T-cell / histiocyte-rich large B-cell lymphoma, THRLBCL

In the WHO classification, this is a variant of diffuse large B-cell lymphoma. It may be a heterogeneous group, with some cases of germinal centre B cell derivation (although lack of t(14:18) and of CD10 expression argues against actual derivation from a preexisting follicular centre cell lymphoma), some related to nodular lymphocyte predominance Hodgkin's disease and even some cases related to classical Hodgkin's disease⁹.

Clinical features

This is a clinically aggressive lymphoma which usually presents at an advanced stage^1,2 with lymph node, splenic and bone marrow involvement, accompanied by B symptoms¹.

Histopathology

There is diffuse effacement of the nodal architecture by sheets of small lymphocytes, with or without histiocytes. Some authors argue that the presence of considerable numbers of histiocytes (which may or may not be of epithelioid type) and scarcity of reactive B cells is a prerequisite for recognising a clinically relevant entity³.

The neoplastic B cells are large and atypical but scattered and obscured by the non-neoplastic component: they constitute less than 10% of the cells⁴. The large cells may resemble L&H cells, Reed-Sternberg cells, centroblasts or immunoblasts⁹.

The T-cells do NOT form rosettes around the neoplastic cells.

There is often fine reticular fibrosis. THRLBCL may occasionally be angiocentric and angiodestructive¹⁰.

Variant

• Splenic micronodular large B-cell lymphoma

Immunohistochemistry (compared to Hodgkin's disease)¹

		T-cell rich B-cell lymphoma	nodular lymphocyte predominant Hodgkin's disease	classical Hodgkin's disease
neoplastic cells	CD45	positive1, positive : difficult to evaluate because of surrounding reactive lymphocytes9	positive1	negative1
	CD20	positive1, with rare exceptions10,30/309	positive1, with rare exceptions10	usually negative1
	CD79a	positive1, 10/17 : weaker than CD209	variably positive1,10	usually negative1
	CD3	negative1	negative1	usually negative1
	CDw75	variable1	positive1	variable1
	CD15	negative1, 1/309	negative1	positive1
	CD30	usually negative1, 8/30 : 4 positive, 4 weak9	negative1/weakly positive in some instances10	positive1
	EMA	variable: 6/101, 10/29 : usually associated with L&H morphology (8/14 cases)9	usually positive1	usually negative1
	bcl-2	negative or focal1, 3/22 : 1 positive, 2 weak9
	bcl-6	positive1, 26/299	positive10	negative10
	CD10	usually negative1, 3/29 : 1 positive, 2 weak9
	BOB.1	positive10	positive10	negative10
	Oct-2	positive, usually overexpressed10	positive, usually overexpressed10	rare10
	PU.1	negative in the few cases tested10	positive10	negative10
	MIB1	most cells1, >90%of tumour cells9
	LMP/EBER (by ISH)	usually negative1	negative1	variably positive1
non-neoplastic cells	CD20	usually <5% of cells1,2	most cells positive1	few cells positive1
	CD3	most cells positive1	scattered cells1	scattered cells1
	bcl-6 / CD57 rosettes	negative1	positive1	negative1
	CD8 and TIA-1	positive1	usually <5% of cells1	positive1
	CD68+ histiocytes	variable10	some10	variable10
	FDCs (with CD21 and CD23)	negative1	positive1	positive1
IgH gene rearrangement		monoclonal1	polyclonal1

Differential diagnosis

• Hodgkin's disease, lymphocyte predominance The presence of significant numbers of small B lymphocytes, especially if there is a vaguely nodular growth patter, raises this diagnosis.

• Hodgkin's disease, classical

• T-cell lymphoma. It is necessary to identify the scattered neoplastic B-cells to avoid this mistaken diagnosis.

• If angiocentric and angio-destructive, may resemble lymphomatoid granulomatosis.

Prognosis

A high mortality was reported initially^5,6, although others have not found it any worse than DLBCL^7,8.

References

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

¹Fraga, M., Sanchez-Verde, L., Forteza, J. T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma. Histopathology 2002;41:216-229.

²Skinnider, B. F., Connors, J. M., Gascoyne, R. D. Bone marrow involvement in T-cell-rich B-cell lymphoma. Am J Clin Pathol 1997;108:570-578.

³De Wolf-Peeters, C., Achten, R. 'T-cell-rich large B-cell lymphoma'-'histiocyte-rich, T-cell-rich large B-cell lymphoma'-'T-cell/histiocyte-rich large B-cell lymphoma': will we ever see the wood for the trees? Histopathology 2002;41:269-71.

⁴World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

⁵Chittal, S.M., Brousset, P., Voigt, J.J. and Delsol, G. Large B-cell lymphoma rich in T-cells and simulating Hodgkin's disease. Histopathology 1991;19:211-20.

⁶Delabie, J., Vandenberghe, E., Kennes, C., Verhoef, G., Foschini, M.P., Stul, M., Cassiman, J.J. and De Wolf-Peeters, C. Histiocyte-rich B-cell lymphoma. A distinct clinicopathologic entity possibly related to lymphocyte predominant Hodgkin's disease, paragranuloma subtype. Am J Surg Pathol 1992;16:37-48.

⁷Greer, J.P., Macon, W.R., Lamar, R.E., Wolff, S.N., Stein, R.S., Flexner, J.M., Collins, R.D. and Cousar, J.B. T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients. J Clin Oncol 1995;13:1742-50.

⁸Mason, D.Y., Cordell, J.L., Brown, M.H., Borst, J., Jones, M., Pulford, K., Jaffe, E., Ralfkiaer, E., Dallenbach, F., Stein, H. and et al. CD79a: a novel marker for B-cell neoplasms in routinely processed tissue samples. Blood 1995;86:1453-9.

⁹Lim, M.S., Beaty, M., Sorbara, L., Cheng, R.Z., Pittaluga, S., Raffeld, M. and Jaffe, E.S. T-cell/histiocyte-rich large B-cell lymphoma: a heterogeneous entity with derivation from germinal center B cells. Am J Surg Pathol 2002;26:1458-66.

¹⁰Pileri, 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.

This page last revised 19.1.2003.

©SMUHT/PW Bishop