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Journal of Clinical Oncology, Vol 24, No 36 (December 20), 2006: pp. 5788-5789 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.08.8732
Childhood Papillary Thyroid Carcinoma With Miliary Pulmonary MetastasesDepartments of Pathology, Pediatric Endocrinology, Pediatric Oncology, Pediatric Radiology, Erasmus MC-University Medical Center and Erasmus MC-Sophia, Rotterdam, the Netherlands A 10-year-old boy, complaining of fatigue, presented with multiple bilaterally enlarged neck lymph nodes. Chest x-ray revealed multiple small nodules in the lung, which was confirmed on computed tomography (CT) analysis. Because of clinical suspicion of miliary tuberculosis, a bronchoalveolar lavage was performed. This specimen showed alveolar macrophages, lymphocytes, granulocytes, normal bronchial epithelium, and some groups of atypical epithelial cells that were interpreted as metaplastic epithelium (Fig 1; x400 magnification). No micro-organisms were detected. Around the same time, fine needle aspiration biopsy was performed from an enlarged neck lymph node. The specimen showed sheets of epithelial cells in a follicular growth pattern and syncytial cell groups with follicles filled with colloid. A diagnosis of metastatic thyroid carcinoma, probably metastatic follicular thyroid carcinoma, was proffered, necessitating thyroid resection. Ultrasound examination of the neck and thyroid showed multiple enlarged lymph nodes and an inhomogeneous nodule in the right thyroid lobe, which was subsequently confirmed to be a cold nodule on 123I-scintigraphy. Serum thyroglobulin was elevated to 1,744 µg/L. Because of these findings, total thyroidectomy with bilateral lymph node resection was performed, yielding a thyroid of 15 g with an irregularly enlarged right lobe and several gray-white nodules in both lobes. Microscopically, these nodules corresponded to an infiltrating epithelial tumor composed of follicular structures, but with overlapping nuclei, that were optically clear in many areas. There were rare papillary structures and psammoma bodies, but sclerosis was not a prominent feature. The tumor was diagnosed as a follicular variant of a papillary thyroid carcinoma, 5 cm in largest diameter, showing lymphangio-invasion, and incompletely removed (Fig 2; x400 magnification). The bilateral lymph node resection yielded 43 lymph nodes of which 21 at levels three to six showed metastases.
At this stage, the original bronchoalveolar lavage specimen was re-evaluated, and the groups of atypical epithelia cells, originally interpreted as metaplastic were now appreciated as groups of cells originating from the papillary thyroid carcinoma (Fig 1). Also, the miliary aspect of the lungs at x-ray and CT was reappreciated as multiple metastases (Fig 3).
After surgical removal, radioactive 131I ablative therapy (first dose 2,960 MBq, second dose 3,700 MBq) was installed for his remaining tumor load in the lungs and thyroid bed and thyroid hormone replacement therapy was given. Presently, the patient is alive and well at 1 year and 6 months postsurgery and has received two doses of ablative therapy with improvement of his thyroglobulin levels, which, however, are still elevated. His general condition is satisfactory.
Thyroid cancer accounts for 1.3% of all malignancies, and papillary thyroid carcinoma (PTC) is the most frequently occurring subtype, representing 80% of patients.1,2 Roughly, these figures also apply to the pediatric age group, in which thyroid carcinomas represent 0.5% to 3.0% of all malignancies, and PTC is the predominant subtype.3 Within the group of PTC, the latest WHO edition describes no fewer than 15 variants.2 The importance of recognizing several of these variants lies partly in their relationship with prognosis (the tall cell and columnar cell variant are known to be associated with a more aggressive clinical behavior), and partly in their distinction from other thyroid tumors, such as the follicular variant, which in the past has frequently been labeled as a follicular thyroid carcinoma. The crucial feature of PTC diagnosis is the nuclear pattern: nuclei are typically enlarged, oval or elongated, and overlapping. In addition, nuclear clearing, grooves, and pseudoinclusions can be appreciated, although the various features may only be present in parts of the lesion. In recent years, the pathogenesis of PTC has been partly elucidated, with frequent mutations or aberrations in one of three genes that belong to the same intracellular signal transduction pathway: RAS, BRAF, and RET-PTC. Such alterations are mutually exclusive and together they amount to 70% or more of PTC.4 In addition, these alterations appear to correlate with specific histologic variants of PTC and were also shown to be related to a specific pattern of gene expression, as has been investigated by DNA microarray analysis.5 With regard to the follicular variant of PTC, several recent studies have shown that these tumors, at least in part, contain the same genetic abnormalities as follicular thyroid adenomas and carcinomas (ie, PAX8-PPAR In conclusion, PTC in childhood may present with multiple lung metastases and a miliary aspect at x-ray or CT, which can be diagnosed by cytology on a bronchoalveolar lavage specimen. Despite such an advanced stage at presentation, adequate treatment still confers an excellent long-term prognosis. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES 1. Chu KC, Kramer BS: Cancer patterns in the United States, in Greenwald P, Kramer BS, Weed DL (eds): Cancer Prevention and Control. New York, Marcel Dekker, 1995, pp 37 2. DeLellis RA, Williams ED: Thyroid and parathyroid tumours: Introduction, in DeLellis RA, Lloyd RV, Heitz PhU, et al (eds): Pathology and Genetics: Tumours of Endocrine Organs. Lyon, IARC Press, 2004, pp 51 3. Millman B, Pellitteri P: Thyroid carcinomas in children and adolescents. Arch Otolaryngol Head Neck Surg 121:1261-1264, 1995[Abstract] 4. Adeniran AJ, Zhu Z, Gandhi M, et al: Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol 30:216-222, 2006[CrossRef][Medline] 5. Giordano TJ, Kuick R, Thomas DG, et al: Molecular classification of papillary thyroid carcinoma: Distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene 24:6646-6656, 2005[CrossRef][Medline] 6. Castro P, Rebocho AP, Soares RJ, et al: PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J Clin Endocrinol Metab 91:213-220, 2006 7. Okada T, Sasaki F, Takahashi H, et al: Management of childhood and adolescent thyroid carcinoma: Long-term follow-up and clinical characteristics. Eur J Pediatr Surg 16:8-13, 2006[CrossRef][Medline] 8. Collini P, Massimino M, Leite SF, et al: Papillary thyroid carcinoma of childhood and adolescence: A 30-year experience at the Istituto Nazionale Tumori in Milan. Pediatr Blood Cancer 46:300-306, 2006[CrossRef][Medline] Related Correspondence
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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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rearrangements and RAS mutations), but do not show the B-RAFV600E mutation, typical for PTC.
