Abstract
Primary myelofibrosis (PMF) is one of the BCR-ABL-negative myeloproliferative neoplasms. The hallmarks of PMF include increased bone marrow (BM) fibrosis, megakaryocytic hyperplasia with hyperchromatic nuclei and abnormal lobation, leukoerythroblastosis, cytopenias, extramedullary hematopoiesis (EMH), and constitutional symptoms that can be debilitating. PMF is associated with the constitutive mobilization of CD34+ cells into the peripheral blood which characteristically occurs in the more clinically advanced phases of the disease. This dysregulation of hematopoietic stem cell (HSC) trafficking likely ultimately leads to the seeding of extramedullary sites with primitive hematopoietic capacity, resulting in EMH within the spleen and liver as well as a variety of other organs. We present a first report of a unique presentation of PMF in a liver transplant-recipient patient as EMH in the transplanted liver graft.
A 76 year-old man with history of cryptogenic cirrhosis received cadaveric liver transplantation in 1996. He maintained a normal graft function and stable hematologic parameters until 2013 when he presented with anemia and progressive fatigue. Extensive work-up did not identify the etiology of the recent decline in his hemoglobin, but graft dysfunction and anti-rejection therapy were implicated. A liver biopsy was deemed necessary to determine the status of the liver and to further guide anti-rejection therapy.
The liver biopsy showed findings of EMH within the sinusoids with increased megakaryocytes, some with atypical morphology. The liver parenchyma was unremarkable with no evidence of rejection or increased fibrosis [fig. 1]. The patient was referred to hematology for further evaluation. Additional work-up included a BM biopsy that revealed a hypercellular marrow (60 percent, normal appearing trilineage hematopoiesis, moderately increased reticulin fibrosis (grade 2/3) and less than 1% blasts. The number and morphology of megakaryocytes were not markedly abnormal [fig. 1]. Cytogenetic studies on the marrow aspirate showed abnormal karyotype: 47, XY, trisomy 8 and add (9) (q34). Polymerase chain reaction (PCR) analysis on the blood for JAK2 mutation was positive for V617F mutation in exon 14. Abdominal imaging showed a normal-size spleen and did not identify any sites of EMH outside of the liver. The diagnosis of intermediate-2 risk PMF was made.
Morphologic findings in liver and bone marrow biopsy. A: H& E stain of Liver, B: H&E stain of bone marrow biopsy, C: Reticulin stain of bone marrow biopsy
Morphologic findings in liver and bone marrow biopsy. A: H& E stain of Liver, B: H&E stain of bone marrow biopsy, C: Reticulin stain of bone marrow biopsy
Extramedullary hematopoiesis is a feature of PMF, especially in advanced stages. Although it has been reported in many organs and tissues, there is tropism of the neoplastic HSC to seed in organs with hematopoietic potential, such as the spleen, liver, and lymph nodes. This case demonstrates predominant tropism to a transplanted liver graft with absence of EMH elsewhere. In fact, the megakaryocytic atypia were more pronounced in the liver compared to the BM, which might indicate that allograft microenvironment, and possible immune deregulation, facilitated the expansion of the malignant clone.
We would like to emphasize that findings of EMH in subjects with no pre-existing hematologic neoplasm should warrant close follow up and assessment.
No relevant conflicts of interest to declare.
