MPNforum Magazine

BMB results — Science, fantasy…or luck?

Not sure of your diagnosis?  The only way to be certain, is to have a bone marrow biopsy done to check for myeloid expansion, clusters of funny looking megakaryocytes and reticulin fiber deposition…or is all that just another urban  myth?

 The European Bone Marrow Working group  Thomas Buhr, et al., reported  in Haematologica (March 1, 2012) on a study of 102 bone marrow trephines, reviewed by six hematopathologists from five countries .  Bottom line: More than half of the trephines could not be reproducibly classified. As a result  the number of unclassified MPNs rose from 2% to 23% and,when incorporating the WHO criteria for primary myelofibrosis, the frequency of PMF among the 102 dropped from 23% to 7%.

Dr. Jurgen Thiele — along with Orazi, Tefferi, Passamonti, Barbui and others –objected to the findings primarily based on the absence of clinical input, also suggesting the hematopathologists were likely unfamiliar with the WHO criteria

In a stinging rebuttal Buhr pointed out all members of the panel were experienced hematopathologists who have used the WHO criteria in their daily practice for many years and cited the many distinguished hematologists who have cast doubt on thye value of  a pre-fibrotic myelofibrosis diagnosis, citing Richard Silver, Jerry Spivak , F.J. Cervantes, and  Claire Harrison among others.

Part of the difficulty may be in defining elements of the biopsy, but part may be definitions of MPN sub-types.  Buhr footnoted a quote from Willam Dameshek on the difficulty of sub-typing MPNs:

“Transitions and overlaps among these various conditions are common, so that were one begins and the other ends is often uncertain….Sometimes as with the various members of the Myeloproliferative syndromes, a supposedly accurate diagnosis can be mosre inaccurate than the use of the rather vague term of a chronic…myeloprolifrative disorder.”

In any event, the search for diagnostic certainty  clearly does not end at the pathologists’s lab.

Bridget Wilkins, histopathologist Guy’s & St Thomas’ NHS,  et al. published a study on bone marrow pathology  and interobserver reliability in Blood testing the usefulness and reliability of identifying MPN disease subtypes.   The conclusion was unequivocal: 

BMBs from 370 patients with ET were studied by three experienced hematopathologists basing their diagnoses on WHO criteria. “Our results show substantial interobserver variability, particularly for overall diagnosis…” a polite way of saying there was little consensus.

And as to the usefulness of the pre-PMF diagnosis: “No differences could be discerned between patients labeled as having prefibrotic myelofibrosis” or “true ET” in clinical and laboratory features at presentation , JAK2 status, survival, thrombosis, major hemorrhage or myelofibrotic transformation….”

Dr. Wilkins did offer up some practical advice for a cooperative, team effort between pathologist and hematologist that might help turn things around. She wrote, In the  Journal of Clnical Pathology,

“There has been a long controversy, reflected in ongoing differences in local practice, as to whether haematologists or histopathologists are best placed to report BM[B]. Clearly, local expertise varies but, with the strengthening position of haematopathology as a subspecialisation in histopathology and a continuing decline in the direct involvement of haematologists in laboratory work, the case for BM[B] to be reported primarily by haematopathologists becomes increasingly persuasive. However, the fundamental caveat in this regard is that haematopathologists cannot work in isolation from their haematology colleagues in this task; clinical information, blood and marrow aspirate findings, genetic and imaging data are all crucial elements in the dialogue required for BM[B] interpretation.”

Taken on its own, bone marrow biopsy cannot always provide conclusive diagnostic conclusions.  For an example of the difficulty of depending solely on blood marrow findings  , here’s  Dr. Richard Silver’s comments on his slide from Morphology of the Blood and Marrow in Clinical Practice (1970) “A more unusual example of hyperplasia in early “myelofibrosis” Biopsy. Note the predominance of megakaryocytes. This picture is indistinguishable from that seen in some patients with idiopathic thrombocythemia, polycythemia vera or chronic granulocytic leukemia. The fact that the disease was myelofibrosis and not one of the others in the myeloproliferative group was shown by other clinical and hematologic characteristics and by the subsequent course of the patient.”

(*Note: In Dr. Wilkins remarks you’ll see BM[B].  This is to indicate our replacement of her term, BMT, referring to bone marrow trephine since it is confused with the American acronym for bone marrow (stem cell) transplant.  Thank you to those who pointed out the confusion.)

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© Zhenya Senyak and MPNforum.com, 2012. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Zhenya Senyak and MPNforum.com with appropriate and specific direction to the original content.