Literature Review: T-Zone Lymphoma

What's different about this disease and why it matters

A classic case of TZL on cytology (EJF personal archive)

Dear Readers,

Following my recent post on large granular lymphocyte (LGL) lymphoma, I wanted to discuss another important variant of lymphoma to be aware of: T-Zone Lymphoma (TZL). Unlike LGL lymphoma, this diagnosis is actually NOT bad news—while it is still technically cancer, it is “indolent” and dogs with TZL usually live for a long time, often without any treatment at all! The key is to recognize it versus a higher-grade lymphoma that would need aggressive chemotherapy. TZL is more common in specific dog breeds, can increase the risk for specific infections, and has other unique features.

With any further ado, let’s learn more about this unusual disease!

—Eric

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What makes T-Zone Lymphoma different?

Vets are familiar with typical large cell multicentric lymphoma. It usually affects multiple lymph nodes, can involve internal organs, and may spread to the blood or bone marrow in the late stages. While multiple studies find slightly different survival times, the usual prognosis for this type of lymphoma arising from B-cells is quoted to be around 9-12 months with the standard of care multi-agent chemotherapy protocol, with T-cell types doing potentially worse (often estimated to be 6 months).

Many vet students remember this through the mnemonic “B is Bad, T is Terrible.” However, as with many things in medicine, the reality is a lot more complex and nuanced:

Lymphoma is not exactly black and white!

In fact, just under 1/3 of lymphoma cases in dogs are indolent or low-grade, meaning they progress slowly and require less aggressive treatment (sometimes none at all). And several early studies¹ found that T Zone Lymphoma is one of the most frequent kinds of indolent lymphoma in dogs, comprising up to 2/3 of those cases.² As you would expect, TZL is comprised of T-cells, so this really throws a wrench into that rule of thumb about B-cell versus T-cell lymphoma! On a related note, this is why I often do not recommend PARR clonality testing in some of these cases, because all it can tell you is you have a cancer of T-cell origin, but it can’t differentiate between the really bad types or the “good” ones:

As Larry David found out on Curb Your Enthusiasm, there is no “good” kind of cancer, only “less bad”

Multiple researchers have found different survival times for TZL, but they are all generally longer than the more common large cell forms:

• Valli 2006:

  • “No dogs with TZL were reported to die of causes related to the lymphoma. The median survival time for dogs with TZL was not yet reached at 22.5 months (range 1–90 months), with two dogs still alive at 19 and 32 months, and one dog lost to follow up at 17 months.”

• Flood-Knapik 2013:

  • “The most common histopathological subtype was T-zone, 61.7%, (Median survival time 33.5 months)”

• Seelig 2014:³

  • “TZL cases had a median survival of 637 days”

• Mizutani 2016:⁴

Given the much better outcomes for patients with TZL, getting the right diagnosis is critical to make sure you don’t inappropriately treat or condemn a dog who will likely die with the disease, not from it. We’ll now discuss testing strategies and some general comments about clinical aspects of the disease.

So, how do you diagnose TZL???