Expression of ‘adhesion’ molecules in anaplastic large cell lymphoma

Sir : The article by Ashton-Key et al. on cadherin expression in reactive lymph nodes and lymphomas brings out an important aspect of anaplastic large cell lymphoma (ALCL). Most of their cases of ALCL showed expression of pan-cadherins. In this context, we would like to share our data on the expression of various adhesion molecules in two cases of ALCL and express our thoughts on this entity. The two cases of ALCL seen by us were positive for CD30 and epithelial membrane antigen (EMA) and negative for CD3, CD45RO and CD15. One case was of B-cell phenotype and was positive for CD20 while the other was of ‘null’ cell phenotype. Tumour cells in both cases expressed ICAM-1, LFA1 , LFA1 , VLA-4, CD44H and CD44v6. Expression of adhesion molecules was investigated by immunohistochemistry on frozen sections and by flow cytometry. Our results are similar to those of Akamatsu et al. A diagnosis of ALCL is made by the characteristic cytological appearance, epithelial pattern of infiltration and expression of CD30 antigen. Furthermore, ALCL is clearly not a single entity but a group of lesions which are phenotypically similar. Primary and secondary forms, and within them, B-cell, T-cell and ‘null’ cell subtypes are recognized. Morphological resemblance to a carcinoma and lack of expression of adhesion molecules are said to be among the common denominators in these lymphomas. This is clearly evident, as most cases express EMA. A few of them express cytokeratins as well. The ultrastructural correlate of this epithelial phenotype is the presence of a ruffled and indented cytoplasmic membrane and microvillous processes. The epithelial phenotype is also accompanied by cell cohesion and a metastatic pattern of involvement of the lymph node. This cell-cell adhesion/ cohesion of the tumour cells (homotypic interactions) may be mediated by adhesion molecules such as cadherins. Aberrant/increased expression of ICAM-1 and LFA1 on the same cell, as in our cases, could also contribute to homotypic interactions. ICAM-1, CD44 and VLA-4 on lymphoid cells are known to interact with molecules on endothelial cells, especially those lining the high endothelial venules. However, little is known about the antigen expression and cellular interactions of the lymph node sinus-lining endothelial cells. Expression of ICAM-1, CD44H and VLA-4, also seen in our cases, could explain the preferential involvement of the lymph node sinuses in ALCL. In the series of Ashton-Key et al., tumour cells expressed a cadherin molecule which was not E-cadherin. Endothelial cells are known to express cadherins with homology to Nand Pcadherins. Thus, lymphoid cells expressing cadherins may not only bind to each other, but may also bind to the endothelial cells. These homotypic interactions between the tumour cells, and heterotypic interactions between the lymphoma cells and the endothelial cells, may also have a bearing on tumour cell growth. Hence, study of adhesion molecule expression in ALCL could explain the morphological characteristics and patterns of lymph node involvement. We suggest that in lymphomas of diverse nature, events leading to expression of activation markers (such as CD30) and/or those leading to aberrant/increased expression of the adhesion molecules (resulting in an epithelial phenotype), will result in an ALCL morphology. Such an event could either be early in the evolution of a primary ALCL or late in the evolution of a secondary ALCL. It is important to investigate the genetic changes that would lead to such aberrant phenotypic expression.