Thyroid gland
Other carcinoma
Medullary carcinoma

Author: Shahidul Islam, M.D., Ph.D. (see Authors page)

Revised: 2 February 2017, last major update March 2009

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: medullary carcinoma thyroid

Related Topics: Microcarcinoma, Mixed medullary-follicular tumors, Paraganglioma-like variant, Small cell variant, Tubular (follicular) variant
Cite this page: Medullary carcinoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/thyroidmedullary.html. Accessed February 23rd, 2017.
Definition / General
  • Neuroendocrine tumor derived from C cells (formerly called parafollicular cells) of ultimobranchial body of neural crest, which secrete calcitonin
  • 5 - 10% of thyroid carcinomas
Terminology
  • Either sporadic (nonhereditary) or hereditary (familial)
  • Sporadic: 75 - 80%, age 40 - 60 years, solitary, usually have paraneoplastic syndromes (diarrhea from VIP, Cushing's syndrome), dysphagia and hoarseness from tumor bulk
  • Familial: 20 - 25%, younger patients (mean age 35 years)
    • Due to MEN 2A or 2B syndromes (have germ line mutations in RET proto-oncogene, Orphanet J Rare Dis 2006;1:45), familial medullary thyroid carcinoma syndrome, von Hippel-Lindau disease or neurofibromatosis
    • Usually bilateral, multicentric with C cell hyperplasia
    • Usually discovered by screening test for serum calcitonin or peripheral blood RET oncogene mutational analysis
Clinical Features
  • Invades locally, metastases to cervical and mediastinal nodes, lung, liver and bone; metastases may be initial presentation of disease and usually contain amyloid
Laboratory
  • High serum calcitonin and chromogranin A levels
  • Can monitor for recurrence with calcitonin levels
  • Only rarely negative for serum calcitonin (World J Surg Oncol 2006;4:97)
Prognostic Factors
Case Reports
Treatment
  • Total thyroidectomy (particularly for familial forms) with cervical lymphadenectomy for node positive patients
Gross Description
  • Single or multiple
  • Typically nonencapsulated
  • Solid, gray / tan / yellow, firm, may be infiltrative
  • Larger lesions have hemorrhage and necrosis, tumor usually in mid or upper portion of gland (with higher concentration of C cells)
Gross Images

Images hosted on PathOut server:

MEN 2A patient with multiple tumor foci (arrows)

Contributed by Dr. Mark R. Wick

Multifocal in MEN2, contributed by Dr. Mark R. Wick



AFIP Images:

Nonfamilial tumor replaces entire left lobe and isthmus

Nodal metastasis

MEN2A patient #1 with single tumor focus

#2 - Tumor of left lobe is
well circumscribed and
fleshy, tumor of right
lobe is finely granular



Images hosted on other servers:

Well circumscribed tumor

Large tumor with
hemorrhage, necrosis
and cystic degeneration

Micro Description
  • Round, polygonal or spindle cells in nests, cords or follicles, defined by sharply outlined fibrous bands
  • Tumor cells have granular cytoplasm and uniform round / oval nuclei with punctate chromatin
  • Stroma has amyloid deposits from calcitonin, prominent vascularity with glomeruloid configuration or long cords of vessels (Am J Surg Pathol 1995;19:642), coarse calcifications
  • Mucin in 42% (Arch Pathol Lab Med 1983;107:70)
  • Often angiolymphatic invasion
  • Occasionally marked neutrophilic infiltrate, oncocytic tumor cells, papillary patterns
  • May entrap follicles
  • C cell hyperplasia present in familial but not sporadic cases
Micro Images

Scroll to see all images.


Images hosted on PathOut server:

AFIP Images:

Lobular pattern accentuated by shrinkage artifact

Solid pattern with small spindle cells

Papillary pattern and extensive inflammatory infiltrate

Pseudopapillary pattern

Encapsulated variant


Amphicrine-type

Round cells in nests

Round cells in nests with plasmacytoid nuclei

Polygonal cells with abundant cytoplasm

Spindle cells


Clusters of giant cells

Clear cells

Clear cells with large mucin filled vacuoles

Vascular invasion

Familial MTC
(bottom) with
amyloid, C cell
hyperplasia (arrows)


With melanin pigment

Oncocytic foci

Oncocytic variant (left: H&E, right: calcitonin)

With squamous cell carcinoma and necrosis

Metastases to
cervical lymph
node are present
in peripheral sinus



Amyloid (AFIP):

Prominent amyloid deposits

Amyloid replaces
almost entire
tumor, is calcified
at periphery

Congo Red+ amyloid deposit

Apple green birefringence
with Congo Red stain
and polarized light



Amyloid, contributed by Dr. Mark R. Wick:

Various images

With amyloid stroma

Polarized congo red



Contributed by Dr. Mark R. Wick:

Various images

Dedifferentiated-anaplastic

Oncocytic variant


Pseudopapillary variant

Signet ring cell variant



Stain images (AFIP):

Calcitonin

Variable calcitonin staining

Calcitonin+ liver metastasis

Low molecular weight keratin

Neuron specific enolase


CEA

Chromogranin A

Grimelius stain demonstrates fine argyrophilic granules

Thyroglobulin stains entrapped follicles, not tumor cells



Stain images, contributed by Dr. Mark R. Wick:

CEA

Calcitonin

Chromogranin

Congo red



Images hosted on other servers:

Spindle cells

Tumor nodules

Oncocytic variant

Papillary variant


Amyloid


MEN2A patient with small tumor

MEN2A patient, tumor nodules and hyperplastic C cells

Tumor cells have
abundant cytoplasm,
round nuclei, finely
dispersed chromatin



Amyloid:

Congo Red



Papillary and medullary carcinomas:

Various images

Follicular variant of
papillary thyroid carcinoma (left)
and medullary carcinoma (right)



Stain images:

Calcitonin

Weak calcitonin staining

CEA

Virtual Slides

H&E

Cytology Description
  • Highly cellular, syncytial arrangement of plasmacytoid (eccentric nuclei, uni- or binucleated), spindle and polygonal cells, cells have abundant cytoplasm, occasionally pink azurophilic granules and intranuclear inclusions, amyloid present occasionally (Am J Clin Pathol 1984;82:552)
Cytology Images

Images hosted on other servers:

Dyscohesive plasmacytoid cells

Spindled cells with scanty ill defined cytoplasm

Orange granular amyloid material

Spindle cells

Atypical spindle cells

Positive Stains
Electron Microscopy Description
  • Single membrane bound electron dense granules in cytoplasm
Electron Microscopy Images

Images hosted on PathOut server:

AFIP Images:

Amyloid deposits have amorphous or finely fibrillary structure

Numerous large type I granules in some cells

Tumor cells with sparse granules

Molecular / Cytogenetics Description
  • Activating mutations of RET different from those in papillary carcinoma
Differential Diagnosis
  • Hürthle cell carcinoma: eosinophilic not amphophilic cytoplasm, no fibrous bands dividing cells into nests
  • Insular carcinoma: thyroglobulin positive, calcitonin negative, no amyloid
  • Metastatic neuroendocrine carcinoma: primary often discovered only on followup; primarily interstitial spread, multiple tumor foci, folliculotropism and rosettes, negative for calcitonin, focal / negative for CEA (Am J Surg Pathol 1997;21:754)
Additional References