Thyroid gland

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The thyroid gland is an important little endocrine organ in the anterior neck. It is frequently afflicted by cancer... but the common cancer has such a good prognosis there is debate about how aggressively it should be treated. The cytopathology of the thyroid gland is dealt with in the thyroid cytology article.

The gland frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.

Thyroid specimens

They come in three common varieties

  • FNA (fine needle aspiration).
  • Hemithyroid.
    • Done to get a definitive diagnosis.
    • May be a "completion" - removal of the other half following definitive diagnosis.
  • Total thyroid.
    • Done for malignancy or follicular lesion.

Gross pathology

  • White nodules - think:
    • Lymphoid tissue.
    • Papillary thyroid carcinoma - may be calcified.[1]

Diagnoses

Common

Pitfalls/weird stuff

  • Thyroid tissue lateral to the jugular vein (often referred to as lateral aberrant thyroid tissue) is generally considered metastatic thyroid carcinoma (papillary thyroid carcinoma) even if it looks benign.[2]
    • This dictum is disputed.[3]
    • The level VI and VII lymph nodes are medial to the jugular.
  • Hashimoto's disease may have so many lymphocytes that it mimics a lymph node -- may lead to misdiagnosis of PTC.
  • Parasitic nodule: clump of thyroid that is attached by a thin thread... but looks like a separate nodule; may lead to misdiagnosis of PTC.

Image:

Diagnostic keys

The following should prompt careful examination:[5]

  • Architecture: microfollicular, trabecular, solid, insular.
  • Thick capsule.
  • Necrosis - rare in the thyroid.

Thyroid IHC - general comments

  • Not really useful.
  • Papers with very small sample sizes abound.

Follicular thyroid carcinoma vs. papillary thyroid carcinoma

  • CD31 more frequently positive in follicular lesions.[6]
    • CD31 is a marker for microvessel density.
  • Galectin-3 thought to be positive in papillary carcinoma.[6]
  • HBME-1 thought to be positive in papillary lesions.[7]

Thyroid lesions per WHO

  • Adapted from the Washington Manual of Surgical Pathology.[8]

Adenoma

  • Follicular adenoma.
  • Hyalinizing trabecular tumour.

Carcinoma

  • Mixed medullary and follicular carinoma.
  • Spindle cell tumour with thymus-like differentiation.
  • Carcinoma showing thymus-like differentiation.

Others

Parathyroid glands

Main article: Parathyroid glands
  • May make an appearance in the context of thyroid surgery.

Benign

Solid cell nest of the thyroid gland

  • AKA solid cell nest of thyroid.

General

  • Embryonic remnants endodermal origin.[9]
  • Incidental finding.

Note:

Microscopic

Features:[9]

  • Cellular solid or cystic cluster of variable size with:
    • Cuboidal cellular morphology.
      • May have columnar morphology.
    • Moderate-to-scant eosinophilic cytoplasm.
    • Round/ovoid nuclei with finely granular chromatin.
  • +/-Goblet cells (~30% of cases).[12]

DDx:[9]

Images

  • Solid cell nest of the thyroid gland - intermed. mag. (WC)

  • Solid cell nest of the thyroid gland - high mag. (WC)

  • Solid cell nest of the thyroid gland - very high mag. (WC)

www:

IHC

Features:[9]

  • p63 +ve.
    • -ve in clear cells.
  • CEA +ve (polyconal).[12]
    • +ve also in clear cells.
  • Chromogranin A +ve ~45% of cases.[12]

Sign out

Solid cell nests of the thyroid gland are usually not reported.

Thyroid gland nodular hyperplasia

Main article: Thyroid gland nodular hyperplasia

Follicular thyroid adenoma

  • AKA follicular adenoma, AKA thyroid follicular adenoma.
Main article: Follicular thyroid adenoma

Graves disease

Main article: Graves' disease

Idiopathic granulomatous thyroiditis

  • AKA granulomatous thyroiditis - non-specific term; granulomas may be due a number of causes.
  • AKA subacute thyroiditis.
  • AKA de Quervain thyroiditis.
    • Should not be confused with de Quervain's disease (AKA gamer's thumb) something completely unrelated to the thyroid.

General

  • Women > men.
  • Etiology: possibly viral.[13]

Clinical:

Management:

  • Medical.
  • Rarely surgery.[15]

Microscopic

Features:[16][13]

  • Granulomas with multinucleated giant cells - usu. with engulfed colloid.
  • Lymphocytes.
  • Plasma cells.
  • +/-Fibrosis.

DDx:

Images

  • Subacute thyroiditis - intermed. mag. (WC)

  • Subacute thyroiditis - high mag. (WC)

  • Subacute thyroiditis - very high mag. (WC)

Stains

  • ZN -ve.
  • GMS -ve.

Palpation thyroiditis

General

  • Granulomatous inflammation due to palpation.
    • Incidence of granulomas higher in surgical thyroid specimens than autopsies.[13]

Microscopic

Features:[13]

  • Granulomas involving the follicle.
    • Histiocytes within the colloid.

DDx:

Stains

  • ZN -ve.
  • GMS -ve.

Riedel thyroiditis

  • AKA invasive fibrous thyroiditis.[17]

General

Clinical features:[17]

  • Extremely rare.
  • Women > men.
  • Usually smokers.
  • May be associated with retroperitoneal fibrosis.
  • May be hypothyroid.
  • +/-Obstructive symptoms.

Microscopic

Features:

  • Fibrosis.
  • Specimen often fragmented as it was difficult to remove.

DDx:

Hashimoto thyroiditis

General

  • This is a clinical diagnosis.
    • The histomorphologic findings, generally, are not diagnostic.

Etiology:

  • Autoimmune disease leading to hypothyroidism.
    • Often genetic/part of a syndrome.

Clinical

Serology:[18]

  • Antimicrosomal (antithyroid peroxidase) +ve.
  • Antithyroglobulin +ve.
    • Normal: <4.0 IU/mL.[19]

Associated pathology:[18]

Microscopic

Features:

  • Lymphocytic infiltrate - key feature.
  • Nuclear clearing common.
  • Polymorphous lymphoplasmacytic infiltrate with germinal centres.[21]
  • +/-Oncocytic metaplasia.

Notes:

  • Histologically often not possible to separate from "non-specific" thyroiditis.[22]

DDx:

IHC

  • Panel to exclude lymphoma may be required, e.g. CD3, CD20, CD10, BCL6, BCL2, kappa, lambda.

Molecular

C-cell hyperplasia

  • Abbreviated CCH.
Main article: C-cell hyperplasia

Malignant neoplasm

There are a bunch of 'em. The most common, by far, is papillary.

Papillary thyroid carcinoma

  • Abbreviated PTC.
Main article: Papillary thyroid carcinoma

Insular carcinoma

Main article: Insular thyroid carcinoma

Follicular thyroid carcinoma

  • AKA follicular carcinoma.
Main article: Follicular thyroid carcinoma

Medullary thyroid carcinoma

  • Abbreviated MTC.
Main article: Medullary thyroid carcinoma

Poorly differentiated thyroid carcinoma

Main article: Poorly differentiated thyroid carcinoma

Anaplastic thyroid carcinoma

Main article: Anaplastic thyroid carcinoma

Lymphomas of the thyroid

Main article: Lymphoma

General

  • Rare.
  • Increased risk with chronic inflammatory conditions.
  • Fit in the the greater category of MALT lymphoma.

Microscopic

Features:

  • Lymphoepithelial lesion - key feature.
  • Plasma cells.
  • "Overgrowth" - thyroid parenchyma displaced by lymphocytes.

Weird stuff

Hyalinizing trabecular tumour

  • AKA hyalinizing trabecular adenoma.
  • Abbreviated HTT.

General

Microscopic

Features:

  • Trabecular arrangement of cells.
    • May have "curved" trabeculae.
  • Extracellular space has hyaline material - key feature.
  • Cytoplasm mimics hyaline material in the extracellular space.

DDx:

Images

  • HHT - low mag. (WC)

  • HHT - intermed. mag. (WC)

  • HHT - high mag. (WC)

  • Thyroid gland - high mag. (WC)

  • HHT - intermed. mag. (WC)

  • HHT - high mag. (WC)

  • HHT - intermed. mag. (WC)

  • HHT - high mag. (WC)

  • HHT - very high mag. (WC)

www:

IHC

  • Thyroglobulin +ve.
  • NSE +ve.

Hürthle cell neoplasm

  • AKA oncocytic neoplasm.
  • Also spelled Hurthle cell neoplasm.

General

  • Incidence: uncommon.
  • This is a general category - includes:
    • Hürthle cell adenoma.
    • Hürthle cell carcinoma.

Adenoma vs. carcinoma

Suggestive for carcinoma:[27]

  • Male.
  • >4 cm
    • Adenomas usu. <3 cm.

Definite for carcinoma:[27]

  • Lymphovascular invasion.
  • Capsular invasion.

Gross

  • Yellow.
  • Encapsulated.

Microscopic

Features:[28]

  • Oncocytes >= 75% of cells:
    • Abundant granular, eosinophilic cytoplasm.
    • Round regular nucleus +/- prominent nucleolus.
  • +/-Degenerative changes.

Negatives:

DDx:[29]

  • Papillary thyroid carcinoma oncocytic variant.
  • Medullary thyroid carcinoma oncocytic variant.
  • Others.

Minocycline associated thyroid pigmentation

  • AKA minocycline thyroid.

General

  • Benign pigmentation of the thyroid due to minocycline, an antibiotic.

Gross

Images:

Microscopic

Features:

  • Granular yellow blobs:
    • Location:
      • Intracytoplasmic in the follicule-lining cells, i.e. follicular cells.
      • Intrafollicular.
    • Variable size ~0.5-4 micrometers.

Notes:

  • Pigment described as lipofuscin-like.[34]

Images

Stains

See also

References

  1. ↑ BEC. 20 October 2009.
  2. ↑ JOHNSON, RW.; SAHA, NC. (Jun 1962). "The so-called lateral aberrant thyroid.". Br Med J 1 (5293): 1668-9. PMC 1958877. PMID 14452106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1958877/.
  3. ↑ Escofet, X.; Khan, AZ.; Mazarani, W.; Woods, WG. (Jan 2007). "Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant?". J R Soc Promot Health 127 (1): 45-6. PMID 17319317.
  4. ↑ URL: http://radiopaedia.org/articles/lymph-node-levels-of-the-neck. Accessed on: 5 November 2012.
  5. ↑ SR. 17 January 2011.
  6. ↑ 6.0 6.1 Rydlova, M.; Ludvikova, M.; Stankova, I. (Jun 2008). "Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study.". Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 152 (1): 53-9. PMID 18795075.
  7. ↑ Papotti, M.; Rodriguez, J.; De Pompa, R.; Bartolazzi, A.; Rosai, J. (Apr 2005). "Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential.". Mod Pathol 18 (4): 541-6. doi:10.1038/modpathol.3800321. PMID 15529186.
  8. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 331. ISBN 978-0781765275.
  9. ↑ 9.0 9.1 9.2 9.3 Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M (January 2003). "p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin". Mod. Pathol. 16 (1): 43–8. doi:10.1097/01.MP.0000047306.72278.39. PMID 12527712. http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html.
  10. ↑ Ozaki, O.; Ito, K.; Sugino, K.; Yasuda, K.; Yamashita, T.; Toshima, K.. "Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma?". World J Surg 16 (4): 685-8; discussion 688-9. PMID 1413837.
  11. ↑ Prichard, RS.; Lee, JC.; Gill, AJ.; Sywak, MS.; Fingleton, L.; Robinson, BG.; Sidhu, SB.; Delbridge, LW. (Feb 2012). "Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis.". Thyroid 22 (2): 205-9. doi:10.1089/thy.2011.0276. PMID 22224821.
  12. ↑ 12.0 12.1 12.2 Mizukami Y, Nonomura A, Michigishi T, et al. (February 1994). "Solid cell nests of the thyroid. A histologic and immunohistochemical study". Am. J. Clin. Pathol. 101 (2): 186–91. PMID 7509563.
  13. ↑ 13.0 13.1 13.2 13.3 Lloyd, Ricardo V. (2002). Endocrine Diseases (AFIP Atlas of Nontumor Pathology). Toronto: American Registry of Pathology. ISBN 978-1881041733. http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735.
  14. ↑ Szczepanek-Parulska, E.; Zybek, A.; Biczysko, M.; Majewski, P.; Ruchała, M. (2012). "What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation.". Endokrynol Pol 63 (2): 138-42. PMID 22538753.
  15. ↑ Volpé, R. (1993). "The management of subacute (DeQuervain's) thyroiditis.". Thyroid 3 (3): 253-5. PMID 8257868.
  16. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 559. ISBN 978-0781740517.
  17. ↑ 17.0 17.1 Fatourechi, MM.; Hay, ID.; McIver, B.; Sebo, TJ.; Fatourechi, V. (Jul 2011). "Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008.". Thyroid 21 (7): 765-72. doi:10.1089/thy.2010.0453. PMID 21568724.
  18. ↑ 18.0 18.1 Poropatich C, Marcus D, Oertel YC (1994). "Hashimoto's thyroiditis: fine-needle aspirations of 50 asymptomatic cases". Diagn. Cytopathol. 11 (2): 141–5. PMID 7813361. http://www3.interscience.wiley.com/journal/112701408/abstract?CRETRY=1&SRETRY=0.
  19. ↑ URL: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/84382. Accessed on: 15 October 2015.
  20. ↑ Ohye, H.; Fukata, S.; Hirokawa, M. (Nov 2007). "[Malignant lymphoma of the thyroid].". Nihon Rinsho 65 (11): 2092-8. PMID 18018576.
  21. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 672. ISBN 978-1416025887.
  22. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 560. ISBN 978-0781740517.
  23. ↑ Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL (December 2000). "Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics". Am. J. Surg. Pathol. 24 (12): 1622–6. PMID 11117782.
  24. ↑ URL: http://path.upmc.edu/cases/case465/dx.html. Accessed on: 17 January 2011.
  25. ↑ Baloch, ZW.; Puttaswamy, K.; Brose, M.; LiVolsi, VA. (2006). "Lack of BRAF mutations in hyalinizing trabecular neoplasm.". Cytojournal 3: 17. doi:10.1186/1742-6413-3-17. PMID 16867191.
  26. ↑ URL: http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html. Accessed on: 1 January 2012.
  27. ↑ 27.0 27.1 27.2 Wasvary, H.; Czako, P.; Poulik, J.; Lucas, R. (Aug 1998). "Unilateral lobectomy for Hurthle cell adenoma.". Am Surg 64 (8): 729-32; discussion 732-3. PMID 9697901.
  28. ↑ 28.0 28.1 Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 104. ISBN 978-0443066856.
  29. ↑ Montone KT, Baloch ZW, LiVolsi VA (August 2008). "The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review". Arch. Pathol. Lab. Med. 132 (8): 1241–50. PMID 18684023.
  30. ↑ 30.0 30.1 Sant'Ambrogio, S.; Connelly, J.; DiMaio, D.. "Minocycline pigmentation of heart valves.". Cardiovasc Pathol 8 (6): 329-32. PMID 10615019.
  31. ↑ Geria AN, Tajirian AL, Kihiczak G, Schwartz RA (2009). "Minocycline-induced skin pigmentation: an update". Acta Dermatovenerol Croat 17 (2): 123–6. PMID 19595269.
  32. ↑ Noble, JG.; Christmas, TJ.; Chapple, C.; Katz, D.; Milroy, EJ. (Jan 1989). "The black thyroid: an unusual finding during neck exploration.". Postgrad Med J 65 (759): 34-5. PMC 2429157. PMID 2780449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429157/.
  33. ↑ 33.0 33.1 Raghavan, R.; Snyder, WH.; Sharma, S. (Mar 2004). "Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland.". Arch Pathol Lab Med 128 (3): 355-6. doi:10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2. PMID 14987144.
  34. ↑ Gordon, G.; Sparano, BM.; Kramer, AW.; Kelly, RG.; Iatropoulos, MJ. (Oct 1984). "Thyroid gland pigmentation and minocycline therapy.". Am J Pathol 117 (1): 98-109. PMC 1900569. PMID 6435454. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1900569/.
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