Primary thymic mucosa-associated lymphoid tissue lymphoma with multiple thin walled lung cysts: case report and literature review

Introduction

Mucosa-associated lymphoid tissue (MALT) lymphoma of the thymus is rare. In 1990, Isaacson et al. first described two cases of primary low-grade thymic lymphoma, both of which had histological and immunophenotypic features of extranodal B-cell lymphoma of MALT, or marginal zone lymphoma (MZL) of MALT as proposed in the World Health Organization classification (1). We described a case of low-grade thymic B-cell lymphoma in order to review the pathologic and clinical features of the reported cases in the literature.

Case report

A 37-year-old woman presented to our hospital after 3 weeks of cough without sputum. The symptom progressed and aggravated while lying down. Physical examination revealed grossly normal. Chest radiograph revealed an anterior mediastinal mass lesion. Chest computed tomography (CT) demonstrated a multiloculated cystic mass, 9.5 cm × 5.3 cm × 2.6 cm in mediastinum prevascular space, closely contacting to adjacent vascular structure, especially brachiocephalic vein and superior vena cava (SVC) (Figure 1). Multiple thin-walled cysts in bilateral lungs were noted (Figure 2).

Figure 1 Chest CT demonstrated multiloculated cystic mass about 9.5 cm × 5.3 cm × 2.6 cm in mediastinum prevascular space, closely contacting to adjacent vascular structure, especially brachiocephalic vein and SVC

Figure 2 Lung window. Multiple thin-walled cysts in bilateral lungs tumor

Chest plain film showed a mediastinum mass (Figure 3). A maximal thymectomy with lymph node dissection via median sternotomy revealed a tumor about 11.8 cm × 6.2 cm × 3.1 cm at thymus with multiple enlarged lymph nodes (Figure 4). The pathology diagnosis was confirmed with thymic extranodal marginal zone B-cell lymphoma of MALT. The thymic extranodal marginal zone B-cell lymphoma of MALT is featuring a proliferation of small irregular monocytoid B cells around and between reactive lymphoid follicles, with extensive invasion of the Hassal corpuscles and the thymic epithelium lining the cystic spaces, forming lymphoepithelial lesions (Figure 5). Under immunohistochemical stains, the neoplastic cells are positive for CD20 and Bcl-2; negative for CD3, CD5, CD23, and CD10 (Figure 6). The plasma cells showed monotypic Ig light chain (Lambda type). The pathology report of the excised regional lymph nodes was reactive hyperplasia.

Figure 3 Chest plain film showed mediastinum mass

Figure 4 The resected thymus measured 11.8 cm × 6.2 cm × 3.1 cm with a mass lesion about 10.2 cm × 6.0 cm × 2.8 cm

Figure 5 Monocytoid cells with centrocyte-like cells diffusely infiltrated the thymus and invaded the Hassall’s corpuscles, forming lymphoepithelial lesion

Figure 6 Immunohistochemistry. Positive for CD20 and Bcl-2, and negative for CD3, CD5, CD23, CD43 and CD10, Lambda more than Kappa

Autoimmune markers were positive for antinuclear antibody (ANA), Sjögren’s syndrome A (SSA), Sjögren’s syndrome B (SSB), and rheumatoid factors (RF), and the elevation of total IgG, IgA and IgE was noted 2 weeks after operation. ANA, anti-SSA and anti-SSB were tested via immunofluorescence test. There were no obvious changes of IgG and IgA 14 months later (Tables 1-4). A bone marrow biopsy obtained 4 months after operation was negative. Sicca symptoms were noted. Shirmer test was 2 and 7 mm. The diagnosis of primary Sjögren’s syndrome was then confirmed (2).

Table 1 The result of nephelometry
Full Table

Table 2 The immunoassay result of total IgE
Full Table

Table 3 The ELISA result of Anti-dsDNA Ab
Full Table

Table 4 The immunofluorescence result of SSA and SSB
Full Table

Discussion

MALT lymphoma of the thymus is rare. Most patients were Asians and associated with autoimmune disease, especially Sjögren’s syndrome. Racial and environmental factors may influence its development (3).

In our case, immunoglobin and antibody abnormalities remain unchanged one half years after thymectomy. Shimizu et al. thought that immunologic disorders are strongly associated with thymic MALT lymphoma tumorigenesis and that thymic MALT lymphoma was not the cause of immunologic disorders (4).

Thymic MALT lymphoma is often presented with macroscopic and microscopic cyst. Cyst formation may be related to the tendency for cystic transformation of medullary duct-epithelium-derived structures (including Hassall’s corpuscles) when tumor grows in the thymic gland (5). Thymic MALT lymphoma needs to be included in the differential diagnosis of Asian patients with thymic masses accompanied by cystic changes and autoimmune diseases (4).

In patient with Sjögren’s syndrome, pulmonary cysts on high-resolution CT (HRCT) scan, isolated or associated with lymphocytic interstitial pneumonitis or lymphoma, may be due to a peribronchiolar infiltration leading to sequelae of fibrosis and a thin walled cyst (6). Our case was presented with Sjögren’s syndrome and the chest CT revealed bilateral, multiple lung thin walled cysts which had progression in the follow-up period. Differential diagnosis should include lymphangioleiomyomatosis.

Elevation of IgA and IgG was presented in our case (Table 1). This IgA expression discriminates thymic MALT lymphoma from nonthymic MALT lymphomas, which typically express IgM, and less often IgG or IgA (3). Therefore, in Asian patients with thymic masses accompanied by cystic changes and autoimmune disease (hyperglobulinemia), thymic MALT lymphoma should be considering (4). Bcl-2 expression is noted only in small neoplastic cells but negative in large cell transformation, like our case (Figure 6A).

Currently, there are no standard therapeutic protocols or guidelines for the treatment of thymic MALT lymphoma. Surgery, chemotherapy, or radiotherapy alone, or in combination has been commonly used. Most patients were reported in good results. In our case, maximal thymectomy with lymph node dissection was performed. Adjuvant therapy was not prescribed due to non-extrathymic involvement.

In conclusion, the presented case is a Chinese woman with Sjögren’s syndrome and elevation of IgA and IgG. Thymic MALT lymphoma with macroscopic and microscopic cysts was identified and surgical resection was done. Multiple lung cysts with progression were noted. No evidence of recurrence of disease was found after 2 years follow-up.

Acknowledgements

Disclosure: The authors declare no conflict of interest.

References

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