flower cells

Happy St. Patrick’s Day, everyone! In celebration of the lovely cloverleaf, we have a guest post from our esteemed medical student and frequent contributor, Richard Huang. Take it away, Richard.

The image above shows a number of flower cells that are pathognomonic of HTLV-induced adult T cell leukemia (ATL). They have absolutely nothing to do with today, St. Patrick’s Day, except that the multilobed nucleus of an ATL cell looks like a cloverleaf, which gives me an excuse to write about them. In fact, such cells are officially named cloverleaf cells or flower cells. (Another interestingly named cell is the “faggot cell“ of acute promyelocytic leukemia.)

The 1970s is best known for its drugs, sex, and rock and roll, a culture that is popularly summed up by the slogan “flower power.” Little did people know how medically appropriate that slogan would be, since the 1970s marked the beginning of one of the biggest scientific discoveries: retroviruses. While the most famous retrovirus to date is the human immunondeficiency virus (HIV), the very first human retrovirus discovered was the human T cell lymphotrophic virus (HTLV).

HTLV can infect various types of cells, including B cells, monocytes, and fibroblasts. The GLUT1 transporter has been identified as a receptor for HTLV, so theoretically, HTLV can infect any cell that uses that particular transporter. However, as the virus’s name suggests, the main cell target is T cells (both CD4+ and CD8+).

One very interesting thing about HTLV is that it spreads within the host via cell-to-cell transmission using virus-induced cell-to-cell synapses (rather than the traditional mechanisms of viral shedding, such as budding, exocytosis, and apoptosis). Consequently, acute HTLV infection is rarely detected using serum viral loads. HTLV infections are usually latent and asymptomatic, and usually do not cause disease until decades later.

The spectrum of diseases caused by HTLV is broad. It includes benign diseases such as dermatitis, more serious diseases like HTLV-associated myelopathy (HAM), and deadly diseases such as the rapidly-fatal adult T cell leukemia (ATL).

The most important viral protein in the oncogenesis of ATL is the functionally pleiotropic viral protein Tax, which both promotes the proliferation of and inhibits the apoptosis of infected T cells by:

  1. stimulating the production of cytokines IL-2 and IL-15, which are growth factors that cause clonal expansion of T cells
  2. facilitating the methylation, and consequently suppression, of the p16 gene, the product of which normally blocks the cell cycle by inhibiting cyclin dependent kinase 4 (CDK4)

For a quick rundown of cytokines and how to memorize them, check out these excellent articles on PathologyStudent.com: All about cytokines in less than 400 words and How to memorize interleukins.

Immunophenotypically, ATL cells have a characteristic profile. The cells are typically:

  1. strongly positive for CD4 or CD8, CD25 (alpha chain of IL-2 receptor), and CD2 (a T cell surface adhesion molecule)
  2. negative for myeloid (CD13, CD33) and B cell lineage (CD10, CD19, CD20, CD21, CD22) markers

For an excellent overview on CD markers, I highly recommend the follow the primer A short list of CD markers and Dr. Kraft’s book “The Complete (but not obsessive) Hematopathology Guide.”

Despite all we know about the involvement of Tax protein and cytokines in ATL, the definitive diagnosis of this disease is still made by seeing flower cells on peripheral blood smears and detecting HTLV within these cells.

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4 Responses to Flower Power

  1. MaryZ says:

    I’m a bit confused. The morphology of the nucleus makes these cells look very much like neutrophils with a flowery-shaped nucleus. The pink cytoplasm is throwing me when it comes to thinking about these cells as ATL. I would expect to see blue cytoplasm. As a bench tech in hemo lab, when I’m doing a diff, I would identify as “others” and refer to pathologist???

  2. Kristine says:

    Hi Mary – Good question! You’re right – neutrophils do have a many-lobed nucleus and they can sometimes look flowery. However, neutrophil nuclei are really more like sausage links piled up on each other, whereas the tumor cells in ATL have nuclei that look more like petals coming out of a central hub. The two cells right in the center of this image, as well as the ones at 3 o’clock and 9 o’clock, are perfect examples.

    But you’re absolutely right – if you see something you can’t place in a particular category, it’s best to count them as “other” and show someone else. The same holds for anyone (medical student, resident, even pathologists sometimes do that!).

    As far as the pink color goes: this image is a bit off on the colors (the background should be white!). Maybe it’s the reproduction of the image, or maybe the original stain was a little heavy on the pink side. Color can be helpful in distinguishing between cells – but it’s not always the best differentiator. The nucleus is usually where it’s at, man (as long as we’re in a 70’s flower power mood…).

  3. Marie says:

    Could you please elaborate more acute promyelocytic leukemia.
    and the other leukemic diseases.

  4. Kristine says:

    Hi Marie –
    Sure! Here’s a post on APL. I also have a lot of posts on other leukemias (just type in whichever leukemia you’re interested in the search box, top right). If you want in-depth information on all the leukemias, you might take a look at our Complete Hematopathology Guide ebook. Good luck!

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