Endocrine Surgical Pathology

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Thyroglossal Duct Cyst

Back 1

Clinical:
-can form fistula, sinus or cyst
-found around hyoid bone 75% of the time
-form from the foramen cecum
-can cause infection or develop thyroid cancer
-found in kids and young adults
-treated with Sistrunk procedure

Gross:
-cyst filled with mucoid or purulent material
-fibrous tract from area of foramen cecum to hyoid bone
-1/3 present as fistula due to infection, solid areas sampled to exclude neoplasm

Micro:
-cyst lined by respiratory or squamous epithelium
-if infected, granulation tissue may replace epithelium
-fibrosis and chronic inflammation in cyst wall
-thyroid tissue identified in up to 2/3 of cases
-if carcinoma is present, 90% are papillary type

DD:
-epidermoid cysts
-degenerative adenomatoid nodules

Front 2

Ultimobranchial Body Remnants

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Clinical:
-small remnant of ultimobranchial apparatus
-associated with development of thyroid c-cells
-incidental in 25% of thyroids
-never in isthmus

Micro:
-small nests or lobulated aggregates of polygonal epithelial cells
-usually about 0.1 mm
-some are partially cystic
-no keratinization or intracellular bridges
-nuclei ovioid, with evenly distributed chromatin
-frequent longitudinal nuclear groove
-occasional clear cells and mucoid material may be seen

IHC: chromogranin, synaptophysin, calcitonin, CEA.

DD: squamous metaplasia, incidental papillary thyroid carcinoma.

Front 3

Black Thyroid

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Clinical:
-Dark discoloration of the thyroid gland due to accumulation of brown-black pigment in follicular cells and colloid
-Associated with use of minocycline and other tetracyclines
-No clinical significance

Gross:
-black or dark brown
-neoplasms may not take up pigment

Micro:
-granular dark brown-black pigment in follicular epithelial cells, and to a lesser degree, colloid

Ancillary studies:
-pigment stains with Fontana stain, lipofuscin stain, PAS; prussian blue for iron is negative; pigment may be mistaken for hemosiderin laden macs on FNA.

DD:
-hemochromatosis, ochronosis, and ceroid storage disease.

Front 4

Acute Thyroiditis

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Clinical:
-acute inflammation of the thyroid parenchyma associated with local or systemic bacterial, viral, or fungal infection
-associated with immunosuppression or trauma

Gross:
-thyroid erythematous, soft, with pockets of purulent exudate or necrosis

Micro:
-infiltration of parenchyma by neutrophils, microabscesses, foci of necrosis, vasculitis common
-organisms may be identified on histology.

DD:
-subacute (granulomatous) thyroiditis.

Front 5

Subacute thyroiditis, deQuervain's disease

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Clinical:
-self-limited inflammatory disorder related to systemic viral illness or autoimmune factors, painful, hyper and hypothyroid

Tx:
-Aspirin, NSAIDs, B blockers for hyperthyroid

Gross:
-asymmetric, firm, nodular

Micro:
-follicle centered, disrupted by lympho-histiocytic infiltrate with neutrophils aggregated in follicle lumens, later, mulinucleate giant cells
-no neutrophils
-destroy follicle epithelium-obscuring
-can regenerate with little fibrosis remaining

FNA:
-aggregates of lymphs, histiocytes, plasma cells, multinucleate giant cells which may contain colloid

DD:
-sarcoid, mycobacteria or fungal granulomatous infection, palpation thyroiditis

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Palpation Thyroiditis

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Clinical:
-microscopic granulomatous foci

Micro:
-small, widely scattered lesions
-aggregates of foamy histiocytes, a few lymphocytes, occasional multinucleated giant cells in follicle
-no neutrophils

DD:
-subacute thyroiditis, sarcoidosis, infections

Front 7

Reidel Disease/Reidel Thyroiditis

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Clinical:
-rare fibrosing from of chronic thyroiditis with extensive replacement of thyroid parenchyma by dense fibrosis
-may affect other organs
-can cause vascular compromise, recurrent laryngeal nerve damage, and hypothyroidism
-benign, self-limited.

Gross:
-diffuse enlargement and adhesions, difficult dissection
-cut surface white with a woody texture.

Micro:
-no specific interface, extensive fibrosis predominates over inflammatory infiltrate
-patchy infiltrate of plasma cells, lymphs, monocytes, neutrophils, and eosinophils -rare follicles entrapped
-occlusive phlebitis

FNA:
-paucicellular

DD:
-undifferentiated thyroid carcinoma, diffuse sclerosing variant of papillary carcinoma, solitary fibrous tumor, fibrous variant of Hashimoto thyroiditis, Hodgkin lymphoma, sarcoma

Front 8

Chronic Lymphocytic Thyroiditis

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Clinical:
-Hashimoto Thyroiditis
-autoimmune chronic inflammatory disorder associated with diffuse enlargement and thyroid autoantibodies
-increased risk of thyroid lymphoma
-diffusely enlarged, nontender thyroid.

Gross:
-enlarged diffusely, lobulated or nodular
-pale white cut surface - resembles lymphoid tissue
-may see nodules or fibrous bands in long-standing disease

Micro:
-diffuse, dense lymphoplasmacytic infiltrate, often with well-developed germinal centers
-follicular atrophy with decrease in colloid
-oxyphilic or Hurthle cell metaplasia (follicular cells with intensely granular eosinophilic cytoplasm)
-squamous metaplasia common
-fibrous variant, dense lymphoid infiltrate, extensive fibrosis and minimal residual follicular epithelium

FNA:
-mixed polymorphic lymphoplasmocytic infiltrate, occasional multinucleate giant cells and histiocytes, oxyphilic epithelial cells in small clusters and sheets, scant colloid in most cases

DD:
-papillary thyroid carcinoma, extranodal marginal zone B-cell lymphoma, Riedel thyroiditis, non-specific lymphocytic thyroiditis.

Front 9

Diffuse Hyperplasia/Grave's Disease

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Clinical:
-autoimmune process, results in clinical hyperthyroidism and histologic diffuse hyperplasia of follicular epithelium
-family history of HLA DR3 and CTLA-4
-thyroid stimulating immunoglobulin.

Gross:
-diffusely enlarged with beefy red gland, treatment may cause nodules and fibrosis

Micro:
-highly cellular gland with little colloid
-hyperplastic redundant follicular epithelium with papillary infoldings
-follicle lumens stellate
-follicle cells columnar with eosinophilic granular cytoplasm
-nuclei are enlarged, round, and basal
-if colloid there, scalloping (clearing around apical side of cell)
-accentuation of lobular pattern, increased fibrosis in interlobular septae
-patchy lymphocytic infiltrate
-after treatment colloid returns but mild hyperplastic changes persist
-after radioactive iodine, gland becomes nodular, increased fibrosis, atypia of follicular epithelial cells

FNA:
-highly cellular, minimal colloid, sheets of follicle epithelial cells, flame cells-follicle cells have abundant granular cytoplasm, nuclei w/compact chromatin

DD:
-papillary carcinoma, toxic nodular goiter (Plummer's Disease), Hashimoto thyroiditis

Front 10

Adenomatoid Nodule (nodular goiter)

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Clinical:
-diffuse enlargement of the thyroid with varying degrees of nodularity, usually associated with some impairment of thyroid hormone production and increased TSH secretion

Gross:
-enlarged gland with multiple nodules of variable size
-may be gelatinous with colloid exuding from the cut surface
-degenerative changes including hemorrhage, central scars, fibrous pseudocapsules, cystic change, calcification, and metaplastic bone formation

Micro:
-nodules lack a capsule but have a pushing border that merges with the surrounding follicles or may have a pseudocapsule
-hemorrhage common, with hemosiderin laden macrophages and cystic change
-most nodules contain large follicles distended with colloid
-the epithelium of flattened follicles may show oxyphilic change
-cellular nodules with increased cellularity and little colloid
-papillary fronds may be dominant but with round basally oriented nuclei

FNA:
-low cellularity, abundant colloid, honeycomb pattern of follicular epithelium, small round dense nuclei, hemosiderin laden macs, cellular nodules may have high cellularity and scant colloid - looks like follicular neoplasm.

DD:
-papillary carcinoma, follicular neoplasm, metastatic thyroid carcinoma versus parasite nodule.

Front 11

Dyshormonogenetic Goiter

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Clinical:
-thyroid hyperplasia with hypothyroidism resulting from a number of inherited defects in thyroid hormone production

Gross:
-thyroid enlarged, assymetric, nodular.

Micro:
-hypercellular nodules, microfollicular or solid patterns, little colloid
-some glands may have hyperplastic appearance similar to Grave's disease, with empty follicles
-fibrosis often prominent and may distort borders of the nodule
-cytologic atypia may be striking, especially in parenchyma

FNA:
-highly cellular, sheets, clusters, no colloid, marked nuclear atypia

DD:
-follicular neoplasm (must have distinctive invasion), diffuse hyperplasia (clinical hyperthyroidism lymphoid aggregates colloid present), radiation thyroiditis

Front 12

Amyloid Goiter

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Clinical:
-thyroid enlargement due to the intercellular deposition of amyloid

Gross:
-diffusely enlarged, firm, pale, tan, waxy cut surface, nodules present

Micro:
-amyloid deposits, usually diffuse may be nodular extracellular accumulation of acellular, homogenous, eosinophilic matrix material with smudgy appearance
-angiocentric deposits and amyloid in walls of blood vessels common
-atrophy of follicular component with scattered follicles entrapped in amyloid deposits
-groups of fat cells scattered throughout the gland
-squamous metaplasia common
-chronic inflammatory infiltrate, sometimes with multinucleate giant cells

Ancillary:
-positive for amyloid AA, maybe AL, metachromatic with crystal violet, thioflavin T-positive
-congo red (most common): deposits are rose colored with apple green birefringence

DD:
-fibrous variant of Hashimoto thyroiditis, Riedel thyroiditis; adenomatoid nodules, lymphoplasmacytic neoplasm

Front 13

Follicular Adenoma

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Clinical: Benign encapsulated tumor with evidence of follicular cell differentiation; painless neck mass, solitary nodule involving one lobe; cold nodule on nuclear imaging.

Gross: Solitary encapsulated mass, well demarcated.

Micro: Surrounded by intact capsule; smooth muscle-walled vessels present in
fibrous connective tissue capsule; histology inside mass is distinct and separate from parenchyma; colloid is usually present; variants include trabecular, oncocytic, fetal, clear cell, signet-ring cell.

IHC: TTF-1, thyroglobulin, keratin; seldom necessary.

FNA: cellular smears, colloid present, follicular groups without nuclear features of
papillary carcinoma, cannot separate between adenomatoid nodule, follicular adenoma and follicular carcinoma.

DD: Cellular/dominant adenomatoid nodule (both are benign, semantic), follicular carcinoma (thickened capsule, tumor necrosis, must have invasion), papillary carcinoma, trabecular neoplasm, metastatic carcinoma.

Front 14

Teratoma

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Clinical: Neoplasm within the thyroid displaying mature or immature tissues from
ectoderm, endoderm, and mesoderm; mass lesion of significant size.

Gross: Multiloculated cysts with white-tan creamy material, brain and grit

Micro:
-thyroid parenchyma should be identified; mature or immature tissues from
all germ cell layers
-squamous, respiratory, glandular and cuboidal epithelium
-neural tissues
-bone, cartilage, muscle and fat

DD:
-Benign: choristoma, hamartoma, heterotopia, dermoid
-Malignant: ewing sarcoma, lymphoma, rhabdomyosarcoma, small cell carcinoma.

Front 15

Hyalinizing Trabecular Tumor

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Clinical:
-hyalinizing trabecular adenoma is a follicular cell tumor with a trabecular growth pattern and heavy intratrabecular hyalinization
-palpable solitary mass, usually asymptomatic

Gross:
-solitary, solid, encapsulated neoplasm, usually small, 2.5cm mean size

Micro:
-thin fibrous connective tissue capsule
-trabecular to insular growth pattern
-scant to absent colloid
-calcific bodies
-medium to large polygonal to fusiform cells
-variable cyptoplasm, sometimes containing yellow paranuclear bodies -promininet nuclear grooves and perinucleolar halos
-prominent intranuclear cytoplasmic inclusions
-hyalinized stroma separating neoplastic cells into trabeculae
-associated lymphocytic thyroiditis

IHC Results:
-thyroglobulin and TTF-1 immunoreactive
-membrane MIB-1 immunoreactivity

FNA:
-cellular aspirates
-elongated nuclei may be misinterpreted as papillary carcinoma
-lumpy basement membrane material

DD: papillary carcinoma, follicular adenoma, follicular carcinoma, medullary thyroid carcinoma, paraganglioma

Front 16

Papillary Carcinoma

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Clinical: A malignant epithelial tumor showing evidence of follicular cell differentiation and characterized by distinctive nuclear features. 1% of all carcinomas. 80% of thyroid malignancies are papillary carcinoma. Excellent long term outcome.

Gross: Grey-white, firm mass with irregular borders, although often circumscribed. Gritty cut surface from calcifications. Extrathyroidal capsular extension can be seen.

Architecture: Variable growth patterns, complex papillae, elongated and twisted follicles, invasive growth, psammoma bodies, bright eosinophilic colloid, intratumoral sclerosis, crystals and giant cells in colloid.

Cytology: Enlarged cells, increased nuclear to cytoplasmic ratio, nuclear enlargement, nuclear overlapping and crowding, loss of polarity, nuclear contour irregularities and grooves, folds or crescent moon, pale nuclear chromatin, nuclear chromatin clearing, intranuclear cytoplasmic inclusions.

IHC: TTF-1, thyroglobulin, S-100 protein, CK19, HBME-1, RET positive.

FNA: Cellular aspirate with papillary and monolayered sheets, cuboidal cells with enlarged and overlapped nuclei, powdery nuclear chromatin with nuclear grooves and intranuclear cytoplsmic inclusions, and ropy, bubble cut colloid.

DD: Adenomatoid nodules, diffuse hyperplasia (Graves’ Disease), dyshormonogenetic goiter, follicular adenoma, follicular carcinoma, medullary carcinoma, metastatic carcinoma.

Front 17

Histological Variants of Papillary Carcinoma

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Follicular Variant: Almost exclusively small follicles with scant colloid. Classic nuclear features of papillary carcinoma.

Macrofollicular Variant: Enlarged follicles with remaining features similar to follicular variant although nuclei are often flattened. Abortive, rigid papillae may be seen. Separation from adenomatoid nodule is imperative.

Oncocytic Variant: >70% papillary architecture. Enlarged cells with abundant oncocytic cytoplasm, apically oriented enlarged nuclei, increased number of intranuclear cytoplasmic inclusions. Degenerative change common.

Clear cell variant: clear cytoplasm, although occasionally oncocytic and clear cells are combined. Must be separated from medullary and metastatic renal cell carcinoma.

Diffuse Sclerosing variant: Diffuse, bilateral involvement, extensive fibrosis, innumerable psammoma bodies, extensive intravascular growth and extrathyroidal extension, florid squamous metaplasia, dense lymphocytic thyroiditis, solid or papillary growth of papillary carcinoma cells.

Tall Cell Variant: >70% of tumor area composed of cells which are at least three times as tall as they are wide, usually oncocytic cytoplasm, sharply defined cellular borders, increased intranuclear cytoplasmic inclusions, centrally placed nuclei within the cell.

Columnar Cell Variant: Prominent papillary growth, parallel follicles (railroad tracks), scant colloid, syncytial architecture with prominent nuclear stratification, coarse nuclear chromatin, subnuclear cytoplasmic vacuolization, squamous metaplasia as morules, and increased mitotic figures.

Solid/Insular variant: Solid or insular pattern with nuclear features of papillary carcinoma.

Size variation: Incidentally found, <1cm papillary carcinoma with a proclivity for thyroid subcapsular location – designated microcarcinoma.

Front 18

Follicular Carcinoma

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Clinical: A malignant epithelial neoplasm with follicular cell differentiation and lacking the nuclear features of papillary carcinoma. About 10% of thyroid malignancies.

Gross: Solitary, encapsulated mass.

Micro: Capsular and/or vascular invasion. Cellular tumors with follicular, solid and trabecular growth. Slightly enlarged cells with round to oval nuclei and coarse nuclear chromatin. Oncocytic cells often have large, centrally placed macronucleoli within the nuclei.

IHC: Thyroglobulin and TTF-1 positive

FNA: Cellular aspirates with dispersed microfollicular arrangements of cells forming small ring-like structures; colloid is scant. Cannot be reliably separated from follicular adenoma and adenomatoid nodules.

DD: Follicular adenoma, papillary carcinoma, medullary carcinoma and adenomatoid nodules.

Front 19

Undifferentiated Carcinoma

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Clinical: Highly malignant neoplasm composed of undifferentiated cells that exhibit immunohistochemical or ultrastructural epithelial differentiation. >90% die of disease within 6 months.

Gross: Large, fleshy masses with necrosis and hemorrhage. Infiltrating, often into adjacent soft tissues and organs.

Micro: Poorly differentiated cells. Polygonal, spindle and epithelioid. Profound pleomorphism. Tumor giant cells and osteoclast-like giant cells are common. Increased mitotic figures, including atypical forms. Necrosis, hemorrhage and degeneration.

IHC: Keratin and EMA, in up to 80% of cases. Vimentin in nearly all cases. Thyroglobulin and TTF-1 are rarely positive.

Ultrastructural features: Tight junctions and tonofilaments (although EM is usually not performed).

FNA: Highly cellular with single cells and focal clusters composed of remarkable atypical cells; mitotic figures are prominent; background necrosis can be seen.

DD: Exclude metastatic disease to thyroid, primary thyroid sarcomas and anaplastic lymphoma.

Front 20

Medullary Carcinoma

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Clinical: A malignant tumor of the thyroid gland showing C-cell differentiation. 20% inherited. Lymphadenopathy is common. Serum calcitonin levels elevated.

Gross: Sporadic tumors are unilateral and solitary. Familial tumors are multifocal and bilateral. Usually encapsulated with a tan-yellow soft to firm cut surface. Calcifications can be seen.

Micro: Pre-neoplastic C-cell hyperplasia has bilateral nodules of >50 cells/aggregate. Multitude of patterns of growth. Entrapment of benign follicular epithelial cells common. Round to oval, spindled to plasmacytoid cells. Round to oval nuclei with stippled, salt and pepper chromatin. Intranuclear cytoplasmic inclusions common. Mitotic figures and necrosis is uncommon. Amyloid is present in up to 80% of tumors.

IHC: Chromogranin, calcitonin, keratin, and CEA positive. TTF-1 positive and thyroglobulin non-reactive. Amyloid positive.

FNA: Cellular aspirates with single cells and small, loosely cohesive clusters. Colloid absent but amyloid present. Round to oval, spindle to polygonal cells. Bi and multinucleated cells with moderate pleomorphism. Plasmacytoid appearance with eccentric nucleus placement. Stippled to coarse nuclear chromatin. Metachromatic red cytoplasmic granules on air-dried preparations.

DD: C-cell hyperplasia can mimic intraglandular spread, solid cell nests and palpation thyroiditis. Follicular adenoma/carcinoma, paraganglioma, hyalinizing trabecular tumor, amyloid goiter and lymphoma.

Front 21

Primary Thyroid Lymphoma

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Clinical: Primary lymphoma arising within the thyroid gland and usually associated with lymphocytic thyroiditis.

Gross: Wide variation in size. Soft to firm, lobular and multinodular. Effacement of the normal thyroid. Cut surface is bulging, tan, and fish-flesh. Usually homogeneous or mottled. Extension into perithyroidal soft tissues.

Micro: Extranodal marginal zone B-cell lymphoma and diffuse large B-cell lymphoma with transitions between the two. Constant background of lymphocytic thyroiditis. Extension into fat and skeletal muscle. Atypical small lymphs, centrocytes, monocytoid B-cells, and plasma cells. Dutcher bodies and Russell bodies. Lymphoepithelial lesions (atypical lymphoid cells within the follicular epithelium) are diagnostic. Diffuse, large, atypical cells with increased mitotic figures suggests transformation into a diffuse large B-cell lymphoma.

IHC: CD20, CD 79a. Kappa and Lambda light chain restriction. Keratin highlights the lymphoepithelial lesions.

FNA: Marginal zone B-cell lymphomas are a dispersed, non-cohesive admixture
of lymphocytes, centrocytes, monocytoid B cells, immunoblasts, plasma cells and
histiocytes – perhaps indistinguishable from a lymphocytic throiditis. Diffuse large B-cell lymphoma aspirates are hypercelluular with dyscohesive, large, atypical neoplastic cells.

DD: Lymphocytic thyroiditis, undifferentiated carcinoma, myeloid sarcoma and
melanoma.