A tale of two T-cells

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A disclaimer: I'm not a pathologist, and I doubt anyone reading this is a pathologist either. I don't assume that we will all understand pathology by the end of this blog. I'm merely using a pedestrian example to make an important point.

If I harp on some things more than others over at the lymphoma boards for supportgroups.com, there's generally a reason. Such is the case with the terrible difficulty faced by pathologists in making an accurate lymphoma diagnosis, and because of this, second opinions are an absolute MUST.

It's not enough for someone to peer through a slide and say "lymphoma!" In fact, in lymphoma, this is so inadequate as to be the same as doing nothing at all.

In lymphoma, unlike other cancers, the stage of the disease often plays second fiddle to the classification subtype. So when a swollen lymph node biopsy is examined, the most important question is … what subtype of lymphoma does this patient have?

Get it right, the patient receives the most appropriate treatment.

Get it wrong, and the patient is subjected to unnecessary, ineffective, and harmful treatments. Valuable time is lost.


How often do they get it wrong? There is no hard data, but one estimate published in a respected journal some years ago put the annual number of misdiagnoses for all cancers at 150,000.

For lymphoma, B-cell lymphomas are generally considered to be much easier to accurately diagnose. However, according to Scott Kogan, MD, associate professor of laboratory medicine at the University of California-San Francisco, "In the world of hematopathology, T-cell lymphoma is the most difficult diagnosis."

In fact, in one study [1] when pathologists considered the morphology (shape, characteristics) of a T-cell lymphoma, their rate of agreement was just 34%. Using additional testing, the agreement rate went up to 76%.


Behold, slides from two biopsies showing two distinct T-cell lymphoid cancers with very different treatment protocols and very different prognoses.



A is T-Cell Prolymphocytic Leukemia (TPLL), categorized as a peripheral t-cell lymphoma. Extremely rare, atrociously aggressive, and thoroughly deadly. Median survival time from diagnosis is seven months.

B is Sézary syndrome (SS), an advanced, chronic form of cutaneous t-cell lymphoma that, depending on when it's found, can be managed and treated (and rarely, cured).

Believe it or not, despite looking virtually the same to our eyes, these two t-cell lymphomas are unlikely to ever be confused with one another because a constellation of clinical and laboratory factors—not just a glimpse through a microscope—determine diagnosis, from physical exams to symptom check to laboratory techniques like flow cytometry, phenotyping, immunohistochemistry, and more.

These techniques tease a lymphoma cell into giving up its secrets. You don't need to understand how they work, what they do, nothing. But you do need to see to it that they're performed.


Going the extra mile in lymphoma diagnosis should be the norm, but that's not always the case. What if you had early-stage SS but were misdiagnosed as having TPLL? You would undergo a number of fairly worthless and toxic treatments, spend lots of time in and out of hospitals, and measure your life in months.

Sure, you'll be happy and surprised to find yourself still alive a year later. But that year has not been good—not just all the needless treatments: your SS has been progressing unabated. You've lost valuable time in getting to the SS early, and now your prognosis is poor, when it would have been good a year ago.


There is a price to pay for a misdiagnosed lymphoma, and it always comes out of the patient's pocket in one form or another.

If an oncologist gives you a diagnosis of a T-cell lymphoma that hasn't been properly reviewed, they should urge a second opinion, especially if the original diagnosis was not made by a blood pathologist or a similar specialist at a designated cancer research center.

If they don't, find another doctor.

By Ross Bonander

[1] Zucca et al. (September 1998). "Management of rare forms of lymphoma." Curr Opin Oncol 10 (5):377-84. PMID 9800105.

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