Ann Thorac Surg 1998;66:1411-1413
© 1998 The Society of Thoracic Surgeons
Case Reports
Extramedullary hematopoiesis mimicking metastatic lung carcinoma
F. Ida Hsu, BAa,
Daniel A. Filippa, MDb,
Hugo Castro-Malaspina, MDc,
Robert J. Downey, MDa
a Division of Thoracic Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York, USA
b Department of Pathology, Memorial-Sloan Kettering Cancer Center, New York, New York, USA
c Department of Medicine, Memorial-Sloan Kettering Cancer Center, New York, New York, USA
Accepted for publication April 24, 1998.
Address reprint requests to Dr Downey, Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021
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Abstract
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Extramedullary hematopoiesis is a rare condition defined as the appearance of hematopoietic elements outside of the bone marrow, which occurs primarily in patients with chronic myeloproliferative disorders or congenital hemolytic anemias. We report a patient who presented with a left lower lobe lung carcinoma and right paravertebral and left pleural masses, initially thought most consistent radiographically with inoperable metastatic disease, until biopsies of the paravertebral and pleural masses established the presence of extramedullary hematopoiesis. The left lower lobe neoplasm was subsequently resected uneventfully.
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Introduction
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Extramedullary hematopoiesis (EMH) is the rare and typically asymptomatic appearance of hematopoietic elements outside of the bone marrow, most often in the spleen, liver, or lymph nodes, and less commonly in the posterior mediastinum [1–3]. It is usually associated with processes that are either neoplastic or accompanied by peripheral cytopenias and inefficient myelopoiesis, including chronic myeloproliferative disorders such as agnogenic myeloid metaplasia with myelofibrosis [4], leukemia [5], and polycythemia rubra vera [6]; hemolytic anemias such as hereditary spherocytosis, the thalassemias [2], and sickle-cell anemia [7]; or bone marrow tumors [5]. Radiographically, EMH often resembles more common conditions such as benign or malignant lymphadenopathy or a metastasis. Here we report intrathoracic extramedullary hematopoiesis occurring in a patient with cancer of nonhematologic origin. This case illustrates that the radiographic appearance of lesions does not prove malignancy.
A 64-year-old woman was referred to the Thoracic Surgery Service at the Memorial Sloan-Kettering Cancer Center after an episode of hemoptysis prompted chest radiographs and thoracic computed tomograms that revealed a left lower lobe mass as well as pleural and paravertebral masses. The patient had a 50 pack-year smoking history, but had quit smoking 5 years before the onset of symptoms. She drank alcohol socially and had no known exposure to tuberculosis, asbestos, or other industrial toxins. Her medical and surgical history included polio, irradiation for an enlarged thymus as a child, a minimally sympomatic hiatal hernia, gout, a cholecystectomy, and a unilateral oophorectomy performed in the 1950’s for benign disease. Her medications were allopurinol and omeprazole.
Physical examination revealed a thin woman without lymphadenopathy, bilaterally clear breath sounds, althought diminished at the left base, and a soft abdomen without masses. Preoperative laboratory findings included a white blood cell count of 4,900/µL with a slight lymphocytopenia (400/µL), a red blood cell count of 3.84 x 106/µL, hemoglobin density of 9.9 g/dL, hematocrit of 29.5%, mean corpuscular volume of 77 µm3, mean cellular hemoglobin of 25.7 pg, and a platelet count of 177,000/µL. Other abnormal findings included a blood urea nitrogen content of 33 mg/dL, creatinine level of 1.4 mg/dL, total bilirubin level of 1.1 mg/dL, albumin level of 3.9 g/dL, chloride level of 111 mEq/L, and a CO2 level of 23 mEq/L. Radiographic studies for metastatic disease including a bone scan and brain magnetic resonance imaging were unrevealing. Repeat computed tomograms of the chest 2 months after the initial evaluation at another institution showed that the left lower lobe mass had increased in size (7.5 cm wide, 9.6 cm anteroposterior, 9.5 cm high), and now extended to the visceral pleura both laterally and posteriorly (Fig 1 ). Centrally, it encased the left pulmonary artery, left main bronchus, proximal left upper lobe bronchus, and most of the lower lobe bronchus, and was now contiguous with the descending aorta. The left anterior pleural-based mass also had increased in size, such that it now measured 3 cm x 2 cm (Fig 2 ). The right paraspinal lesions were unchanged. Subcentimeter right paratracheal, anterior mediastinal, aortopulmonary window, and subcarinal lymph nodes had increased in size since the previous examination. Additional examination of the abdomen demonstrated splenomegaly without evidence of metastatic disease to the liver or adrenal glands.
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Fig 1. Computed tomographic scan at a lower thoracic level demonstrates multiple right paraspinal masses measuring up to 1.5 cm, suggestive of metastatic involvement of the right inferior pulmonary ligament lymph nodes.
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Fig 2. Computed tomographic scan at a midthoracic level (2 cm below the aortic arch) reveals a left anterior pleural-based mass, borderline right paratracheal adenopathy, and a left lower lobe mass.
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A fine-needle aspirate of the left pleural lesion demonstrated mesothelium, lymphoid cells, and giant multinucleated cells with an appearance and immunophenotype (factor VIII positive, CAM 5.2 and CD-45 negative) consistent with megakaryocytes. Fine-needle aspirate of the left lower lobe mass revealed adenocarcinoma consistent with lung origin. Mediastinoscopy with biopsy of the mediastinal lymph nodes demonstrated only benign enlargement. Video-assisted thoracoscopy revealed the right paraspinal masses to be soft reddish-brown lobulated masses consistent with previously published descriptions of EMH (Fig 3 ); results of biopsies were consistent with EMH. A bone marrow biopsy revealed mild hypercellularity with trilineage hematopoiesis. The myeloid:erythroid ratio was mildly decreased, but the number of megakaryocytes, the amount of reticulin fibers, and karyotype were normal. Left pneumonectomy with mediastinal lymph node dissection was performed. A second biopsy of the left pleural-based mass confirmed the presence of EMH involving fibroadipose tissue with a normal myeloid:erythroid ratio, unremarkable maturation of all cell lines including megakaryocytes, and normal karyotype, although final analysis showed some megakaryocytes with dysplastic changes. Postoperative pathologic analysis of the left lower lobe did not demonstrate evidence of EMH within the lung parenchyma or the mediastinal lymph nodes. Final TNM classification of the cancer was T2 N2 M0, stage IIIA.
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Fig 3. Operative photograph of extramedullary hematopoiesis at the right costovertebral angle. The lung is retracted to the lower right corner; ribs are visible to the left.
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Comment
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Extramedullary hematopoiesis is a rare condition usually associated with chronic myeloproliferative disorders and congenital hemolytic anemias. The most common sites of EMH are the liver and spleen, but foci can occur in many other organs and tissues, including lymph nodes and the paraspinal area of the posterior mediastinum [7]. The presence of EMH in the lung parenchyma or anterior mediastinum is even rarer [1, 9]. Extramedullary hematopoiesis is generally assumed to be a compensatory hyperplastic phenomenon when associated with anemia or space-occupying bone marrow disease. In some myeloproliferative disorders, transformed stem cells may circulate outside of the bone marrow to seed hematopoeisis at atypical sites. In this case of EMH occurring in a patient with nonhematologic cancer without bone marrow invasion, it is probable that the lung malignancy was secreting a paracrine growth factor that stimulated regional hyperplasia of circulating hematopoietic progenitors [8, 9]. Our patient was anemic, but whether this was congenital and unrelated to her cancer or a manifestation of malignancy is not clear; however, her anemia was not as severe as most of those that have been reported in the literature as associated with EMH [10].
Characteristic radiographic findings of intrathoracic EMH consist of multiple smooth or lobulated, well-circumscribed masses of homogeneous density, lying either unilaterally or bilaterally against the vertebral bodies and adjacent ribs between vertebrae T-6 and T-12, usually without evidence of bony erosion or spiculization [2]. Associated radiographic findings that may be helpful in diagnosing this condition include hepatosplenomegaly and the bony changes that frequently accompany chronic hemolytic anemia or myelosclerosis [2]. Pathologically, the foci appear as soft, reddish nodules that may grossly resemble hematomas (see Fig 3). Microscopically, all marrow elements should be identifiable, often with marked erythroid hyperplasia [7].
The presence of paraspinal masses, even multiple thoracic masses, in lung cancer patients should not be held to be unresectable metastasis [10] until open biopsy or fine-needle aspiration has been performed to confirm the malignant nature of such lesions. Should the presence of EMH be suspected, careful biopsy under direct vision has been suggested, because of the risk of bleeding [11]. Attempts at complete resection are usually not advised, unless symptoms arise because of compression of neighboring tissue, such as the spinal cord [1, 2]. As this tissue is radiosensitive, radiation therapy in small doses may also be effective in relieving symptoms of a minor nature [2, 9].
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References
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Abstract
Introduction
