A Rare Myeloproliferative Disorder

hypereosinophilic

A 59-year-old male presents with skin lesions, hepatosplenomegaly and cardiomyopathy. A representative field of his blood smear is shown here. Of the following, what is the most likely diagnosis?

  • A. Chronic myeloid leukemia
  • B. Multiple myeloma
  • C. Metastatic prostate carcinoma
  • D. Hypereosinophilic syndrome
  • E. Bacterial sepsis

The diagnosis in this case is hypereosinophilic syndrome, a rare myeloproliferative disorder characterized by a marked and persistent elevation in the eosinophil count. Although this disease is primarily a hematopoietic disorder, it usually affects many other organ systems, such as the cardiovascular, nervous, respiratory, and gastrointestinal systems. Typical presenting symptoms include cardiomyopathy, skin lesions, thromboembolic disease, neuropathy, hepatosplenomegaly, and pulmonary disease. The pathophysiology behind the damage in these organs isn’t well understood, but it probably has something to do with the release of eosinophil granules in those tissues.

You need to have three things in order to make the diagnosis:
1. Persistent eosinophilia (absolute eosinophil count >1500/μL)
2. No other cause for the eosinophilia
3. Signs and symptoms of organ involvement

Other more common causes of eosinophilia, such as drug reactions, allergic reactions and autoimmune disease, must be ruled out before making the diagnosis.

Usually, patients aren’t treated unless or until they have symptoms (because the treatment itself has its risks). These patients are monitored closely with serum troponin levels (to monitor for MI), echocardiograms and pulmonary function tests.

Some patients with hypereosinophilic syndrome have a tiny deletion in 4q12, which ends up producing a fusion transcript called FIP1LI-PDGFRA (which is also present in some cases of systemic mastocytosis). Imatinib works very well in the majority of these patients.

Patients who have symptoms (but not FIP1LI-PDGFRA) are generally treated with steroids first. If those don’t work, interferon alpha and hydroxyurea are used. If those don’t work either, then imatinib is the treatment of choice (it doesn’t work as well as it does in patients withFIP1LI-PDGFRA, but it does seem to work in at least some of these patients).

Here are the reasons the other answers are incorrect.

  1. Myeloma is a monoclonal disease of plasma cells which manifests mainly in the bone marrow. In the blood, the main thing you see is rouleaux (red cells stacking up on top of each other). This blood smear just has a lot of eosinophils – so it’s not consistent at all with myeloma. The clinical history also doesn’t fit. In myeloma, patients usually have bone pain, signs of anemia (fatigue, palpitations), and maybe signs of renal failure. Hepatosplenomegaly, skin lesions, and cardiomyopathy aren’t generally seen in myeloma.
  2. In CML, you see a massive leukocytosis which is composed of neutrophils and precursors. There is a big left shift and a basophilia. This smear just has a ton of eosinophils, which is not consistent with CML. The patient’s hepatosplenomegaly would be consistent with CML (especially the splenomegaly part) – but the skin lesions and cardiomyopathy don’t go along with that diagnosis.
  3. In metastatic prostate cancer, it’s possible that you might see a rare tumor cell in the blood; you might also see a monocytosis (you occasionally can see that with solid tumors). Eosinophilia, however, is not consistent with prostate cancer. The history is also unsupportive. Patients with advanced prostate cancer may have urinary symptoms (trouble urinating, blood in the urine), abdominal or pelvic pain, or signs of metastasis (bone pain, particularly in the spine).
  4. The characteristic blood finding in bacterial sepsis is a neutrophilia, with or without a left shift. You may also see toxic changes in the neutrophils: toxic granulation, Döhle bodies, and/or cytoplasmic vacuolization. Bacterial infections generally don’t produce an eosinophilia – but some parasitic infections can.

Krafts

-Kristine Krafts, MD, is an Assistant Professor of Pathology at the University of Minnesota School of Medicine and School of Dentistry and the founder of the educational website Pathology Student.

3 thoughts on “A Rare Myeloproliferative Disorder”

  1. It’s really hard to tell that those are eos in the picture. The dark granules are confusing me. Are they toxic granules in eos???

    1. Hi Mary – Good question! You’re right – some of the granules do look sort of darker than usual in this photo. They are not toxic granules, though – toxic granules only occur in neutrophils. These are benign, non-infection-related eosinophils, and the darker granules are of no particular significance.

      There is only one disorder I can think of that is characterized by eosinophils with dark granules. This disorder is AML-M4Eo, or acute myelomonocytic leukemia with abnormal eosinophils. This particular AML is associated with an inv(16), and is characterized morphologically by eosinophils with abundant, deep purple granules.

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