FINAL DIAGNOSIS: MEDIASTINAL B-CELL LYMPHOMA
This 39-year old man died of complications arising from an entity known as primary mediastinal B-cell lymphoma. This lymphoma tends to occur in younger patients (median age 42, compared to median age 68 in peripheral diffuse large B-cell lymphoma), has a slight female predominance, and comprises approximately 7% of diffuse large B-cell tumors . Patients present with a locally invasive anterior mediastinal mass originating in the thymus, and frequently display symptoms of airway compromise and superior vena cava syndrome . In one report of 30 patients, SVC syndrome was present in 57 percent at presentation . In addition, other patients without SVC obstruction had evidence of compression of this vessel by computed tomography scan; in total, 80 percent had some evidence of SVC compromise. This lymphoma has a tendency to spread to extranodal sites, including the liver, gastrointestinal tract, kidneys, ovaries, and central nervous system.
Histologically, the lymphoma presents as a diffuse proliferation of large cells with abundant eosinophilic cytoplasm, large vesicular nuclei, and prominent nucleoli. These cells have a spectrum of nuclear morphology, and can resemble centroblasts, large centrocytes, multilobed cells, and immunoblasts. Mitotic figures are numerous, and Reed-Sternberg-like cells may be present.
The cytoplasm often shows clear changes, thought to represent a fixation artifact, although an unusual subtype of clear cell lymphoma exhibiting prominent clearing of the cytoplasm also has been described and accounts for 10 percent of cases of diffuse large cell lymphoma in the mediastinum [5,6]. In some cases, the abundant clear cytoplasm can displace the nuclei to the periphery, resulting in a signet-ring appearance . On small biopsies, these tumors may be misdiagnosed as clear cell carcinomas or metastatic signet ring carcinoma of gastrointestinal origin.
A characteristic feature of mediastinal large cell lymphoma is the presence of a sclerosing stroma, seen in approximately 40% of cases. Stromal fibrosis in the form of thick hyaline connective tissue compartmentalizes the tumor into epithelial-like solid nests, which can mimic a carcinoma or seminoma. In some cases, thin and delicate strands of fibrous tissue surround individual cells, resulting in an artifactual distortion of the cells, which show spindle cell morphology reminiscent of sarcomas. Areas of storiform appearance may give the pattern of lymphoma, with prominent spindle-cell features . The nuclear pleomorphism in large cell lymphoma of the mediastinum can be so prominent that the neoplasm resembles an anaplastic carcinoma or sarcoma rather than a lymphoid proliferation. These pleomorphic cell lymphomas exhibit noncohesive sheets of large, pleomorphic tumor cells with extensive areas of necrosis .
Immunohistochemistry is an important tool in the diagnosis of large cell malignancies in the mediastinum. An extensive panel of antibodies is helpful in distinguishing different neoplasms and should include lymphoid markers of B cell and T cell types, Hodgkin's disease markers (CD30, CD15), and HMB-45, keratin, and PLAP in order to exclude melanoma, thymoma, and seminoma. Most large cell lymphomas of the mediastinum are B-cell lymphomas; they express B cell-associated antigens (CD19, CD20, CD22, CD79a) and are usually CD45 positive and CD15 negative. A small percentage of cases may have a T cell immunophenotype. Expression of CD30 is often present, but is weak.
Although early studies suggested an unusually aggressive (median survival of 18 months), incurable tumor, more recent publications have reported cure rates similar to those for other large cell lymphomas with aggressive therapy, usually combining chemotherapy with mediastinal irradiation [1,3,4]. However, the presence of pleural effusions, extra-thoracic involvement, and bulky mediastinal masses are all associated with a poor prognosis .
Contributed by Lawrence B Fialkow, DO, Beth Z Clark, MD, and Larry Nichols, MD