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

What is Your diagnosis?

 Hyalinizing trabecular adenoma  Papillary carcinoma  Medullary carcinoma  Hurthle cell carcinoma

Medullary carcinoma of the thyroid

Calcitonin

 Prevalence : 3-10% of all thyroid malignancy  MEN II : Unilateral, young age, man non MEN: woman Sporadic: bilateral, 5-6 decades, woman Familial MEN II non MENSporadic Medullary carcinoma

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 shapeRound, 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,Follicul ar Carcinoma & adenoma )  Hurthle cell carcinoma  Papillary carcinoma  Insular carcinoma  Anaplastic carcinoma  Carcinoid tumor, lymphoma, melanoma

Medullary carcinomaHTA CellularityVariable Presentation Mostly isolated or loosely cohesive isolated or loosely cohesive & tissue fragment or trabecular Cells Monomorphic 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 Nucleus Eccentric, 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 Cytoplasm Variable, azurophilic granules Abundant, pale Background Clean, amorphus, acellular, amyloid Clean, amorphus, cellular, Negative for amyloid IHC Calcitonin + thyroglobulin _ Calcitonin – thyroglobulin +

Medullary carcinomafollicular adenoma or carcinoma CellularityVariable Presentation Mostly isolated or loosely cohesive Syncytial tissue fragment with or without follicular pattern Cells Monomorphic 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 Nucleus Eccentric, 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 Cytoplasm Variable, azurophilic granules Scant, no cytoplasmic process Background amyloid +/-,colloid absentAmyloid absent, colloid+ IHCCalcitonin + thyroglobulin _ Calcitonin – thyroglobulin +

Medullary carcinomahurthle cell carcinoma Cellularity VariableHighly cellular Presentation Mostly isolated or loosely cohesiveisolated or groups, syncytial tissue fragment Cells Monomorphic 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 Nucleus Eccentric, bi- & multi, pleomorphic, round, oval, spindle, salt & pepper granular chromatin, not nucleoli, inclusion Central to eccentric, binucleation frequent, round, macronucleoli, finely granular chromatin, inclusion+/- Cytoplasm Variable, azurophilic granulesVariable, usually scant, granular to dense, blue granules Background Clean, amorphus, acellular, amyloid, colloid absent, necrosis - +/-, Negative for amyloid, collloid necrosis +/- IHC Calcitonin + thyroglobulin _ Calcitonin – thyroglobulin + Ulra structure Neurosecretory granulesAbundant mitochondria

Medullary carcinomapapillary carcinoma Cellularity VariableHighly cellular Presentation Mostly isolated or loosely cohesiveMostly isolated or groups, rarely syncytial tissue fragment Cells Monomorphic 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 Nucleus Eccentric, 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 Cytoplasm Variable, azurophilic granulesVariable, pale clear or vacuolated, azurophylic granules not present Background Clean, amorphus, acellular, amyloid, colloid absent Negative for amyloid, collloid +/- IHC Calcitonin + thyroglobulin _ Calcitonin – thyroglobulin +

Medullary carcinomaAnaplastic carcinoma Cellularity VariableHighly cellular, can be low with markedly dismoplastic cancer Presentation Mostly isolated or loosely cohesiveisolated, loosely cohesive, syncytial tissue fragment Cells Monomorphic 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 Nucleus Eccentric, 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 Cytoplasm Variable, azurophilic granules, uniplar cytoplasmic process Variable, can be abundant & dense, cytoplasmic process rare Background Clean, amorphus, acellular, amyloid, colloid absent, necrosis - Amyloid -, collloid +/-, necrosis + IHC Calcitonin + thyroglobulin _ Calcitonin – thyroglobulin - Ulra structure Neurosecretory granulesNo Neurosecretory granules