Thymoma: a fatal case report of recurring pneumonia from Tanzania

Introduction and importance:

Thymomas present either concurrently with myasthenia gravis, with local pressure symptoms, or asymptomatically as a mediastinal mass. Due to its variable presentation, the incidence is low, as not all cases would be identified. Thymomas can present with a rare entity of combined T-cell and B-cell immunodeficiency in adults. Thymectomy is the most important prognostic factor, including preventing autoimmune manifestations of thymoma, but immunodeficiency may persist after thymectomy.

Case presentation:

The authors report a case of thymoma with evidence of immunodeficiency, manifesting as recurrent pneumonia and respiratory distress in an HIV-seronegative 62-year-old man with a suspected diagnosis 3 years before admission. During his bouts of pneumonia, blood cultures revealed methicillin-resistant Staphylococcus aureus, which was initially treated with vancomycin and then with clindamycin. Although hypogammaglobulinemia was not established in our low-resource setting, there was a reduced CD4-cell count with an abnormal CD4/CD8 ratio. The patient responded well to the first course of antibiotics. However, the second attempt was unsuccessful, which led to his demise.

Conclusion:

Clinicians should be aware that thymoma can cause immunodeficiency. Clinical suspicion should be raised in patients who present with recurrent infections, particularly in thymoma cases with adult-onset immunodeficiency.

Introduction

Highlights

• Thymomas are rare mediastinal tumors with low incidence but a fatal outcome if untreated.

• Methicillin-resistant Staphylococcus aureus infection is uncommon in Good’s syndrome.

• Suspect immunodeficiency in patients with recurrent infections and a mediastinal mass.

Thymomas are rare mediastinal tumors that occur primarily in the fourth to the seventh decade of life, with male and female incidences being comparable1,2. Thymomas present either concurrently with myasthenia gravis, with local pressure symptoms, or asymptomatically as a mediastinal mass on chest radiography2. Thymomas can be classified as benign or malignant based on the degree of capsular invasion. Because of the variable presentation, the incidence would likely be low, as not all cases would be identified.

With a thymoma incidence of 0.19 and 0.17 per 100 000 population in the United States and Europe, respectively3, the incidence in Africa is unknown. We present the case of a 62-year-old man who died as a result of acute respiratory distress syndrome, a mediastinal mass, and a recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection.

The main purpose of this case described here is to report a case of recurrent pneumonia caused by MRSA in an immunodeficient man with a mediastinal mass, which is a rare association.

This case report has been submitted in accordance with the Surgical CAse REport (SCARE) guideline criteria 20204.

Case presentation

A 62-year-old male presented with 3 years of central chest pain and a productive cough for 1 year, which were associated with difficulty breathing and chest tightness. He came from a low socioeconomic family and worked as a peasant farmer. Three years before admission, he was found to have a mediastinal mass but decided not to proceed with any therapy. Over the past year, he had been using over-the-counter cough medications and antibiotics that did not relieve his symptoms. He progressively worsened with time and was referred to our center. Apart from occasional alcohol consumption, there was no significant social or familial medical history.

On examination, he was conscious, afebrile with a temperature of 36.9°C, dyspneic at rest with oxygen saturation at 85%, needing oxygen, with grade 2 finger clubbing, but no lower limb edema. His blood pressure was 98/68 mm Hg, and his pulse rate was 92 bpm. With reduced symmetrical chest expansion, bilateral crepitations, and reduced breath sounds bilaterally, it was suggested that he was in respiratory failure.

His chest radiography showed features of a large mediastinal mass and bilateral ground-glass opacities (Fig. 1A). A rapid antigen test for severe acute respiratory syndrome coronavirus 2 was negative. The serology for HIV was negative. His hematological investigations revealed a leukocyte count of 5.0×10⁹/l with normocytic anemia of 9.1 g/dl and an elevated erythrocyte sedimentation rate of 48 mm/h. His biochemical investigations revealed lactate of 2.8, alanine transaminase of 388.8 U/l, aspartate transaminase of 80.7 U/l, amylase of 80 U/l, and creatinine of 130 µmol/l.

Figure 1.

Posterior anterior chest radiography (A) shows a left anterior mediastinal mass overlying the left hilum and left cardiac border. Hazy ground-glass opacities are seen in both lung fields. Control chest radiography (B) shows an increase in ground-glass opacities and infiltrates in both lung fields, in keeping with acute respiratory distress syndrome. The left anterior mediastinal mass remained unchanged.

He was started on intravenous ceftriaxone 1 g once daily until his blood culture results revealed MRSA, which was sensitive to vancomycin. The patient was switched to intravenous vancomycin 1 g three times daily. He improved clinically as his respiratory distress resolved, but was still dependent on low-flow oxygen.

Noncontrasted computed tomography of the chest revealed an anterior mediastinal mass measuring 7 cm (Fig. 2), and a biopsy was taken, which revealed a tumor with mixed cellularity, having both spindle and epithelioid cells, suggesting a differential of thymoma or sarcoma. Immunohistochemistry revealed a pan-cytokeratin-positive and terminal deoxynucleotidyl transferase (TdT)-negative type A thymoma (Fig. 3). According to the Masaoka–Koga classification, the thymoma was stage IIB. His CD4 was 407 cells/µl with a CD4/CD8 ratio of 0.8.

Figure 2.

Axial (A and B) and coronal (C) noncontrast computed tomography of the chest show a well-defined left anterior mediastinal mass with peripheral calcification exerting pressure on the main pulmonary trunk on the left upper lobe.

Figure 3.

Histopathology shows a thymic tumor exhibiting epithelial islands that are intertwined with bundles of delicate spindle cells (A), which are pan-cytokeratin-positive (B), and TdT-negative (C).

Surgical and oncological teams were consulted, and tumor excision surgery was arranged. However, he started to have difficulty breathing again while in the ward. His repeat full blood count revealed a leukocyte count of 3.1×10⁹/l and normocytic anemia of 8.3 g/dl. A repeat rapid antigen test for severe acute respiratory syndrome coronavirus 2 was negative. A control chest radiography revealed acute respiratory distress syndrome (Fig. 1B), and he was started on intravenous piperacillin-tazobactam 4.5 g thrice daily. A repeat blood culture grew MRSA with a different antimicrobial sensitivity pattern, specifically to clindamycin. The patient was switched to intravenous clindamycin 600 mg every 6 h. A blood sample for immunoglobulin G was sent outside the hospital, which revealed him to have hypogammaglobulinemia of 397 mg/dl (normal 600–1600 mg/dl). However, his clinical condition deteriorated, and he developed septic shock, which led to his death.

Discussion

Patients with thymoma present with several syndromes, generally autoimmune conditions, compared with local symptoms5. Abnormal regulation of lymphocytes in the thymus gland can result in immunodeficiency or autoimmunity, causing myasthenia gravis, red cell aplasia, or Good’s syndrome. In our case, we suspect that our patient had immunodeficiency, which led to recurrent MRSA infection and respiratory distress, which led to his demise.

Since its first description in 1954, Good’s syndrome is a rare, adult-onset, acquired immunodeficiency in thymoma with reduced to no B cells, a low CD4 T-cell count, an abnormal CD4:CD8 T-cell ratio, and hypogammaglobulinemia6. The pathogenesis of Good’s syndrome is still not known, as the literature suggests that bone marrow abnormalities, autoimmunity, and T-cell abnormalities play major roles7. Respiratory tract infections are the hallmark of Good’s syndrome due to defects in cell-mediated immunity and B-cell deficiency, causing opportunistic infections.

Patients with Good’s syndrome are susceptible to various infections, including encapsulated bacteria (Haemophilus, Pseudomonas, Klebsiella, and Streptococcus), fungi (Candida, Pneumocystis jirovecii), viral (Cytomegalovirus), and protozoal (Giardia) infections8. However, S. aureus is not commonly identified in Good’s syndrome.

In our case, the patient presented with respiratory distress, which may have been caused by a MRSA infection. Due to his immunodeficiency, the infection may have led to severe inflammation of the lungs. However, thymomas also cause dyspnea, particularly when they cause compression of the trachea, superior vena cava syndrome, phrenic nerve paralysis, and myasthenia gravis9.

The spindle cells of thymoma with pan-cytokeratin are probably either type A or type AB thymoma. However, the presence of a TdT-positive lymphoid population in a spindle cell thymoma is probably a type AB thymoma10. Most TdT-negative thymomas are either type A or type B3. Because of the negative TdT immunohistochemistry and mixed cellularity of the tumor, our patient was most likely suffering from a type A thymoma. In type A thymoma, neuroendocrine tumors, paraganglioma, and synovial sarcomas should be considered in the differential diagnosis. Although no association has been found between the types of thymoma and autoimmune complications, the diagnosis of hypogammaglobulinemia is seen in relatively equal proportions8. However, most types of thymoma with Good’s syndrome are benign and are characterized as spindle cell types6.

The treatment of thymoma is based on staging, but surgical resection is the most important prognostic factor. The specific treatment of Good’s syndrome includes high-dose intravenous immunoglobulin to improve the humoral immune response and prevent opportunistic infections. Thymectomy prevents autoimmune manifestations of thymoma, but reports suggest that hypogammaglobulinemia persists after thymectomy6.

Conclusion

Good’s syndrome should be suspected in patients with acute respiratory distress syndrome and a mediastinal mass, even in those presenting with uncommon recurrent infections. Physicians should be aware of the complications of a thymoma, and early recognition and diagnosis are recommended in any suspicious case.

Ethical approval

Our institution does not require ethical approval for reporting individual cases or case series.

Consent

Written informed consent was obtained from the patient’s wife for the publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

There was no funding.

Author contribution

A.S., R.M., E.K., and F.K. were involved with patient management and preparation of the manuscript. A.S. reviewed the inherent literature and edited the manuscript. R.M., F.K., A.S., and G.N. were involved with relevant investigations. A.S. and G.N. provided the images. All authors approved the final version of the manuscript.

Conflicts of interest disclosure

The authors declare no conflicts of interest.

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