Radiology
Haesun Choi, MD Cynthia L. David, MD Ruth L. Katz, MD Donald A. Podoloff, MD
Case 69: Extramedullary Hematopoiesis1 HISTORY 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/L (50 ⫻ 109/L), and a white blood cell count of 6,500/L (6.5 ⫻ 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 to-
Part 1 of this case appeared 4 months previously and may contain larger images.
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 Published online 10.1148/radiol.2311020673 Radiology 2004; 231:52–56 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:
[email protected]).
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mography (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.
IMAGING FINDINGS 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.
DISCUSSION 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 hemato-
Radiology
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.
poietic 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 enVolume 231
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hancement (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 99m Tc–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 111 InCl3 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 99m Tc–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 Extramedullary Hematopoiesis
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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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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. Acknowledgments: The authors thank Susan O’Brien, MD, for her support regarding the clinical aspects of this case and Beth Wagner for her editorial assistance. References 1. Aster J, Kumar V. White cells, lymph nodes, spleen, and thymus. In: Ramzi SC, ed. Pathologic basis of disease. 6th ed. Philadelphia, Pa: Saunders, 1999; 644 – 695. 2. Redlin L, Francis RS, Orlando MM. Renal abnormalities in agnogenic myeloid metaplasia. Radiology 1976; 121:605– 608. 3. Sharma AK. Tumefactive extramedullary hematopoiesis of the kidney in a patient with idiopathic thrombocytopenic purpura. AJR Am J Roentgenol 1996; 167:795–796. 4. Moskovitz B, Malberger E, Brenner B, Gaitini D, Vardi Y, Bolkier M. Renal extramedullary hematopoiesis simulating hypernephroma. Eur Urol 1991; 19:343–345. 5. Gryspeerdt S, Oyen R, Van Hoe L, Baert AL, Boogaerts M. Extramedullary hematopoiesis encasing the pelvicalyceal system: CT findings. Ann Hematol 1995; 71:53–56. 6. Tuite MJ, Weiss SL. Ultrasound and computed tomographic appearance of extramedullary hematopoiesis encasing the renal pelvis. J Clin Ultrasound 1991; 19:238 –240.
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Rapezzi D, Racchi O, Ferraris AM. Perirenal extramedullary hematopoiesis in agnogenic myeloid metaplasia: MR imaging findings. AJR Am J Roentgenol 1997; 168:1388 –1389. Wright RE. Case report: pararenal extramedullary haematopoietic tissue—an unusual manifestation of myelofibrosis. Clin Radiol 1991; 44:210 –211. Wong-You-Cheong JJ, Wagner BJ, Davis CJ Jr. Transitional cell carcinoma of the urinary tract: radiologic-pathologic correlation. RadioGraphics 1998; 18:123–148. Urban BA, Fishman EK. Renal lymphoma: CT patterns with emphasis on helical CT. RadioGraphics 2000; 20:197–212. Anselmo G, Rizzotti A, Felici E, Bassi E, Maccatrozzo L. Multiple simultaneous bilateral urothelial tumours of the renal pelvis. Br J Urol 1987; 60:312–315. Vieras F, Boyd CM, Mora PA. Diffuse pulmonary uptake of indium-111 chloride in idiopathic myelofibrosis. Radiology 1979; 130:749 –750. Bronn LJ, Paquelet JR, Tetalman MR. Intrathoracic extramedullary hematopoiesis: appearance on 99mTc sulfur colloid marrow scan. AJR Am J Roentgenol 1980; 134:1254 –1255. Urman M, O’Sullivan RA, Nugent RA, Lentle BC. Intracranial extramedullary hematopoiesis: CT and bone marrow scan findings. Clin Nucl Med 1991; 16:431– 434. Alam R, Padmanabhan K, Rao H. Paravertebral mass in a patient with thalassemia intermedia. Chest 1997; 112:265–267. Mishkin FS, Freeman LM. Miscellaneous applications of radionuclide imaging. In: Freeman LM, ed. Freeman and Johnson’s clinical radionuclide imaging. Vol 2. 3rd ed. Orlando, Fla: Grune & Stratton, 1984: 1365–1460. Harnsberger HR, Datz FL, Knochel JQ, Taylor AT. Failure to detect extramedullary hematopoiesis during bone-marrow imaging with indium-111 or technetium-99m sulfur colloid. J Nucl Med 1982; 23:589 –591.
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, Tucuma´n, 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, Bogota´, Colombia Roge´ rio Pedreschi Caldana, Sa˜o Paulo, Brazil Marı´a Jesu´ s Dı´az Candamio, La Corun ˜ a, Spain Antonio Cavalcanti, MD, Sa˜o 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, Y´stanbul, Turkey T. Dhurairaj, Pennsauken, NJ Shella Farooki, Dublin, Ohio Gabriel C. Ferna´ ndez Pe´ rez, Vigo, Spain Volume 231
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Roberto Garcı´a Figueiras, MD, Santiago de Compostela, Spain Marta Fite´ , Barcelona, Spain Jordi Catala Forteza, Barcelona, Spain Akira Fujikawa, Tokyo, Japan Ann S. Fulcher, MD, Richmond, Va Cristine Norwig Galvaˆ o, 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 Extramedullary Hematopoiesis
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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, Co´ rdoba, 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
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T. N. Anuradha Rao, Toronto, Ontario, Canada Enrique Remartinez Escobar, MD, Melilla, Spain Luiz Antonio Rossi, MD, Sa˜ o Paulo, Brazil Dr N. Saravanan, MD, Chandigarh, India Pierre J. Sauvage, MD, Maˆ con, 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 Meric¸ Tu ¨ zu ¨ n, 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
Choi et al
