Difference between revisions of "Thyroid gland"

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*p63 +ve.
*p63 +ve.
**-ve in clear cells.
**-ve in clear cells.
*CEA +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
*[[CEA]] +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
**+ve also in clear cells.
**+ve also in clear cells.
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>
Line 207: Line 207:
==Riedel thyroiditis==
==Riedel thyroiditis==
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal  | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal  | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
===General===
{{Main|Riedel thyroiditis}}
Clinical features:<ref name=pmid21568724/>
*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:
*[[Anaplastic thyroid carcinoma|Anaplastic carcinoma]], spindle cell variant.


==Hashimoto thyroiditis==
==Hashimoto thyroiditis==
Line 230: Line 215:
*Abbreviated ''CCH''.
*Abbreviated ''CCH''.
{{Main|C-cell hyperplasia}}
{{Main|C-cell hyperplasia}}
==Adenolipoma of the thyroid==
{{Main|Adenolipoma of the thyroid}}


=Malignant neoplasm=
=Malignant neoplasm=
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*[[AKA]] ''hyalinizing trabecular adenoma''.
*[[AKA]] ''hyalinizing trabecular adenoma''.
*Abbreviated ''HTT''.
*Abbreviated ''HTT''.
===General===
{{Main|Hyalinizing trabecular tumour}}
*Considered by some (e.g. Silvia Asa) to be a variant of [[papillary thyroid carcinoma]].<ref name=pmid11117782>{{cite journal |author=Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL |title=Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics |journal=Am. J. Surg. Pathol. |volume=24 |issue=12 |pages=1622–6 |year=2000 |month=December |pmid=11117782 |doi= |url=}}</ref>
*Behaviour similar to papillary thyroid carcinoma - indolent.
 
===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:
*[[Papillary thyroid carcinoma]] (if one believes this is a separate entity).
*[[Medullary thyroid carcinoma]] - not trabecular, nuclei not [[PTC]]-like.
*[[Paraganglioma]].<ref>URL: [http://path.upmc.edu/cases/case465/dx.html http://path.upmc.edu/cases/case465/dx.html]. Accessed on: 17 January 2011.</ref>
 
====Images====
<gallery>
Image: Hyalinized trabecular tumour - low mag.jpg | HHT - low mag. (WC)
Image: Hyalinized trabecular tumour - intermed mag.jpg | HHT - intermed. mag. (WC)
Image: Hyalinized trabecular tumour - high mag.jpg | HHT - high mag. (WC)
Image: Thyroid gland - high mag.jpg | Thyroid gland - high mag. (WC)
 
Image: Hyalinized trabecular tumour - 2 - intermed mag.jpg | HHT - intermed. mag. (WC)
Image: Hyalinized trabecular tumour - 2 - high mag.jpg | HHT - high mag. (WC)
 
Image: Hyalinized trabecular tumour - 3 - intermed mag.jpg | HHT - intermed. mag. (WC)
Image: Hyalinized trabecular tumour - 3 - high mag.jpg | HHT - high mag. (WC)
Image: Hyalinized trabecular tumour - 3 - very high mag.jpg | HHT - very high mag. (WC)
</gallery>
www:
*[http://archive.biomedcentral.com/1742-6413/3/17/figure/F2?highres=y HTT (biomedcentral.com)].<ref name=pmid16867191>{{Cite journal  | last1 = Baloch | first1 = ZW. | last2 = Puttaswamy | first2 = K. | last3 = Brose | first3 = M. | last4 = LiVolsi | first4 = VA. | title = Lack of BRAF mutations in hyalinizing trabecular neoplasm. | journal = Cytojournal | volume = 3 | issue =  | pages = 17 | month =  | year = 2006 | doi = 10.1186/1742-6413-3-17 | PMID = 16867191 }}</ref>
*[http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.article-g01.fs.jpg HTT (ispub.com)].<ref>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 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.</ref>
 
===IHC===
*Thyroglobulin +ve.
*NSE +ve.


==Hürthle cell neoplasm==
==Hürthle cell neoplasm==
*[[AKA]] ''oncocytic neoplasm''.
*[[AKA]] ''oncocytic neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.
 
{{Main|Hürthle cell neoplasm}}
===General===
*Incidence: uncommon.
*This is a general category - includes:
**Hürthle cell adenoma.
**Hürthle cell carcinoma.
 
*Some advocate ''total thyroidectomy'' for all Hürthle cell neoplasms, as it is difficult to reliably differentiate adenomas and carcinomas.<ref name=pmid9697901>{{Cite journal  | last1 = Wasvary | first1 = H. | last2 = Czako | first2 = P. | last3 = Poulik | first3 = J. | last4 = Lucas | first4 = R. | title = Unilateral lobectomy for Hurthle cell adenoma. | journal = Am Surg | volume = 64 | issue = 8 | pages = 729-32; discussion 732-3 | month = Aug | year = 1998 | doi =  | PMID = 9697901 }}</ref>
*It can be understood as a special type of ''follicular neoplasm'' (including ''[[follicular thyroid adenoma]]'' and ''[[follicular thyroid carcinoma]]'').<ref name=Ref_EP104>{{Ref EP|104}}</ref>
*High stage HCC has a poor prognosis.<ref name=pmid25259908>{{Cite journal  | last1 = Chindris | first1 = AM. | last2 = Casler | first2 = JD. | last3 = Bernet | first3 = VJ. | last4 = Rivera | first4 = M. | last5 = Thomas | first5 = C. | last6 = Kachergus | first6 = JM. | last7 = Necela | first7 = BM. | last8 = Hay | first8 = ID. | last9 = Westphal | first9 = SA. | title = Clinical and molecular features of Hürthle cell carcinoma of the thyroid. | journal = J Clin Endocrinol Metab | volume = 100 | issue = 1 | pages = 55-62 | month = Jan | year = 2015 | doi = 10.1210/jc.2014-1634 | PMID = 25259908 }}</ref>
 
====Adenoma vs. carcinoma====
Suggestive for carcinoma:<ref name=pmid9697901/>
*Male.
*>4 cm
**Adenomas usu. <3 cm.
Definite for carcinoma:<ref name=pmid9697901/>
*Lymphovascular invasion.
*Capsular invasion.
 
===Gross===
*Yellow.
*Encapsulated.
 
===Microscopic===
Features:<ref name=Ref_EP104>{{Ref EP|104}}</ref>
*Oncocytes >= 75% of cells:
**Abundant granular, eosinophilic cytoplasm.
**Round regular nucleus +/- prominent nucleolus.
*+/-Degenerative changes.
 
Negatives:
*Lack nuclear features of [[papillary thyroid carcinoma]].
*Lack features of [[medullary thyroid carcinoma]].
 
DDx:<ref name=pmid18684023>{{cite journal |author=Montone KT, Baloch ZW, LiVolsi VA |title=The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=8 |pages=1241–50 |year=2008 |month=August |pmid=18684023 |doi= |url=}}</ref>
*Papillary thyroid carcinoma oncocytic variant.
*Medullary thyroid carcinoma oncocytic variant.
*Others.
 
===IHC===
Features:
*TTF-1 (2 of 6 cases<ref name=pmid10981870>{{Cite journal  | last1 = Bejarano | first1 = PA. | last2 = Nikiforov | first2 = YE. | last3 = Swenson | first3 = ES. | last4 = Biddinger | first4 = PW. | title = Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms. | journal = Appl Immunohistochem Mol Morphol | volume = 8 | issue = 3 | pages = 189-94 | month = Sep | year = 2000 | doi =  | PMID = 10981870 }}</ref>).
*Thyroglobulin (6 of 6 cases<ref name=pmid10981870/>).
*CK7 (4 of 6 cases<ref name=pmid10981870/>).


==Minocycline associated thyroid pigmentation==
==Minocycline associated thyroid pigmentation==
Line 389: Line 297:
===Stains===
===Stains===
*[[Fontana-Masson stain]] +ve.<ref name=pmid10615019>{{Cite journal  | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month =  | year =  | doi =  | PMID = 10615019 }}</ref>
*[[Fontana-Masson stain]] +ve.<ref name=pmid10615019>{{Cite journal  | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month =  | year =  | doi =  | PMID = 10615019 }}</ref>
==Sclerosing mucoepidermoid carcinoma with eosinophilia==
{{Main|Sclerosing mucoepidermoid carcinoma with eosinophilia}}


=See also=
=See also=

Latest revision as of 03:43, 20 March 2018

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]
Main article: Riedel thyroiditis

Hashimoto thyroiditis

Main article: Hashimoto's thyroiditis

C-cell hyperplasia

  • Abbreviated CCH.
Main article: C-cell hyperplasia

Adenolipoma of the thyroid

Main article: Adenolipoma of the thyroid

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.
Main article: Hyalinizing trabecular tumour

Hürthle cell neoplasm

  • AKA oncocytic neoplasm.
  • Also spelled Hurthle cell neoplasm.
Main article: Hürthle cell neoplasm

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.[22]

Images

Stains

Sclerosing mucoepidermoid carcinoma with eosinophilia

Main article: Sclerosing mucoepidermoid carcinoma with eosinophilia

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. ↑ 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 Sant'Ambrogio, S.; Connelly, J.; DiMaio, D.. "Minocycline pigmentation of heart valves.". Cardiovasc Pathol 8 (6): 329-32. PMID 10615019.
  19. ↑ Geria AN, Tajirian AL, Kihiczak G, Schwartz RA (2009). "Minocycline-induced skin pigmentation: an update". Acta Dermatovenerol Croat 17 (2): 123–6. PMID 19595269.
  20. ↑ 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/.
  21. ↑ 21.0 21.1 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.
  22. ↑ 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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