Medullary Carcinoma

 

Epidemiology:

    • Peak incidence 40s-50s (sporadic)
    • MEN-2a and FMTC:
      •  teens, some in childhood
    • MEN-2b
      • May occur at <1y

 

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
      • may be papillary
    • 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)