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Journal of Clinical Oncology, Vol 24, No 21 (July 20), 2006: pp. 3500-3502 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.04.9932
Hyperthyroidism Associated With Philadelphia-Chromosome–Positive Acute Lymphoblastic LeukemiaFirst Department of Internal Medicine, Osaka Medical College, Takatsuki City, Osaka, Japan
First Department of Internal Medicine, Osaka Medical College, Takatsuki City, Osaka, Japan
First Department of Internal Medicine, Osaka Medical College, Takatsuki City, Osaka, Japan A 35-year-old Japanese man presented with general fatigue. Laboratory findings demonstrated increased WBCs at 13.0 x 103 cells/µL with 37.0% abnormal cells, and elevated serum lactate dehydrogenase (650 U/mL). Bone marrow aspiration (BMA) showed 88.5% infiltration of abnormal large cells with high nuclear cytoplasmic ratio, homogeneous nuclear chromatin, and inconspicuous nucleoli. Karyotypic analysis with Giemsa band staining showed 46, X, Y, addition(1)(q32), deletion(9;15)(q10;q10), t(9;22)(q34;q11). Interphase fluorescence in situ hybridization detected minor BCR/ABL transcription in 797 of 1,000 cells. The clinical findings led to the diagnosis of Philadelphia-chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), according to the WHO classification.3 Although the patient exhibited no clinical signs of hyperthyroidism and had no familial history, his right lobe was diffusely enlarged and thyroid function testing demonstrated free thyroxine of 2.64 ng/dL (normal range, 0.80 to 1.70), total triodothyronine of 6.68 pg/mL (normal range, 2.30 to 4.30), and a thyrotropin level of 0.01 µg/mL (normal range, 4.34 to 5.00). Particle-agglutination tests for thyroglobulin were positive: the titers were higher than 80 M2 (normal range, < 10 M2), respectively. Ultrasound (US) demonstrated a heterogeneous parenchyma, but no hypoechoic area. Power Doppler sonography demonstrated accelerated intrathyroidal blood flow in the right thyroid lobe (Fig 1A). Neck enhancing computed tomography (CT) revealed a large, inhomogeneous thyroid gland with a low-density mass (Fig 2A; arrows). Fine-needle aspiration biopsy (FNAB) revealed infiltration with Ph+ ALL cells (Fig. 3A and 3B; white arrow, normal thyroid follicular cell; black arrow, ALL cell). The patient underwent one course of chemotherapy for ALL with lenograstim 5 µg/kg per day by subcutaneous injection, which was administered until the WBC count increased to above 10,000/µL. After the chemotherapy, BMA showed cytogenic complete remission (CR) with fluorescence in situ hybridization. Thyroid function was normal, which included free thyroxine of 1.42 ng/dL, free triiodothyronine (FT3) of 3.10 pg/mL, and a thyrotropin level of 0.958 µg/mL. Power Doppler sonography showed normal flow, and neck CT demonstrated normal thyroid (Figs 1B and 2B).
FNAB showed normal thyroid gland cells. The thyroid gland is a rare focus for metastatic involvement from primary carcinoma of other organs. Leukemia commonly infiltrates the thyroid. Thyroid metastases have been reported in 15% of 332 cases of leukemia, but US or CT imaging have not been described.1 US is commonly used to evaluate thyroid disease. US exhibits high sensitivity when compared with clinical examination (92% and 70%, respectively)4 and high specificity when combined with fine needle aspiration cytology (95%).5 Sonographic patterns in thyroid diseases have been reported in the medical literature, and thyroid lymphomas typically exhibit an hypoechoic area. Thyroid lymphomas are nonenhancing on CT scanning, while the unaffected lobe exhibits normal contrast enhancement.6 In this case we were not able to detect an abnormal mass with US for thyroid. However, Power Doppler sonography demonstrated accelerated intrathyroidal blood flow in the infiltrated thyroid lobe, while neck CT and FNAB revealed infiltration of ALL cells. These findings might be due to iodine uptake in the tumor with hyperfunction. Thyroid function is not usually altered by metastatic infiltration, as reported previously in at least six cases.1,2 Thyroid lymphomas usually exhibit normal thyroid function. However, there have been a few cases of hyperthyroidism associated with thyroid lymphoma, and most of these cases exhibited aggressive courses.1,7 The etiology of hyperthyroidism is considered to be subacute thyroiditis due to rapid disruption of thyroid follicles by malignancy with release of thyroid hormone into the circulation.8 Ph+ ALL is known to exhibit an aggressive course, which might be associated with developing hyperthyroidism. The role of high-resolution US for neck node evaluation has been well established. There is the potential for circumstances in which US appears normal, but CT and other examinations appear abnormal, as in this case. Therefore we must diagnose these cases with a combination of US, Power Doppler sonography, CT, and FNAB for thyroid tumors with altered thyroid function. To the best of our knowledge, this is the first reported case of hyperthyroidism in a patient with Ph+ ALL, in which US showed normal thyroid, and CT and other examinations revealed infiltration of abnormal cells. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES
1. Shimaoka K, VanHerle AJ, Dindogru A: Thyrotoxicosis secondary to involvement of the thyroid with malignant lymphoma. J Clin Endocrinol Metab 43:64-68, 1976 2. Sirota DK, Goldfield EB, Eng YF, et al: Metastatic infiltration of the thyroid gland causing hypothyroidism. J Mt Sinai Hosp NY 35:242-245, 1968 3. Jaffe ES, Harris NL, Stein H, et al: World Health Organization Classification of Tumours: Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues. Lyon, France, IARC Press, 2001 4. Bruneton JN, Roux P, Caramella E, et al: Ear, nose, and throat cancer: Ultrasound diagnosis of metastasis to cervical lymph nodes. Radiology 152:771-773, 1984 5. Baatenburg de Jong RJ, Rogen RJ: Ultrasoundguided fine-needle aspiration cytology of neck nodes. Arch Otolaryngol Head Neck Surg 117:402-404, 1991 6. Balachandran S, Harper RR, Boyd CM: Lymphoma of the thyroid gland associated with mycosis fungoides: Sonographic, scintigraphic and CT features. Radiat Med 2:211-213, 1984[Medline] 8. Compagno J, Oertel JE: Malignant lymphoma and other lymphoproliferative disorders of the thyroid gland: A clinicopathologic study of 245 cases. Am J Clin Pathol 74:1-11, 1980[Medline] 9. Eriksson M, Ajmani SK, Mallette LE: Hyperthyroidism from thyroid metastasis of pancreatic adenocarcinoma. JAMA 238:1276-1278, 1977
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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