Medullary Carcinoma
Epidemiology:
- Peak incidence 40s-50s (sporadic)
- MEN-2a and FMTC:
- MEN-2b
Common sites:
Gross features:
- solitary or multiple
- firm
- pale gray to tan
- infiltrative, non-encapsulated
- multicentric in familial cases
- necrosis, hemorrhage often
- may extend outside thyroid “capsule”
Histologic features:
- nests, trabecullae, follicles
- polygonal to spindle cells
- indistinct cell borders
- may contain small, more anaplastic cells, even
predominantly
- may be Hurthle
cells
- amyloid deposits in stroma often (derived from
calcitonin molecules)
- familial cases:
- C-cell hyperplasia in surrounding thyroid
parenchyma
Cytologic features:
- Dispersed cellular infiltrate
- Moderate to high cellularity
- Poorly cohesive cells
- Variable cell size and shape
- Polygonal, ovoid, or spindled shape most
commonly
- Pleomorphism in size and shape maybe
- Mixed cell population is a clue to medullary CA
- Often eccentric nuclei in the polygonal or
ovoid cell types
- Multinucleate cells maybe
- Occasional bizarre giant cells maybe
- Cytoplasmic granularity
- MGG stain – fine, typically pink, cytoplasmic
granularity in a proportion of cells
- May be evident in Pap stain but less so
- Calcitonin positive on IHC
- Typically speckled chromatin pattern
- Nucleoli small and inconspicuous
- Nuclear pleomorphism
maybe
- Occasional nuclear grooves and intranuclear cytoplasmic inclusions maybe
- Mitoses rare
- Amyloid (often small amounts, in up to 50% of
cases)
- MGG – blue-magenta amorphous or fibrillary
material
- Pap – pink/orange
Immunophenotype:
Marker:
|
Sensitivity:
|
Specificity:
|
CEA
|
Excellent
|
Excellent
|
Calcitonin
|
Most
|
|
Congo Red
(stroma)
|
|
|
Thyroglobulin
(neg)
|
|
|
Chromogranin A
|
|
|
Molecular features:
- (20%) familial form in MEN-2
- germline RET mutations
- leading to constitutive action of the receptor
(cell migration…)
- RET mutations also seen in sporadic cancers
- NOT seen:
- Chromosomal rearrangements involving RET (like
in papillary CA)
Other features:
- Calcitonin secreting
- Sometimes somatostatin, serotonin, and VIP
- EM – membrane-bound dense granules
- Octreoscan can image it via somatostatin
receptors (as all neuroendocrine tumours)
References:
- Robbins & Cotran Pathologic Basis of Disease
(2005)
- Gray W (ed.) Diagnostic Cytopathology, 2nd
ed. (2003)