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

  • Nodular hyperplasia -- most common.
  • Lymphocytic thyroiditis.
  • Papillary thyroid carcinoma (PTC) -- most common cancer.
  • Follicular adenoma.
  • Follicular thryoid carcinoma.
  • Parathyroid tissue.

Pitfalls/weird stuff

  • Thyroid tissue lateral to the jugular vein = metastatic PTC... even if it looks benign.
  • 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.

Diagnostic keys

The following should prompt careful examination:[2]

  • 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.[3]
    • CD31 is a marker for microvessel density.
  • Galectin-3 thought to be positive in papillary carcinoma.[3]
  • HBME-1 thought to be positive in papillary lesions.[4]

Thyroid lesions per WHO

  • Adapted from the Washington Manual of Surgical Pathology.[5]

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.[6]
  • Incidental finding.

Note:

Microscopic

Features:[6]

  • 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).[9]

Images:

DDx:[6]

IHC

Features:[6]

  • p63 +ve.
    • -ve in clear cells.
  • CEA +ve (polyconal).[9]
    • +ve also in clear cells.
  • Chromogranin A +ve ~45% of cases.[9]

Sign out

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

Thyroid gland nodular hyperplasia

General

  • Clinical diagnosis: goitre, AKA sporadic goitre, AKA multinodular goitre (MNG).
  • Most common diagnosis in the thyroid.
    • If you've seen a handful of thyroids you've seen this.

Notes:

  • Large lesions may be clonal; however, this is clinically irrelevant.

Microscopic

Features:

  • Follicles of variable size - key feature.
    • Should be obvious at low power, i.e. ~2.5x objective.
  • Nodules maybe well circumscribed (on gross), but do not have a thick fibrous capsule.

Negatives:

  • No nuclear features suggestive of malignancy (at lower power).
    • One should not look at high power.
  • Not cellular.

Follicular thyroid adenoma

  • AKA follicular adenoma, AKA thyroid follicular adenoma.

General

  • Most common neoplasm of thyroid.[10]
  • Encapusled lesion (surrounded by fibrous capsule).

Gross

  • Thick capsule.

Notes:

  • The entire capsule should be submitted.[11]
    • A good start for most thyroid specimens with a thick capsule is 10 blocks.

Microsopic

Features:

  • Cellular.
  • Thick capsule - key feature.

Negatives.

Graves disease

General

Clinical:

  • TSH-receptor antibody +ve.[12]

Gross

Features:[13]

  • Enlarged 50-150 g.
  • "Beefy-red" appearance, looks like raw beef.

Microscopic

Features:

  • Classic:
    • Hypercellular
    • Patchy lymphocytes.
    • Little colloid.
  • Scalloping of colloid; colloid has undulating border.
    • Non-specific finding.
  • +/-Nuclear clearing.
  • +/-Papillae (may mimic papillary thyroid carcinoma in this respect).

Notes:

  • Usually has an unimpressive appearance... as it is treated, i.e. history is important.
  • Nuclear clearing and papillae are usu. diffuse in Graves disease - unlike in papillary thyroid carcinoma.

Image:

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.[15]

Microscopic

Features:[16][15]

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

DDx:

Images:

Stains

  • ZN -ve.
  • GMS -ve.

Palpation thyroiditis

General

  • Granulomatous inflammation due to palpation.
    • Incidence of granulomas higher in surgical thyroid specimens than autopsies.[15]

Microscopic

Features:[15]

  • 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.

Associated pathology:[18]

Microscopic

Features:

  • Lymphocytic infiltrate - key feature.
  • Nuclear clearing common.
  • Polymorphous lymphoplasmacytic infiltrate with germinal centres.[20]
  • +/-Oncocytic metaplasia.

Notes:

  • Histologically often not possible to separate from "non-specific" thyroiditis.[21]

DDx:

IHC

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

Molecular

C-cell hyperplasia

General

Gross

  • Not visible.

Microscopic

Features:

  • Location:[23]
    • Mid portion of lobe to upper third of lobe.
      • Not at the poles.
      • Not in the isthmus.
  • Definitions vary.[24]

One definition - either of the following:[22]

  1. >50 C-cells per low-power field (x100).
    • This part of the definition suffers from LPFitis. The paper should have been rejected.
  2. Confined to the thyroid gland and no larger than 10 mm in greatest dimension.

Another definition:

  • Invasion of the basement membrane with stromal reaction.

A third definition:

  • "Several clusters" of more than six C cells.

Images:

Malignant neoplasm

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

Papillary thyroid carcinoma

  • Abbreviated PTC.

General

Medical school memory device P's:

  • Palpable nodes.
  • Popular (most common malignant neoplasm of the thyroid).
  • Prognosis is good.
  • Pre-Tx iodine scan.
  • Post-Sx iodine scan.
  • Psammoma bodies.

Notes:

  • PTC is associated with radiation exposure.[25]
  • Papillary thyroid microcarcinoma is defined as a tumour with a maximal dimension of 1.0 cm or less.[26]

Prognosis

Prognosis can be predicted by MAICS score. It which includes:[27]

  • Metastases.
  • Age.
  • Invasion of surround tissues.
  • Ccompleteness of excision.
  • Size of tumour.

Microscopic

Features:

  • Nuclear changes - key feature.
    1. "Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy nuclear membrane -- usu. easy to find.
    2. Nuclear inclusions - usu. harder to find; have high specificity.
    3. Nuclear grooves.
    4. Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
  • Overlap of nuclei - "cells do not respect each other's borders" (easy to see at key feature at low power).
  • Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
    • Absence of papillae does not exclude diagnosis.
  • Psammoma bodies.
    • Circular, acellular, eosinophilic whorled bodies.
    • Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
    • Arise from infarction & calcification of papilla tips.[28]

Notes:

  • Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
    • If there are no papillae structures -- you're unlikely to see psammoma bodies.
  • At low power look for cellular areas/loss of follicles.
  • Nuclear clearing seen in:
    • Hashimoto's and papillary thyroid carcinoma.[29]
    • May be an artifact of fixation/processing.
  • Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
  • Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
  • Papillae may be seen in Graves disease.

DDx:

Subtypes of papillary thyroid carcinoma

There are many.

Poor prognosis variants:

Papillary thyroid carcinoma tall cell variant
General
  • ~10% of PTC.[33]
  • Often large > 6 cm.
Microscopic

Features:[34]

  • 50% of cells with height 2x the width.[35]
    • There is some disagreement on these criteria;[35] Raphael believes the height ought to be ~3x width, for 50% of the cells.[36]
  • Eosinophilic cytoplasm.
  • Well-defined cell borders.
  • Nucleus stratified; basal location, i.e. closer to the basement membrane.

Negative:

  • Nuclei not pseudostratified, if pseudostratified consider columnar cell variant.

Images:

Papillary thyroid carcinoma columnar cell variant
General

Epidemiology:

  • Poor prognosis.
  • Very rare.
Microscopic

Features:[37]

  • Elongated nuclei (similar to colorectal adenocarcinoma) - key feature.
  • +/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from tall cell variant.
  • Nuclear stratification - key feature.
  • "Minimal" papillary features.
  • "Tall cells".
  • Clear-eosinophilic cytoplasm.
  • Mitoses common.

Image: Columnar variant PTC (wiley.com).

Papillary thyroid carcinoma follicular variant
General
  • May be confused with follicular carcinoma or follicular adenoma.
Microscopic

Features:

  • Prominent follicles.
  • Typically have less nuclear pseudoinclusions than the conventional type.
  • +/-Capsule.
Papillary thyroid carcinoma cribriform-morular variant
General
Microscopic

Features:

  • Cribriform architectural pattern.
  • Morules - balls of tissue.
Papillary thyroid carcinoma diffuse sclerosing variant
General
  • Usually young adults, children.
Microscopic

Features:[39]

  • Papillae - usu. prominent.
  • Squamous morules - key features.[40]
  • Lymphocytes - abundant.
  • Fibrosis.

DDx:

  • Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).
Papillary thyroid carcinoma warthin-like variant
Microscopic

Features:[37]

  • Eosinophilic cytoplasm.
  • Lymphocytic thyroiditis.
  • Papillae.
Papillary thyroid carcinoma solid variant

Features:[31]

  • Some studies suggest this has a poor prognosis.
  • More common in children.
  • Associated with Chernobyl nuclear accident.
Microscopic

Features:

  • Solid sheets >50% of tumour mass.[31]

IHC

  • Thyroglobulin +ve.
  • TTF-1 (thyroid transcription factor-1) +ve.
  • CD15 +ve. (???)

Molecular

  • Currently not widely used in a diagnostic context.

Tabular summary

Molecular changes in papillary thyroid carcinoma as per Adeniran et al:[41]

Molecular change Frequency Histology Notes
BRAF point mutations ~ 40% tall cell variant poorer prognosis, older individuals
RET/PTC rearrangments ~ 20% papillary architecture, psammoma bodies younger individuals
RAS point mutations ~ 15% exclusively follicular variant -

Insular carcinoma

General

Features:[42]

  • Rare - approximately 5% of all thyroid carcinomas.
  • Thought to be a separate tumour from papillary thyroid carcinoma and follicular thyroid carcinoma with a focal insular pattern.
  • Some lump this entity with papillary carcinoma, i.e. consider it a variant of papillary thyroid carcinoma.

Microscopic

Features:[42]

  • Islands of cells - key feature.
  • Scant cytoplasm.
  • Nuclei monomorphic and round.

DDx:[43]

Follicular thyroid carcinoma

  • AKA follicular carcinoma.

Clinical

Medical school memory device 4 Fs:

  • FNA NOT diagnosable.
  • Far away mets (sometimes).
  • Female predominant.
  • Favourable prognosis.

Notes:

  • Usu. has a hematologic spread.
    • PTC usu. spread via lymphatics.

Microscopic

Features:

  • Defined by either:
    1. Invasion through the capsule:
      • Should be all the way through.[44]
        • 1/2 does not count.
        • Fibrous reaction does not count.
        • "Above the contour" does not count.
    2. Vascular invasion (all of the following):
      1. In a small vein (not a capillary), that is outside of the tumour mass.
      2. Tumour adherent to the side of the vessel.
      3. Tumour must be re-endothelialized.

Notes:

  • Impossible to differentiate from follicular adenoma on FNA (no cytologic differences).
  • Described as "over-diagnosed" ... misdiagnoses: PTC follicular variant, follicular adenoma, multinodular goitre with a thick capsule.

Images:

Medullary thyroid carcinoma

  • Abbreviated MTC.

General

Medical school memory device - 3 M's:

Epidemiology:

  • Very rare.
  • Poor prognosis.
  • May be genetic (MEN IIa/b syndrome).
  • Arises from C cells (which produce calcitonin).

Syndromic tumours - typically:[45]

Gross

Features:[45]

  • Usu. well-circumscribed.
  • White, gray or yellow.
  • Gritty.
  • Firm.

Image:

Microscopic

Features:

  • Nuclei with "neuroendocrine features".
    • Small, round nuclei.
    • Coarse chromatin (salt and pepper nuclei).
  • +/-Amyloid deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
  • +/-C-cell hyperplasia - seen with familial forms of MTC.
    • C cells (AKA parafollicular cell): abundant cytoplasm - clear/pale.

Note:

  • The amyloid is formed from calcitonin.[46]

Images:

IHC

Features:[47]

  • Calcitonin +ve - it arises from C cells (which produce calcitonin).
  • Congo-red +ve (amyloid present) - mnemonic: CRAP -- congo red amyloid protein.
  • Neuroendocrine markers.
  • CEA +ve (often better staining than calcitonin).[48]
  • Thyroglobulin usu. -ve.[49]

EM

  • Neurosecretory granules.
    • Feature seen in neuroendocrine tumours.

Images: Neurosecretory granules (ucsf.edu).

Anaplastic thyroid carcinoma

Epidemiology

  • Very rare.
  • Horrible prognosis.
  • Often presents with obstruction.
  • Typically there is a history of a thyroid mass.

Microscopic

Features:

Notes:

  • May have features of other thyroid carcinomas, e.g. psammoma bodies, papillae, nuclear changes of PTC.

Image: Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma (WC).

DDx:

IHC

  • Keratin (AE1/AE3) +ve.
  • Vimentin +ve, >90%.[50]
  • Thyroglobulin - rarely +ve (~15%).[50]
  • CEA -ve, calcitonin -ve; to r/o medullary.
  • p53 +ve.
  • TTF-1 +ve.

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.

Images:

DDx:

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:[55]

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

Definite for carcinoma:[55]

  • Lymphovascular invasion.
  • Capsular invasion.

Gross

  • Yellow.
  • Encapsulated.

Microscopic

Features:[56]

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

Negatives:

DDx:[57]

  • 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.[61]

Images:

Stains

  • Fontana-Masson stain +ve.[58]

See also

References

  1. ↑ BEC. 20 October 2009.
  2. ↑ SR. 17 January 2011.
  3. ↑ 3.0 3.1 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 6.0 6.1 6.2 6.3 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 9.0 9.1 9.2 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.
  10. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 51. ISBN 978-0443066856.
  11. ↑ SR. 17 January 2011.
  12. ↑ Massart, C.; Gibassier, J.; d'Herbomez, M. (Sep 2009). "Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay.". Clin Chim Acta 407 (1-2): 62-6. doi:10.1016/j.cca.2009.06.033. PMID 19576193.
  13. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 30. ISBN 978-0443066856.
  14. ↑ URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html. Accessed on: 4 December 2011.
  15. ↑ 15.0 15.1 15.2 15.3 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.
  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. ↑ Ohye, H.; Fukata, S.; Hirokawa, M. (Nov 2007). "[Malignant lymphoma of the thyroid].". Nihon Rinsho 65 (11): 2092-8. PMID 18018576.
  20. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 672. ISBN 978-1416025887.
  21. ↑ 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.
  22. ↑ 22.0 22.1 Machens A, Hoffmann F, Sekulla C, Dralle H (December 2009). "Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer". Endocr. Relat. Cancer 16 (4): 1291–8. doi:10.1677/ERC-09-0136. PMID 19726541. http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291.
  23. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf. Accessed on: 7 April 2012.
  24. ↑ SR. 17 January 2011.
  25. ↑ 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. 564. ISBN 978-0781740517.
  26. ↑ Sethom, A.; Riahi, I.; Riahi, K.; Akkari, K.; Benzarti, S.; Miled, I.; Chebbi, MK. (Jan 2011). "[Management of thyroid microcarcinoma. Report of 13 cases].". Tunis Med 89 (1): 23-5. PMID 21267823.
  27. ↑ Hay, ID.; Thompson, GB.; Grant, CS.; Bergstralh, EJ.; Dvorak, CE.; Gorman, CA.; Maurer, MS.; McIver, B. et al. (Aug 2002). "Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients.". World J Surg 26 (8): 879-85. doi:10.1007/s00268-002-6612-1. PMID 12016468.
  28. ↑ 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. 565. ISBN 978-0781740517.
  29. ↑ 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. 566. ISBN 978-0781740517.
  30. ↑ Baloch, ZW.; LiVolsi, VA. (Jun 2006). "Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens.". Am J Clin Pathol 125 Suppl: S135-44. PMID 16830963.
  31. ↑ 31.0 31.1 31.2 31.3 31.4 Gonzalez-Gonzalez, R.; Bologna-Molina, R.; Carreon-Burciaga, RG.; Gómezpalacio-Gastelum, M.; Molina-Frechero, N.; Salazar-Rodríguez, S. (2011). "Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature.". ISRN Oncol 2011: 915925. doi:10.5402/2011/915925. PMC 3302055. PMID 22432054. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302055/.
  32. ↑ URL: http://emedicine.medscape.com/article/849000-overview#a0104. Accessed on: 1 May 2012.
  33. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 505. ISBN 978-0781779425.
  34. ↑ Urano M, Kiriyama Y, Takakuwa Y, Kuroda M (April 2009). "Tall cell variant of papillary thyroid carcinoma: Its characteristic features demonstrated by fine-needle aspiration cytology and immunohistochemical study". Diagn. Cytopathol.. doi:10.1002/dc.21086. PMID 19373912.
  35. ↑ 35.0 35.1 Ghossein R, Livolsi VA (November 2008). "Papillary thyroid carcinoma tall cell variant". Thyroid 18 (11): 1179–81. doi:10.1089/thy.2008.0164. PMID 18925842.
  36. ↑ S. Raphael. 17 January 2011.
  37. ↑ 37.0 37.1 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 506. ISBN 978-0781779425.
  38. ↑ Groen EJ, Roos A, Muntinghe FL, et al. (September 2008). "Extra-intestinal manifestations of familial adenomatous polyposis". Ann. Surg. Oncol. 15 (9): 2439–50. doi:10.1245/s10434-008-9981-3. PMC 2518080. PMID 18612695. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518080/?tool=pubmed.
  39. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1122. ISBN 978-1416031215.
  40. ↑ Hirokawa, M.; Kuma, S.; Miyauchi, A.; Qian, ZR.; Nakasono, M.; Sano, T.; Kakudo, K.. "Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia.". APMIS 112 (4-5): 275-82. doi:10.1111/j.1600-0463.2004.apm11204-0508.x. PMID 15233643.
  41. ↑ Adeniran, AJ.; Zhu, Z.; Gandhi, M.; Steward, DL.; Fidler, JP.; Giordano, TJ.; Biddinger, PW.; Nikiforov, YE. (Feb 2006). "Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas.". Am J Surg Pathol 30 (2): 216-22. PMID 16434896.
  42. ↑ 42.0 42.1 Rufini V, Salvatori M, Fadda G, et al. (September 2007). "Thyroid carcinomas with a variable insular component: prognostic significance of histopathologic patterns". Cancer 110 (6): 1209–17. doi:10.1002/cncr.22913. PMID 17665497.
  43. ↑ Endo. fellow. 17 September 2009.
  44. ↑ SR. 17 January 2011.
  45. ↑ 45.0 45.1 Nosé, V. (Apr 2011). "Familial thyroid cancer: a review.". Mod Pathol 24 Suppl 2: S19-33. doi:10.1038/modpathol.2010.147. PMID 21455198.
  46. ↑ Khurana, R.; Agarwal, A.; Bajpai, VK.; Verma, N.; Sharma, AK.; Gupta, RP.; Madhusudan, KP. (Dec 2004). "Unraveling the amyloid associated with human medullary thyroid carcinoma.". Endocrinology 145 (12): 5465-70. doi:10.1210/en.2004-0780. PMID 15459123.
  47. ↑ URL: http://pathologyoutlines.com/thyroid.html#medullary. Accessed on: 17 January 2011.
  48. ↑ SB. 7 January 2010.
  49. ↑ de Micco, C.; Chapel, F.; Dor, AM.; Garcia, S.; Ruf, J.; Carayon, P.; Henry, JF.; Lebreuil, G. (Mar 1993). "Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies.". Hum Pathol 24 (3): 256-62. PMID 8454270.
  50. ↑ 50.0 50.1 Ordóñez NG, El-Naggar AK, Hickey RC, Samaan NA (July 1991). "Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases". Am. J. Clin. Pathol. 96 (1): 15–24. PMID 1712540.
  51. ↑ 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.
  52. ↑ 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.
  53. ↑ 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.
  54. ↑ URL: http://path.upmc.edu/cases/case465/dx.html. Accessed on: 17 January 2011.
  55. ↑ 55.0 55.1 55.2 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.
  56. ↑ 56.0 56.1 Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 104. ISBN 978-0443066856.
  57. ↑ 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.
  58. ↑ 58.0 58.1 Sant'Ambrogio, S.; Connelly, J.; DiMaio, D.. "Minocycline pigmentation of heart valves.". Cardiovasc Pathol 8 (6): 329-32. PMID 10615019.
  59. ↑ 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/.
  60. ↑ 60.0 60.1 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.
  61. ↑ 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/.
  62. ↑ URL: http://flylib.com/books/en/2.953.1.50/1/. Accessed on: 11 March 2012.
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