From a pathological viewpoint, diagnosing this patient with concurrent cervical thymoma and DLBCL was challenging, and it highlights the need for careful histological evaluation and high-quality histological sections stained with H&E. The initial local hospital misdiagnosis of both masses having DLBCLs resulted from immunostaining having only been conducted on the forearm mass. Conversely, if immunostaining had only been performed on the neck mass, the cortical thymocytes in that mass might have been misinterpreted as T lymphoblasts, leading to a misdiagnosis of T-LBL.
If a pathologist suspects type B1 thymoma, immunostaining for AE1/AE3 cytokeratins will reveal the typical reticular pattern of neoplastic thymic epithelial cells needed for a definitive diagnosis. There is another potential pitfall for diagnosing a neck mass as metastatic thymoma or cervical type B1 thymus: pathologist–clinician communication is essential to ascertain whether a patient has a mediastinal mass. To discriminate between an LN and thymus, careful gross examination of tissue samples (including the capsule) is crucial. A lack of subcapsular sinuses will confirm the absence of an LN and the presence of an undescended cervical thymus. Immunostaining for D2-40, a marker for lymphatic lining cells, will determine whether a mass is an LN. As D2-40+ lymphatic lining cells were absent in our patient, the diagnosis was cervical type B1 thymoma.
From a hematologic viewpoint, concurrent cervical thymoma and lymphoma are rare. Thymoma patients have increased risks of autoimmune diseases and malignancies caused by T-cell dysregulation [1, 3], associated with T-cell stimulation by neoplastic thymus epithelial cells. In contrast, B-cell lymphoma is coincident with thymoma due to T-cell dysregulation, leading to uncontrolled B-cell growth.[1, 4] Only eight cases of concurrent thymoma and hematological malignancy have been published since 1990 (Table 1); all had anterior mediastinal masses. Our patient is the only reported case of cervical thymoma with MG concurrent with DLBCL.
Surprisingly, the forearm mass persisted for 2 years before growing rapidly. Possibly, it was an indolent lymphoma that completely transformed to DLBCL. It is not known whether the indolent lymphoma was not controlled by T-cell dysregulation when the cervical thymoma developed, leading to a complete transformation to DLBCL. Unfortunately, the forearm mass was not initially thoroughly sampled microscopically, and no remaining formalin-fixed tissue was available to detect indolent lymphoma.
To suspect and diagnose rare cases such as this correctly and early, one needs an experienced pathologist who can recognize the different morphologies of the mononuclear cells in the two masses. Additionally, type B1 thymoma should always be considered in the differential diagnosis of T lymphoblastic lymphoma. To this end, using immunostaining for AE1/AE3 cytokeratins will highlight the reticular pattern of neoplastic thymic epithelial cells. MG is an uncommon paraneoplastic syndrome in lymphoma; therefore, concurrent thymoma should be considered. The lack of a mediastinal mass in chest imaging should raise the possibility of ectopic thymoma (cervical thymoma in our case). Moreover, in patients who present with multiple masses that have a discordant response to standard chemotherapy, biopsy of the enlarged mass is recommended to confirm the diagnosis.
The treatment modality for patients with concurrent thymoma and malignant lymphoma depends on the staging of thymoma and the aggressiveness of concurrent lymphoma. If thymoma occurs locally, only surgery with or without local radiation is adequate to control the disease [5,6,7,8,9]. The treatment of lymphoma is inhomogeneous according to the type. Aggressive lymphomas such as DLBCL and T-LBL require systemic chemotherapy [6, 9]. Moreover, the level of fitness of a patient is an important consideration for decision-making on the chemotherapy regimen. The majority of reported cases were diagnosed at advanced age. Thymomas of these patients were excised; in some cases, this was followed by local radiation. Two patients with concurrent thymoma and DLBCL achieved complete remission after being treated with rituximab-based regimens plus multiple chemotherapy agents [6, 8].