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History  52-year-old woman  Transient symptomatic hyperthyroidism (TSH – 0.03) followed by hypothyroidism.  Current medication: Synthroid  Ultrasound – Left thyroid lobe occupied by a predominantly ill-defined hypoechoic structure – suspicious for anaplastic carcinoma Case 1 What is your cytomorphologic diagnosis? Surgical excision of left lobe Sub-acute Thyroiditis (SAT) / Granulomatous Thyroiditis Before & After de Quervain Granulomatous Thyroiditis Historical Descriptions  “Acute inflammation of the healthy thyroid gland” 1. Cynanche Thyroidea (Ph. Fr. Walther – 1817) 1. Cynanche : Any disease of the tonsils, throat, or windpipe, attended with inflammation, swelling, and difficulty of breathing and swallowing. Thyroiditis acuta (Frank Joseph -1823) 3. Angina Thyroidea (Weitenweber -1845) 2. THE JOURNAL OF LARYNGOLOGY, RHINOLOGY, AND OTOLOGY. VOL. IX. MARCH, 1895. No. 3. Original Articles are accepted by the Editors of this Journal on the condition that they have not previously been published elsewhere. Twenty-five reprints are allowed each author. If more are required it is requested that this be stated when the article is first forwarded to this Journal. Such extra reprints will be charged to the author. The Editors are not responsible for opinions expressed in original Articles 01 Abstracts in this Journal. Editorial Communications are to be addressed to " Editors of JOURNAL OF LARYNGOLOGY, care of F. J. Rebman, Albion Chambers, 11, Adam Stieet, Strand, London, IV. C." THYROIDITIS ACUTA SIMPLEX.1 By HOLGER MYGIXD, M.D. De Quervain  Fritz de Quervain (May 4, 1868 – January 24, 1940) was a Swiss surgeon born in Sion. He was a leading authority on thyroid disease.  In 1892 he received his doctorate from the University of Bern, and several years later became director of the surgical department at a hospital in La Chaux-de-Fonds in the canton of Neuchâtel.  In 1910 he was appointed to the chair of surgery at the University of Basel, and from 1918 was a professor of surgery at Bern and director of the Inselspital.  De Quervain published many papers devoted to thyroid disease, ranging from the epidemiology of the disease to technical procedures on thyroidectomy. His book Spezielle chirurgische Diagnostik (Special Surgical Diagnosis) was a leading textbook on surgery in its day.  He is responsible for introducing iodized table salt in order to help prevent Goitre. Two eponymous diseases are named after De Quervain: Sub-acute thyroiditis (SAT)  Self-limiting inflammatory, possible viral associated disorder.  Preceding upper respiratory infection  Elevated titers of several viral antibodies  Seasonal and geographic clusters  Early spring and fall  Japan & Turkey  Two thirds of patients with SAT have HLA B35  Symptoms  Pain in the thyroid region – 94%  Weeks to months if left untreated  Various symptoms associated with thyrotoxicosis Sub-acute thyroiditis (SAT)  Clinical features & Laboratory Evaluation - critical first 7 days (Nishihara E, et.al Intern Med 2008;47:725-9, 852 patients with SAT 1996-2004)  Body temperature >100 Fahrenheit  Thyrotoxicosis  Low TSH, High FT3, FT4  High AST, ALT, CRP, ESR  Antithyroid antibodies Ultrasound Examination - SAT  Hypoechoic area corresponding to the area of pain in thyroid  Focal  Diffuse  Hypo-echogenecity reflects the degree of inflammation – 32 patients (Omori N et.al – Endo J 2008) SAT – Fine-needle aspiration (Solano et.al DiCy 1997) Most Relevant Cytologic Findings  Plump transformed follicular cells  Epitheliod granulomas  Multinucleated giant cells (97.2%)  Follicular cells with intra-vacuolar granules ( 77.7%)  Mature lymphocytes (100%)  Macrophages (100%)  Neutrophils ( 88.8%)  Oncocytic cells  Transformed lymphocytes  Hypertrophic follicular cells  Fire-flare follicular cells Cellular composition of SAT  Numerous plasmacytoid monocytes closely associated with the granulomas. The       giant cells were CD68+, thyroglobulin– and cytokeratin–. Usually, small lymphocytes in the granulomas are CD3+, CD8+, CD45RO+ cytotoxic T cells. In the non-granulomatous lesion, the follicles were often infiltrated by CD8+ Tlymphocytes, plasmacytoid monocytes and histiocytes, resulting in disrupted basement membrane and rupture of the follicles. Lymphoid follicles with or without active germinal centers were not observed. Moreover, no residual follicular dendritic cell networks were detected by CD23 and CAN.42 immunostains. In the interfollicular area, scattered plasma cells were observed among infiltrating cells. Neither human herpes virus 8 nor EBER-positive cells were detected Cellular immune response may play an important role in the pathogenesis of SAT . SAT Clinical Follow-up  Recovery in most patients  Permanent hypothyroidism 5-31% of patients.  More common in patients treated with corticosteroids (Mayo clinic data 2003)  Isolated cases of Graves’ disease and ophthalmopathy.  Recurrence of SAT – 4-10%