Medullary thyroid carcinoma

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:

aMyloid.
Median node dissection done.
MEN IIa syndrome/MEN IIb syndrome.
- Medullary thyroid carcinoma.
- Pheochromocytoma.
- Parathyroid adenoma.

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]

Present in 30s or 40s.
+/-Multifocal.
+/-Bilateral.
C-cell hyperplasia.

Serology:

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

Gross

Features:^[1]

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

Image:

MTC (nature.com).

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:

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

www:

Parafollicular cells (anatomyatlases.org).

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]

Calcitonin +ve - it arises from C cells (which produce calcitonin).
Neuroendocrine markers.
- Chromogranin A.
- Synaptophysin.
CEA +ve (often better staining than calcitonin).^[5]
Thyroglobulin usu. -ve.^[6]
TTF-1 +ve

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.

References

↑ ^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.
↑ 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.
↑ 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.
↑ URL: http://pathologyoutlines.com/thyroid.html#medullary. Accessed on: 17 January 2011.
↑ SB. 7 January 2010.
↑ 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.

[pmid21455198-1] 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.

[pmid24470736-2] 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.

[pmid15459123-3] 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.

[pmid8454270-6] 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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Medullary thyroid carcinoma

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