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Thyroid gland

Bethesda guidelines for Cytology


Reviewer: Michael Constantinescu, M.D., Overton Brooks VA Medical Center (see Reviewers page)
Revised: 22 March 2011, last major update March 2011
Copyright: (c) 2010-2011, PathologyOutlines.com, Inc.


● Use when diagnostic features of malignancy are seen (e.g. papillary carcinoma, medullary carcinoma, metastatic carcinoma)
● Risk for actual malignancy is 97-99%

Papillary thyroid carcinoma


● Papillary/syncytial-like follicle cells, sometimes with “cartwheel” pattern
● Nuclear features: large nuclei, oval or molded, irregular membranes, nuclear clearing (“Orphan Annie” eyes, image) with powdery chromatin, nuclear grooves, one or more marginally placed micronucleoli, nuclear crowding/overlapping
● May have psammoma bodies or multinucleated giant cells
Follicular variant: hypercellular sample, microfollicles, isolated neoplastic follicles (e.g. sheets, branched), dense thick colloid; nuclear features are more subtle, but only cases with diagnostic nuclear features should be given this diagnosis
Macrofollicular variant: flat/monolayered sheets of epithelial cells with atypia, follicles of variable sizes, abundant colloid (thick or thin fragments); the nuclear features of papillary carcinoma are more subtle, but should be present for definitive diagnosis
Oncocytic variant: papillary configuration, sheets or single oncocytic cells (polygonal, abundant blue cytoplasm on DiffQuick, green on Pap or pink on H&E) with nuclear features of papillary thyroid carcinoma; lymphocytes are absent or scant
Tall cell variant: tall cells (height/width > 3:1) comprising 50% or more of tumor cells, usually in papillary clusters; have abundant granular dense cytoplasm, nuclear features characteristic for papillary thyroid carcinoma; often multiple intranuclear pseudoinclusions (“soap bubbles”); nuclei may have less powdery chromatin and more granular chromatin
Columnar cell variant: papillary configuration, clusters, sheets or follicles, consisting of cells with oval, stratified, dark, elongated nuclei with less prominent features of papillary thyroid carcinoma, cytoplasm has supra or subnuclear vacuolization; resembles respiratory epithelium or metastatic colon carcinoma
Hyalinizing trabecular tumor: neoplastic cells with many intranuclear pseudoinclusions and nuclear grooves; radially disposed around hyaline material reminiscent of amyloid; cytoplasm may have “yellow bodies” with paranuclear location

● Management is surgical, either lobectomy or total thyroidectomy, depending on size of the lesion, patient age, history of radiation therapy, ultrasound findings

Sample reports:
(1) Malignant - Papillary thyroid carcinoma

Medullary thyroid carcinoma


● Moderately or markedly cellular, single cells and clusters (syncytial-like)
● Plasmacytoid, spindle, round or polygonal cells with mild to moderately pleomorphic nuclei, eccentrically located
● Cytoplasm is granular, variable in amount, sometimes with red granules on DiffQuck and rarely melanin pigment
● Nuclei are round with “salt and pepper” chromatin, occasional intranuclear pseudoinclusions and prominent nucleoli
● Multinucleated or binucleated cells are common, occasionally bizarre giant cells
● Amyloid, an amorphous dense material reminiscent of colloid (Congo red positive), is often seen
● Tumor cells are positive for calcitonin, TTF-1, CEA, chromogranin and synaptophysin, but negative for thyroglobulin

● Management is surgical, usually total thyroidectomy with lymph node dissection

Sample report:
(1) Malignant - Medullary Thyroid Carcinoma

Poorly Differentiated Thyroid Carcinoma


● Cellular material with solid, insular or trabecular patterns
● Uniform population of follicular cells with scant cytoplasm with some plasmacytoid forms
● Follicular cells have high N/C ratio and nuclear atypia
● Mitoses and apoptotic forms are present; often necrosis

● Management: more aggressive than well differentiated carcinoma, including surgery plus post-operative radioactive iodine therapy; use radiation therapy in T3 or T4 tumors

Sample report:
(1) Malignant - Papillary carcinoma with poorly differentiated features, suggestive of poorly differentiated thyroid carcinoma

Undifferentiated (Anaplastic) Carcinoma


● Moderate to increased cellularity, with single cells or groups of various sizes
● Cells are epithelioid (round or polygonal) or spindled, small to giant; plasmacytoid or rhabdoid forms are seen
● Nuclei are large and pleomorphic with irregular membranes, clumped chromatin, prominent nucleoli, nuclear inclusions; often eccentrically located and multinucleated
● Necrosis and inflammatory infiltrates are common
● Nonneoplastic osteoclast-like giant cells are scattered in some cases
● Many mitoses are present

● Management is complete surgical resection with pre-op radiation therapy and chemotherapy

Squamous Cell Carcinoma of Thyroid


● Large pleomorphic keratinized cells with necrosis

Metastatic tumors

Metastatic Renal Cell Carcinoma
● Moderate to marked cellularity, with single cells and clusters, fragments of papillary structures, sheets
● Cytoplasm is pale, vacuolated, granular or clear
● Nuclei are round or oval, with prominent large nucleoli
● Often prominent vascularity

Metastatic Malignant Melanoma
● Moderate to marked cellularity with noncohesive pleomorphic cells, some plasmacytoid, spindled or anaplastic
● Cytoplasm is finely granular, but melanin pigment is not commonly seen
● Nuclei are large, eccentric with intranuclear inclusions
● Histiocytes with coarse granules are common
● Tumor cells are immunoreactive for S100, Melan-A (MART-1), HMB-45

Metastatic Breast Carcinoma
● Moderate to marked cellularity with oval or polygonal cells isolated or in clusters
● Intracytoplasmic magenta inclusions (due to mucin) are common
● The single cells retain cytoplasm
● Tumor cells are usually immunoreactive for ER and PR, negative for TTF-1, thyroglobulin and calcitonin

Metastatic Lung Carcinoma
● Adenocarcinoma has round balls or sheets of medium to large cells with prominent nucleoli and intracytoplasmic mucin; nuclei are more pleomorphic than thyroid follicular neoplasms
● Small cell carcinoma has neuroendocrine features, friable nuclei, crush artifact

Lymphoma involving the thyroid
● Cellular sample with noncohesive cells with oval or round nuclei
● Lymphoglandular bodies are common (better seen on DiffQuick)
● Marginal zone (MALT) lymphoma has cells 2x size of small lymphocytes, with vesicular open nuclei
● Diffuse large B-cell lymphoma has cells with moderate bluish cytoplasm, course chromatin, conspicuous nucleoli, necrotic debris

End of Thyroid gland > Bethesda guidelines for Cytology > Malignant

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