Thyroid gland
Miscellaneous non-neoplastic disorders
Thyroid inclusions in cervical lymph nodes

Author: Andrey Bychkov, M.D., Ph.D. (see Authors page)

Revised: 14 January 2016, last major update January 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Thyroid inclusions [title] cervical lymph nodes

Cite this page: Thyroid inclusions in cervical lymph nodes. PathologyOutlines.com website. http://pathologyoutlines.com/topic/thyroidlymphnodes.html. Accessed December 8th, 2016.
Definition / General
  • Thyroid tissue incidentally discovered in cervical lymph nodes during histological examination of neck dissections performed for non thyroid disease, e.g. head and neck cancer (Eur Arch Otorhinolaryngol 2015 Oct 12)
  • May represent metastatic carcinoma or benign thyroid tissue; evaluate with extreme caution (Laryngoscope 2005;115:470)
Terminology
  • Ectopic thyroid tissue in cervical lymph nodes; benign thyroid inclusions in cervical lymph nodes
  • Lateral aberrant thyroid: usually due to metastatic thyroid carcinoma in cervical lymph nodes
Epidemiology
  • Incidence of unsuspected benign thyroid tissue in lymph nodes of patients with head and neck carcinoma treated with neck dissection is 0.6 - 1.5% (Clin Endocrinol Metab 1981;10:337, Laryngoscope 2005;115:470)
  • Meticulous study of cervical lymph nodes found benign thyroid inclusions in 4.7% of unselected autopsies (Cancer 1969;24:302)
  • Total number of well proven cases of benign nodal thyroid inclusions is < 30
Sites
Pathophysiology / Etiology
  • Aberrations during migration of embryonic thyroid may result in entrapment of structures that terminally differentiate to thyroid follicles and remain quiescent in lymph nodes (heterotopia)
    • In addition, hypothetically, enlarging lymph node may enclose neighboring ectopic islet of thyroid tissue
  • May be explained by benign lymphatic transport ("benign metastasis"), when tiny fragments of ruptured thyroid tissue float into sentinel lymph nodes (JAMA 1965;194:1); similar to proposed mechanism for endometriosis
  • Theoretically, may represent nodal metastasis of occult thyroid carcinoma with further complete regression of the primary (Head Neck 2001;23:885, J Oral Maxillofac Surg 2008;66:2566)
Clinical Features
Diagrams / Tables
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Differential diagnosis

Diagnosis
  • Only after exclusion of suspected primary thyroid carcinoma on extensive workup (imaging and even surgery)
Radiology Description
  • It is believed that current imaging modalities are unable to detect true benign nodal thyroid inclusions (Eur Arch Otorhinolaryngol 2015 Oct 12)
  • Features suggestive of metastatic lymph nodes from papillary thyroid carcinoma (Head Neck 2015;37:E106):
    • US: focally or diffusely increased nodal echogenicity, intranodal calcifications, intranodal cystic component(s), and an abnormal vascular pattern (a chaotic or peripheral vascular pattern)
    • CT: strong enhancement without hilar vessel enhancement, heterogeneous enhancement, intranodal calcifications and intranodal cystic component
Prognostic Factors
  • The prognosis for benign nodal thyroid inclusions is excellent
  • Similarly, occult papillary thyroid carcinoma with incidental nodal micrometastasis usually does not progress
Case Reports
Treatment
  • Thyroid imaging is mandatory for all cases with thyroid inclusions in cervical lymph nodes
    • If primary thyroid carcinoma is detected, the extent of further thyroid surgery depends on age, comorbidities, control of primary upper aerodigestive cancer and patient preference
  • "Wait and watch" is recommended if imaging is negative
  • Option of further surgery can be considered as well
  • Unequivocally benign inclusions confirmed by morphology and negative thyroid imaging may require no further action, but clinical correlation and follow up is advisable (Eur Arch Otorhinolaryngol 2015 Oct 12)
Gross Description
  • Lymph nodes are unremarkable, <5 mm (range 2 - 15 mm)
Gross Images

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Larynx w/ adjacent lymph node, left thyroid

Micro Description
  • Inclusions are 0.1 to 2.3 mm and contain up to 100 (average 30) normal appearing thyroid follicles, usually arranged in a wedge shaped focus with the base adjacent to the nodal capsule and the apex directed towards the cortex (Eur Arch Otorhinolaryngol 2015 Oct 12)
  • Benign inclusion should be located within the nodal capsule or in the marginal sinus (subcapsular), and in not more than two cervical lymph nodes
  • Metastatic papillary carcinoma is suspected by the large extent of thyroid tissue replacing lymph node (often cystic) and the presence of papillary structures, psammoma bodies, grooved nuclei, marginated chromatin, intranuclear pseudoinclusions
  • The same features of papillary cancer can be found in the thyroidectomy specimen, which may require exhaustive sectioning, including multiple levels and "flipping" of paraffin blocks (Wenig: Atlas of Head and Neck Pathology, 3rd Edition)
Micro Images

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Ectopic thyroid follicles



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Subcapsular nodal thyroid inclusion

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Apparently benign thyroid tissue within lymph node and occult papillary thyroid cancer

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Lymph node with metastatic papillary thyroid carcinoma

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Nodal micrometastasis, papillary cancer

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Thyroglobulin+ lymph node (potential pitfall)

Virtual Slides
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Case 11, metastatic thyroid cancer

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Case 1, metastatic thyroid cancer

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Case 17, thyroid tissue

Cytology Description
  • The probability of obtaining tiny benign thyroid inclusions during cervical lymph node aspiration is extremely low, with only one case reported (Head Neck 2015;37:E106)
  • As such, the presence of thyroid follicles in cervical lymph node aspirate should be considered to be metastatic thyroid carcinoma or a technical error (if orthotopic or heterotopic thyroid/parasitic nodule is sampled instead of the lymph node)
  • Metastases in lymph nodes are identified by papillary fragments, psammoma bodies and classic nuclear features of papillary thyroid carcinoma
Cytology Images

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Metastatic papillary carcinoma

Positive Stains
  • Thyroglobulin and TTF1, with these limitations:
    • Macrophages in lymph nodes draining thyroid tumors may engulf thyroglobulin (J Clin Pathol 2001;54:314)
    • TTF1 is not entirely thyroid specific, e.g. TTF1+ lung cancer can metastasize to cervical lymph nodes
Negative Stains
Molecular / Cytogenetics Description
  • Benign inclusions are typically negative for molecular markers of thyroid cancer (BRAF and RAS mutations, RET / PTC rearrangements), although one study found BRAF mutation in "benign" inclusions (Endocr Pathol 2006;17:183)
  • Benign inclusions, as with normal or ectopic thyroid, are polyclonal on HUMARA assay, but metastatic tumor is monoclonal (Hum Pathol 1998;29:187)
Differential Diagnosis