DOI: 10.1148/radiol.2311020673
(Radiology 2004;231:52-56.)
© RSNA,
Case 69: Extramedullary Hematopoiesis1
Haesun Choi, MD,
Cynthia L. David, MD,
Ruth L. Katz, MD and
Donald A. Podoloff, MD
1 From the Divisions of Diagnostic Imaging (H.C., C.L.D., D.A.P.) and Pathology (R.L.K.), University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, PO Box 57, Houston, TX 77030. Received June 4, 2002; revision requested July 16; revision received September 18; accepted November 18. Address correspondence to H.C. (e-mail: hchoi@di.mdacc.tmc.edu).
Index terms: Abdomen, CT, 775.1211, 81.1211 • Abdomen, radionuclide studies, 775.12171, 81.1217 • Diagnosis Please • Hematopoiesis, extramedullary, 44.659, 775.659, 81.659 • Kidney, diseases, 81.659 • Spleen, abnormalities, 775.372
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HISTORY
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A 66-year-old man was found to be anemic and thrombocytopenic during his annual physical examination. Work-up with bone marrow evaluation revealed mild marrow fibrosis with marked megakaryocytic hyperplasia, a finding that is consistent with early myelofibrosis with myeloid metaplasia. The diagnosis was confirmed with cytogenic study of the bone marrow. Initial peripheral blood smear revealed a hemoglobin level of 8.6 g/dL (86 g/L), a platelet count of 50,000/µL (50 x 109/L), and a white blood cell count of 6,500/µL (6.5 x 109/L), with no blasts. The patient had remarkably few symptoms, other than occasional fatigue.
Initial treatment with prednisone (Roxane Laboratories, Columbus, Ohio), epoetin alfa (Procrit; Ortho Biotech, Bridgewater, NJ), and oxymetholone (Anadrol; Unimed Pharmaceutical, Marietta, Ga) failed to relieve anemia. Allogenic stem cell transplantation was suggested. Meanwhile, the patient was treated with packed red blood cell transfusion every 3–4 weeks, which increased in frequency during a 3-year period. Further treatment with thalidomide (Thalomid; Celgene, Warren, NJ) and cyclosporin (Sandimmune; Novartis, Parsippany, NJ) failed to reduce the frequency of transfusions. The possibility of investigational treatment was discussed.
Contrast material–enhanced and unenhanced computed tomography (CT) was performed as part of the work-up for investigational treatment, and a technetium 99m (99mTc) sulfur colloid bone marrow examination was performed on the same day.
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IMAGING FINDINGS
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The initial contrast-enhanced CT scan showed hypoattenuating soft tissue in the area of the renal pelves (Fig 1). The process in the right renal pelvis was expanding the renal pelvis. The soft tissue was homogeneous, with minimal enhancement. Massive splenomegaly was present and displaced and deformed the left kidney. The 99mTc–sulfur colloid bone marrow examination, which was performed on the same day, showed severe splenomegaly (Fig 2). No other abnormal uptake was identified in the abdomen. Follow-up CT scans were obtained 2 months later and showed that the findings in the renal pelves and the splenomegaly were stable.
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Figure 1. A, Transverse unenhanced CT scan of the upper abdomen. B and C, contrast-enhanced CT scans of the upper abdomen. Images demonstrate hypoattenuating homogeneous soft tissue (arrows) in both renal pelves with minimal enhancement. Notice massive splenomegaly (S). A large cyst (arrowheads) is noted in the anterior cortex of the left kidney. L = liver.
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Figure 2. A, Anterior whole-body image obtained with 99mTc-sulfur colloid bone marrow imaging. B, Posterior whole-body image. These images demonstrate no substantial peripheral marrow expansion. The hot spot in the left thigh was caused by contamination and is not pertinent. Massive splenomegaly (S) is noted. C, Anterior image obtained with 99mTc-sulfur colloid bone marrow imaging with a wide window setting. D, Posterior image. These images demonstrate radiotracer uptake in only the liver (L) and the spleen. Notice that the region of the kidneys shows no appreciable radiotracer uptake.
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DISCUSSION
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In this patient with transfusion-dependent chronic myelofibrosis, the bilateral homogeneous hypoattenuating infiltration in the renal pelves on CT scans should raise extramedullary hematopoiesis (EMH) as a possible diagnosis. The 99mTc–sulfur colloid examination, however, failed to demonstrate the presence of reticuloendothelial elements of bone marrow in the renal pelvic masses. Ultrasonographic (US)-guided fine-needle aspiration biopsy revealed a polymorphous infiltrate composed of immature erythroid cells, myeloid cells, and lymphocytes, a finding that was consistent with EMH.
EMH is a response to erythropoiesis failure in bone marrow. It is an entity that is rarely encountered in general radiologic practice, but it is one of the common features of chronic myeloproliferative disorders. Myeloproliferative disorders include chronic myelogenous leukemia, polycythemia vera, essential thrombocytosis, and myelofibrosis with myeloid metaplasia. The neoplastic stem cells have the capacity to circulate and migrate to secondary hematopoietic organs, particularly the spleen, where they give rise to EMH. This occurs most frequently in patients with myelofibrosis with myeloid metaplasia EMH. In comparison with other chronic myeloproliferative disorders, the hallmark of myelofibrosis with myeloid metaplasia is an early progression to marrow fibrosis suppressing bone marrow hematopoiesis and displacing the hematopoietic elements of the marrow—including the stem cells—leading to peripheral blood cytopenias and extensive neoplastic EMH (1).
EMH occurs most often in the spleen and liver and occasionally in the lymph nodes (1). Involvement of other organs, such as the pleura, lungs, gastrointestinal tract, breast, skin, brain, kidneys, and adrenal glands, has been reported (13). Renal involvement can be parenchymal, intrapelvic, or perirenal. In the parenchymal type of renal involvement, the kidneys may be enlarged diffusely or have either single or multiple small focal lesions (2–4). Pelvic involvement is often an extension of parenchymal involvement but can be isolated, as was the case in our patient (5,6). In the perirenal type of renal involvement, a hypoattenuating mass or nodules are seen either around or encasing the kidneys (7,8). The intrapelvic and perirenal types of renal involvement are often bilateral but can also be unilateral (2).
EMH is usually asymptomatic, although patients may present with abdominal discomfort. Renal failure is the most serious complication and occurs due to diffuse parenchymal involvement or ureteral obstruction. In one report (2), two of the five patients with renal involvement died of renal failure.
Differential diagnoses of isolated renal pelvic masses with CT include urothelial tumors and lymphoma. Intrapelvic transitional carcinoma typically manifests as a sessile filling defect (9) and demonstrates expansile growth (10). Bilateral simultaneous involvement of renal pelves occurs in only 1%–2% (11) of patients with transitional cell carcinomas with variable enhancement (9). Renal involvement with lymphoma is reported in 3%–5% of all patients at routine CT staging (10). Nodular involvement of renal parenchyma is far more common than isolated intrapelvic lymphoma, but when it does occur, it is difficult to differentiate from EMH. Some authors have reported that, unlike lymphoma, EMH in the renal pelvis is seen to enhance on CT scans (6). The masses in our patient, however, showed only minimal enhancement. Renal pelvic involvement of lymphoma is typically an extension of retroperitoneal lymphadenopathy (10). In our patient with chronic myelofibrosis, a diagnosis of lymphoma was favored over a diagnosis of transitional carcinoma if the abnormalities were malignant, which led us to perform US-guided biopsy. In the right clinical setting, CT scans can indicate a diagnosis of EMH. The presence of substantial splenomegaly is useful to support the diagnosis.
The role of nuclear medicine bone marrow imaging in the evaluation of EMH has not yet been clarified. Bone marrow imaging with indium 111 (111In) chloride (111InCl3) and 99mTc–sulfur colloid has been useful in the evaluation of patients suspected of having EMH (12–15). Bone marrow consists of erythropoietic, myelopoietic, and reticuloendothelial elements. 99mTc–sulfur colloid is used as a colloidal reticuloendothelial system imaging agent, and it is taken up by reticuloendothelial cells in bone marrow. 111InCl3 was initially developed as a pure erythropoietic agent to be used as a substitute for iron, but reticuloendothelial cells also take up 111InCl3 when transferrin is saturated (16).
In our patient, 99mTc–sulfur colloid bone marrow imaging failed to depict renal EMH. One instance of failed bone marrow imaging, which was later identified with both 111InCl3 and 99mTc–sulfur colloid imaging, was reported in a patient with retroperitoneal and mesenteric EMH; however, the cause was not described (17). In our patient, there were negligible reticuloendothelial cells in the cell block prepared from needle aspiration biopsy of the soft-tissue infiltration in the renal pelvis, which might have led to the inability of 99mTc–sulfur colloid bone marrow imaging to depict the renal EMH. Also, the massive splenomegaly and markedly increased number of reticuloendothelial cells might be responsible, having taken most of the injected colloids. Regardless of the reason 99mTc–sulfur colloid bone marrow imaging failed to depict the EMH, it should be noted that negative bone marrow imaging findings do not exclude the possibility of EMH. A biopsy is necessary to confirm the diagnosis of EMH in patients with discordant CT findings and bone marrow imaging findings, as was the case in our patient.
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ACKNOWLEDGMENTS
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The authors thank Susan O’Brien, MD, for her support regarding the clinical aspects of this case and Beth Wagner for her editorial assistance.
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FOOTNOTES
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Part 1 of this case appeared 4 months previously and may contain larger images.
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REFERENCES
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Congratulations to the 131 individuals who submitted the most likely diagnosis (Extramedullary Hematopoiesis) for Diagnosis Please, Case 69. The names and locations of the individuals, as submitted, are as follows:
- Pablo J. Abbona, MD, Mar del Plata, Argentina
- Hisashi Abe, Osaka, Japan
- Gholamali Afshang, MD, Tinley Park, Ill
- Dr Jorge Ahualli, Tucumán, Argentina
- Oguz Akin, MD, New York, NY
- Albert J. Alter, Madison, Wis
- J. Andreu, Barcelona, Spain
- Javier Arce, Barcelona, Spain
- A. Rhett Austin, MD, Kingsport, Tenn
- Ken Baliga, Rockford, Ill
- Aldo Benjamim R. Barbosa, Barretos, Brazil
- Ufuk Bayraktar, MD, Antalya, Turkey
- Debra M. Berger, MD, New York, NY
- Antonio Botero, MD, Bogotá, Colombia
- Rogério Pedreschi Caldana, São Paulo, Brazil
- María Jesús Díaz Candamio, La Coruña, Spain
- Antonio Cavalcanti, MD, São Paulo, Brazil
- Luisa Fernanda Cervantes, Miami, Fla
- Henry H. Chen, MD, Carbondale, Ill
- Michael H. Childress, MD, Silver Spring, Md
- Timothy Clark, Greenville, NC
- James W. Cole, MD, Cincinnati, Ohio
- Y-S Cordoliani, MD, Paris, France
- Marc G. de Baets, Lugano, Switzerland
- Wagner Diniz de Paula, MD, Brasilia, Brazil
- J. F. K. de Villiers, Gisborne, New Zealand
- Jon De Witte, Phoenix, Ariz
- Mustafa Kemal Demir,
stanbul, Turkey
- T. Dhurairaj, Pennsauken, NJ
- Shella Farooki, Dublin, Ohio
- Gabriel C. Fernández Pérez, Vigo, Spain
- Roberto García Figueiras, MD, Santiago de Compostela, Spain
- Marta Fité, Barcelona, Spain
- Jordi Catala Forteza, Barcelona, Spain
- Akira Fujikawa, Tokyo, Japan
- Ann S. Fulcher, MD, Richmond, Va
- Cristine Norwig Galvâo, Barretos, Brazil
- Douglas Gardner, MD, Windsor, Ontario, Canada
- Dr Roberto E. Perez Gautrin, Sonora, Mexico
- Ted A. Glass, MD, Jackson, Miss
- Mark Goldshein, MD, Andover, Mass
- Tom Grant, DO, Chicago, Ill
- Aleksandar Grgic, MD, Homburg, Germany
- Flavius Guglielmo, MD, Basking Ridge, NJ
- Hiroto Hatabu, MD, PhD, Boston, Mass
- Helen T. Ho, MD, Chicago, Ill
- Alfred L. Horowitz, MD, Asheville, NC
- Dr Kartik Jhaveri, Toronto, Ontario, Canada
- Dr Sudhir Kumar Kale, Chennai, India
- Masako Kataoka, Cambridge, United Kingdom
- Nurettin Katranci, MD, Antalya, Turkey
- Dr Taswinder Kaur, Chandigarh, India
- Takuji Kiryu, MD, Gifu, Japan
- Mitchell A. Klein, MD, Milwaukee, Wis
- Steven A. Klein, MD, Shrewsbury, Mass
- Arlene Klink, MD, Irvine, Calif
- Jacob Sam Koruth, MD, Worcester, Mass
- Glenn Krinsky, New York, NY
- Stefanos Lachanis, MD, Athens, Greece
- Mario Laguna, West Allis, Wis
- Roger Lao, MD, Dix Hills, NY
- John T. Lim, MD, Newport Coast, Calif
- David A. Lisle, Brisbane, Australia
- Julio L. Loureiro, MD, Buenos Aires, Argentina
- Dr Smita Mahajan, Ulhasnagar, India
- Pierre D. Maldjian, MD, Newark, NJ
- N. B. S. Mani, MD, Nassau, Bahamas
- Frank McKowne, MD, Vancouver, Wash
- Dr Breda McManus, Salford, Manchester, United Kingdom
- Luis Mendez-Uriburu, Tucuman, Argentina
- Prof Dr Med Michael Meves, Berlin, Germany
- Peter Miltner, MD, Heidelberg, Germany
- Manabu Minami, MD, Tokyo, Japan
- Dr Adrian Mizzi, Glasgow, United Kingdom
- Sankar Ranjan Mondal, MD, Nassau, Bahamas
- Dr J. Edmund Moses, Chandigarh, India
- Tetsuro Nakahara, Shiga, Japan
- Tammam Nehme, MD, Wenatchee, Wash
- Karl F. R. Neufang, MD, Euskirchen, Germany
- Chris Ng, Nashville, Tenn
- Mizuki Nishino, MD, Boston, Mass
- Laura Oleaga, Bilbao, Spain
- Mike O’Loughlin, MD, West Hartford, Conn
- Sanford M. Ornstein, MD, Phoenix, Ariz
- Peter A. Ory, MD, Mercer Island, Wash
- Ann Owen, MD, Murfreesboro, Tenn
- Harish Panicker, MD, Washington, DC
- Narendrakumar P. Patel, MD, Newburgh, NY
- Ernesto Oscar Pearson, MD, Córdoba, Argentina
- Dennis N. Peters, Philadelphia, Pa
- Alex Petersen, Nowra, Australia
- Hilton W. Pittman, Pensacola, Fla
- Mario P. Pliego, MD, Bloomington, Minn
- Adilson Prando, MD, Campinas, Brazil
- Lisa K. Quane, MD, Orange, Calif
- Shawn P. Quillin, MD, Charlotte, NC
- Jan Rabe, MD, Karlsruhe, Germany
- T. N. Anuradha Rao, Toronto, Ontario, Canada
- Enrique Remartinez Escobar, MD, Melilla, Spain
- Luiz Antonio Rossi, MD, São Paulo, Brazil
- Dr N. Saravanan, MD, Chandigarh, India
- Pierre J. Sauvage, MD, Mâcon, France
- Abdelhafid Sbihi, MD, Rabat, Morocco
- Stephen I. Schabel, Charleston, SC
- Andrew Schechter, Upper Saddle River, NJ
- Steven M. Schultz, MD, Fort Worth, Tex
- Mustafa Secil, MD, Izmir, Turkey
- Mahomed Seedat, Toowoomba, Australia
- Matt Shapiro, MD, Staunton, Va
- Taro Shimono, MD, Osaka, Japan
- Michael Keith Silberman, Durham, NC
- Darrin S. Smith, MD, Fresno, Calif
- David Sobel, MD, La Jolla, Calif
- James D. Sprinkle, Jr, MD, Spotsylvania, Va
- Dr Marius Stellmann, Stade, Germany
- Dr Anne Stroh Marcy, Arras, France
- Kouichi Sugiyama, Hamamatsu, Japan
- Norio Takahashi, MD, Fukui, Japan
- Satoru Takahashi, MD, Osaka, Japan
- Luis Tata, MD, Amadora, Portugal
- Douglas L. Teich, MD, Brookline, Mass
- Eugene Tong, MD, Austin, Tex
- Meriç Tüzün, Ankara, Turkey
- Hiroyuki Ueda, Kyoto, Japan
- Lieven Van Hoe, MD, PhD, Aalst, Belgium
- Piet Vanhoenacker, MD, Moorsel, Belgium
- Elida Vazquez, MD, Barcelona, Spain
- Christopher Vittore, MD, Rockford, Ill
- Jeff West, MD, Jacksonville, Fla
- Joe Yut, Olathe, Kan
- Jeffrey H. Zapolsky, MD, Oshkosh, Wis
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TOP
HISTORY
IMAGING FINDINGS
