Paratracheal Extramedullary Hematopoiesis

International Journal of

HEMATOLOGY

Paratracheal Extramedullary Hematopoiesis C. Kurtman,a M. K. Özbilgin,b M. Nalça Andrieu,a B. Çelebio˘glua a

b

Department of Radiation Oncology, Ankara University Medical Faculty, Ankara; Department of Histology-Embryology, Celal Bayar University Medical Faculty, Manisa, Turkey Received May 5, 2000; received in revised form January 15, 2001; accepted January 19, 2001

Abstract Extramedullary hematopoiesis (EMH) is a rare finding in hematology. A 73-year-old female patient with a 1-week history of severe progressive dyspnea was examined, and computed tomography (CT) showed a paratracheal mass 3 cm in size located 1 cm below the vocals cords and causing obliteration of the tracheal airway. Cytology of a needle biopsy revealed EMH. External radiotherapy of 200-cGy fractions to a total dose of 2000 cGy was administered with 3-dimensional conformal planning to treat the progressive symptoms. The patient’s clinical symptoms started to improve 2 days after radiotherapy and had completely disappeared after 7 days. CT scans showed complete response on follow-up at 1 week to 5 months after radiotherapy. Mature and immature hematopoietic cells and many adipose cells were seen in the pretreatment samples. Histologic findings in the posttreatment samples showed that these cells had completely disappeared due to the conformal radiotherapy. On the basis of clinical, radiologic, and histologic results, we suggest that conformal radiotherapy may be useful for the treatment of paratracheal localization of EMH because good tumoral irradiation was obtained in this case, with the protection of normal tissues. Int J Hematol. 2001;73:492-495. ©2001 The Japanese Society of Hematology Key words: Conformal Radiotherapy; Paratracheal; Extramedullary hematopoiesis

versity of Ankara with severe dyspnea and hoarseness. Postero-anterior chest radiography was normal and computerized tomography (CT) of the neck and thorax taken for the diagnosis of the progressive dyspnea showed a posterior right lateral mass that had invaded cricoid and tracheal cartilage and the anterior esophageal wall (Figure 1). Tracheoscopy showed a 3-cm mass that was 1 cm below the vocal cords and was causing a 95% obliteration of the tracheal space. Needle biopsy was taken from this hard and nonfragile mass for histopathologic evaluation, and then an intratracheal wall stent was applied to open the airway. The biopsy sample was prepared as a smear and histochemically stained with hematoxylin-eosin (H-E). Cytological findings of the biopsy material revealed EMH, and the patient was admitted to the Radiation Oncology clinic of our hospital for 3-dimensional conformal radiotherapy. After CT simulation had been performed using a Picker IQ CT Simulator (Picker International, Cleveland, OH, USA), the tumor, normal tissues, and isocenter were marked with Picker Voxel Q machine and 3-dimensional anatomic algorithms. The treatment plan, isodose distribution, and dose-volume histograms (DVH) [20] were taken using Varian Cad Plan 3-dimensional conformal radiotherapy planning software (Varian Medical Systems, Palo Alto, CA, USA). Multileaf collimators were used for normal tissue blocking. Three treatment ports were selected: first, anterior

1. Introduction Extramedullary hematopoiesis (EMH) is a rare pathological finding that can occur in the perirenal, adrenal, presacral [1], paraspinal [2-4], intracranial [5-7], and intrathoracic [2,816] regions. However, paratracheal localization is uncommon. Hematological diseases such as anemia, myelofibrosis, thalassemia [3,17-19], and hemoglobinopathies have been reported with EMH. Surgery, steroids, successful treatment of underlying hematologic disorders, and radiotherapy are the possible treatments for this pathology. We report here a case of paratracheal location of EMH that caused tracheal obstruction and the clinical, radiologic, and histologic findings of the effect of treatment by radiotherapy.

2. Patient and Methods A 73-year-old female patient was admitted to the Department of Chest Diseases in the Medical Faculty of the Uni-

Correspondence and reprint requests to: Cengiz Kurtman, Ankara University Medical Faculty, Department of Radiation

Oncology, Cebeci Hospital, 06100-Dikimevi, Ankara, Turkey; 90 312 3194057; fax: 90 312 3197884 (e-mail: kurtman@dialup. ankara.edu.tr).

492

Paratracheal Extramedullary Hematopoiesis

493

Figure 1. Pretreatment computed tomography (CT) shows a posterior right lateral mass and posttreatment CT shows no evidence of tumoral mass. 0°; second, anterior right 40° oblique with 30° wedge; and third, anterior left 50° oblique with 30° wedge. Tumor volume was covered by 95% of the isodose line and was controlled with DVH. The volume of the spinal cord was 60% out of the isodose line. The patient was treated with Varian Clinac 2300 C/D, 6-mV photon, and 200-cGy fraction/day, 5 fractions per week, and a total dose of 2000 cGy was given over 2 weeks with the patient in the supine position. Steroid therapy was used for anti-inflammatory effects during radiotherapy. Paratracheal tissue samples were obtained after radiotherapy by punch biopsy and were fixed in 10% neutral buffered formalin for a maximum of 24 hours and subsequently embedded in paraffin. Serial tissue sections were cut to 4-µm thickness, placed on Histostick-coated slides (Accurate, Westbury, NY, USA) and baked in a 37°C oven overnight. Prior to staining, sections were washed in xylene and rehydrated through a graded series of alcohols to water. The first slide of the serial sections was stained with H-E and the second slide was stained with CD34 monoclonal antibody (MoAb) (Phanningen 343 71 A, San Diego, CA, USA), which reacts with immature hematopoietic cells, vascular endothelium, and some tissue fibroblast via the streptavidinbiotin immunoperoxidase technique. Samples were counterstained with Mayer’s hematoxylin.

3. Results The patient’s clinical symptoms had improved completely after 7 days. A control CT scan taken 1 week after radiotherapy showed that the tumoral mass had completely disappeared (Figure 1). There were no acute or chronic complications due to the side effects of radiotherapy at 1 week to 5 months follow-up, and the patient had complete clinical remission. No hematopoietic pathology or infectious diseases were found on follow-up. Histologic results confirmed the patient’s clinical improvement. Although many kinds of mature bone marrow cells (erythrocytes, neutrophils, eosinophils, basophils, and lymphocytes) and progenitor bone marrow cells (proerythroblasts, monoblasts, and myeloblasts) were observed by histologic examinations of the pretreatment

slides stained with H-E (Figure 2), they were not seen in the posttreatment slides (Figure 3). Furthermore, a posttreatment slide stained with CD34 MoAb showed that capillary endothelial cells were stained but that they were not CD34+ mature cells but were immature hematopoietic cells. The posttreatment biopsy material was found to be mostly covered by pseudostratifed columnar epithelium, which is the normal epithelium of the trachea. The stratified squamous epithelial area was also seen as a small island on the previous tumor area (Figure 3).

4. Discussion EMH is a rare and pathological benign finding that localizes in the perirenal [21], adrenal [22-25], presacral, intracranial [5-7], paraspinal, and intrathoracic regions [2,8-16]. Paratracheal location is uncommon, and in this study we report the case of a patient with this rare localization evaluated using radiologic and histologic examinations and successfully treated using conformal radiotherapy. The patient’s main clinical symptom in this case was compression of the airway, which caused progressive dyspnea. EMH can compress structures such as the spinal cord, neural roots, and renal tissue, and airway compression when the bronchioles were affected has been reported by Lara et al [26] and Gowitt et al [27]. Therefore, EMH should be considered as a possible cause of dyspnea. CT scan is useful to show the localization of airway obstruction, and in our study CT showed a posterior right lateral mass invading the cricoid and tracheal cartilage and the anterior esophageal wall. Differential diagnoses of paratracheal locations are laryngeal tumors, tracheal tumors, thyroid tumors, esophageal tumors, lymphomas, lung cancers, and granulamatosis [12,13,15,17], and differential diagnosis of EMH can only be established using cytologic or histologic examination (1,15,19). Our findings confirmed the diagnosis of EMH because of the presence of mature and immature hematopoietic cells. Treatment options for EMH include surgery, steroids, successful treatment of underlying hematologic disorders, decompression with intraluminary wall stent, and radiotherapy [4,21,24]. Many authors have suggested that EMH

494

Kurtman et al / International Journal of Hematology 73 (2001) 492-495

Figure 2. Pretreatment sample: many mature bone marrow cells such as lymphocytes (L), eosinophils (E), neutrophils (N), and erythrocytes (e) and bone marrow progenitor cells such as adipocytes (Ad), promyelocytes (Py) and promonocytes (Pm) were seen (hematoxylin-eosin, original magnification 200). responds rapidly to a moderate dose of radiotherapy (7503500 cGy) because of the radiosensitivity of hematopoietic tissues and that if a recurrent mass appears, a second moderate dose can be given [2,18,28-30]. We administered a moderate dose of conformal radiotherapy for 2 weeks, which was completely successful. It has been suggested that 3-dimensional conformal radiotherapy can protect the normal tissues [31-33]. In this study, we found that pseudostratified columnar epithelium was mostly protected from radiotherapy but stratified squamous epithelial metaplasia, which may originate due to radiation,

was detected in the posttreatment specimens. We speculate that the protection of this normal epithelium in most of the areas with the presence of small metaplasia was the result of the good restriction of radiotherapy to the planned areas. In conclusion, the rapid improvement of the patient’s symptoms, complete disappearance of the tumoral mass detected by CT, and the disappearance of the hematopoietic cells in cytology suggest that 3-dimensional conformal planning and moderate-dose conformal radiotherapy were useful in this case for the treatment of paratracheal localization of EMH.

Figure 3. Posttreatment sample: the border (arrow) between pseudostratified columnar epithelium (ce) and stratified squamous epithelium can be seen on the surface area. Lymphoid tissue (L) was found beneath the epithelium (hematoxylin-eosin, original magnification 100).

Paratracheal Extramedullary Hematopoiesis

References 1. Yang GC, Coleman B, Daly JM, Gupta PK. Presacral myelolipoma: report of case with needle aspiration cytology and immunohistochemical and histochemical studies. Acta Cytol. 1992;36:932-936. 2. Guermai A, Miaux Y, Chiras J. Imaging of spinal cord compression due to thoracic extramedullary haematopoiesis in myelofibrosis. Neuroradiology. 1997;39:733-736. 3. Munn RK, Kramer CA, Arnold SM. Spinal cord compression due to extramedullary hematopoiesis in beta-thalassemia intermediate. Int J Radiat Oncol Biol Phys. 1998;42:607-609. 4. Singhal S, Sharma S, Dixit S, et al. The role of radiation therapy in the management of spinal cord compression due to extramedullary hematopoiesis in thalassemia. J Neurol Neurosurg Psychiatry. 1992; 55:310-312. 5. Chishti MK, Bannister CM. Foci of extramedullary haematopoiesis in a cerebellar haemangioblastoma. Br J Neurosurg. 1992;6: 157-162. 6. Sitton JE, Reimund EL. Extramedullary hematopoiesis of cranial dura and anhydrotic ectodermal dysplasia. Neuropediatrics. 1992; 23:108-110. 7. Zee N, Cera P, Towfighi J. Extramedullary hematopoiesis in cerebellar hemangioblastoma. Neurosurgery. 1991;29:34-37. 8. Bastion Y, Coiffier B, Felman P, et al. Massive mediastinal extramedullary hematopoiesis in hereditary spherocytosis: a case report. Am J Hematol. 1990;35:253-265. 9. Catinella FP, Boyd AD, Spencer FC. Intrathoracic extramedullary hematopoiesis simulating anterior mediastinal tumour. J Thorac Cardiovasc Surg. 1985;89:580-584. 10. Gumbs RV, Higginbotham Ford EA, Teal JS, Kletter GG, Castro O. Thoracic extramedullary hematopoiesis in sickle-cell disease. Am J Roentgenol. 1987;149:889-893. 11. Murakami T, Dixon AC, Ho RC, et al. Asymptomatic intrathoracic extramedullary hematopoiesis: a report of three cases. Hawaii Med J. 1998;48:430-432. 12. Papavasiliou C, Gouliamos A, Deligiorgi E, et al. Masses of myeloadipose tissue: radiological and clinical considerations. Int J Radiat Oncol Biol Phys. 1990;19:985-993. 13. Savader SJ, Otero RR, Savader BL. MR imaging of intrathoracic extramedullary hematopoiesis. J Comput Assist Tomogr. 1988;12: 878-880. 14. Smith PR, Manjoney DL, Teiteher JB, et al. Massive hemothorax due to intramedullary hematopoiesis in a patient with thalassemia intermedia. Chest. 1988;94:658-660. 15. Spanta R, Saleh HA, Khatib G. Fine needle aspiration diagnosis of extraadrenal myelolipoma presenting as a pleural mass: a case report. Acta Cytol. 1999;43:295-298. 16. Wu JH, Shih LY, Kuo TT, et al. Intrathoracic extramedullary hematopoietic tumour in hemoglobin H disease. Am J Hematol. 1992;41:285-288. 17. Chaljub G, Guinto F, Crow W, et al. MRI diagnosis of spinal cord compression in beta-thalassemia. Spine. 1991;16:583-584. 18. Kaufinan T, Coleman M, Giardina P, et al. The role of radiation

19. 20.

21.

22.

23. 24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

495

therapy in the management of hematopoietic neurologic complications in thalassemia. Acta Hematol. 1991;85:156-159. Mann K, Yue C, Chan K, et al. Paraplegia due to extramedullary hematopoiesis in thalassemia. J Neurosurg. 1987;66:938-940. Lawrence TS, Kessler ML, Ten Haken RK. Clinical interpretation of dose-volume histograms: the basis for normal tissue preservation and basis for normal tissue preservation and tumour dose escalation. In: Meyer JL, Purdy JA, eds. Frontiers of Radiation Therapy Oncology. Basel, Switzerland: Kargel; 1996:57-66. 3-D Conformal Radiotherapy; vol. 29. d’Addressi A, Racioppi M, Fanasca A, et al. A rare case of perirenal myelolipoma: diagnostic approach and therapeutic strategy. Scand J Urol Nephrol. 1997;31:579-581. Hofinockel G, Dammrich J, Manzanilla GH, et al. Myelolipoma of the adrenal gland associated with contra lateral renal cell carcinoma: case report and review of the literature. J Urol. 1995;155: 129-132. Linos DA, Stylopoulus N, Raptis S. Adrenaloma: a call for more aggressive management. World J Surg. 1996;20:788-792. Spinelli C, Materazzi G, Berti P, et al. Symptomatic adrenal myelolipoma: therapeutic considerations. Eur J Surg Oncol. 1995; 21:403-407. Yamakita N, Saitoh M, Mercado-Asis LB, et al. Asymptomatic adrenal tumour: 386 cases in Japan including our 7 cases. Endocrinol Jpn. 1990;37:671-684. Lara JF, Rosen PP. Extramedullary hematopoiesis in a bronchial carcinoid tumour: an unusual complication of agnogenic myeloid metaplasia. Arch Pathol Lab Med. 1990;114:1283-1285. Gowitt GT, Zaatari GS. Bronchial extramedullary hematopoiesis preceding chronic myelogenous leukaemia. Hum Pathol. 1985;16: 1069-1071. Done F, Pardini S, Gaviano E, et al. Recurrence of spinal cord compression from extramedullary hematopoiesis in thalassemia intermedia treated with low dose radiotherapy [letter]. Am J Hematol. 1993;44:148. Issaragrisil S, Piankijagum A, Wasi P. Spinal cord compression in thalassemia: report of 12 cases and recommendations for treatment. Arch Intern Med. 1981;141:1033-1036. Pistevou-Gompaki K, Skaragas G, Paraskevopoulous P, et al. Extramedullary hematopoiesis in thalassemia: results of radiotherapy: a report of three patients. R Coll Radiol. 1996;8:120-122. Burman C, Kutcher GJ, Emami B, et al. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys. 1991;21:123-135. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21: 109-122. International Commission on Radiation Units and Measurements. ICRU Report No. 50: Prescribing, Recording and Reporting Photon Beam Therapy. Bethesda, Md: ICRU; 1993.