June 2009
Written by Peter M. Banks, M.D., Director of Hematopathology, Carolinas Medical Center, Charlotte, North Carolina.

Submitting Pathologist
Michael Wolff, M.D., Pathology Associates of Greenville, PA, Greenville, South Carolina.

Diagnosis
ALK-positive diffuse large B-cell lymphoma, involving bone marrow.

Clinical History
This 37 year old male had constitutional symptoms and was found to have multiple lesions in his liver and bone. An iliac crest bone marrow biopsy was obtained.

Microscopy
Sections of the bone marrow biopsy show most medullary tissues to be replaced by a highly cellular process with necrosis at one end of the sample (see Figure 1).

At higher magnification the process can be seen to consist of a uniform expanse of large cells with abundant amphophilic cytoplasm and large vesicular oval or round nuclei with prominent central nucleoli (see Figure 2).
There are occasional mitotic figures. No distinct plasma cellular features can be discerned among the tumor cells.

Ancillary Studies
A large battery of immunohistochemical stains showed the neoplastic cellularity to be negative for both CD20 and CD30, but strongly positive for ALK-1 protein (see Figure 3).

Tumor cells were strongly, uniformly positive for CD138, with variable expression of both CD45 and epithelial membrane antigen (EMA) - see Figure 4.
There was no staining for kappa or lambda light chain, and in-situ hybridization studies for EBV were negative.

Discussion
This variant of large B-cell lymphoma is very rare and may affect patients of any age (1). In some cases, there is some visible plasmablastic differentiation, however, conventional B-cell markers such as CD20 are usually negative (2). Although immunoglobulin light chains are usually not expressed, heavy chains, in particular alpha, are most often demonstrable. While the ALK protein is expressed, this is not based on the nucleophosmin translocation t(2;5), as is the case in the majority of T-cell anaplastic large-cell lymphomas. Rather, other genetic events underlie this expression of the protein, most commonly the clathrin t(2;17) translocation (3).

In contrast to T-cell anaplastic large-cell lymphomas with ALK expression, those of B-cell type are usually clinically very unfavorable (4). This case is unusual in its presentation with bony lesions, as bone marrow is commonly spared involvement by this rare form of lymphoma.

References

1. Delsol G, Campo E, Gascoyne R.
   Alk-positive Large B-cell Lymphoma. In Swerdlow S, Campo E, Harris N, et al., (Eds.) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France, IARC Press, 2008: p254-255.
2. Reichard KK, McKenna RW, Kroft SH.
   ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature. Mod Pathol. 2007; 20: 310-319. More online »
3. Chikatsu N, Kojima H, Suzukawa K, Shinagawa A, Nagasawa T, Ozawa H, Yamashita Y, Mori N.
   ALK+, CD30-, CD20- large B-cell lymphoma containing anaplastic lymphoma kinase (ALK) fused to clathrin heavy chain gene (CLTC). Mod Pathol. 2003; 16: 828-832. More online »
4. Gascoyne RD, Lamant L, Martin-Subero JI, Lestou VS et al.
   ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases. Blood. 2003; 102: 2568-2573. More online »

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