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 ThyroiditisHistorical Descriptions

� “Acute inflammation of the healthy thyroid gland”1. CynancheThyroidea (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)

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

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THYROIDITIS ACUTA SIMPLEX.1By 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 Speziellechirurgische 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+ cytotoxicT 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%