Thyr

oid

4

Thyroglossal Duct Cyst

KEY FACTS

ETIOLOGY/PATHOGENESIS• Derived from thyroglossal duct, which is connection

between median anlage, foramen cecum, and descendedthyroid gland

• Thyroglossal duct cyst (TGDC) is result of persistence ofthyroglossal duct

CLINICAL ISSUES• Fistulas may develop secondary to infection and may drain

into skin or pharynx• Papillary thyroid carcinoma may arise in TGDC

IMAGING• Ultrasound and CT scan

○ Shows cyst intimately associated with hyoid bone withfluid density

CYTOPATHOLOGY• Ciliated respiratory-type cells &/or squamous cells• Mature lymphocytes

MACROSCOPIC• Cysts vary greatly in size

○ 1- to 4-cm in diameter• Usually contains clear fluid• Smooth-walled cystic structure

MICROSCOPIC• Midline location and distinct lining with lymphoid follicles

○ Helpful establishing diagnosis• Cyst lined by respiratory epithelium• Cyst wall may contain thyroid follicles

TOP DIFFERENTIAL DIAGNOSES• Branchial cleft cyst and other benign embryologic

abnormalities• Cystic degeneration of colloid nodule in multinodular

hyperplasia• Lymphatic malformation• Abscess

(Left) Sagittal oblique graphicshows the course of athyroglossal duct cyst fromthe foramen cecum st to thethyroid bed. Note the closerelationship to the midportionof the hyoid bone. The cyst canoccur anywhere along thistract. (Right) Thyroglossalduct cyst shows ciliatedrespiratory-type epitheliumlining cells in juxtapositionto scattered thyroid follicles.The cyst fluid is usually clear,fibrinous, and acellular.

Graphic of Thyroglossal Duct and Cyst Thyroglossal Duct Cyst

(Left) The high-power viewhighlights the cyst wall linedby a cylindrical, ciliated-typerespiratory epithelium and asubmucosa with lymphocyticinfiltration. (Right) Histologicsections of a thyroglossal ductcyst shows both respiratory-type epithelium and anadjacent epithelium withsquamous metaplasia .Note a lymphoid follicle in thecyst wall , a characteristicfeature of thyroglossal ductcysts.

High Power of Thyroglossal Duct Cyst Cyst Wall of Thyroglossal Duct Cyst

Thyroid

5

Thyroglossal Duct Cyst

TERMINOLOGYAbbreviations• Thyroglossal duct cyst (TGDC)

Definitions• Developmental anomaly derived from persistence of

thyroglossal duct○ Leading to development of cysts and fistulas

ETIOLOGY/PATHOGENESISDevelopmental Anomaly• Derived from thyroglossal duct, which is connection

between median anlage, foramen cecum, and descendedthyroid gland○ TGDC is result of persistence of thyroglossal duct

• Knowledge of typical course of thyroid primordium duringembryologic development is essential to understandvariant locations along this path where thyroid tissue can befound

• Migration of thyroid primordium begins at foramen cecumat base of tongue and then loops around hyoid boneanteriorly and inferiorly and descends anteriorly tothyrohyoid membrane into orthotopic location in infrahyoidportion of neck

• Thyroid ectopia is categorized into 1 of 4 typical locationswith respect to this embryologic course○ Base of tongue○ Adjacent to hyoid bone○ Midline infrahyoid portion of neck○ Rarely in lateral part of neck

CLINICAL ISSUESEpidemiology• Incidence

○ No predisposition for male or female gender○ Usually presents before 4th decade of life○ 685 patients were recently described (344 males; 341

females)– Age at presentation was bimodal (1st and 5th

decades) and ranged from 0.8-87.0 years (mean: 31.3years)

– Males predominate in children (150:111); females inadults (230:194)

Presentation• Most frequently present with mobile midline neck mass in

infrahyoid location• Located at or below level of hyoid bone in anterior midline

of neck• Usually between 1-4 cm in diameter

○ Average cyst size: 2.4 cm○ Pediatric patients have smaller cysts (mean: 2.1 cm) than

adults (mean: 2.8 cm)• Fistulas may develop secondary to infection and may drain

into skin or pharynx• Radiological studies demonstrate midline cystic area

○ Expansion or destruction of cartilaginous structure ofhyoid may occur

Treatment• Surgery

○ Necessary to avoid potential complications of fistulas– In rare instances, TGDCs can rupture and lead to life-

threatening complications

Prognosis• Cancer has been reported in TGDCs

○ Most common is papillary thyroid carcinoma– Occurs in 3.2% of all TGDCs in series of 685 cases

□ 22 patients (17 females, 5 males)□ Aged 12-64 years (mean: 39.9 years; median: 39.0

years)– Typical cytologic and morphologic features of

papillary thyroid carcinoma in context of cyst– Papillary thyroid carcinoma in TGDC is more common

in women than men, tends to have classicmorphologic features of papillary carcinoma, andcarries similar prognosis

– All of tumors are classic PTC, showing sclerotic andinfiltrative pattern

○ Other malignancies– Adenosquamous cell carcinoma arising in TGDC

• Infection, rupture○ May lead to life-threatening complications if not treated

early• Recurrence after surgery: 10%

IMAGINGCT Findings• Imaging characteristics of TGDC as simple cyst and of

ectopic thyroid tissue as hyperattenuating soft tissue massat CT

• From retrospective study of all CT and MR imaging studiesobtained in head and neck region○ From over 60,00 CT and MR images, 69 cases (0.1%) had

TGDCs○ Ages ranged from 3 days to 17 years old,with the mean

age at 5 years○ Locations varied with majority at base of tongue (83%)

followed by hyoid (13%) then infrahyoid straps (4%)○ Sizes ranged from 2-28 mm with average size at 8 mm

MACROSCOPICGeneral Features• 1- to 4-cm cyst; usually contains clear fluid• Smooth-walled cystic structure

○ May contain brown fluid○ When infected, may contain purulent material

• Fistulas may occur secondary to inflammation and infection○ May open into pharynx or skin○ May have drainage

MICROSCOPICHistologic Features• Cysts are usually lined by ciliated respiratory-type

epithelium○ ~ 38% are lined by respiratory epithelium alone○ ~ 10% are lined by squamous epithelium alone

Thyr

oid

6

Thyroglossal Duct Cyst

○ ~ 50% are lined by both respiratory and squamousepithelium

• Cyst wall contains lymphoid aggregates and lymphoidfollicles

• Squamous metaplasia may be present○ Occurs in setting of chronic inflammation within TGDC

– Squamous cell carcinoma subtypes may rarely occur insetting of TGDC

• Granulation tissue and loss of epithelium may be seen afterinflammation and infection○ It may be associated with skin fistula in ~ 10% of cases

• Cyst wall may contain thyroid follicles○ ~ 70% TGDC has associated thyroid gland tissue present

within cyst wall• Papillary thyroid carcinoma was identified in 22 patients

(3.2%) in series of 685 cases• Xanthogranulomatous inflammation with accumulation of

foamy histiocytes, multinucleated giant cells (Touton type),cholesterol clefts, and chronic inflammatory cells may occur

Cytologic Features• Squamous or respiratory cells

○ Inflammatory cells usually composed of maturelymphocytes

DIFFERENTIAL DIAGNOSISNeoplastic vs. Nonneoplastic• Carcinoma, lymphoma

○ Metastatic cystic papillary thyroid carcinoma may bedifficult to distinguish from papillary thyroid carcinomaoccurring within TGDC– Presence of respiratory or squamous epithelium as

well as anatomic location helps in differentiation○ Squamous cell carcinoma

• Other benign cysts○ Epidermoid cysts may be present in thyroid gland

– Lined by squamous epithelium□ They may be filled with keratin□ Does not contain lymphoid follicles in wall

○ Branchial cleft cyst and other benign embryologicabnormalities

○ Cystic degeneration of colloid nodule in multinodularhyperplasia

○ Lymphatic malformation○ Abscess○ Saccular cyst○ Relationship of mass to landmarks as

– Foramen cecum, hyoid bone, strap muscles,thyrohyoid membrane, and thyroid cartilage

– May help differentiate TGDC and ectopic thyroidtissue from other anterior neck masses whenembryologic thyroid course is considered

DIAGNOSTIC CHECKLISTPathologic Interpretation Pearls• Look for respiratory epithelium as well as gross features• Squamous metaplasia occurs in setting of chronic

inflammation within TGDC• Be wary of carcinomas found incidentally within TGDCs

excised without clinical suspicion of cancer

SELECTED REFERENCES1. Bakkar S et al: The extent of surgery in thyroglossal cyst carcinoma.

Langenbecks Arch Surg. 402(5):799-804, 20162. O'Neil LM et al: Wide anterior neck dissection for management of recurrent

thyroglossal duct cysts in adults. J Laryngol Otol. 130 Suppl 4:S41-4, 20163. Shemen L et al: Imaging characteristics and findings in thyroglossal duct cyst

cancer and concurrent thyroid cancer. BMJ Case Rep. 2016, 20164. Thompson LD et al: Thyroglossal duct cyst carcinomas: a clinicopathologic

series of 22 cases with staging recommendations. Head Neck Pathol.11(2):175-185, 2016

5. Thompson LD et al: A clinicopathologic series of 685 thyroglossal ductremnant cysts. Head Neck Pathol. 10(4):465-474, 2016

6. Zizic M et al: Upper neck papillary thyroid cancer (UPTC): A new proposedterm for the composite of thyroglossal duct cyst-associated papillary thyroidcancer, pyramidal lobe papillary thyroid cancer, and Delphian node papillarythyroid cancer metastasis. Laryngoscope. 126(7):1709-14, 2016

7. Baglam T et al: Does papillary carcinoma of thyroglossal duct cyst develop denovo? Case Rep Otolaryngol. 2015:382760, 2015

8. Taskin OC et al: Thyroglossal duct cyst associated withxanthogranulomatous inflammation. Head Neck Pathol. 9(4):530-3, 2015

9. Rohof D et al: Recurrences after thyroglossal duct cyst surgery: results in 207consecutive cases and review of the literature. Head Neck. 37(12):1699-704,2014

10. Rossi ED et al: Thyroglossal duct cyst cancer most likely arises from a thyroidgland remnant. Virchows Arch. 465(1):67-72, 2014

11. Zander DA et al: Imaging of ectopic thyroid tissue and thyroglossal ductcysts. Radiographics. 34(1):37-50, 2014

12. Wilsher MJ: IgG4 related disease of the thyroglossal duct. Pathology.45(6):618-22, 2013

13. Yamada S et al: Papillary carcinoma arising in thyroglossal duct cyst in thelateral neck. Pathol Res Pract. 209(10):674-8, 2013

14. Altay C et al: CT and MRI findings of developmental abnormalities andectopia varieties of the thyroid gland. Diagn Interv Radiol. 18(4):335-43,2012

15. Kinoshita N et al: Adenosquamous carcinoma arising in a thyroglossal ductcyst: report of a case. Surg Today. 41(4):533-6, 2011

16. Rosenberg TL et al: Evaluating the adult patient with a neck mass. Med ClinNorth Am. 94(5):1017-29, 2010

17. Ozolek JA: Selective pathologies of the head and neck in children: adevelopmental perspective. Adv Anat Pathol. 16(5):332-58, 2009

18. Turkyilmaz Z et al: Congenital neck masses in children and their embryologicand clinical features. B-ENT. 4(1):7-18, 2008

19. Mussak EN et al: Surgical and medical management of midline ectopicthyroid. Otolaryngol Head Neck Surg. 136(6):870-2, 2007

20. Falvo L et al: Papillary thyroid carcinoma in thyroglossal duct cyst: casereports and literature review. Int Surg. 91(3):141-6, 2006

21. Foley DS et al: Thyroglossal duct and other congenital midline cervicalanomalies. Semin Pediatr Surg. 15(2):70-5, 2006

22. Magro G et al: [Unusual non-neoplastic lesions in the "surgical pathology" ofthe thyroid.] Pathologica. 98(2):119-38, 2006

23. Niedziela M: Pathogenesis, diagnosis and management of thyroid nodules inchildren. Endocr Relat Cancer. 13(2):427-53, 2006

24. Sauvageau A et al: Fatal asphyxia by a thyroglossal duct cyst in an adult. J ClinForensic Med. 13(6-8):349-52, 2006

25. Burnell I et al: Mucin-secreting papillary adenocarcinoma of the hyoid bone:a unique case. J Laryngol Otol. 119(6):498-502, 2005

26. Tarnaris A et al: Lymphoma mimicking a thyroglossal duct cyst in anadolescent. J Laryngol Otol. 119(3):216-8, 2005

Thyroid

7

Thyroglossal Duct Cyst

(Left) Axial CECT shows athyroglossal duct cyst at thelevel of the hyoid boneembedded in strap muscles st.The cyst abuts the hyoid bone and impinges on thepreepiglottic space st. (Right)Thyroglossal duct cyst shows acyst lined by a ciliatedepithelium-lined wall withlymphoplasmacytic infiltrationst in the submucosa. Notedilated vessels in the wall andan amorphous material in thelumen.

CT of Thyroglossal Duct Cyst Cyst Wall of Thyroglossal Duct Cyst

(Left) Microphotograph showsa papillary thyroid carcinomathat arose in a thyroglossalduct cyst with the typicalnuclear features of papillarycarcinoma and with thepresence of psammoma bodies. (Right) Histologicalsection shows a papillarythyroid carcinoma, classicvariant, arising within athyroglossal duct cyst. Thepapillary architecture and thenuclear features arecharacteristic of papillarycarcinoma.

Papillary Thyroid Carcinoma Arising WithinThyroglossal Duct Cyst

Papillary Thyroid Carcinoma WithinThyroglossal Duct Cyst

(Left) Thyroglossal duct cyst isshown with areas of papillarythyroid carcinoma. Theseareas show TTF-1immunostain positivity in thispapillary thyroid carcinoma.These tumors have a similarimmunophenotype as thetumors from thyroid origin.(Right) BRAF immunostainshows immunopositivity in thecytoplasm of the tumor cellsof this papillary thyroidcarcinoma arising within athyroglossal duct cyst. TheBRAF immunopositivitycorrelates with the BRAF V600mutation.

Immunohistochemistry for TTF-1 inThyroglossal Duct Cyst With Carcinoma

BRAF in Papillary Thyroid CarcinomaArising in Thyroglossal Duct Cyst