Thymic lymphoma with thymic cyst.

The thymic lymphoid tissue is occasionally a source of lymphoma while thymic epithelium may give rise to thymic cyst. However, co-occurrence of these two lesions is rather unusual. We describe such a curious association in a young Saudi male and discuss its pathogenesis.

Case Report

A 27-year-old Saudi male presented with a two month history of generalized fatigue, chest pain and palpitations with no dyspnea during vigorous exercise. The chest x-ray and the computed tomography (CT) scan with contrast enhancement revealed a well-demarcated “solid mass” in the left anterior mediastinum with peripheral and irregular central calcification (Figure 1). The pulmonary function tests suggested a mild upper airway obstruction.

FIGURE 1

CT scan of thymic lymphoma with a large thymic cyst. Note the peripheral rimming by calcification. (Bar - 10 cm).

The mass was resected in toto. Subsequently, the patient received adriamycin, cyclophosphamide and prednisone daily. About eight months later, he developed bilateral pleural effusion and ascites. The CT scan at that time revealed enlarged mesenteric lymph nodes. The ascitic and pleural fluid contained malignant T cells (stage II thymocytes). On lymphoma chemotherapy, his mesenteric lymph nodes disappeared but pleural effusion persisted. Afterward, he developed Campylobacter jejuni enteritis. Despite aggressive treatment, this patient’s general health deteriorated, ending in death approximately one year after his first presentation to the hospital.

Pathological Examination

A 220 g, 13.5×8×6 cm smooth, shiny and multiseptate cyst containing chocolate colored clotted blood was received (Figure 2). The cyst wall and surrounding tissue contained a few 1 cm to 2.5 cm diameter fish flesh soft nodules. Some nodules were present on both sides of the cyst in dumbbell fashion. The cyst wall was focally calcified.

FIGURE 2

Gross appearance of the cyst. Note the “solid” area in the cyst wall.

Histologically, the cyst wall focally contained hyperplastic thymic epithelium. There were focal hemosiderin deposits, cholesterol clefts and calcification in the cyst wall. The adjacent tissue contained residual thymic parenchyma.

The tumor nodules were composed of numerous neoplastic lymphoblasts with prominent starry sky pattern and focal brisk mitoses (Figure 3A). The malignant cells were about twice the size of normal lymphocytes and had irregular cell membranes, better appreciated at oil immersion magnification (Figure 3B). The tumor cell nuclei were round to oval with occasional indentations and convolutions and possessed finely dispersed granular and irregular chromatin. One or two small nonprominent basophilic nucleoli were seen. The cytoplasm was scanty and amphophilic.

FIGURE 3

A. The lymphoblasts with convoluted nuclei and fine chromatin, scanty cytoplasm and starry sky appearance. (Hematoxylin and eosin 400×). B. (Inset Hematoxylin and eosin 1000×).

The electron microscopy revealed large lymphoblastic nuclei with indented nuclear membranes. The chromatin was rather powdery. The cytoplasmic organellae were quite sparse. The thymic epithelial cells were large with relatively low nuclear/cytoplasmic ratio. The cytoplasm was organelle-rich and contained many mitochondria, desmosomes and occasional tonofilaments (Figure 4). The immunoperoxidase staining for keratin was strongly positive in the thymic epithelium (Figure 5). The lymphoma cells were negative for keratin, immunoglobulins and light chains. The pleural fluid lymphoma cells were positive for primitive T cell lymphoblasts (thymocytes stage II) markers.

FIGURE 4

Thymic epithelial hyperplasia in the thymic cyst, positive for keratin. (Anti-keratin immunoperoxidase staining: 100×).

FIGURE 5

The thymic epithelial cell showing intercellular junction and tonofilaments (arrow) (EM 2800×).

Discussion

The thymus arises from the third branchial pouch derived thymopharyngeal duct.1 The persistent remnant of this may give rise to a thymic cyst in the anterior mediastinum2 and rarely, in the neck.3 The vast majority of the thymic cysts, however, appear to be acquired. These are secondary to inflammatory, degenerative and/or neoplastic processes. The epithelial cells from cortical, subcortical and Hassall’s corpuscles may become hyperplastic and give rise to such cysts.4 Frequently, the epithelial lining of the cyst is completely lost, leaving embedded thymic tissue behind to foretell its thymic origin.

The lymphomas constitute the single largest malignant entity of the anterior mediastinum.5 They may arise from the lymph nodes within the mediastinum or from the thymus itself. In the latter case, usually prominent thymic tissue is present adjacent to the lymphoma.6 The majority of the mediastinal lymphomas are B cell type. These arise from nonthymus B lymphocytes.7 The mediastinal T cell lymphomas arise from both thymic lymphoid cells and nonthymic T lymphocytes.

The thymomas and lymphomas may undergo cystic degeneration with hyperplasia of thymic epithelium.8,9 Although such possibility cannot be completely excluded here, prominent thymic tissue, hyperplastic thymic epithelium and conspicuous calcification in the cyst wall suggest that the cyst probably existed prior to development of lymphoma.

Differentiating lymphocytic thymoma from a lymphoma may at times be quite taxing.10 The young age of the patient and aggressive behavior of the disease, particularly metastases below the diaphragm, favored the lymphoma over thymoma. The lymphocytes in thymomas are benign appearing while in the present case, they were quite aggressive with brisk mitoses and starry sky pattern. The ultrastructure and immunocytochemical markers also substantiated our diagnosis of lymphoma. In view of these criteria and clinical course, Levine and Rosai accepted very small numbers of reported cases as truly metastatic thymomas.11

It is a well-known fact that thymic epithelium plays a crucial role in normal T cell (thymocyte) differentiation and maturation. Hence, nude athymic mice are quite immunodeficient and permit easy heterologous tumor implantation. It is therefore tempting to explore the role of the thymic epithelium in genesis of thymic lymphoma and thymic epithelial hyperplasia. Subclassifying mediastinal lymphomas on thymic and nonthymic origins may be an important step in this direction.