Adelaide, Australia — The cutaneous lymphoma classification proposed by the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) reflects a welcome consensus of the two organizations' existing classifications of cutaneous B-cell lymphomas.

Presented by Rein Willemze, M.D., from the department of dermatology, Free University Hospital, Amsterdam, the Netherlands at the Madrid meeting of the EORTC Cutaneous Lymphoma Taskforce in September, the newly proposed cutaneous lymphoma classification identifies three principal types of primary cutaneous B-cell lymphomas (PCBCL): marginal zone B-cell lymphoma, follicle center lymphoma (PCFCL) and diffuse large B-cell lymphoma (PCDLBCL), leg type.

Eliminating 'leg type' But of even greater significance to David Ellis, M.B., B.S., F.R.C.P.A.,was the growing recognition that lymphomas morphologically and prognostically identical to PCDLBCL, leg type, appear elsewhere on the body.

"In relation to the B-cell diseases, the general consensus was that PCDLBCL of the leg may better be defined by: a) morphology ("cell roundness" - e.g., centroblastic or immunoblastic); b) Bcl-2 expression by the tumor cells; and c) MUM1 expression by the tumor cells," says Dr. Ellis, a pathologist at Clinpath Laboratories in Adelaide, Australia. At the Australasian Dermatopathology Society Conference recently, he proposed eliminating "leg type" from any classification of PCDLBCL.

"Historically, presentation on the leg has been convincingly shown to hold prognostic significance for cutaneous B-cell lymphoma," Dr. Ellis says. "In fact, however, numerous multicenter and some multivariate analyses have now clearly shown that morphology (the presence of large numbers of (round) cells — centroblasts and/or immunoblasts is the strongest prognostic indicator.

"In an earlier published study of 21 cutaneous B-cell lymphomas, six of 21 cases involved the legs, four of six leg lesions were diffuse large cell, and four of seven diffuse large cell lymphomas were on the legs," Dr. Ellis says. "The researchers concluded that diffuse large B-cell lymphoma of the leg of centroblastic type was no more aggressive than at any other cutaneous site."

According to Dr. Ellis, the study also documented a biological difference between diffuse large B-cell lymphoma and other forms of cutaneous B-cell lymphomas.

"At this stage, there is no substantial evidence that PCDLBCL, leg type, differs from systemic or nodal diffuse large B-cell lymphoma of similar stage," he says.

Of the three principal PCBCL types identified in the proposed WHO/ EORTC classification, Dr. Ellis says marginal zone B-cell lymphoma and follicular center lymphoma generally remain localized to the skin and have an excellent prognosis. Both can be successfully treated by surgical excision, local radiation, or intralesional therapy with rituximab (Rituxan, IDEC/ Genentech) or interferon.

PCDLBCL, however, "is more closely related to systemic diffuse large B-cell lymphoma," Dr. Ellis says.

"Primary cutaneous diffuse large B-cell lymphoma is an aggressive disease. Treatment requires hemato-oncological assessment and usually combination chemotherapy as for systemic or nodal diffuse large B-cell lymphoma," he adds.

Because the treatments differ as radically as the success rates — five-year survival rates of >95 percent and 52 percent, respectively — morphology is a critical diagnostic factor.

"Depending on the age of the lesion and the area selected for biopsy, PCFCL may have a diffuse architecture and consist predominately of large B-cells, with no adverse effect," he says. "This must not be confused with PCDLBCL, leg type, which differs by centroblastic and/or immunoblastic morphology, bcl-2 expression and MUM1 expression."

By the same token, the relationship between these diseases is not yet welldefined.

"Gene expression microarray studies have shown that primary cutaneous diffuse large B-cell lymphomas express an 'activated B-cell' signature resembling that of systemic diffuse large B-cell lymphoma, rather than a 'germinal center' signature," Dr. Ellis says.