Difference between revisions of "Medullary thyroid carcinoma"

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Line 9: Line 9:
| LMDDx      =
| LMDDx      =
| Stains    = congo red +ve (amyloid deposits)
| Stains    = congo red +ve (amyloid deposits)
| IHC        = calcitonin +ve, CEA +ve, chromogranin A +ve, synaptophysin +ve, thyroglobulin -ve (usually)
| IHC        = calcitonin +ve, [[CEA]] +ve, chromogranin A +ve, synaptophysin +ve, thyroglobulin -ve (usually)
| EM        =
| EM        =
| Molecular  =
| Molecular  =
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| Gross      = usu. well-circumscribed, white, gray or yellow, gritty, firm
| Gross      = usu. well-circumscribed, white, gray or yellow, gritty, firm
| Grossing  =
| Grossing  =
| Staging    = [[thyroid cancer staging]]
| Site      = [[thyroid gland]]
| Site      = [[thyroid gland]]
| Assdx      = [[C-cell hyperplasia]]
| Assdx      = [[C-cell hyperplasia]]
Line 83: Line 84:
*Amphophilic, somewhat granular cytoplasm
*Amphophilic, somewhat granular cytoplasm
*Cells may have a more bizarre appearance
*Cells may have a more bizarre appearance
*Good clue is the interstitial oedema, giving the appearance that the cells are 'falling apart'
*Cells may appear to be 'falling apart'due to interstitial oedema.


Stroma
Stroma
Line 104: Line 105:


DDx:
DDx:
Other thyroid tumor
*Other thyroid tumours:
*[[Anaplastic thyroid carcinoma]].
**[[Anaplastic thyroid carcinoma]].
*[[Papillary thyroid carcinoma]].
**[[Papillary thyroid carcinoma]].
*[[Hurthle cell carcinoma]]
**[[Hurthle cell carcinoma]]
**The oncocytic variant of medullary carcinoma can be confused with Hurthle cell carcinoma. Clues to suggest medullary 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  
****Cytoplasm is amphophilic as opposed to eosinophilic  
***Nests of tumour cells separated by fibrous septa
****Nests of tumour cells separated by fibrous septa
*[[C-cell hyperplasia]]
*[[C-cell hyperplasia]].
**Invasive medullary carcinoma shows fibrosis around tumor cells and stains more weakly for calcitonin.
**Invasive medullary carcinoma shows fibrosis around tumor cells and stains more weakly for calcitonin.
 
*Other neuroendocrine tumours - primary or metastatic:
Other neuroendocrine tumor (primary or metastatic)
**[[Paraganglioma]] - negative for keratin, calcitonin and [[CEA]].
*[[Paraganglioma]] - Negative for keratin, calcitonin and CEA
**[[Carcinoid]] - negative for calcitonin.
*[[Carcinoid]] - Negative for calcitonin
*Metastatic [[melanoma]].
*[[Melanoma]] -
**Pigment.
**Pigment -
**Melanoma markers positive, calcitonin and CEA negative.
**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>
Line 163: Line 159:
**[[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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