Thyroid gland
Competency Assessment
7. Malignant

Author: Ricardo R. Lastra, M.D., Michelle R. Pramick, M.D., Zubair W. Baloch, M.D. (see Authors page)

Revised: 23 January 2017, last major update November 2013

Copyright: (c) 2013-2017, PathologyOutlines.com, Inc.

See also Bethesda guidelines for Cytology, Malignant
Cite this page: Malignant. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidcompmalignant.html. Accessed May 29th, 2017.
Follicular Cell Derived - Papillary Thyroid Carcinoma
Medical knowledge
  1. Understand the epidemiology of papillary thyroid carcinoma and the risk factors associated to its development
  2. Recognize the classic nuclear features of papillary thyroid carcinoma
    • Nuclear enlargement
    • Nuclear clearing
    • Peripherally placed micronucleoli
    • Nuclear membrane irregularities including nuclear grooves
    • Nuclear pseudoinclusions
  3. Recognize the variants of papillary thyroid carcinoma according to architectural and cytologic characteristics
    • Classic variant
    • Follicular variant
    • Macrofollicular variant
    • Cystic variant
    • Tall cell variant
    • Columnar cell variant
    • Diffuse Sclerosing variant
    • Oncocytic cell variant
    • Solid variant
    • Warthin-like variant
    • Cribriform morular variant
  4. Recognize features commonly associated with the presence of papillary thyroid carcinoma
    • Psammoma bodies
    • Multinucleated giant cells
    • Dense "bubble gum" colloid

Practice based learning
  1. Understand the clinical and surgical implication of diagnosing papillary thyroid carcinoma in a thyroid FNA specimen
  2. Recognize cases with features considered suspicious but insufficient for a diagnosis of papillary thyroid carcinoma and understand the utility of repeat FNA or molecular testing in these instances
    • Atypia of undetermined significance "AUS"
  3. Understand that certain variants of papillary thyroid carcinoma act more aggressively
    • Diffuse Sclerosing variant
    • Tall cell variant
    • Columnar cell variant
    • Oncocytic cell variant
  4. Recognize cystic degeneration of papillary thyroid carcinoma as a common occurrence yielding hypocellular specimens


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Images hosted on PathOut server:

Cytology images:

Classical type, contributed by Dr. Mark R. Wick



Images hosted on other servers:

Cytology images:

Papillary architecture


Classic nuclear features

Focal nuclear crowding and nuclear grooves

Intranuclear inclusions


Sheets of cells with sparse colloid

Ground glass nuclei

Psammoma bodies

Cell block


Cellular swirls


See also PathologyOutlines - Papillary carcinoma
Follicular Cell Derived - Poorly Differentiated Carcinoma
Medical knowledge
  1. Understand the epidemiologic and clinical characteristics of poorly differentiated carcinoma of the thyroid
  2. Recognize the altered architectural pattern characteristic of poorly differentiated thyroid carcinoma
    • Insular pattern
    • Solid pattern
    • Trabecular pattern
  3. Recognize the cytologic characteristics of poorly differentiated thyroid carcinoma
    • Uniform cell population with high nucleus to cytoplasm ration and occasional plasmacytoid appearance
    • Variable nuclear atypia
    • Mitosis
    • Single cell apoptosis and necrosis
  4. Recognize that poorly differentiated thyroid carcinoma lacks the nuclear features characteristic of papillary thyroid carcinoma

Practice based learning
  1. Understand the clinical and surgical implication of diagnosing poorly differentiated thyroid carcinoma in a thyroid FNA specimen
  2. Understand that poorly differentiated thyroid carcinoma may be associated to a better differentiated component of papillary thyroid carcinoma or follicular carcinoma
  3. Recognize the limitations of thyroid FNA in diagnosing poorly differentiated thyroid carcinoma given its overlapping features with follicular neoplasms and understand the use of additional information in making this distinction
    • Clinical history
    • Radiology
  4. Recognize metastatic malignancy to the thyroid as a major differential diagnosis of poorly differentiated thyroid carcinoma


Images hosted on other servers:

Cytology images:

Nesting pattern of cells

Cellular smear has overlapping cells with round, regular nuclei

Large clusters and
single cells, inset shows
vacuolated cytoplasm


Cellular nests of loosely cohesive cells

Overlapping cells with mild atypia

Small microfollicle of tumor cells

Cells have finely
vacuolated cytoplasm
and round / oval nuclei


See also PathologyOutlines - Insular carcinoma
Follicular Cell Derived - Anaplastic Carcinoma
Medical knowledge
  1. Understand the epidemiology and characteristic aggressive clinical presentation of anaplastic carcinoma of the thyroid
  2. Recognize the architectural and cytologic characteristics of anaplastic thyroid carcinoma
    • Hypercellular specimen with isolated cells
    • Markedly atypical epithelioid and / or spindle cells
    • Nuclear membrane irregularities
    • Prominent nucleoli
    • Plasmacytoid or rhabdoid morphology with frequent multinucleation
    • Mitosis with abnormal mitotic figures
    • Necrosis

Practice based learning
  1. Understand the clinical implication of diagnosing anaplastic thyroid carcinoma in a thyroid FNA specimen
  2. Understand the potentially high false negative rate of FNA in cases with extensive fibrosis or tumor necrosis
  3. Understand that anaplastic thyroid carcinomas arise from well differentiated follicular or papillary thyroid carcinomas and are often associated to foci of well differentiated tumor
  4. Recognize metastatic malignancy to the thyroid as a major differential diagnosis of anaplastic thyroid carcinoma


Images hosted on other servers:

Cytology images:

Bizarre tumor giant cells

Atypical cells

Giant cell type has large, bizarre cells

Spindle cell type has dyscohesive spindled cells


See also PathologyOutlines - Anaplastic carcinoma
Follicular Cell Derived - Other
Medical knowledge
  1. Recognize the cytologic criteria of less common primary thyroid malignancies derived from the follicular cells
    • Squamous cell carcinoma
    • Mucoepidermoid carcinoma
    • Adenoid cystic carcinoma
    • Mucinous signet ring cell carcinoma

Practice based learning
  1. Understand that these common primary thyroid malignancies are indistinguishable from metastatic disease to the thyroid and that pertinent clinical information is essential in making these diagnosis
  2. Recognize the aggressive behavior of primary thyroid squamous cell carcinoma


Images hosted on other servers:

Cytology images:

Atypical pleomorphic cells

Metastases from esophagus

C Cell Derived - Medullary Thyroid Carcinoma
Medical knowledge
  1. Recognize medullary thyroid carcinoma as an neuroendocrine tumor arising from the C cells of the thyroid
  2. Understand the epidemiology and clinical characteristics of medullary thyroid carcinoma
  3. Understand that both sporadic and familiar cases of medullary thyroid carcinoma occur and recognize the main mutation associated to familiar cases
  4. Recognize the main syndromes associated to development of medullary thyroid carcinoma
    • MEN IIA
    • MEN IIB
  5. Recognize the architectural and cytologic characteristics of medullary thyroid carcinoma
    • Hypercellular specimen
    • Isolated single cells and / or syncytial growth pattern
    • Variable cell morphology - epithelioid, plasmacytoid and spindle cells
    • Characteristic granular "salt and pepper" chromatin
    • Inconspicuous nucleoli
    • Occasional pseudoinclusions, multinucleation and bizarre giant cells
    • Presence of dendritic cytoplasmic processes
  6. Recognize the presence of background amyloid as an important characteristic in diagnosing medullary thyroid carcinoma

Practice based learning
  1. Understand the clinical and surgical implication of diagnosing medullary thyroid carcinoma in a thyroid FNA specimen
  2. Recognize the utility of calcitonin levels in the diagnosis and followup of medullary thyroid carcinoma
  3. Recognize potential mimics of medullary thyroid carcinoma
    • Oncocytic follicular neoplasms
    • Hyalinizing trabecular adenoma
    • Plasmacytoma
    • Metastatic malignancy to thyroid - melanoma


Images hosted on other servers:

Cytology images:

Dyscohesive plasmacytoid cells

Spindled cells with scanty, ill defined cytoplasm

Orange granular amyloid material

Spindle cells

Atypical spindle cells

Lymphoma
Medical knowledge
  1. Recognize the existence of primary thyroid lymphomas
    • Extranodal marginal zone B cell lymphoma
    • Diffuse large B cell lymphoma
  2. Understand the increased incidence of lymphomas arising in association with chronic lymphocytic thyroiditis
  3. Recognize the main cytologic criteria necessary to consider a diagnosis of thyroid lymphoma

Practice based learning
  1. Be able to differentiate lymphoma arising in the thyroid gland from cases with exuberant chronic lymphocytic thyroiditis
  2. Recognize the need to identify cases suspicious for lymphoma during onsite evaluation to obtain additional material for flow cytometric analysis
  3. Understand that pertinent clinical information is crucial to differentiate primary from metastatic lymphoma in the thyroid


Images hosted on PathOut server:

Cytology images, diffuse large B cell lymphoma:

Large cell type, contributed by Dr. Mark R. Wick



Images hosted on other servers:

Cytology images, diffuse large B cell lymphoma:

Large and irregular lymphoid cells

High grade lymphoma shows atypical cells

Diffuse large B cell lymphoma misdiagnosed as anaplastic carcinoma

CD45 / LCA+, CD20+, keratin negative


Cytology images, other:

Intermediate grade lymphoma

MALT lymphoma

Metastatic Carcinoma
Medical knowledge
  1. Recognize metastatic disease to the thyroid as a relatively common occurrence
  2. Recognize malignancies known to often metastasize to the thyroid
    • Renal cell carcinoma
    • Malignant melanoma
    • Breast adenocarcinoma
    • Lung adenocarcinoma

Practice based learning
  1. Recognize metastatic disease to the thyroid as a mimic of primary thyroid malignancies
  2. Recognize the value of clinical history in evaluation of malignant thyroid nodules
  3. Recognize the limitations of thyroid FNA in the workup of metastatic disease to the thyroid
  4. Recognize the use of obtaining additional material at time of onsite evaluation for potential additional ancillary tests
    • Immunohistochemistry
    • Molecular studies


Images hosted on other servers:

Cytology images:

Esophageal squamous cell carcinoma

Lung squamous cell carcinoma

Melanoma

Melanoma - HMB45

Parotid gland adenoid cystic carcinoma