Thyroid gland

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The thyroid gland is an important little endocrine organ in the anterior neck. It is not infrequently 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. It frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.

Thyroid specimens

They come in 3 common varieties

  • 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.
  • FNA (fine needle aspiration).

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]

Parathyroid tissue

General:

  • Identification of normal can be tricky.

Features:[5]

  • Low power:
    • May vaguely resemble lymphoid tissue - may have hyperchromatic cytoplasm.
      • Does not have follicular centres like a lymph node.
    • May form gland-like structure and vaguely resemble the thyroid at low power.
    • Cytoplasm may be clear[6] - key feature.
    • Surrounded by a thin fibrous capsule.
  • High power:
    • Mixed cell population:[7]
      • Chief cells - predominant cell type, small, cytoplasm has variable staining (hyperchromatic-clear-eosinophilic).
      • Oxyphil cells (acid staining cells[8]) - abundant cytoplasm.
      • Adipocytes - increased with age, may be used to help differentiate from thyroid - key feature.


Name Staining (cytoplasm) Quantity of cells Cytoplasm (quantity) Function
(parathyroid) chief cells intense hyperchromatic to eosinophilic (see note) abundant moderate manufacture PTH
oxyphil cells moderate/light hyperchromatic to eosinophilic rare abundant ?

Notes:

  • Cytoplasmic staining varies considerably on H&E preparations - it may vary from hyperchromatic[9] to clear to eosinophilic[10].
  • Chief cells tend to stain more intensely than oxyphil cells.

Thyroid vs. parathyroid (see: parathyroid image):

  • Parathyroid cytoplasm:
    • Hyperchromatic.

Parathyroid vs. lymphoid tissue (see parathyroid image):

  • Parathyroid:
    • No germinal centres.
    • Gland-like/follicular-like arrangement -- much smaller than normal follicles of
    • Occasional cell with rim of clear cytoplasm (oxyphil?).

Images:

Parathyroid hyperplasia

  • Parathyroid hyperplasia - classically assoc. with renal failure.
  • Chief cell hyperplasia - associated with MEN I, MEN IIa.[11]

Parathryoid adenoma

  • One parathyroid is big... the others are small.
  • Associated with MEN I and MEN IIa/b (II/III).

MEN I:

MEN IIa/IIb (II/III):

Image: Parathyroid adenoma (med.utah.edu).[12]

Benign

Solid cell nest of thyroid

General

  • Embryonic remnants endodermal origin.[13]
  • Incidental finding.

Microscopic

Features:[13]

  • Solid or cystic cluster or variable size.
  • Cuboidal-to-columnar morphology.
  • Eosinophilic cytoplasm.
  • Round/ovoid nuclei with finely granular chromatin.
  • +/-Goblet cells (~30% of cases).[14]

Image:

DDx:[13]

  • C-cell hyperplasia.
  • Medullary carcinoma.
  • Squamous lesions.

IHC

Features:[13]

  • p63 +ve.
    • -ve in clear cells.
  • CEA +ve (polyconal).[14]
    • +ve also in clear cells.

Nodular hyperplasia

General

  • AKA 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 adenoma

General

  • Most common neoplasm of thyroid.[15]
  • Encapusled lesion (surrounded by fibrous capsule).

Gross

  • Thick capsule.

Notes:

  • The entire capsule should be submitted.[16]
    • A good start for most thyroid specimens with a thick capsule is 10 blocks.

Microsopic

Features:

  • Cellular.

Negatives.

Graves disease

General

  • Often misspelled "Grave's disease".
  • Autoimmune disease leading to hyperthyroidism.
  • Eye problems not resolved with thyroid removal. (???)
  • Higher risk of papillary thyroid carcinoma.

Gross

Features:[17]

  • 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.

Granulomatous thyoiditis

General

  • AKA de Quervain disease, AKA subacute thyroiditis.[18]
  • Women > men.

Microscopic

Features:[19]

Ridel thyroiditis

General

Microscopic

Features:

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

DDx:

  • Anaplastic carcinoma - spindle cell variant.

Hashimoto's thyroiditis

General

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

Associations:[20]

  • Antimicrosomal (antithyroid peroxidase) +ve.
  • Antithyroglobulin +ve.
  • Increased risk of B-cell lymphoma.

Microscopic

Features:

  • Lymphocytic infiltrate.
  • Nuclear clearing common.
    • May confuse with papillary carcinoma.
  • Polymorphous lymphoplasmacytic infiltrate with germinal centres.[21]
  • +/-Oncocytic metaplasia.

Notes:

  • Histologically often not possible to separate from "nonspecific" thyroiditis.[22]

C cell hyperplasia

General

  • Screening for C cell hyperplasia/medullary thyroid carcinoma done with serum calcitonin level.[23]

Microscopic

Features:

  • Definitions vary.[24]

One definition - either of the following:[23]

  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.

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]

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.[27]

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.[28]
    • 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.

Subtypes of papillary thyroid carcinoma

There are many.

Tall cell variant

General

  • ~10% of PTC.[29]
  • Often large > 6 cm.

Microscopic

Features:[30]

  • 50% of cells with height 2x the width.[31][32]
    • There is some disagreement on these criteria;[32] SR believes height ought to be ~3x width, for 50% of the cells.[33]
  • 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.

Columnar cell variant

General

Epidemiology:

  • Poor prognosis.
  • Very rare.

Microscopic

Features:[34]

  • 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).

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.

Cribriform-morular variant

General

Microscopic

Features:

  • Cribriform architectural pattern.
  • Morules - balls of tissue.

Diffuse sclerosing variant

General

  • Usu. young adults, children.

Microscopic

Features:[36]

  • Papillae - usu. prominent.
  • Solid areas with squamous metaplasia.
  • Lymphocytes - abundant.
  • Fibrosis.

DDx:

  • Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).

Warthin-like variant

Microscopic

Features:[34]

  • Eosinophilic cytoplasm.
  • Lymphocytic thyroiditis.
  • Papillae.

Insular carcinoma

General

Features:[37]

  • 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:[37]

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

DDx:[38]

  • Medullary thyroid carcinoma.
  • Poorly differentiated thyroid carcinoma.

Follicular thyroid 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.[39]
        • 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.

Medullary thyroid carcinoma

General

  • Abbreviated MTC.

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).

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 (associated with familial forms of MTC).
    • C cells (AKA parafollicular cell): abundant cytoplasm - clear/pale.

Images:

IHC

Features:[40]

  • 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).[41]

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:

  • Cytologically malignant:
    • Huge NC ratio.
    • Mitoses.
  • +/-Necrosis.

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).
  • Vimentin +ve, >90%.[42]
  • Thyroglobulin - rarely +ve (~15%).[42]
  • 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

General

  • AKA hyalinizing trabecular adenoma.
  • Considered by some (e.g. SL Asa) to be a variant of papillary thyroid carcinoma.[43]
  • Behaviour similar to papillary thyroid carcinoma - indolent.

Microscopic

Features:[44]

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

Image:

DDx:

  • Papillary thyroid carcinoma (if one believes this is a separate entity).
  • Medullary thyroid carcinoma.
  • Paraganglioma.[45]

IHC

  • Thyroglobulin +ve.
  • NSE +ve.

Hürthle cell neoplasm

  • This is a general category.
  • AKA oncocytic neoplasm.

DDx:

  • Hürthle cell adenoma.
  • Hürthle cell carcinoma.

General

  • Uncommon.

Gross

  • Yellow.
  • Encapsulated.

Microscopic

Features:

  • Oncocytes:
    • Abundant eosinophilic cytoplasm.

Negatives:

  • Lack nuclear features of papillary thyroid carcinoma.
  • Lack features of medullary thyroid carcinoma.

DDx:[46]

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

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. ↑ http://www.medicalhistology.us/twiki/pub/Main/ChapterFourteenSlides/b56b_parathyroid_40x_he_labeled.jpg
  6. ↑ http://pathology.mc.duke.edu/research/Histo_course/parathyroid2.jpg
  7. ↑ http://www.bu.edu/histology/p/15002loa.htm
  8. ↑ http://dictionary.reference.com/search?q=oxyphil%20cell
  9. ↑ http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg
  10. ↑ http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm
  11. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970475-2. Accessed on: 29 July 2010.
  12. ↑ URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html. Accessed on: 6 December 2010.
  13. ↑ 13.0 13.1 13.2 13.3 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.
  14. ↑ 14.0 14.1 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.
  15. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 51. ISBN 978-0443066856.
  16. ↑ SR. 17 January 2011.
  17. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 30. ISBN 978-0443066856.
  18. ↑ SR. 17 January 2011.
  19. ↑ 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.
  20. ↑ 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.
  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. ↑ 23.0 23.1 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.
  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. ↑ 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.
  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. 566. ISBN 978-0781740517.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ http://pathologyoutlines.com/thyroid.html#tallcellvariant
  32. ↑ 32.0 32.1 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.
  33. ↑ SR. 17 January 2011.
  34. ↑ 34.0 34.1 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.
  35. ↑ 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.
  36. ↑ 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.
  37. ↑ 37.0 37.1 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.
  38. ↑ Endo. fellow. 17 September 2009.
  39. ↑ SR. 17 January 2011.
  40. ↑ URL: http://pathologyoutlines.com/thyroid.html#medullary. Accessed on: 17 January 2011.
  41. ↑ SB. 7 January 2010.
  42. ↑ 42.0 42.1 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.
  43. ↑ 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.
  44. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)71558-3. Accessed on: 17 January 2011.
  45. ↑ URL: http://path.upmc.edu/cases/case465/dx.html. Accessed on: 17 January 2011.
  46. ↑ 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.
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