The Classic Myeloproliferative Neoplasms
Optimizing Laboratory Testing for Hematologic Disorders Series
Beyond Hot Topic is an opportunity for viewers to submit questions to the Hot Topic presenter. The opportunity to submit questions for this topic is now closed.
The following questions were submitted by viewers and answered by the presenter, Curtis A. Hanson, MD of the Division of Hematopathology at Mayo Clinic in Rochester, Minnesota. Questions are presented as submitted (unedited).
We frequently have a bone marrow on a patient with thrombocytosis which is not diagnostic of ET. If the JAK2V617F is negative, what should be the next step?
If the bone marrow does not have definitive morphologic features of a myeloproliferative neoplasm (MPN) with clusters of large atypical megakaryocytes and the thrombocytosis remains clinically unexplained, then a MPL mutation analysis would be appropriate. Only about 10% of ET’s will have a MPL mutation, so the diagnostic return is low. However, if the MPL mutation is present, it allows for a definitive diagnosis of a MPN to be made.
If the bone marrow shows subtle signs of myelodysplasia in a patient with thrombocytosis, what should be the approach?
It obviously depends on the degree and type of dysplasia. Subtle changes in erythroid precursors are one of the most common morphologic overcalls in bone marrow morphology assessment. If that is the only finding, it is likely to be unimportant and should not detract you from making a diagnosis of a myeloproliferative neoplasm (MPN). If definitive dysgranulopoiesis is present, then that usually trumps all other findings. However, poor preparations and mediocre stains may make it difficult to assess dysgranulopoiesis.
Thrombocytosis is not uncommonly found in patients with a del(5q), so dysmegakaryopoiesis in the form of small, dysplastic megakaryocytes may be identified in patients who present with a thrombocytosis. These patients with del(5q) may also have ring sideroblasts present. These cases should be signed out as isolated del(5q) syndrome.
The provisional WHO classification of refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) is a controversial category. It is our belief that many of those cases are actually ETs with ring sideroblasts. However, there are likely real RARS-T cases that do not have the morphologic features of ET (clusters of large atypical megakaryocytes) but present with ring sideroblasts and thrombocytosis.
A significant thrombocytosis would be uncommon in the vast majority of myelodysplastic syndrome (MDS) cases and should raise questions as to the correct classification of that case. If you are contemplating a MDS in a patient who has a thrombocytosis, then I would: 1) look closely at the megakaryocyte morphology: are they small and monolobated, are there clusters of large megakaryocytes in the biopsy, 2) evaluate for ring sideroblasts, 3) correlate with cytogenetic findings, in particular a del(5q), and 4) ask myself if I am overcalling the dysplastic features!