| Session: Ph- chronic myeloproliferative disease |
| Case number: 181 |
Submitter(s): Angel Ruiz, Jaroslaw P. Maciejewski, Eric D. Hsi.
Clinical history
A 71 year old man with a past medical history of hepatitis C, hypertension, and congestive heart failure presented with intractable pruritis which had been progressive over the past year. Prior evaluation had yielded no specific diagnosis. The patient was found to be anemic and thrombocythemic. His physical examination was unremarkable (no hepatosplenomegaly was detected). A bone marrow biopsy was performed. At the time of the bone marrow: WBC 5.03 x 109/L; Hgb 7.4 g/dL; MCV 101.3 fL; RDW 19.6; PLT 1068 x 109/Ldiff: Segs 58; Lymph 23; Mono 17; Eos 2; Baso 0.
Details of gross/microscopic pathology:
The blood demonstrated a marked thrombocytosis and macrocytic anemia. Macrovalocytes were present. Dysplastic neutrophils were seen. The bone marrow aspirate was cellular with trilineage hematopoiesis.
The differential (200 cells) was: Blasts 1; Pro 0; Myelo/meta/band/seg 66; Eo 2; Bas 0; Mono 1; Erythroid precursors 17; Lymphocytes 12; Plasma cells 1.
Although blasts were not substantially increased, dysgranulopoiesis and mildly megaloblastoid erythropoiesis were present. Storage iron and ringed sideroblasts were not identified. The biopsy showed a hyperplastic marrow with abnormal large, hyperlobulated megakaryocytes. Loose clusters of megakaryocytes were seen and a reticulin stain showed diffuse fibrosis.
Immunophenotype (flow cytometry/immunohistochemistry):
Immunostains: Phospho-STAT5(Y694/Y699): nuclear megakaryocytic positivity.
Cytogenetics:
46, XY.
Molecular analysis:
JAK2 V617F negative
MPL W515L positive
Interphase FISH for BCR-ABL1 negative.
Interesting feature(s) of submitted case:
The patient was given a red cell transfusion, iron supplements, and started on hyroxyurea. The patient was managed conservatively and suffered multiple episodes of gastrointestinal bleeding. 15 months after diagnosis, he died of complications from intractable bleeding.
This case has many features of essential thrombocythemia (ET) and iron deficiency (likely related to GI bleeding). However, there are some atypical pathologic findings such as dysplastic features and reticulin fibrosis. Thus, an unclassifiable MPD/MDS or conversion to post-ET myelofibrosis may be considered. JAK2 V617F was absent; however, we did find a MPL W515L mutation. This mutation has been recently reported in a small percentage of essential thromobocythemia and chronic idiopathic myelofibrosis cases.
We have recently reported abnormal nuclear phospho-STAT5 expression in megakaryocytes from JAK2 V617F+ chronic myeloproliferative disorders (CMPDs). Unusual cases were found that demonstrated this phenotypic abnormality yet they lacked a JAK2 V617F mutation. Such cases likely have other abnormalities that activate a similar abnormal signaling pathway involving STAT5. This case demonstrates that the recently described MPL W515L mutation also shows this abnormal immunophenotypic feature.
Proposed diagnosis:
Essential thrombocythemia (vs. myeloproliferative/myelodysplastic syndrome, unclassifiable), MPL W515L+ and phospho-STAT5+.
Panel diagnosis:
agree with proposed differential diagnosis
Comments:
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