CASE REPORT
A 57-year-old man with CALR-mutated myelofibrosis presented to our institution with new-onset fatigue and abdominal swelling. Physical exam was notable for hepatomegaly 5 cm below the right costal margin and splenomegaly 10 cm below the left costal margin. His laboratory tests revealed a white blood cell count of 0.6 K/μL, a hemoglobin level of 6.5 g/dL, and a platelet count of 72 K/μL. There were 28% circulating myeloblasts in the peripheral blood.
The patient was admitted for more evaluation of his pancytopenia and hepatosplenomegaly. A computed tomography (CT) scan demonstrated marked hepatosplenomegaly (Fig 1A); bilateral, enhancing perinephric soft tissue thickening that involved the pelvicalyceal urothelium and proximal ureters; and subsequent mild bilateral hydronephrosis without parenchymal invasion, suspicious for extramedullary hematopoiesis (Fig 1B). To better elucidate the nature of the enhanced perinephric soft tissue, a technetium-99m (99mTc) sulfur colloid scan was performed. The 99mTc sulfur colloid scan revealed uptake in the liver greater than the spleen and in the bilateral soft tissue thickening of the pelvicalyceal urothelium, proximal ureters, or perinephric soft tissue thickening.
FIG 1.
Bilateral hydronephrosis in a patient with myelofibrosis and massive hepatosplenomegaly. Axial computed tomography scan with intravenous contrast revealed (A) massive hepatosplenomegaly with areas of splenic infarction and (B) bilateral, enhancing soft tissue in the pelvicalyceal urothelium.
Multiple urine specimens were negative for carcinoma or infection. A transcutaneous biopsy was not feasible; therefore, a cystoscopy with right ureteroscopy was performed. There was no evidence of tumor within the renal collecting system and no discrete lesion amenable to a needle biopsy. Brush biopsy of a slightly abnormal thickening of the anterior surface of the right renal pelvis was negative for carcinoma.
A bone marrow core biopsy was hypocellular (10% cellularity) with grade 3 myelofibrosis and no overtly increased blasts (Fig 2). The hypocellular bone marrow with increased peripheral blast count, in conjunction with increased enhancement in the kidneys without cytologic evidence of carcinoma and uptake of 99mTc sulfur colloid scan, suggested an ectopic source of blast production and was consistent with a diagnosis of extramedullary hematopoiesis.
FIG 2.
Bone marrow biopsy showed extensive fibrosis and very little remaining hematopoietic elements. This suggests that the 28% circulating blasts seen in the patient’s peripheral blood were coming from sites of extramedullary hematopoiesis.
DISCUSSION
Extramedullary hematopoiesis is most often associated with primary myelofibrosis or other chronic myeloproliferative neoplasms as well as with chronic hemolytic states, such as thalassemia and sickle cell anemia.1 The mechanism responsible for extramedullary hematopoiesis in myelofibrosis is unclear; however, it is thought to be due to the release of bone marrow precursor cells into the circulation, loss of splenic filtering capability, or an excess of circulating hematopoietic-stimulating cytokines.2 Although the liver and spleen are the most common locations for extramedullary hematopoiesis, nonhepatosplenic extramedullary hematopoiesis has been reported in tissues throughout the body. Common locations of involvement, as reported in a large case series, include the thoracic perivertebral space, lymph nodes, retroperitoneum, lungs, and the genitourinary system, though case reports record many other involved sites.3
Affected patients may be asymptomatic or may present with symptoms specific to the organ involved, such as dyspnea with lung involvement, focal neurologic symptoms with central nervous system involvement, or general malaise and night sweats. Our patient had the unusual presentation of bilateral hydronephrosis, which was incidentally found on CT scan of the abdomen. On imaging, organs can be diffusely infiltrated, or mass-like foci of hematopoiesis may be present. These foci can be confused for another primary neoplastic process, as was initially the concern in our case. CT and magnetic resonance imaging also may reveal iron deposition and/or fatty infiltration in addition to an increased density of the liver and spleen.4 The diagnosis can be confirmed with a surgical biopsy; with fine-needle aspiration; or with characteristic imaging findings, such as uptake on 99mTc sulfur colloid scan.5
Treatment of symptomatic foci of extramedullary hematopoiesis can involve surgery or radiation therapy; responses occur at rates of 70% to 80% and are durable. Because our patient was asymptomatic, he was treated with decitabine 20 mg/m2 for 5 days for myelofibrosis transformed to acute myeloid leukemia. He is currently doing well and has had resolution of his hydronephrosis.
ACKNOWLEDGMENT
J.T. is supported by the Conquer Cancer Foundation of the American Society of Clinical Oncology, the American Association for Cancer Research, the American Society of Hematology, the Robert Wood Johnson Foundation, and National Institutes of Health, National Cancer Institute Grant No. 1K08CA230319-01. These funders did not play any role in the design, collection, interpretation or writing of this study.
AUTHOR CONTRIBUTIONS
Conception and design: Alexander J. Pronko, Eytan Stein, Justin Taylor
Provision of study material or patients: Eytan Stein, Justin Taylor
Collection and assembly of data: Evan Rosenbaum, Alexander J. Pronko, Natasha Lewis, Mariko Yabe, Eytan Stein, Justin Taylor
Data analysis and interpretation: Michele Stanchina, Evan Rosenbaum, Yuzou Liu, Eytan Stein, Justin Taylor
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Extramedullary Hematopoiesis of the Renal Pelvis in a Patient With Myelofibrosis
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jop/site/ifc/journal-policies.html.
Natasha Lewis
Consulting or Advisory Role: United States Drug Testing Laboratories
Mariko Yabe
Consulting or Advisory Role: Y-mAb Therapeutics
Eytan Stein
Stock and Other Ownership Interests: Auron Therapeutics
Consulting or Advisory Role: Celgene, Agios, Bayer, Novartis, Pfizer, PTC Therapeutics, BiolineRx, Syros Pharmaceuticals, Astellas Pharma, Daiichi Sankyo, AbbVie
Research Funding: Agios, Syros Pharmaceuticals, Celgene, Bayer, Amgen
Travel, Accommodations, Expenses: Daiichi Sankyo, Astellas Pharma, Celgene, Syros Pharmaceuticals, AbbVie, Novartis
No other potential conflicts of interest were reported.
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