Difference between revisions of "Medullary thyroid carcinoma"

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{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Medullary thyroid carcinoma - 2 - high mag.jpg
| Width      =
| Caption    = Medullary thyroid carcinoma. [[H&E stain]].
| Synonyms  =
| Micro      = nuclei with neuroendocrine features (round nuclei with salt-and-pepper chromatin), +/-[[amyloid]] deposits (fluffy appearing acellular eosinophilic material), +/-[[C-cell hyperplasia]]
| Subtypes  =
| LMDDx      =
| Stains    = congo red +ve (amyloid deposits)
| IHC        = calcitonin +ve, [[CEA]] +ve, chromogranin A +ve, synaptophysin +ve, thyroglobulin -ve (usually)
| EM        =
| Molecular  =
| IF        =
| Gross      = usu. well-circumscribed, white, gray or yellow, gritty, firm
| Grossing  =
| Staging    = [[thyroid cancer staging]]
| Site      = [[thyroid gland]]
| Assdx      = [[C-cell hyperplasia]]
| Syndromes  = [[multiple endocrine neoplasia IIa]], [[multiple endocrine neoplasia IIb]]
| Clinicalhx =
| Signs      =
| Symptoms  =
| Prevalence = uncommon
| Bloodwork  = +/-serum calcitonin elevated
| Rads      =
| Endoscopy  =
| Prognosis  = poor
| Other      =
| ClinDDx    =
| Tx        =
}}
'''Medullary thyroid carcinoma''', abbreviated '''MTC''', is an uncommon epithelial [[malignancy]] of the thyroid gland that may be syndromic.
'''Medullary thyroid carcinoma''', abbreviated '''MTC''', is an uncommon epithelial [[malignancy]] of the thyroid gland that may be syndromic.


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*May be genetic (MEN IIa/b syndrome).
*May be genetic (MEN IIa/b syndrome).
*Arises from C cells (which produce calcitonin).
*Arises from C cells (which produce calcitonin).
Sporadic tumours
*~80%
*Slightly older age at presentation (~45)
*Tend to be solitary


Syndromic tumours - typically:<ref name=pmid21455198>{{Cite journal  | last1 = Nosé | first1 = V. | title = Familial thyroid cancer: a review. | journal = Mod Pathol | volume = 24 Suppl 2 | issue =  | pages = S19-33 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.147 | PMID = 21455198 |URL = http://www.nature.com/modpathol/journal/v24/n2s/full/modpathol2010147a.html }}</ref>
Syndromic tumours - typically:<ref name=pmid21455198>{{Cite journal  | last1 = Nosé | first1 = V. | title = Familial thyroid cancer: a review. | journal = Mod Pathol | volume = 24 Suppl 2 | issue =  | pages = S19-33 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.147 | PMID = 21455198 |URL = http://www.nature.com/modpathol/journal/v24/n2s/full/modpathol2010147a.html }}</ref>
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*+/-Bilateral.
*+/-Bilateral.
*[[C-cell hyperplasia]].
*[[C-cell hyperplasia]].
Serology:
*Serum calcitonin classically elevated.<ref name=pmid24470736>{{Cite journal  | last1 = Vainas | first1 = I. | last2 = Marthopoulos | first2 = A. | last3 = Chrisoulidou | first3 = A. | last4 = Raptou | first4 = K. | last5 = Tziomalos | first5 = K. | last6 = Pazaitou-Panayiotou | first6 = K. | title = Calcitonin stimulation tests for the early diagnosis and follow-up of patients with C cell disease: a descriptive analysis. | journal = Hippokratia | volume = 17 | issue = 3 | pages = 246-51 | month = Jul | year = 2013 | doi =  | PMID = 24470736 }}</ref>
*CEA may also be elevated.


==Gross==
==Gross==
Line 33: Line 74:


==Microscopic==
==Microscopic==
Features:
Architecture - various
*Nested with delicate vascular septa
*Trabecular
*Tubular/glandular
*Pseudo-papillary
 
Cells
*Polygonal to spindle to small cells
*Amphophilic, somewhat granular cytoplasm
*Cells may have a more bizarre appearance
*Cells may appear to be 'falling apart'due to interstitial oedema.
 
Stroma
*+/-[[Amyloid]] deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
*Stroma is vascular and can show haemorrhage, hyalinised collagen, oedema or metaplastic bone
*Coarse calcification
*True psammoma bodies may be present
 
Nuclei
*Nuclei with "neuroendocrine features".
*Nuclei with "neuroendocrine features".
**Small, round nuclei.
**Small, round nuclei.
**Coarse chromatin (''salt and pepper nuclei'').
**Coarse chromatin (''salt and pepper nuclei'').
*+/-[[Amyloid]] deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
 
Surrounding Thyroid
*+/-[[C-cell hyperplasia]] - seen with familial forms of MTC.
*+/-[[C-cell hyperplasia]] - seen with familial forms of MTC.
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.
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Note:
Note:
*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>
DDx:
*Other thyroid tumours:
**[[Anaplastic thyroid carcinoma]].
**[[Papillary thyroid carcinoma]].
**[[Hurthle cell carcinoma]]
***The oncocytic variant of medullary carcinoma can be confused with [[Hurthle cell carcinoma]]. Clues to suggest medullary carcinoma:
****Cytoplasm is amphophilic as opposed to eosinophilic
****Nests of tumour cells separated by fibrous septa
*[[C-cell hyperplasia]].
**Invasive medullary carcinoma shows fibrosis around tumor cells and stains more weakly for calcitonin.
*Other neuroendocrine tumours - primary or metastatic:
**[[Paraganglioma]] - negative for keratin, calcitonin and [[CEA]].
**[[Carcinoid]] - negative for calcitonin.
*Metastatic [[melanoma]].
**Pigment.
**Melanoma markers positive, calcitonin and CEA negative.


===Images===  
===Images===  
www:
www:
*[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://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)].
<gallery>
<gallery>
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Image:Medullary_thyroid_carcinoma_-_high_mag.jpg | MTC - high mag. (WC)
Image:Medullary_thyroid_carcinoma_-_high_mag.jpg | MTC - high mag. (WC)
Image: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)
Image:Thyroid MedullaryCarcinoma 216 PA.JPG|Thyroid - Medullary carcinoma - low power (SKB)
Image:Thyroid MedullaryCarcinoma 217 PA.JPG|Thyroid - Medullary carcinoma - low power (SKB)
Image:Thyroid MedullaryCarcinoma Amyloid RBWH.JPG|Thyroid - Medullary carcinoma - amyloid (SKB)
Image:Thyroid MedullaryCarcinoma Amyloid MP3 PA.JPG|Thyroid - Medullary carcinoma - amyloid - medium power (SKB)
Image:Thyroid MedullaryCarcinoma Amyloid MP2 PA.JPG|Thyroid - Medullary carcinoma - amyloid - medium power (SKB)
Image:Thyroid MedullaryCarcinoma Amyloid MP4 PA.JPG|Thyroid - Medullary carcinoma - amyloid - medium power (SKB)
Image:Thyroid MedullaryCarcinoma Amyloid MP PA.JPG|Thyroid - Medullary carcinoma - amyloid - medium power (SKB)
Image:Thyroid MedullaryCarcinoma Amyloid HP PA.JPG|Thyroid - Medullary carcinoma - amyloid - high power (SKB)
Image:Thyroid MedullaryCarcinoma Comedonecrosis LP2 CTR.jpg|Thyroid - Medullary carcinoma - comedonecrosis - low power (SKB)
Image:Thyroid MedullaryCarcinoma Comedonecrosis LP CTR.jpg|Thyroid - Medullary carcinoma - comedonecrosis - medium power (SKB)
Image:Thyroid MedullaryCarcinoma Comedonecrosis HP CTR.jpg|Thyroid - Medullary carcinoma - comedonecrosis - high power (SKB)
Image:Thyroid MedullaryCarcinoma SpindleCell LP PA.JPG|Thyroid - Medullary carcinoma - Spindle cell variant - low power (SKB)
Image:Thyroid MedullaryCarcinoma SpindleCell MP PA.JPG|Thyroid - Medullary carcinoma - Spindle cell variant - medium power (SKB)
Image:Thyroid MedullaryCarcinoma SpindleCell LP2 PA.JPG|Thyroid - Medullary carcinoma - Spindle cell variant - low power (SKB)
Image:Thyroid MedullaryCarcinoma SpindleCell HP PA.JPG|Thyroid - Medullary carcinoma - Spindle cell variant - high power (SKB)
Image:Thyroid MedullaryCarcinoma SmallCell HP PA.JPG|Thyroid - Medullary carcinoma - Small cell variant - high power (SKB)
Image:Thyroid MedullaryCarcinoma SmallCellVariant MP CTR.jpg|Thyroid - Medullary carcinoma - small cell variant - medium power (SKB)
Image:Thyroid MedullaryCarcinoma SmallCellVariant HP CTR (3).jpg|Thyroid - Medullary carcinoma - small cell variant - high power (SKB)
Image:Thyroid MedullaryCarcinoma MP CTR (2).jpg|Thyroid - Medullary carcinoma - medium power (SKB)
Image:Thyroid MedullaryCarcinoma HP2 CTR.jpg|Thyroid - Medullary carcinoma - high power (SKB)
</gallery>
</gallery>
==Stains==
*Congo-red +ve (amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.


==IHC==
==IHC==
Features:<ref>URL: [http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]. Accessed on: 17 January 2011.</ref>
Features:<ref>URL: [http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]. Accessed on: 17 January 2011.</ref>
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*Congo-red +ve (amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.
*Neuroendocrine markers.
*Neuroendocrine markers.
**[[Chromogranin A]].
**[[Chromogranin A]].
**[[Synaptophysin]].
**[[Synaptophysin]].
*CEA +ve (often better staining than calcitonin).<ref>SB. 7 January 2010.</ref>
*[[CEA]] +ve (often better staining than calcitonin).<ref>SB. 7 January 2010.</ref>
*Thyroglobulin usu. -ve.<ref name=pmid8454270>{{Cite journal  | last1 = de Micco | first1 = C. | last2 = Chapel | first2 = F. | last3 = Dor | first3 = AM. | last4 = Garcia | first4 = S. | last5 = Ruf | first5 = J. | last6 = Carayon | first6 = P. | last7 = Henry | first7 = JF. | last8 = Lebreuil | first8 = G. | title = Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. | journal = Hum Pathol | volume = 24 | issue = 3 | pages = 256-62 | month = Mar | year = 1993 | doi =  | PMID = 8454270 }}</ref>
*Thyroglobulin usu. -ve.<ref name=pmid8454270>{{Cite journal  | last1 = de Micco | first1 = C. | last2 = Chapel | first2 = F. | last3 = Dor | first3 = AM. | last4 = Garcia | first4 = S. | last5 = Ruf | first5 = J. | last6 = Carayon | first6 = P. | last7 = Henry | first7 = JF. | last8 = Lebreuil | first8 = G. | title = Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. | journal = Hum Pathol | volume = 24 | issue = 3 | pages = 256-62 | month = Mar | year = 1993 | doi =  | PMID = 8454270 }}</ref>
*TTF-1 +ve


==EM==
==EM==
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Images: [http://pathhsw5m54.ucsf.edu/case7/image77.html Neurosecretory granules (ucsf.edu)].
Images: [http://pathhsw5m54.ucsf.edu/case7/image77.html Neurosecretory granules (ucsf.edu)].
==Sign out==
<pre>
Lesion, Liver, Core Biopsy:
- METASTATIC MEDULLARY THYROID CARCINOMA, see comment.
Comment:
Stains/IHC confirm the morphologic findings; the tumour stains as follows:
POSITIVE: calcitonin, CEAp, synaptophysin, CD56, TTF-1 (focal, moderate), congo red (confirms the presence of amyloid).
NEGATIVE: thyroglobulin, CDX2.
</pre>
===Micro===
The sections show cells of intermediate size without apparent nucleoli, moderate eosinophilic cytoplasm, arranged in nests, focally associated with amorphous acellular cotton candy-like material.
The cotton candy-like material has a light apple-green appearance when polarized.


==See also==
==See also==

Latest revision as of 12:49, 26 April 2018

Medullary thyroid carcinoma
Diagnosis in short

Medullary thyroid carcinoma. H&E stain.
LM nuclei with neuroendocrine features (round nuclei with salt-and-pepper chromatin), +/-amyloid deposits (fluffy appearing acellular eosinophilic material), +/-C-cell hyperplasia
Stains congo red +ve (amyloid deposits)
IHC calcitonin +ve, CEA +ve, chromogranin A +ve, synaptophysin +ve, thyroglobulin -ve (usually)
Gross usu. well-circumscribed, white, gray or yellow, gritty, firm
Staging thyroid cancer staging
Site thyroid gland
Associated Dx C-cell hyperplasia
Syndromes multiple endocrine neoplasia IIa, multiple endocrine neoplasia IIb
Prevalence uncommon
Blood work +/-serum calcitonin elevated
Prognosis poor

Medullary thyroid carcinoma, abbreviated MTC, is an uncommon epithelial malignancy of the thyroid gland that may be syndromic.

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).

Sporadic tumours

  • ~80%
  • Slightly older age at presentation (~45)
  • Tend to be solitary

Syndromic tumours - typically:[1]

Serology:

  • Serum calcitonin classically elevated.[2]
  • CEA may also be elevated.

Gross

Features:[1]

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

Image:

Microscopic

Architecture - various

  • Nested with delicate vascular septa
  • Trabecular
  • Tubular/glandular
  • Pseudo-papillary

Cells

  • Polygonal to spindle to small cells
  • Amphophilic, somewhat granular cytoplasm
  • Cells may have a more bizarre appearance
  • Cells may appear to be 'falling apart'due to interstitial oedema.

Stroma

  • +/-Amyloid deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
  • Stroma is vascular and can show haemorrhage, hyalinised collagen, oedema or metaplastic bone
  • Coarse calcification
  • True psammoma bodies may be present

Nuclei

  • Nuclei with "neuroendocrine features".
    • Small, round nuclei.
    • Coarse chromatin (salt and pepper nuclei).

Surrounding Thyroid

  • +/-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.[3]

DDx:

Images

www:

  • MTC - low mag. (WC)

  • MTC - high mag. (WC)

  • MTC and amyloid - high mag. (WC)

  • Thyroid - Medullary carcinoma - low power (SKB)

  • Thyroid - Medullary carcinoma - low power (SKB)

  • Thyroid - Medullary carcinoma - amyloid (SKB)

  • Thyroid - Medullary carcinoma - amyloid - medium power (SKB)

  • Thyroid - Medullary carcinoma - amyloid - medium power (SKB)

  • Thyroid - Medullary carcinoma - amyloid - medium power (SKB)

  • Thyroid - Medullary carcinoma - amyloid - medium power (SKB)

  • Thyroid - Medullary carcinoma - amyloid - high power (SKB)

  • Thyroid - Medullary carcinoma - comedonecrosis - low power (SKB)

  • Thyroid - Medullary carcinoma - comedonecrosis - medium power (SKB)

  • Thyroid - Medullary carcinoma - comedonecrosis - high power (SKB)

  • Thyroid - Medullary carcinoma - Spindle cell variant - low power (SKB)

  • Thyroid - Medullary carcinoma - Spindle cell variant - medium power (SKB)

  • Thyroid - Medullary carcinoma - Spindle cell variant - low power (SKB)

  • Thyroid - Medullary carcinoma - Spindle cell variant - high power (SKB)

  • Thyroid - Medullary carcinoma - Small cell variant - high power (SKB)

  • Thyroid - Medullary carcinoma - small cell variant - medium power (SKB)

  • Thyroid - Medullary carcinoma - small cell variant - high power (SKB)

  • Thyroid - Medullary carcinoma - medium power (SKB)

  • Thyroid - Medullary carcinoma - high power (SKB)

Stains

  • Congo-red +ve (amyloid present) - mnemonic: CRAP -- congo red amyloid protein.

IHC

Features:[4]

EM

  • Neurosecretory granules.
    • Feature seen in neuroendocrine tumours.

Images: Neurosecretory granules (ucsf.edu).

Sign out

Lesion, Liver, Core Biopsy:
- METASTATIC MEDULLARY THYROID CARCINOMA, see comment.

Comment:
Stains/IHC confirm the morphologic findings; the tumour stains as follows:
POSITIVE: calcitonin, CEAp, synaptophysin, CD56, TTF-1 (focal, moderate), congo red (confirms the presence of amyloid).
NEGATIVE: thyroglobulin, CDX2.

Micro

The sections show cells of intermediate size without apparent nucleoli, moderate eosinophilic cytoplasm, arranged in nests, focally associated with amorphous acellular cotton candy-like material.

The cotton candy-like material has a light apple-green appearance when polarized.

See also

References

  1. ↑ 1.0 1.1 Nosé, V. (Apr 2011). "Familial thyroid cancer: a review.". Mod Pathol 24 Suppl 2: S19-33. doi:10.1038/modpathol.2010.147. PMID 21455198.
  2. ↑ Vainas, I.; Marthopoulos, A.; Chrisoulidou, A.; Raptou, K.; Tziomalos, K.; Pazaitou-Panayiotou, K. (Jul 2013). "Calcitonin stimulation tests for the early diagnosis and follow-up of patients with C cell disease: a descriptive analysis.". Hippokratia 17 (3): 246-51. PMID 24470736.
  3. ↑ 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.
  4. ↑ URL: http://pathologyoutlines.com/thyroid.html#medullary. Accessed on: 17 January 2011.
  5. ↑ SB. 7 January 2010.
  6. ↑ 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.
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