Lymphoma of the ankle. Really?

Scanning the daily oncology journal headlines as I do every day, I landed on something from the most recent issue of the Journal of the American Podiatric Medical Association, not a journal I'm accustomed to seeing. A paper there reports on the case of a woman in her 60s who was diagnosed with diffuse large B-cell lymphoma of the ankle. [Mendeszoon MJ, Wire KR. "Diffuse Large B-Cell Lymphoma of the Ankle." J Am Podiatr Med Assoc 100(6): 505–510, 2010].

I've heard of twisted ankles, broken ankles, even cankles. But not ankle cancer.

It reminded me of the astonishing level of confusion that persists in the lymphoma world, and the relatively arbitrary nature of the cancer discussion in general.

LYMPHOID NEOPLASMS

All the dozens and dozens of subtypes of Hodgkin's and non-Hodgkin's lymphomas, amounting to almost 70 heterogeneous cancers, are technically known as lymphoid neoplasms.

The American Joint Committee on Cancer (AJCC) and the World Health Organization make these kinds of decisions, and they made this one a few years ago. Any cancer affecting the B-cells, T-cells or NK cells is a lymphoid neoplasm. If it presents with a mass or affects lymph nodes or extranodal sites, it's given the clinical descriptor 'lymphoma'. If it presents no mass, affecting the bone marrow or peripheral blood, it's a 'leukemia'.

If it's presenting both, it's a lymphoma/leukemia.

REVISION, REVISION, REVISION

For about a decade lymphomas were differentiated according to the Working Formulation, a noble if feeble classification attempt that in sum identified ten subtypes. That was replaced in 1994 with 'REAL', or the Revised European-American Lymphoma classification, which tripled the subtypes to about 30. In 2001, the WHO Classification came along which was based on REAL but expanded to capture another dozen or so subtypes. Although still currently in use, the WHO needs an upgrade.

With at least 950 annotated genes implicated in cancer, and another 7400 genes likely implicated in cancer, the estimated 60-70 lymphomas is a woefully conservative figure. Gene expression profiling, flow cytometry, immunohistochemical analysis, all continue to tease new combinations of cell-surface protein expression and chromosomal translocation from the cells of these tumors and subtypes, earning temporary, nearly unpronounceable ID's that are helpless beyond noting the variation. After spending even a short time at the Atlas of Genetics and Cytogenetics in Oncology and Hematology, you begin to worry that the sky is the limit here. We may have 1,000 lymphoma variants identified by 2030. And no way they can all be named, even though it's possible they all may require differing treatments.

This makes the wildly broad diagnosis of "non-Hodgkin's lymphoma" more digestible, even if it hardly begins to scratch the surface of the cancer.

• Patient: "What's the diagnosis? In layman's terms please."
• Oncologist: "We think you have cancer of the lower-case-t-open parentheses-three-semicolon-six close parentheses open parentheses queue twenty-seven semicolon pee twenty-one close parentheses space capital SFRS three slash BCL six."
• Patient: "Dear God ..."

Continued in the next part…