Difference between revisions of "Thyroid gland"

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*The amyloid is formed from ''calcitonin''.<ref name=pmid15459123>{{Cite journal  | last1 = Khurana | first1 = R. | last2 = Agarwal | first2 = A. | last3 = Bajpai | first3 = VK. | last4 = Verma | first4 = N. | last5 = Sharma | first5 = AK. | last6 = Gupta | first6 = RP. | last7 = Madhusudan | first7 = KP. | title = Unraveling the amyloid associated with human medullary thyroid carcinoma. | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5465-70 | month = Dec | year = 2004 | doi = 10.1210/en.2004-0780 | PMID = 15459123 }}</ref>
*The amyloid is formed from ''calcitonin''.<ref name=pmid15459123>{{Cite journal  | last1 = Khurana | first1 = R. | last2 = Agarwal | first2 = A. | last3 = Bajpai | first3 = VK. | last4 = Verma | first4 = N. | last5 = Sharma | first5 = AK. | last6 = Gupta | first6 = RP. | last7 = Madhusudan | first7 = KP. | title = Unraveling the amyloid associated with human medullary thyroid carcinoma. | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5465-70 | month = Dec | year = 2004 | doi = 10.1210/en.2004-0780 | PMID = 15459123 }}</ref>


Images:
====Images====
*www:
www:
**[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
*[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
**[http://www.nature.com/ki/journal/v70/n11/fig_tab/5001888f2.html C cell hyperplasia (nature.com)].
*[http://www.nature.com/ki/journal/v70/n11/fig_tab/5001888f2.html C cell hyperplasia (nature.com)].
**[http://lifesci.rutgers.edu/~babiarz/Review3/Lp6/scope8.htm C cell (rutgers.edu)].
*[http://lifesci.rutgers.edu/~babiarz/Review3/Lp6/scope8.htm C cell (rutgers.edu)].
**[http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate287.jpg Parafollicular cells (anatomyatlases.org)].
*[http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate287.jpg Parafollicular cells (anatomyatlases.org)].
*[[WC]]:
<gallery>
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_low_mag.jpg MTC - low mag. (WC)].
Image:Medullary_thyroid_carcinoma_-_low_mag.jpg | MTC - low mag. (WC)
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg MTC - high mag. (WC)].
Image:Medullary_thyroid_carcinoma_-_high_mag.jpg | MTC - high mag. (WC)
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_2_-_high_mag.jpg MTC and amyloid - high mag. (WC)].
Image:Medullary_thyroid_carcinoma_-_2_-_high_mag.jpg | MTC and amyloid - high mag. (WC)
</gallery>


===IHC===
===IHC===

Revision as of 04:40, 19 November 2013

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

  • 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

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

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.

Gross

Features:

  • Enlarge thyroid gland.
  • +/-Distinct (well-circumscribed) nodules.

Microscopic

Features:

  • Follicles of variable size - key feature.
    • Should be obvious at low power, i.e. with the 2.5x objective.
  • +/-Nodules.
    • Do not have a thick fibrous capsule.
    • May have a high cellularity.
    • Architecture: solid or microfollicular.[13]

Negatives:

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

DDx:

Sign out

HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- CELLULAR ADENOMATOID NODULE ON A BACKGROUND OF NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.

Follicular thyroid adenoma

  • AKA follicular adenoma, AKA thyroid follicular adenoma.

General

  • Most common neoplasm of thyroid.[14]
  • Encapusled lesion (surrounded by fibrous capsule).

Gross

  • Thick capsule.

Notes:

  • The entire capsule should be submitted.[15]
    • A good start for most thyroid specimens with a thick capsule is 10 blocks.

Microsopic

Features:

  • Cellular.
  • Thick capsule - key feature.

Negatives.

DDx:

Graves disease

General

Clinical:

  • TSH-receptor antibody +ve.[16]

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.

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.[19]

Clinical:

Microscopic

Features:[21][19]

  • 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.[19]

Microscopic

Features:[19]

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

DDx:

Stains

  • ZN -ve.
  • GMS -ve.

Riedel thyroiditis

  • AKA invasive fibrous thyroiditis.[22]

General

Clinical features:[22]

  • 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:[23]

  • Antimicrosomal (antithyroid peroxidase) +ve.
  • Antithyroglobulin +ve.

Associated pathology:[23]

Microscopic

Features:

  • Lymphocytic infiltrate - key feature.
  • Nuclear clearing common.
  • Polymorphous lymphoplasmacytic infiltrate with germinal centres.[25]
  • +/-Oncocytic metaplasia.

Notes:

  • Histologically often not possible to separate from "non-specific" thyroiditis.[26]

DDx:

IHC

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

Molecular

C-cell hyperplasia

  • Abbreviated CCH.

General

Gross

  • Not visible.

Microscopic

Features:

  • Location:[28]
    • Mid portion of lobe to upper third of lobe.
      • Not at the poles.
      • Not in the isthmus.
  • Definitions vary.[29]

One definition - either of the following:[27]

  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.

Insular carcinoma

General

Features:[32]

  • 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:[32]

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

DDx:[33]

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.[34]
        • 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:[35]

Gross

Features:[35]

  • 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.[36]

Images

www:

IHC

Features:[37]

  • 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).[38]
  • Thyroglobulin usu. -ve.[39]

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%.[40]
  • Thyroglobulin - rarely +ve (~15%).[40]
  • CEA -ve, calcitonin -ve; to r/o medullary.
  • p53 +ve.
  • TTF-1 +ve.

Lymphomas of the thyroid

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

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:[45]

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

Definite for carcinoma:[45]

  • Lymphovascular invasion.
  • Capsular invasion.

Gross

  • Yellow.
  • Encapsulated.

Microscopic

Features:[46]

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

Negatives:

DDx:[47]

  • 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.[51]

Images:

Stains

  • Fontana-Masson stain +ve.[48]

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.
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  18. URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html. Accessed on: 4 December 2011.
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  28. URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf. Accessed on: 7 April 2012.
  29. SR. 17 January 2011.
  30. Guyétant, S.; Josselin, N.; Savagner, F.; Rohmer, V.; Michalak, S.; Saint-André, JP. (Aug 2003). "C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients.". Mod Pathol 16 (8): 756-63. doi:10.1097/01.MP.0000081727.75778.0C. PMID 12920219.
  31. URL: http://www.forpath.org/workshops/0201/html/case_7.asp. Accessed on: 21 May 2013.
  32. 32.0 32.1 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.
  33. Endo. fellow. 17 September 2009.
  34. SR. 17 January 2011.
  35. 35.0 35.1 Nosé, V. (Apr 2011). "Familial thyroid cancer: a review.". Mod Pathol 24 Suppl 2: S19-33. doi:10.1038/modpathol.2010.147. PMID 21455198.
  36. 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.
  37. URL: http://pathologyoutlines.com/thyroid.html#medullary. Accessed on: 17 January 2011.
  38. SB. 7 January 2010.
  39. 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.
  40. 40.0 40.1 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.
  41. 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.
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