Metastatic Adenocarcinoma Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions Metastatic Adenocarcinoma Authors Snehal Patel (Fellow) and Jean Lopategui (Attending) Subject Molecular Pathology Clinical History The patient is a 52 year old female who presents to with a rapidly growing right thyroid nodule and enlarged right neck lymph nodes lateral to the carotid artery. The patient subsequently underwent a fine needle aspiration of the right thyroid nodule (Figure 1) and right neck lymph node (Figure 2). There were no grossly identified lesions in the thyroid gland. Based on the findings, a total thyroidectomy (Figure 3) and right neck (Figures 4 & 5) and right paratracheal lymph node dissection was performed. Based on the immunohistochemical findings (Figures 6-8) additional molecular testing was performed. Diagnosis Metastatic adenocarcinoma most consistent with lung primary Discussion This is an unusual case of a patient presenting with a rapidly enlarging "thyroid gland" nodule and right neck and paratracheal lymph nodes. While the FNA of the "thyroid nodule" showed malignant cells, no gross or microscopic lesion was identified in the thyroidectomy specimen. Furthermore, immunohistochemistry was positive for TTF-1 but negative for Thyroglobulin. CT scan showed extensive supraclavicular, mediastinal, and hilar lymphadenopathy, as well as scattered lung nodules. A lung origin is favored by the fact that 1) no lesion was identified in the thyroid gland, 2) CT scan shows multiple lung lesions, and immunoprofile is more consistent with a lung origin than a thyroid origin. EGFR and KRAS molecular testing was negative. However, ALK FISH was positive for a translocation. The patient responded with an FDA-approved drug, crizotinib, an ALK tyrosine kinase inhibitor. ALK translocations are seen in 3-7% of NSCLC, are exceptional in thyroid carcinomas, and are mutually exclusive with other driver mutations (as seen in our case with negative EGFR and KRAS). They are usually seen in younger patients and light/never-smokers. Other tumors that harbor ALK translocations include anaplastic large cell lymphoma and inflammatory myofibroblastic tumors [1] .EML4 is the most common fusion partner. However, other partner genes may also be seen. Therefore, a FISH breakapart strategy is used to maximize the clinical sensitivity. The Vysis ALK break apart FISH test is an FDA-approved companion diagnostic test. A positive test predicts sensitivity to crizotinib [2]. After 9 months, the patient acquired resistance to crizotinib and was switched to ceretinib, a second generation ALK tyrosine kinase inhibitor and had a good response. References 1. Chatziandreou, I., et al., Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations. PLoS One, 2015. 10(7): p. e0133859. 2. Lindeman, N.I., et al., Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn, 2013. 15(4): p. 415-53. 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