a 75 y/o woman with solitary hypo function cold nodule of upper pole of right lobe

A 75 y/o woman with Solitary hypo function cold nodule of upper pole of right lobe

Hyalinizing trabecular adenoma Papillary carcinoma Medullary carcinoma Hurthle cell carcinoma

Medullary carcinoma of the thyroid

Calcitonin

Calcitonin

Calcitonin

Prevalence : 3-10% of all thyroid malignancy

MEN II : Unilateral, young age, mannon MEN: womanSporadic: bilateral, 5-6 decades, woman

CellularityUsually very cellular

PresentationMostly isolated & rarely in tissue fragments forming nests , trabeculae, follicular or papillary. Dispersed pattern characteristic

CellsUniform to pleomorfic size: small to large shape: round, cuboidal, plasmacytoid, polygonal, racket-shaped, triangular, spindle-shaped ( unipolar ). Cell border : well to poorly defined

Nuclear locationAlways eccentric

Nuclear numberBi-multinucleation

Nuclear shape Round, oval, spindle, smooth nuclear membrane

ChromatinCoarsely granullar

Parachromtin clearing

Not common

Nucleoli+/-

Nuclear grooves-

Intranuclear inclusions

Almost always present

Mitotic activity-

cytoplasmScant to abundant. Clear, pale, granular to dense, cytoplasmic process. Azurophylic cytoplasmic granules

Psammoma bodiesRare

BackgroundHyaline, amorphous, fluffy, acellular material( positive for amyloid). Necrosis absent.

hystochemistryArgylophilic granules

IHCPositive for : calcitonin, LMWK, CEA, Neuroendocrine markers & TTF-1. Negative for TG

Ultra structuresElectron dense, membrane-bound neurosecretory granules

Nodular goiter Amyloidosis or amyloid goiter Follicular neoplasm ( HTA,Follicular Carcinoma &

adenoma ) Hurthle cell carcinoma Papillary carcinoma Insular carcinoma Anaplastic carcinoma Carcinoid tumor, lymphoma, melanoma

Medullary carcinomaHTA

CellularityVariableVariable

PresentationMostly isolated or loosely cohesive

isolated or loosely cohesive & tissue fragment or trabecular

CellsMonomorphic to pleomorphic, round, plasmacytoid, unipolar spindle cells, well to poorly defined borders, N/C ratio variable

Round, oval, bipolar spindle cells, well to poorly defined cell border, low N/C ratio

NucleusEccentric, bi- & multi, pleomorphic, round, oval, spindle, salt & pepper granular chromatin, not nucleoli, inclusion

Central to eccentric round to oval, bi & multi not seen micronucleoli, finely granular chromatin, inclusion

CytoplasmVariable, azurophilic granules

Abundant, pale

BackgroundClean, amorphus, acellular, amyloid

Clean, amorphus, cellular, Negative for amyloid

IHCCalcitonin +thyroglobulin _

Calcitonin –thyroglobulin +

Medullary carcinomafollicular adenoma or carcinoma

CellularityVariableVariable

PresentationMostly isolated or loosely cohesive

Syncytial tissue fragment with or without follicular pattern

CellsMonomorphic to pleomorphic, round, plasmacytoid, unipolar spindle cells, well to poorly defined borders, N/C ratio variable

Small,Round to cuboidal, ill defined cell border, high N/C ratio

NucleusEccentric, bi- & multi, pleomorphic, round, oval, spindle, salt & pepper granular chromatin, not nucleoli, inclusion

Central, round with smooth nuclear membrane, micronucleoli +/-, coarsely granular chromatin, inclusion absent

CytoplasmVariable, azurophilic granules

Scant, no cytoplasmic process

Backgroundamyloid +/-,colloid absentAmyloid absent, colloid+

IHCCalcitonin +thyroglobulin _

Calcitonin –thyroglobulin +

Medullary carcinomahurthle cell carcinoma

CellularityVariableHighly cellular

PresentationMostly isolated or loosely cohesiveisolated or groups, syncytial tissue fragment

CellsMonomorphic to pleomorphic, round, plasmacytoid, unipolar spindle cells, well to poorly defined borders, N/C ratio variable

Round, oval to plasmacytoid, uniform, well defined cell border, high N/C ratio

NucleusEccentric, bi- & multi, pleomorphic, round, oval, spindle, salt & pepper granular chromatin, not nucleoli, inclusion

Central to eccentric, binucleation frequent, round, macronucleoli, finely granular chromatin, inclusion+/-

CytoplasmVariable, azurophilic granulesVariable, usually scant, granular to dense, blue granules

BackgroundClean, amorphus, acellular, amyloid, colloid absent, necrosis -

+/- , Negative for amyloid, collloid necrosis +/-

IHCCalcitonin +thyroglobulin _

Calcitonin –thyroglobulin +

Ulra structureNeurosecretory granulesAbundant mitochondria

Medullary carcinomapapillary carcinoma

CellularityVariableHighly cellular

PresentationMostly isolated or loosely cohesiveMostly isolated or groups, rarely syncytial tissue fragment

CellsMonomorphic to pleomorphic, round, plasmacytoid, unipolar spindle cells, well to poorly defined borders, N/C ratio variable

Small, round to cuboidal, short columnar, well to ill-defined cell border, high N/C ratio

NucleusEccentric, bi- & multi, pleomorphic, round, oval, spindle, salt & pepper granular chromatin, not nucleoli, inclusion

Central to eccentric, round, oval, smooth nuclear membrane, powdery chromatin, inclusion always present

CytoplasmVariable, azurophilic granulesVariable, pale clear or vacuolated, azurophylic granules not present

BackgroundClean, amorphus, acellular, amyloid, colloid absent

Negative for amyloid, collloid +/-

IHCCalcitonin +thyroglobulin _

Calcitonin –thyroglobulin +

Medullary carcinomaAnaplastic carcinoma

CellularityVariableHighly cellular, can be low with markedly dismoplastic cancer

PresentationMostly isolated or loosely cohesiveisolated, loosely cohesive, syncytial tissue fragment

CellsMonomorphic to pleomorphic, round, plasmacytoid, unipolar spindle cells, well to poorly defined borders, N/C ratio variable

Variable sized, slender to plump spindle shape, well defined cell border, variable N/C ratio, giant form frequent

NucleusEccentric, bi- & multi, pleomorphic, round, oval, spindle, salt & pepper granular chromatin, not nucleoli, inclusion+, mitoses -

Central to eccentric, very pleomorphic, multinucleation coaesely granular chromatin, inclusion+, mitotic activity+ with normal or abnormal mitoses, multiple micro/macro nucleoli

CytoplasmVariable, azurophilic granules, uniplar cytoplasmic process

Variable, can be abundant & dense, cytoplasmic process rare

BackgroundClean, amorphus, acellular, amyloid, colloid absent, necrosis -

Amyloid -, collloid +/- , necrosis +

IHCCalcitonin +thyroglobulin _

Calcitonin –thyroglobulin -

Ulra structureNeurosecretory granulesNo Neurosecretory granules