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

What is your cytomorphologic diagnosis?

Case 1

Surgical excision of left lobe

Before & After de Quervain

Sub-acute Thyroiditis (SAT) /Granulomatous Thyroiditis

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.

2.  Thyroiditis acuta (Frank Joseph -1823) 3.  Angina Thyroidea (Weitenweber -1845)

THE JOURNAL OF LARYNGOLOGY, RHINOLOGY, AND OTOLOGY. VOL. IX. MARCH, 1895. No. 3.

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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.

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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+ T-

lymphocytes, 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%