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14. Piwnica-Worms D, Kronauge JF, Delmon L, et al. Effect of metabolic inhibition on technetium-99m-MIBI kinetics in cultured chick myocardial cells. J NucÃ-Med 1990:31:464-472. 15. Chiù ML. Kronauge JF. Piwnica-Worms D. Monitoring mitochondria! plasma mem brane potentials with a new l''""Tc-based lipophilic cation [Abstract]. J Gen Physio/ 1989:94:41 A. 16. Vykoupil KF. Thiel J. Stangel W. et al. Polycythemia vera. I. Histopathology. ultrastructure and cytogenetics of the bone marrow in comparison with secondary polycythemia. Virchov/s Archiv A Path Anal Hislol 1980:389:307-324. 17. Van Dyke D. Anger HO. Parker H. et al. Markedly increased blood flow in myelofibrosis. J NucÃ-Med 1971:12:506-512. Scintigraphic Diagnosis of Intrathoracic Extramedullary Hematopoiesis in Alcohol-Related Macrocytosis Frank De Geeter and Dirk Van Renterghem Departments of Nuclear Medicine and Pneumolog\>, Saint John 's General Hospital, Brugge, Belgium We report the scintigraphic diagnosis of thoracic extramedullary hematopoiesis in a case of alcohol-related macrocytosis. A patient with liver cirrhosis and alcohol-related macrocytosis showed multi ple rounded masses in the low thoracic paraspinal region on chest radiography and CT. Whole-body scintigraphy and SPECT imaging of the thorax, after nanocolloid administration, demonstrated expan sion of the bone marrow in the humen and femora and uptake of the tracer in the mediastinal masses, establishing the diagnosis of mediastinal extramedullary hematopoiesis. Thoracic extramedullary hematopoiesis may occur in conjunction with alcohol-related mac rocytosis. Scintigraphy with ""Tc-nanocolloids is a suitable nonin- vasive method to establish the presence of extramedullary marrow. Key Words: technetium-99m-colloid; bone marrow scintigraphy; extramedullary hematopoiesis; posterior mediastinal tumor; macro cytosis J NucÃ- Med 1996; 37:473-475 E> jxtramedullary hematopoiesis is defined as the recurrence after birth of normal marrow outside the skeleton. It occurs in chronic hemolytic states, ineffective erythropoiesis, myeloph- tisic conditions and in myeloproliferative disorders as an attempt to compensate for the anemia (1-3). Most frequently, the extraskeletal marrow is present in liver and spleen. We report on a case of intrathoracic extramedullary hematopoiesis in conjunction with alcohol-related macrocytosis. Scintigraphy with nanocolloids was instrumental in the differential diagnosis of the intrathoracic masses. CASE REPORT A 73-yr-old man with known alcoholic liver cirrhosis presented with dyspnea and asthenia. Fifteen months earlier, he had been examined because of macrocytic anemia. At that time, bone marrow biopsy had revealed a megaloblastic appearance of the red and myeloid precursors and a bone marrow aspirate had shown dyserythropoietic characteristics such as megaloblastic elements, deshemoglobinisation, anisocytosis and anisokaryosis. Serum lev els of vitamin B12 and folie acid as well as erythrocytic levels of folie acid were normal. Bone marrow findings were attributed to substantial alcohol abuse. The patient, now admitted, continued consumption of 4-to-5 alcoholic beverages a day. At physical examination, an anemic facies, spider naevi, a slightly enlarged liver and ascites were Received Jan. 9, 1995; revision accepted Jul. 5, 1995. For correspondence or reprints contact: Frank De Geeter, MD, Department of Nuclear Medicine, Algemeen Ziekenhuis Sint-Jan, Ruddershove 10, 8000 Brugge, Belgium. FIGURE 1. CT shows multiple rounded masses in the paraspinal region at the low thoracic level. found. Chest radiography showed small bilateral pleural effusion and suggested a space-occupying lesion projected upon the right hilum. Computed tomography of the thorax (Fig. I) revealed the presence of a paraspinal polynodular mass at the mid and low dorsal levels. A diagnosis of neurinoma was suggested by the radiologist. The erythrocyte sedimentation rate was 36 mm/hr; the hematocrit was 29% and the hemoglobin level 9.7 mg/dl. The mean corpuscular volume was 117.8 fl. White blood cell counts as well as platelet counts were normal. Gamma-glutamyl transferase was 100 m(//ml (normal values up to 65 mLVml). Since thoracic extramedullary hematopoiesis was considered as a differential diagnosis, bone marrow scintigraphy was performed 1 hr after intravenous injection of 20 mCi 99rnTc-nanocolloid. Whole-body images (Fig. 2) revealed marked activity in the femora and humeri, extending to their most distal parts, and thus were indicative of marrow expansion (4). Moreover, paraspinal activity was present at the low thoracic level. SPECT (Fig. 3) enabled us to locate the activity in the paraspinal region corresponding to the masses seen on CT. We therefore concluded that these represented foci of extramed ullary hematopoiesis secondary to alcoholic macrocytosis. The patient refused further examination and treatment. No histologie confirmation could be obtained. THORACICEXTRAMEDULLARY HEMATOPOIESIS • De Geeter and Van Renterghem 473 by on July 31, 2020. For personal use only. jnm.snmjournals.org Downloaded from

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Page 1: ScintigraphicDiagnosisofIntrathoracic ...jnm.snmjournals.org › content › 37 › 3 › 473.full.pdf · 14.Piwnica-WormsD,KronaugeJF,DelmonL,etal.Effectofmetabolicinhibitionon technetium-99m-MIBIkineticsinculturedchickmyocardialcells.JNucÃMed

14. Piwnica-Worms D, Kronauge JF, Delmon L, et al. Effect of metabolic inhibition ontechnetium-99m-MIBI kinetics in cultured chick myocardial cells. J NucíMed1990:31:464-472.

15. Chiù ML. Kronauge JF. Piwnica-Worms D. Monitoring mitochondria! plasma membrane potentials with a new l''""Tc-based lipophilic cation [Abstract]. J Gen Physio/

1989:94:41 A.

16. Vykoupil KF. Thiel J. Stangel W. et al. Polycythemia vera. I. Histopathology.

ultrastructure and cytogenetics of the bone marrow in comparison with secondarypolycythemia. Virchov/s Archiv A Path Anal Hislol 1980:389:307-324.

17. Van Dyke D. Anger HO. Parker H. et al. Markedly increased blood flow inmyelofibrosis. J NucíMed 1971:12:506-512.

Scintigraphic Diagnosis of IntrathoracicExtramedullary Hematopoiesis inAlcohol-Related MacrocytosisFrank De Geeter and Dirk Van RenterghemDepartments of Nuclear Medicine and Pneumolog\>, Saint John 's General Hospital, Brugge, Belgium

We report the scintigraphic diagnosis of thoracic extramedullaryhematopoiesis in a case of alcohol-related macrocytosis. A patientwith liver cirrhosis and alcohol-related macrocytosis showed multiple rounded masses in the low thoracic paraspinal region on chestradiography and CT. Whole-body scintigraphy and SPECT imagingof the thorax, after nanocolloid administration, demonstrated expansion of the bone marrow in the humen and femora and uptake of thetracer in the mediastinal masses, establishing the diagnosis ofmediastinal extramedullary hematopoiesis. Thoracic extramedullaryhematopoiesis may occur in conjunction with alcohol-related macrocytosis. Scintigraphy with ""Tc-nanocolloids is a suitable nonin-

vasive method to establish the presence of extramedullary marrow.Key Words: technetium-99m-colloid; bone marrow scintigraphy;extramedullary hematopoiesis; posterior mediastinal tumor; macrocytosisJ NucíMed 1996; 37:473-475

E>jxtramedullary hematopoiesis is defined as the recurrenceafter birth of normal marrow outside the skeleton. It occurs inchronic hemolytic states, ineffective erythropoiesis, myeloph-tisic conditions and in myeloproliferative disorders as anattempt to compensate for the anemia (1-3). Most frequently,the extraskeletal marrow is present in liver and spleen. Wereport on a case of intrathoracic extramedullary hematopoiesisin conjunction with alcohol-related macrocytosis. Scintigraphywith nanocolloids was instrumental in the differential diagnosisof the intrathoracic masses.

CASE REPORTA 73-yr-old man with known alcoholic liver cirrhosis presented

with dyspnea and asthenia. Fifteen months earlier, he had beenexamined because of macrocytic anemia. At that time, bonemarrow biopsy had revealed a megaloblastic appearance of the redand myeloid precursors and a bone marrow aspirate had showndyserythropoietic characteristics such as megaloblastic elements,deshemoglobinisation, anisocytosis and anisokaryosis. Serum levels of vitamin B12 and folie acid as well as erythrocytic levels offolie acid were normal. Bone marrow findings were attributed tosubstantial alcohol abuse.

The patient, now admitted, continued consumption of 4-to-5alcoholic beverages a day. At physical examination, an anemicfacies, spider naevi, a slightly enlarged liver and ascites were

Received Jan. 9, 1995; revision accepted Jul. 5, 1995.For correspondence or reprints contact: Frank De Geeter, MD, Department of Nuclear

Medicine, Algemeen Ziekenhuis Sint-Jan, Ruddershove 10, 8000 Brugge, Belgium.

FIGURE 1. CT shows multiple rounded masses in the paraspinal region atthe low thoracic level.

found. Chest radiography showed small bilateral pleural effusionand suggested a space-occupying lesion projected upon the righthilum. Computed tomography of the thorax (Fig. I) revealed thepresence of a paraspinal polynodular mass at the mid and lowdorsal levels. A diagnosis of neurinoma was suggested by theradiologist. The erythrocyte sedimentation rate was 36 mm/hr; thehematocrit was 29% and the hemoglobin level 9.7 mg/dl. The meancorpuscular volume was 117.8 fl. White blood cell counts as wellas platelet counts were normal. Gamma-glutamyl transferase was100 m(//ml (normal values up to 65 mLVml).

Since thoracic extramedullary hematopoiesis was considered asa differential diagnosis, bone marrow scintigraphy was performed1 hr after intravenous injection of 20 mCi 99rnTc-nanocolloid.

Whole-body images (Fig. 2) revealed marked activity in the femoraand humeri, extending to their most distal parts, and thus wereindicative of marrow expansion (4). Moreover, paraspinal activitywas present at the low thoracic level. SPECT (Fig. 3) enabled us tolocate the activity in the paraspinal region corresponding to themasses seen on CT.

We therefore concluded that these represented foci of extramedullary hematopoiesis secondary to alcoholic macrocytosis. Thepatient refused further examination and treatment. No histologieconfirmation could be obtained.

THORACICEXTRAMEDULLARYHEMATOPOIESIS•De Geeter and Van Renterghem 473

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FIGURE 2. Posterior view of whole-body nanocolloid scintigraph showsmarked activity in both femora, reaching to the most distal parts, and activityof the proximal two-thirds of both hu

men, indicating marrow expansion.Additional tracer accumulations areseen to the right and to the left of thelower thoracic spine.

DISCUSSIONMediastinal extramedullary hematopoiesis is an unusual con

dition. It is typically present in rounded, often lobulatedparaspinous masses at the T6-T12 level (5-8). Most often,

these masses are multiple and bilateral and usually remainasymptomatic. In rare cases, however, these masses may becomplicated by spinal cord compression due to epidural involvement or by hemothorax. Most frequently, intrathoracicextramedullary hematopoiesis has been reported as a consequence of chronic anemia, such as thalassemia, hereditaryspherocytosis, sideroblastic anemia and sickle cell disease(2,7). Rarer causes of intrathoracic extramedullary hematopoiesis include: myeloid metaplasia, polycythemia vera, leukemia,lymphoma, carcinomatosis, erythroblastosis fetalis (9) andGaucher's disease (10). Our case resembles a study in which

intrathoracic extramedullary hematopoiesis with macrocytosis(mean corpuscular volume 110 fl) could be ascribed to vitaminB12 and folate deficiencies (6). It is also similar to anotherinstance of mediastinal hematopoietic tumors in which a MCVof 110 fl was the only abnormality present in the peripheralblood. This abnormality, however, could ultimately be attributed to refractory anemia (7).

The differential diagnosis of posterior mediastinal massesincludes: neurogenic tumors, lymphoma, meningocele, gastro-

i i ver^ spleen^

W m v my*iv*r% s P leen

FIGURE 3. Transaxial (left) and frontal (right) slices of nanocolloid SPECTshow normal activity in liver, spleen and vertebral column (v). Paravertebralmasses (m) at low thoracic level also show tracer uptake, which proves thatthey correspond to foci of extramedullary hematopoiesis.

enteric or esophageal cysts, gastric herniation, mesenchymaltumors, metastasis and paraspinous abscess. The exact diagnosis is important given the different therapeutic strategies forthese conditions. Differential diagnostic elements may comefrom a clinical context and radiologie studies. Anemia maypoint to the diagnosis of extramedullary hematopoiesis (8) butcan be mild (6,7,10). Radiologie clues include the absence ofbony erosion, thus arguing against malignancy. Low density ofthe hematopoietic masses on CT (6,7) and the high signal onboth Tl and T2-weighted MRI (//) are both suggestive of fatdeposition but offer no definitive evidence that the mediastinaltumors consist of bone marrow. Histologie diagnosis requirestransthoracic biopsy or thoracic surgery. Since the extraskeletalmarrow is highly vascular, these procedures are not withoutrisk. Moreover, in asymptomatic cases, therapy should only bedirected at the underlying disorder. Therefore, noninvasiveprocedures to explore the nature of the tissue are a welcomealternative. Several tracers are available to visualize bonemarrow, which correspond to the different physiologic functions of the marrow (12).

Radio-iron is the most specific marker for hematopoietictissue. Both 59Fe (13) and 52Fe (2) have been used to

demonstrate extramedullary hematopoiesis. Iron-52, however,is short-lived, cyclotron-produced and requires a PET camerafor adequate imaging. Iron-59 emits high-energy photons,making it unsuitable for imaging with standard gamma-cameracollimators.

Indium-111-chloride distributes in the skeletal system similarly to iron isotopes or microcolloids (4). Presumably, it istransported into the reticulocyte after binding to transferrin (14)and, once cell-associated, it appears to be incorporated intoheme (15). This tracer has been used to identify a case ofpulmonary extramedullary hematopoiesis (16). A false-negative with a retroperitoneal mass has been described (17).

In general, erythropoietic and reticuloendothelial tissue aresimilarly distributed in the bone marrow, with the exception ofaplastic states or after irradiation (18). Colloids are taken upby macrophages and thus trace the reticulo-histiocytic system.Colloidal 198Auwas the first agent used to demonstrate a site of

intrathoracic extramedullary hematopoiesis (19). Technetium-99m-colloid has also been utilized successfully to identifyextramedullary hematopoiesis (1,3,20-22), although one false-negative result has been reported (17).

In our patient, we used nanocolloids produced from micro-aggregated human serum albumin. Their small size (less than 80nm in more than 95%) causes increased marrow uptake compared with the larger conventional colloids (12).

At last, 99mTc-labeled murine monoclonal antibodies directed

against nonspecific cross-reacting antigen 95 (NCA-95) can beused to trace bone marrow. Developed as an in vitro label ofgranulocytes (23), the antigen can recognize a differentiationantigen, which is expressed beyond the differentiation stage ofpromyelocytes, and therefore distributes primarily to the bonemarrow after intravenous injection (24).

CONCLUSIONFor reasons of availability, imaging characteristics, dosimetry

and cost, we believe that 99mTc-colloids currently are the best

choice for routine marrow imaging as well as for assessingpossible extramedullary hematopoiesis. In the case of intrathoracic extramedullary hematopoiesis, same-day spatial-resolution allows one to separate the masses from the spine as well asfrom liver and spleen. SPECT localizes the masses in theposterior mediastinum (22).

474 THE JOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 3 •March 1996

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REFERENCES1. Bronn JL, Paquelet JR. Tetalman MR. Intrathoracic extramedullary hematopoiesis:

appearance of 9limTc sulfur colloid marrow scan. Am J Roenlgenol 1980; 134:1254-

1255.2. Borgies P, Ferrant A, Leners N, et al. Diagnosis of heterotopic bone marrow in the

mediastinum using "Fe and PET. Ear J NucíMed 1990;15:761-763.

3. Sebes JI, Massie JD, White TJ III, Kraus AP. Pelvic extramedullary hematopoiesis. JNucíMed 1984:25:209-210.

4. Datz FL, Taylor A Jr. The clinical use of radionuclidc bone marrow imaging. SeminNucíMed 1985;15:239-259.

5. Long JA, Doppman JL, Nienhuis AW. Computed tomographic studies for thoracicextramedullary hematopoiesis. J Compai Assisi Tomogr 1980:4:67-70.

6. Fielding JR, Owens M, Naimark A. Intrathoracic extramedullary hematopoiesissecondary to BI2 and folate deficiency: CT appearance. J Compai Assisi Tomogr1991:15:308-310.

7. De Montpréville VT, Dulmet EM. Chapelier AR, Dartevelle PG, Verley JM.Extramedullary hematopoietic tumors of the posterior mediastinum related to asymptomatic refractory anemia. Chest 1993:104:1623-1624.

8. Gumbs RV. Higginbotham-Ford EA, Teal JS, Kletter GG, Castro O. Thoracicextramedullary hematopoiesis in sickle-cell disease. Am J Roemgenol 1987:149:889-

893.9. Ross P, Logan W. Roentgen findings in extramedullary hematopoiesis. Am J

Roemgenol Radium Ther NucíMed 1969:106:604-613.10. Ch'en IY, Lynch DA, Shroyer KR, Schwarz Ml. Gaucher's disease: an unusual cause

of intrathoracic extramedullary hematopoiesis. Chest 1993:104:1923-1924.

11. Savader SJ, Otero RR, Savader BL. MR imaging of intrathoracic extramedullaryhematopoiesis. J Compai Assist Tomogr 1988:12:878-880.

12. Reske SN. Recent advances in bone marrow scanning. Ear J NucíMed 1991;18:203-221.

13. Robinson AE, Rosse WF, Goodrich JK. Intrathoracic extramedullary hematopoiesis: ascan diagnosis. J NucíMed 1968;9:416-419.

14. Lilien DL. Berger HG. Anderson DP. Bennett LR. lndium-111-chloride: a new agentfor bone marrow imaging. J NucíMed 1973:14:184-186.

15. Adatepe MH, Penkoske P. Van Amburg A, et al. Red cell and plasma protein labelingwith inmln. ¡nlJAppI Radial 1971:22:498-501.

16. Vieras F, Boyd CM, Mora PA. Diffuse pulmonary uptake of indium-111 chloride inidiopathic myelofibrosis. Radiology 1979:130:749-750.

17. Harnsbcrger HR, Datz FL, Knöchel JQ, et al. Failure to detect extramedullaryhematopoiesis during bone-marrow imaging with indium-Ill or technetium-99m-sulfur colloid. J NucíMed 1982;23:589-591.

18. Vandyke D. Price D. Surkin C. et al. Differences in distribution of erythropoietic andreticuloendothelial marrow in hématologiedisease. Blood 1967:30:364-374.

19. Papavasitiou CG. Tumor simulating intrathoracic extramedullary hemopoiesis. Am JRoemgenol 1965:93:695-702.

20. Stebner FC, Bishop CR. Bone marrow scan and radioiron uptake of an intrathoracicmass. Clin NucíMed 1982;7:86-87.

21. Wosick WF, Bedmutha S, Small B. Radionuclide bone marrow scanning andcomputerized tomography in the diagnosis of extramedullary hematopoiesis presentingas an intrathoracic paravertebral mass. Clin NucíMed 1984:9:419.

22. Alden Parker L. Vincent LM. Mauro MA. Perry JR. Extramedullary hematopoiesis:demonstration by transmission and emission computed tomography. Clin NucíMed1986:11:1-3.

23. Joseph K. HöffkenH, Bosslet K, Schorlemmer HU. In vivo labeling of granulocyteswith WmTc anti-NCA monoclonal antibodies for imaging inflammation. Ear J Nucí

Med 1988:14:367-373.

24. Duncker CM, Carrio I, Berna L, et al. Radioimmune imaging of bone marrow inpatients with suspected bone métastasesfrom primary breast cancer. J NucíMed1990:31:1450-1455.

Scatter (Continuedfrom page 3A)

options. After exhausting each option, I was asked again if I wanted anything else. Did Iwant to see them again? "Take your time, doctor. Takeas much time as you want" Did I

want some more coffee?While 1had formed an opinion about the merits of the case, I was more disturbed

about how unfair it all was. Unfair to the patient, to all patients. Unfair to the nuclearphysician, to all physicians. Who asks physicians caring for patient after patient in alarge medical center if they need more time? Who asks them if they need anything elseto help them make a decision. Who attends to their physical comfort so that they canfocus on each problem without distraction? Who provides them with a technician withnothing else to do but manipulate the displays over and over? I had never had suchluxury in practice in a county hospital, or in a university teaching hospital. "Takeyourtime, doctor. Take as much time as you want" It had never happened to me. The system

simply cannot afford it. Nor can it afford enough doctors, assistants or resources.Ironically, if something goes awry, limitless time and resources appear available. For

what purpose? To accuse or punish a physician who was too busy to review a findingrepeatedly or to review the dictated note letter by letter to make sure it was accurate andprecisely reflected what he thinks and may have to defend someday?

Why are there so many resources available after an untoward event? To compensatethe possibly wronged patient? Would not all the patients benefit if resources spent afterthe problem occurred had been available before it occurred? Would not our societybenefit more by supporting the overburdened elements of our medical care deliverysystem instead of providing the negative reinforcement which now exists?

Stanley J. Goldsmith, Ml)Editor-in-Chief, The Journal of Nuclear Medicine

March 1996

THORACICEXTRAMEDULLARYHEMATOPOIESIS•De Geeter and Van Renterghem 475

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1996;37:473-475.J Nucl Med.   Frank De Geeter and Dirk Van Renterghem  Alcohol-Related MacrocytosisScintigraphic Diagnosis of Intrathoracic Extramedullary Hematopoiesis in

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