in accordance with the CARE reporting checklist (available at https://med.amegroups.com/article/view/10.21037/med-25-17/rc).

Case presentation

Summary

• This case involves a very rare splenic metastasis of a thymoma;
• The patient additionally developed Good’s syndrome, a rare thymoma-related immunological disorder.

After incidental diagnosis of an anterior mediastinal mass on routine CT scan of the chest in the planning of a prostate carcinoma treatment, an 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) scan in June 2022 confirmed this lesion, highly suspicious for a thymoma due to mild ¹⁸F-FDG uptake with standardized uptake value (SUV) of 8.63 and metabolic tumoral volume (MTV) of 122.1 mL (Figure 1). On August 28, 2022 a radical thymo-thymectomy was performed through median sternotomy approach. Due to tumoral invasion of the left brachiocephalic vein, a wedge resection of the vessel wall en bloc with the tumor and reconstruction was performed with a pericardial patch. Histologic examination showed a thymoma of 7.5 cm in size, type B2-focally B3 without evidence of lymphovascular or perineural invasion. Conclusion of pathological staging was a thymoma Masaoka-Koga III, tumor-node-metastasis (TNM): pT3N0 (8^th edition) (2), without lymph node involvement but with invasion of the vessel wall of the left brachiocephalic vein. During follow-up, ground glass opacities were identified on consecutive CT scans of the chest with unclear etiology. Therefore, an additional ¹⁸F-FDG-PET/CT was performed in January 2024 which showed a heterogeneous lesion of 48 mm caudomedial in the spleen with an SUV of 4.24 and an MTV of 63.1 mL (Figure 2). In retrospect, this lesion was already visible on the PET/CT performed in June 2022, although smaller (24 mm). The lesion could not be further differentiated on dedicated magnetic resonance imaging (MRI) of the spleen and a broad differential diagnosis remained. At the multidisciplinary board meeting a surgical resection of the lesion was advised given the uncertain diagnosis and evolution suggesting malignancy. A laparoscopic splenectomy was performed in June 2024 and histological examination confirmed the presence of a metastasis of a bifocal thymoma type B2: 6 and 2 cm respectively, resected entirely. During the postoperative multidisciplinary evaluation it was decided that there was no indication to administer adjuvant systemic therapy. The patient was referred for follow-up with ¹⁸F-FDG-PET/CT every three months. In September 2024, hypermetabolic lesions were seen in both lungs as well as a hypermetabolic lymph node in the left paratracheal space on ¹⁸F-FDG-PET/CT, which were strongly suspicious for metastatic lesions (Figure 3). A video-assisted thoracoscopic surgery (VATS) was performed showing a nodular infiltrate in the right upper and right lower lobe for which a wedge resection was performed. Small brown nodules on the visceral pleura were also biopsied and sent for pathology. On histology these lesions on the visceral pleura were confirmed to be droplet metastases of the known thymoma (Figure 4). Surprisingly, the lung lesions were no metastases, but histologically confirmed abnormalities related to Pneumocystis jiroveci infection. Together with hypogammaglobulinemia [immunoglobulin G (IgG) 4 g/L] and deep absolute and relative lymphopenia (Table 1), these findings match the triad of Good’s syndrome: thymoma, hypo-gammaglobulinemia and infectious complications. Therefore, the patient was treated with intravenous immunoglobulins (Privigen^® once a week 0.1 mg/kg). Unfortunately, the patient died due to sepsis and respiratory insufficiency after thorough intensive care treatment in January 2025.

Figure 1 ¹⁸F-FDG-PET/CT of suspected thymoma at diagnosis (06-2022, white arrows). ¹⁸F-FDG-PET/CT, 18F-fluorodeoxyglucose-positron emission tomography/computed tomography.

Figure 2 ¹⁸F-FDG-PET/CT during follow-up, detecting splenic lesion (01-2024, white arrows). ¹⁸F-FDG-PET/CT, 18F-fluorodeoxyglucose-positron emission tomography/computed tomography.

Figure 3 ¹⁸F-FDG-PET/CT (coronal and axial image) during follow-up in 09-2024 detecting hypermetabolic lung lesions, together with CT scan of the lungs. After VATS wedge resection these infiltrates were confirmed due to P. jirovecii infection (09-2024, white arrows). ¹⁸F-FDG-PET/CT, 18F-fluorodeoxyglucose-positron emission tomography/computed tomography; VATS, video-assisted thoracoscopic surgery.

Figure 4 Histopathological images of following specimens (H&E, 2.5× magnification): (A) original thymoma; (B) splenic metastasis; (C) lung involvement: tumoral deposits visceral pleura. H&E, hematoxylin and eosin.

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

Thymomas are the most common primary tumors of the anterior mediastinum, typically arising in 40–70-year-old patients and constitute half of malignant tumors found here. Commonly, the World Health Organization (WHO) histopathological classification of TETs is used: A, AB, B1, B2 and B3 for Ts and C for TCs, respectively (2). Generally, extrathoracic metastases of a thymoma are considered rare, with an incidence ranging between 3–6% (1-4). The 5-year survival rate is 78% (5). In this regard, Huang et al. (6) compared 112 patients with TETs in terms of sites of disease progression: 97 thymomas and 23 thymic carcinomas, respectively. In 15 cases where thymoma progression was seen (15.4%), this was merely locoregional in 13 (86.7%) and presented with distant metastasis (to the lung) in only 2 cases (13.3%). For thymic carcinomas, progression was seen in 10 cases (43.5%): only 4 were locoregional (40%), the rest were distant metastases to the lung, bone, liver or brain (60%). We could find two cases in the literature describing a solitary splenic metastasis from a thymic carcinoma (7,8).

Concerning isolated splenic metastases of Ts, Aoki et al. (5) claimed in 2018 to be the first to report this systemic manifestation, however already in 1986, Tabbaa et al. (9) reported a case of malignant thymoma with solitary splenic metastasis. Wu et al. described a third case in 2022 (4). In our opinion we report herein the fourth case of an isolated metastasis to the spleen from a thymoma.

Detection of a hypodense or isodense mass of the spleen on a CT abdomen, renders a relatively broad differential diagnosis. These diagnoses non-exhaustively include inflammatory pseudotumor, hemangioma, lymphangioma, extramedullary hematopoiesis, inflammatory myofibroblastic tumor, lymphoma, hamartoma, sclerosing angiomatoid nodular transformation (SANT) and spleen metastasis (10-12). Histological confirmation brought clarity of the correct diagnosis of metastatic thymoma after laparoscopic splenectomy. Comparing our case to previous reports, Tabbaa et al. in their 1986 report did not specify the time after which the splenic metastasis was diagnosed, only stating an abnormality on postoperative radiography was found. Wu and Yang (4) and Aoki et al. (5) diagnosed the spleen lesion on CT scan of the abdomen 10 and 8 years, respectively, from the initial radical thymectomy. The histological type was a mixed epithelioid and lymphocytic thymoma in both the report of Tabbaa et al. (9) and Wu and Yang (4). None of these case reports mentioned thymoma-associated complications like Good’s syndrome.

Furthermore, during follow-up 2 years after thymoma resection, hypermetabolic lesions were seen on ¹⁸F-FDG-PET/CT, necessitating VATS biopsies. These concerned two solid lesions, one in each lung, and smaller lesions on the visceral pleura. The latter were confirmed droplet metastases whereas the former showed infectious lesions caused by Pneumocystis jiroveci.

These case developments are highly suggestive for Good’s syndrome: a combination of thymoma with immunodeficiency due to hypo-gammaglobulinemia or absent B cells leading to deficient B-, and T-lymphocyte mediated immunity. As a result, patients have increased susceptibility to bacterial infections with encapsulated organisms and opportunistic viral and fungal infections. A review by Kelleher and Misbah (13) reveals the first description of a case of thymoma together with hypogammaglobulinaemia already in 1954. Incidence of hypogammaglobulinaemia is 6–7% in thymoma patients. Clinically, different initial manifestations of the syndrome have been described ranging from locoregional symptoms like cough, vena cava superior syndrome, dyspnoea and hoarseness to recurrent sinopulmonary infections. Due to the defect in humoral and/or cellular immunity patients are at risk for infection with opportunistic germs: gastrointestinal cytomegalovirus (CMV)-, pulmonary Pneumocystis jiroveci-, or mucocutaneous Candida-infections. Autoimmune conditions like pure red cell aplasia, aplastic anemia, diabetes mellitus and idiopathic thrombocytopenia are often co-existent. Biochemically, anemia can be observed in half of the patients, neutropenia in 18% and thrombocytopenia in 20%. Immunological abnormalities are hypogammaglobulinaemia, B-lymphopenia in 80% of cases, abnormal T cell counts and function and reduced serum immunoglobulins of type IgG, M and A. It is recommended that all patients with thymoma have immunoglobulin values and B and T cell subsets measured. The TETs histology in Good’s syndrome is usually the spindle cell variant and almost never thymic carcinoma. Cause and pathogenesis of Good’s syndrome is unknown. The treatment is analogous to the treatment of thymoma: complete resection with adjuvant chemo-radiotherapy in stages 3 to 4 and replacement of IgG immunoglobulins to adequate values. To note is that 10-year survival of patients with Good’s syndrome is only 33%.

Conclusions

This case report describes the fourth case worldwide of an isolated splenic metastasis from a thymoma. To find extrathoracic metastatic thymoma is extremely rare. Furthermore, during follow-up, this patient proved to have Good’s syndrome, an associated immunological syndrome in approximately 7% of patients with thymoma which predilects for opportunistic bacterial, viral and fungal infection as a thymoma-related defect in B- and T-lymphocyte cell-mediated immunity. Unfortunately, the patient died due to Pneumocystis jiroveci-mediated sepsis in January.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://med.amegroups.com/article/view/10.21037/med-25-17/rc

Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-25-17/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-25-17/coif). P.M.C. reports that his institution received consulting fees from MSD, Merck and Servier in the last 36 months, that he is a participant from the Data Safety Monitoring board at MSD and that he has a leadership role at CTG/CRM Belgium. T.T. reports that he is a senior clinical investigator at FWO Belgium and holds a Fundamental Clinical Mandate (FKM) from the Research Foundation - Flanders (FWO-1801825N). The other 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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