Mediastinal (thymic) large B-cell lymphoma, Med-DLBCL

Definition

This is a subtype of diffuse large B-cell lymphoma arising in the mediastinum, with a distinct immunophenotype. The origin of this lymphoma is uncertain, but follicle centre cell, thymic and monocytoid B-cell derivations have all been suggested. The positivity for CD23 argues for an origin from activated dendritic thymic B cells3.

Epidemiology

It is relatively uncommon, accounting for 2.4% of all non-Hodgkin's lymphomas. It most commonly occurs in young adults (median 35 years), with a strong female predominance.

Clinical features

Patients usually present with an (anterior) mediastinal mass, which results in SVC obstruction in 25-30% of patients2. There is a tendency for spread to unusual sites(brain, liver, ovaries, kidneys, adrenals and intestines).

Histopathology

The morphology is variable, but sclerosis, cells with relatively abundant clear or acidophilic cytoplasm, and multilobated nuclei are common features. The fibrosis is compartmentalizing. In most cases, the cells have abundant pale cytoplasm. Small numbers of benign lymphocytes and eosinophils may be present. Thymic remnants may be seen, recognition being facilitated by immunohistochemistry.

Rarely there is an association with Hodgkin lymphoma, nodular sclerosis, so called "composite lymphoma".

Immunohistochemistry (with nodal and extranodal DLBCL lymphoma for comparison)

Differential diagnosis

• Diffuse large B-cell lymphoma secondarily involving the mediastinum. The morphology does not allow a clear distinction, but a combination of TRAF1 and c-Rel are said to be specific for primary mediastinal B-cell lymphoma. Positivity for CD23 may help to differentiated mediastinal large B-cell lymphomas from other DLBCL. CD30 is more often expressed in mediastinal large B-cell lymphomas, while CD10 is less often expressed.

• Sclerosing mediastinitis

• Hodgkin's disease, nodular sclerosing, especially if small lymphocytes and eosinophils are present. Positivity for CD45 helps to exclude HL. There is probably an overlap between mediastinal large B-cell lymphoma and nodular sclerosing classical Hodgkin lymphoma, sometimes referred to as "mediastinal gray zone lymphoma".

• Clear-cell thymoma

• seminoma / dysgerminoma

• In association with mediastinal large B-cell lymphoma, thymic remnants may form clusters, mimicking carcinoma.

Prognosis

Mediastinal large B-cell lymphoma often responds well to aggressive therapy2. Prognosis depends on the stage of the disease, but 80% of patients achive complete remission and 60% are alive at 5 years2..

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1 de Leval, L., Ferry, J. A., Falini, B., Shipp, M., Harris, N. L. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Path 2001;25:1277-1282.

2 Pileri, S.A., Dirnhofer, S., Went, P., Ascani, S., Sabattini, E., Marafioti, T., Tzankov, A., Leoncini, L., Falini, B. and Zinzani, P.L. Diffuse large B-cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification. Histopathology 2002;41:482-509.

3 Calaminici, M., K. Piper, et al. (2004). "CD23 expression in mediastinal large B-cell lymphomas." Histopathology 45(6): 619-24.

4 Rodig SJ, Savage KJ, LaCasce AS, et al. Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. Am J Surg Pathol 2007; 31:106-12

This page last revised 26.5.2007.