ENT Flashcards
Granulomatous thyroiditis: Hormonal status.
Initial phase: T4 and T3 often elevated.
Resolution: Usually euthyroid, but can be hypothyroid.
Granulomatous thyroiditis:
A. Age group.
B. Symptoms.
A. Middle-aged women.
B. Thyroidal tenderness, fever, sore throat, malaise.
Granulomatous thyroiditis: Histology (3).
Foreign-body granulomas centered on follicles.
Giant cells with ingested colloid; neutrophils early; mononuclear cells.
Variable fibrosis.
Granulomatous thyroiditis vs. sarcoidosis.
Sarcoidosis: Granulomas are in the interstitium rather than centered on follicles.
Granulomatous thyroiditis vs. fungal thyroiditis.
Fungal thyroiditis: Usually acute inflammation with necrosis; granulomas are less frequent.
Granulomatous thyroiditis vs. Hashimoto’s thyroiditis.
Hashimoto’s thyroiditis:
- Germinal centers.
- Oncocytic change.
Granulomatous thyroiditis vs. palpation thyroiditis.
Palpation thyroiditis:
- Fewer giant cells and mononuclear cells within thyroid follicles.
- No neutrophils.
Hashimoto’s thyroiditis:
A. Geography.
B. Associated HLA types.
A. Areas with abundant iodine.
B. DR3, DR5.
Hashimoto’s thyroiditis: Associated genetic diseases (3).
Turner’s syndrome.
Down’s syndrome.
Familial Alzheimer’s disease.
Hashimoto’s thyroiditis: Pitfalls in diagnosis (2).
Parasitic nodules may be confused with nodal metastases.
Optically clear nuclei may be overdiagnosed as papillary thyroid carcinoma.
Hashimoto’s thyroiditis: Lymphocytes.
Mixture of B and T cells.
Hashimoto’s thyroiditis vs. nonspecific lymphocytic thyroiditis (3).
Nonspecific lymphocytic thyroiditis:
− Fewer germinal centers.
− No oncocytic change.
− Minimal fibrosis.
Riedel’s thyroiditis:
A. Age group.
B. Associated fibrosing disorders (3).
A. Peak in the fifth decade.
B. Mediastinal fibrosis; retroperitoneal fibrosis; sclerosing cholangitis.
Riedel’s thyroiditis: Inflammation.
Lymphocytes, plasma cells, neutrophils, histiocytes, eosinophils.
No giant cells, no germinal centers.
Riedel’s thyroiditis: Vascular change.
“Occlusive phlebitis”: Lymphocytes and plasma cells cause thickened wall and myxoid change.
Riedel’s thyroiditis vs. undifferentiated thyroid carcinoma.
The carcinoma contains scattered malignant cells; IHC may help.
Riedel’s thyroiditis:
A. Treatment.
B. Outcome.
A. Corticosteroids or tamoxifen; surgery as needed.
B. Hypothyroidism in half of cases.
Graves’ disease: Associated HLA types.
DR3, B8.
Histology of Graves’ disease:
A. Untreated.
B. After treatment with radioactive iodine.
A. Hyperplastic thyroid follicles with decreased colloid; variable lymphocytic inflammation.
B. Nuclear atypia, stromal fibrosis, more colloid.
Amyloid goiter:
A. Location of amyloid.
B. Other histologic features (2).
A. Around vessels and between thyroid follicles.
B. Squamous metaplasia, secondary atrophy of follicles.
Dyshormogenetic goiter: Most common functional defect.
Inability to incorporate iodine.
Dyshormogenetic goiter: Most commonly associated malignancy.
Follicular carcinoma.
Dyshormogenetic goiter: Gross appearance.
Enlarged, nodular thyroid gland.
Dyshormogenetic goiter: Histologic architecture (2).
Small follicles contain scant colloid and form clusters that are separated from one another by fibrous bands.
Follicular cells may form papillae.
Dyshormogenetic goiter: Cytology.
Often hypercellular and pleomorphic.
Thyroglossal-duct cyst:
A. Lining epithelium.
B. Stroma.
A. Respiratory or squamous.
B. Mucus glands and thyroid follicles.
Thyroglossal-duct cyst: Most commonly associated malignancy.
Papillary thyroid carcinoma.
Causes of finding of ciliated cells on FNA of the thyroid gland (2).
Thyroglossal-duct cyst.
Tracheal aspirate.
Branchial-cleft cyst:
A. Anatomic site.
B. Origins (4).
A. Anterolateral neck.
B. 1st, 2nd, 3rd, or 4th branchial pouch.
Branchial-cleft cyst: Age group.
Children and young adults.
Unusual in older adults.
Branchial-cleft cyst: Lining epithelium.
Squamous, columnar, or ciliated.
Lining may contain mucinous, serous, or sebaceous glands.
Branchial-cleft cyst:
A. Stroma.
B. Contents.
A. Lymphoid.
B. Anucleate squames, histiocytes, or cholesterol clefts.
Nodal metastasis of SCC mimicking a branchial-cleft cyst: Most common sites of primary tumor.
Tonsils, base of tongue.
Nodal metastasis of PTC mimicking a branchial-cleft cyst: Recognition (4).
Nuclear features of papillary thyroid carcinoma.
IHC for TTF-1, thyroglobulin.
Presence of thyroglobulin in FNA fluid.
Presence of thyroid tissue in the lateral neck implies metastasis.
Teratoma of the thyroid gland:
A. Basic types (3).
B. How grade is assigned.
A. Benign (mature), immature, malignant.
B. Based on the maturation of the neural component.
Teratoma of the thyroid gland: Relevance of age to likelihood of malignancy (2).
Infants: >90% are benign.
Adolescents and adults: Half are malignant.
Hyalinizing trabecular tumor: Histologic architecture.
Trabeculae and insulae of cells separated by hyaline bands.
Hyalinizing trabecular tumor: Cytology (3).
Large, elongated cells.
Oval nuclei with nuclear grooves and INCIs.
Halo may surround nucleus.
Hyalinizing trabecular tumor: Genetics.
Some tumors exhibit rearrangements of RET/PTC gene.
Hyalinizing trabecular tumor vs. papillary thyroid carcinoma.
Papillary thyroid carcinoma shows invasive growth.
? Anything else ?
Hyalinizing trabecular tumor vs. medullary thyroid carcinoma (2).
Medullary thyroid carcinoma:
- Amyloid may be present.
- Negative for thyroglobulin.
Follicular adenoma: Associations (2).
Iodine deficiency.
Cowden’s syndrome.
Follicular adenoma:
A. Thickness of capsule.
B. Variant that is most prone to infarction after FNA.
A. Thinner than that of follicular carcinoma.
B. Oncocytic variant.
Follicular adenoma: Histology of toxic variant.
Mimics that of Graves’ disease.
Atypical adenoma: Synonym.
Follicular lesion of uncertain malignant potential.
Atypical adenoma: Histology (4).
May show necrosis or mitotic activity.
Thickened capsule with partial invasion.
Follicular adenoma: Genetics (3).
Aneuploidy (one fourth of cases).
Mutations in RAS.
Rearrangements of PAX8 with PPARγ.
Follicular carcinoma: Association.
Iodine deficiency.
Follicular carcinoma: Histology of capsular invasion (2).
The tumor must fully penetrate the capsule and not merely be present within the capsule.
Hemorrhage and reactive changes suggest FNA artifact.
Follicular carcinoma: Histology of vascular invasion (3).
Vessels must be within or outside the capsule.
There must be at least focal attachment of the tumor to the lining of the vessel.
Some require endothelium on the tumor focus or fibrin deposition.
Follicular carcinoma: Genetics (2).
Some cases show
− t(2;3) :: PAX8−PPARγ.
− Mutations of KRAS, NRAS, or HRAS.
Follicular carcinoma: Metastasis.
Hematogenous, most often to lung and bone.
WHAFFT.
Worrisome histologic alterations following FNA of thyroid.
Papillary thyroid carcinoma: Nuclear features that are essential to diagnosis (3).
Hypochromasia.
Grooves.
Pseudoinclusions.
Metastasis of papillary thyroid carcinoma to regional lymph nodes:
A. Incidence.
B. Effect on prognosis.
A. Occurs in about half of cases.
B. Does not affect long-term prognosis.
Papillary thyroid carcinoma: Appearance of metastasis to lymph node.
Tumor cells may appear flattened.
Papillary thyroid microcarcinoma:
A. Frequent location.
B. Frequent histology.
A. Subcapsular.
B. Scar-like.
Papillary thyroid carcinoma, diffuse sclerosing variant: Location.
Often diffusely involves both lobes of the gland.
Papillary thyroid carcinoma, diffuse sclerosing variant: Histology (4).
Extensive fibrosis.
Squamous metaplasia.
Psammoma bodies.
Lymphocytic infiltrate.
Papillary thyroid carcinoma, diffuse sclerosing variant: Behavior.
Often metastasizes to cervical lymph nodes and to lungs, due to increased lymphovascular invasion.
Papillary thyroid carcinoma, oncocytic variant: Histology (3).
Cells resemble Hürthle cells but have nuclear features of classic PTC.
Nuclear overlap may be absent due to abundance of cytoplasm.
Lymphoid stroma may be present.
Papillary thyroid carcinoma, tall-cell variant: Histology.
Cells are three times as tall as they are wide and have basal nuclei.
Papillary thyroid carcinoma, columnar-cell variant: Histology (3).
Cells contain basal cytoplasmic vacuoles and show squamous metaplasia.
Nuclei are pseudostratified and luminal.
Papillary thyroid carcinoma, tall-cell and columnar variants: Shared morphology (3).
Often . . .
− Large.
− Extend beyond thyroid gland.
− Invade vessels.
Papillary thyroid carcinoma: Genetics.
Point mutation in exon 15 of BRAF.
Rearrangements of RET with many other genes.
Rearrangements of TRK with many other genes.
Papillary thyroid carcinoma: Relevance of genetics to histology.
Mutations of NRAS are seen in the follicular variant.
Papillary thyroid carcinoma: Relevance of genetics to therapy.
Tumors with mutations in BRAF and/or RET may respond to inhibitors of tyrosine kinases.
Medullary thyroid carcinoma: Relative frequency of sporadic and hereditary cases.
Sporadic: 80%.
Hereditary: 20%.
Medullary thyroid carcinoma: Incidence of nodal metastasis at presentation.
About 50%.
Medullary thyroid carcinoma: Tumor markers.
Calcitonin: Postoperative monitoring.
CEA: Usually elevated only in late, progressive disease.
Medullary thyroid carcinoma: Diseases associated with hereditary tumors (3).
Familial medullary thyroid carcinoma: No other endocrine abnormalities.
MEN IIA and MEN IIB.
MEN IIA and MEN IIB: Tumors.
Medullary thyroid carcinoma: Often multiple.
Pheochromocytoma; parathyroid adenoma or hyperplasia.
MEN IIB: Mucosal and ocular ganglioneuromas also.
Medullary thyroid carcinoma: Hereditary type with the best prognosis.
Familial medullary thyroid carcinoma (non-MEN).
Medullary thyroid carcinoma: Location in the thyroid gland.
Upper and middle third of lobes.
Medullary thyroid carcinoma: Shapes of tumor cells.
Round, polygonal, spindled, plasmacytoid.
Medullary thyroid carcinoma: Nuclear features (3).
Pseudoinclusions or grooves.
“Salt-and-pepper” chromatin.
Binucleation is common.
Medullary thyroid carcinoma: Stromal contents (3).
Amyloid in 80% of cases; may induce foreign-body reaction.
Calcifications.
Psammoma bodies (rare).
Medullary thyroid carcinoma: Histologic features suggesting germline mutation (2).
Bilaterality.
Presence of C-cell hyperplasia.
Medullary thyroid carcinoma: Immunohistochemistry (4,1,1).
Positive: Calcitonin, synaptophysin, chromogranin, CEA.
Usually positive: TTF-1.
Negative: Thyroglobulin.
Medullary thyroid carcinoma: Genetics (2).
Hereditary cases: Germline mutation in RET.
Sporadic cases: 20-80% have mutated RET.
Medullary thyroid carcinoma vs. reactive hyperplasia of C cells.
Reactive hyperplasia:
- Fewer C cells.
- No fibrosis.
Nodular hyperplasia of C cells: Histology.
Nodules contain >50 C cells.
No fibrosis, no infiltration.
Identified on H and E stain and confirmed by IHC.
Poorly differentiated thyroid carcinoma:
A. Former name.
B. Cell of origin.
A. Insular carcinoma.
B. The follicular cell; may arise from follicular carcinoma or papillary thyroid carcinoma.
Poorly differentiated thyroid carcinoma: Gross pathology (2).
Usually large (>5 cm) and invasive of soft tissues.
Poorly differentiated thyroid carcinoma: Histology (2).
Nests (insulae) of cells with high N:C ratio.
May show convoluted nuclei, necrosis, or mitotic activity (>3 per 10 hpf).
Poorly differentiated thyroid carcinoma: Immunohistochemistry (2,2,1).
Positive: PAX8, cytokeratin.
Variable: Thyroglobulin, TTF-1.
Negative: Calcitonin.
Carcinoma showing thymus-like elements:
A. Age group.
B. Prognosis.
A. Fifth decade.
B. Metastasis in one third of cases.
Carcinoma showing thymus-like elements:
A. Histology.
B. Immunohistochemistry.
A. Moderately pleomorphic cells form sheets and nests with dense fibrosis.
B. Positive for CD5; negative for TTF-1, thyroglobulin, calcitonin.
Spindle-cell tumor with thymus-like elements: Age group.
Second and third decades.
Spindle-cell tumor with thymus-like elements:
A. Histology.
B. Immunohistochemistry.
A. Well-circumscribed biphasic tumor of spindled and epithelial cells forming glands, tubules, and sheets.
B. Negative: TTF-1, thyroglobulin, calcitonin.
Undifferentiated thyroid carcinoma:
A. Synonyms (2).
B. Cell of origin.
C. Prognosis.
A. Anaplastic carcinoma, pleomorphic carcinoma.
B. Follicular cell; most tumors arise from a preexisting thyroid carcinoma.
C. Death in 6 months.
Undifferentiated thyroid carcinoma: Histologic patterns (3).
Squamoid.
Spindle-cell.
Giant-cell.
Undifferentiated thyroid carcinoma: Histology of squamoid pattern.
Resembles non-keratinizing SCC, albeit rarely with squamous pearls.
Undifferentiated thyroid carcinoma: Histology of spindle-cell pattern (2).
Resembles a sarcoma.
Most likely of the three patterns to contain heterologous elements.
Undifferentiated thyroid carcinoma: Histology of giant-cell pattern.
Highly pleomorphic (anaplastic); usually solid growth.
Undifferentiated thyroid carcinoma: Immunohistochemistry.
Positive: Cytokeratin, EMA, vimentin.
Variable: Thyroglobulin, TTF-1.
Undifferentiated thyroid carcinoma: Genetics.
Strong association with mutations in TP53.
Undifferentiated thyroid carcinoma: Important items in the differential diagnosis (4).
Medullary carcinoma: Calcitonin, amyloid.
Sarcoma: Cytokeratin negative.
Lymphoma: CD45 positive.
Metastatic carcinoma.
Thyroid lymphoma: Most common type overall.
Diffuse large B-cell lymphoma.
Thyroid lymphoma: Most common Hodgkin’s type.
Nodular sclerosis.
Thyroid lymphoma vs. thyroiditis and Graves’ disease (3).
Thyroid lymphoma:
− Atypical lymphoid cells.
− Expansion or effacement of germinal centers.
− Neoplastic lymphocytes infiltrate thyroid follicles.
Thyroid lymphoma: Putative origin of plasmacytoma.
MALT lymphoma with plasmacytic differentiation.
Metastases to the thyroid gland: Most common origins (6).
Melanoma.
Breast.
Lung.
Kidney.
Gastrointestinal tract.
Head and neck (mostly SCC).
Parathyroid cyst: Function.
Only a minority cause hyperparathyroidism.
Histology of parathyroid cyst:
A. Lining.
B. Wall.
A. Cells are flat or cuboidal and have basal nuclei and clear cytoplasm.
B. Fibrous.
Parathyroid cyst: Origin.
Some arise from degenerated adenoma or area of hyperplasia.
Parathyroid cyst: Ancillary studies (2).
PTH is positive by IHC and in cyst fluid.
Parathyroid cyst vs. cyst of the 3rd pharyngeal pouch.
Cyst of the 3rd pharyngeal pouch contains both parathyroid and thymic tissue.
Parathyroid hyperplasia:
A. Number of enlarged glands.
B. Relationship to hyperparathyroidism.
A. More than one; usually all 4.
B. Causes about 15% of cases of hyperparathyroidism.
Chemical findings in hyperparathyroidism:
A. Primary.
B. Secondary.
A. High calcium and low phosphate; high PTH.
B. Low calcium and high phosphate (due to renal failure); high PTH.
Parathyroid hyperplasia in MEN syndromes:
A. Which syndromes?
B. Which cells?
A. MEN I, MEN IIA, and MEN IIB.
B. Chief cells.
Parathyroid hyperplasia: Normal weight of parathyroid gland.
Up to 40 mg.
Histology of parathyroid hyperplasia:
A. Cells.
B. Growth patterns.
C. Stroma.
A. Chief cells, oncocytic cells, transitional cells, clear cells, or mixed.
B. Solid, glandlike, or in cords.
C. Decreased fat (decreased within cells also).
MEN syndromes: Genes and their locations.
MEN I: Gene for menin on 11q.
MEN IIA and IIB: RET on 10q.
Parathyroid hyperplasia vs. parathyroid adenoma (2).
Parathyroid adenoma:
− More likely when only one gland is enlarged.
− Rim of compressed normal parathyroid tissue.
Parathyroid hyperplasia: Treatment.
Excision of 3½ parathyroid glands.
Parathyroid adenoma:
A. Cell of origin.
B. Atypical anatomic sites (3).
A. The chief cell.
B. Intrathyroidal, mediastinal, retroesophageal.
Parathyroid adenoma: Relationship to hyperparathyroidism.
Accounts for about 80% of cases of hyperparathyroidism.
Parathyroid adenoma: Inherited syndromes.
MEN I, MEN IIA, MEN IIB.
Hyperparathyroidism−jaw tumor syndrome.
Parathyroid adenoma: Typical weight.
More than 300 mg.
Parathyroid adenoma:
A. Mitotic rate.
B. Growth patterns (4).
A. Usually absent; never high.
B. Solid, nested, glandlike, or pseudopapillary.
Parathyroid adenoma: Contents of cystic structures.
PAS-positive fluid.
Parathyroid adenoma: Features of atypical adenoma (2).
Thickened capsule.
Thick fibrous bands.
No invasion of vessels or of adjacent structures.
Hyperparathyroidism−jaw tumor syndrome.
A. Gene, location, product.
B. Histology of parathyroid adenoma.
A. HRPT2, 1q25, parafibromin.
B. Often cystic.
Parathyroid adenoma: IHC.
Positive: Cytokeratin, PTH, chromogranin.
Parathyroid adenoma: Genetics (2).
Loss of 11q.
Rearrangement of cyclin D1 (PRAD1).
Parathyroid adenoma: Age-related possible mimic.
Oncocytic nodule.
Parathyroid carcinoma:
A. Age group.
B. Degree of hypercalcemia.
A. 45-55 years: 10 years younger than for adenoma.
B. Usually marked: Higher than for adenoma.
Parathyroid carcinoma: Mean weight.
6 grams.
Parathyroid carcinoma: Intraoperative appearance (2).
Invades adjacent structures.
Usually no nodal disease.
Histology of parathyroid carcinoma:
A. Cells (2).
B. Other possible features (3).
A. Usually show only mild or moderate pleomorphism; only 50% show mitotic activity.
B. Thicker capsule than in adenoma, thick fibrous bands, necrosis.
Histology of parathyroid carcinoma: Findings diagnostic of malignancy (2).
Extension into adjacent structures.
Vascular invasion.
Histology of parathyroid carcinoma: Definition of vascular invasion.
Tumor cells are attached to the inside of a vessel located outside the main mass.
Parathyroid carcinoma: Genetics (2).
Loss of 13q (region of RB and BRCA2).
Mutation of HRPT2.
Parathyroid carcinoma: Immunohistochemistry (2).
Positive: Cytokeratin, chromogranin.
Loss of parafibromin may indicate mutation in HRPT2.
Parathyroid carcinoma: Metastasis (3).
To cervical lymph nodes, lung, liver, typically occurring late.
Metastases to the parathyroid glands: Most common origins (5).
Breast.
Skin.
Lung.
Soft tissue.
Leukemia.
Infectious sialadenitis: Causes.
Viruses.
Gram-positive cocci.
Gram-negative bacteria.
Chronic sialadenitis: Rheumatological association.
Rheumatoid arthritis.
Necrotizing sialometaplasia: Histology (3).
Coagulative necrosis of acini.
Squamous metaplasia.
Pseudoepitheliomatous hyperplasia of overlying mucosa.
Necrotizing sialometaplasia: Site.
Any site; palate is the most common.
Benign lymphoepithelial lesion: Histology (3).
Epimyoepithelial islands.
Background lymphoid infiltrate.
Intercellular hyaline matter.
Lymphocytes in benign lymphoepithelial lesion:
A. In the epimyoepithelial islands.
B. In the background.
A. Monocytoid B cells.
B. Mainly T cells.
Benign lymphoepithelial lesion vs. lymphoma (3).
Lymphoma:
− Large aggregates of monocytoid B cells.
− Extension into adjacent fat and connective tissue.
− Monoclonality by IHC.
Lymphoepithelial cyst: Sites and origins (2).
Parotid gland: Remnant of branchial apparatus.
Lymph node: Cystic formation in nests of intranodal salivary-gland tissue.
Lymphoepithelial cyst: Infectious association.
HIV: Cysts are often bilateral.
Histology of lymphoepithelial cyst: Typical (3).
Multilocular.
Glandular and squamous lining.
Hyperplastic lymphoid follicles with germinal centers.
Histology of lymphoepithelial cyst: HIV infection.
Multifocal.
Florid lymphoid hyperplasia.
Salivary-duct cyst:
A. Site.
B. Etiology.
A. Mainly parotid gland.
B. Ductal obstruction.
Salivary-duct cyst: Histology (3).
Squamous lining.
Densely fibrous wall.
Surrounding inflammation and parenchymal atrophy.
Mucocele vs. mucus-retention cyst.
A. Mucocele: Younger patients; extravasation of salivary fluid; no epithelial lining.
B. Mucus-retention cyst: Any age; type of salivary-duct cyst; epithelial lining.
Most common benign tumor of salivary origin.
Pleomorphic adenoma.
Most common tumor of salivary glands in children.
Pleomorphic adenoma.
Pleomorphic adenoma: Most common sites (4).
Parotid gland.
Palate.
Upper lip.
Buccal mucosa.
Pleomorphic adenoma: Most common associated tumor.
Warthin’s tumor.
Pleomorphic adenoma: Effect on facial nerve.
May compress it (resulting in facial paralysis), but does not invade it.
Pleomorphic adenoma: Capsule.
Usually present, but less often in
− Tumors of minor salivary glands.
− Tumors of the myxoid type.
Pleomorphic adenoma: Possible features of the mesenchymal component (4).
Myxoid, hyaline, cartilaginous, or osseous differentiation.
Pleomorphic adenoma: Main variants (2).
Cellular: Mostly epithelial.
Myxoid: Mostly myxochondromatous.
Pleomorphic adenoma: Genetics (2).
Clonal chromosomal rearrangements of
− 8q12.
− 12q13-15.
Pleomorphic adenoma vs. polymorphous low-grade adenocarcinoma (3).
Polymorphous low-grade adenocarcinoma:
− Perineural growth.
− Infiltration of adjacent tissues.
− Tubules or cords of cells at the periphery.
Myoepithelioma: Variants (3).
Spindle-cell.
Plasmacytoid.
Epithelioid.
Myoepithelioma, spindle-cell variant: Histology (2).
Interlacing fascicles of uniform, elongated spindle cells.
Minimal, myxoid stroma.
Myoepithelioma, plasmacytoid variant: Histology.
Cells are plasmacytoid.
Most common variant.
Myoepithelioma, epithelioid variant: Histology (3).
Epithelioid cells with round to oval vesicular nuclei and inconspicuous nucleoli.
Occasional microcystic areas.
Myxoid or hyaline stroma.
Myoepithelioma vs. myoepithelial carcinoma (3).
Myoepithelial carcinoma:
− Infiltrative borders.
− Cellular pleomorphism.
− Possible perineural or vascular invasion.
Myoepithelioma: Type that may be confused with metastatic renal-cell carcinoma.
Clear-cell myoepithelioma lacks the prominent vascular of RCC.
Second most common benign tumor of the salivary glands.
Warthin’s tumor.
Warthin’s tumor: Gross pathology.
Finely nodular and papillary surface.
Brown, turbid fluid in cystic spaces.
Warthin’s tumor vs. oncocytoma.
Oncocytoma:
− Usually solid.
− No lymphoid component.
Warthin’s tumor: Atypical site.
Within an intra-parotid lymph node.
Warthin’s tumor: Associated tumors (2).
Rare association with
− Mucoepidermoid carcinoma.
− Oncocytic carcinoma.
Oncocytoma:
A. Gross pathology.
B. Nucleus.
A. Red-brown tumor with a central scar.
B. Contains large nucleolus.
Oncocytoma: Histologic variations (2).
Clear cells.
Cystic areas.
Oncocytoma: Electron microscopy.
Many mitochondria.
Oncocytoma: Special stain.
PAS highlights cellular glycogen.
Oncocytoma: Treatment.
Excision.
Avoid radiotherapy.
Oncocytoma vs. Warthin’s tumor.
Warthin’s tumor:
− Papillae.
− Lymphoid stroma.
− Squamous metaplasia (sometimes).
Congenital polycystic disease:
A. Definition.
B. Histology.
A. Congenital malformation of the ductal system.
B. Many apocrine-lined cysts filled with spheroliths.
Salivary-gland cystadenoma: Sites.
Parotid gland, minor salivary glands.
Salivary-gland cystadenoma vs. intraductal papilloma.
Intraductal papilloma:
− Unicystic.
− More epithelial proliferation.
Salivary-gland cystadenoma vs. low-grade papillary cystadenocarcinoma.
Cystadenocarcinoma: Infiltration of adjacent tissue.
Hemangioma of the salivary gland:
A. Epidemiology.
B. Basic types.
A. 80% of tumors occur in females.
B. Capillary and cavernous.
Hemangioma of the salivary gland: Juvenile vs. adult.
Juvenile type: More cellular; smaller vascular spaces; more mitotic activity.
Such findings in an adult hemangioma should raise suspicion for malignancy.
Basal-cell adenoma:
A. Age group.
B. Focality.
A. Sixth and seventh decades.
B. May be multifocal if membranous subtype.
Basal-cell adenoma: Histology (2).
Monotonous (monomorphic adenoma) proliferation of basal cells without the myxochondromatous stroma of mixed tumors.
Squamous differentiation can occur.
Basal-cell adenoma: Subtypes (4).
Solid: Resembles BCC.
Membranous: Resembles cylindroma.
Trabecular: Interlacing narrow bands of basaloid cells.
Tubular: Many small lumens.
Basal-cell adenoma vs. pleomorphic adenoma.
Pleomorphic adenoma:
- Myxochondromatous stroma.
- No sharp interface between epithelial and stromal elements.
Basal-cell adenoma vs. basal-cell adenocarcinoma.
Basal-cell adenocarcinoma: Infiltrative growth, even with bland cytology.
Canalicular adenoma: Site.
Mainly upper lip.
Canalicular adenoma: Histology.
Thin (2 cells thick) cords that often form small cystic spaces.
Loose stroma.
Sebaceous lymphadenoma: Histology (2).
Sebaceous islands; cysts lined by various types of epithelium.
Densely lymphoid stroma, sometimes with germinal centers.
Sebaceous adenoma: Histology (2).
Squamous and/or sebaceous islands or ducts.
Fibrous stroma.
Adenoid-cystic carcinoma: Sites.
May occur in any salivary gland.
Most common malignant tumor of the submandibular gland.
Adenoid-cystic carcinoma: Possible presenting complication.
Paralysis of the facial nerve.
Adenoid-cystic carcinoma: Gross pathology (2).
Falsely appears well circumscribed.
Tends to grow along nerves.
Adenoid-cystic carcinoma: Cellular components (2).
Ductal epithelial cells.
Myoepithelial cells.
Adenoid-cystic carcinoma: Major patterns of growth (3).
Cribriform (most common).
Tubular.
Solid.
Adenoid-cystic carcinoma, solid pattern: Cytology.
More pleomorphism than in other types.
More mitotic figures.
More necrosis.
Adenoid-cystic carcinoma, solid pattern: How to distinguish from other basaloid tumors.
Look for areas of cribriform and/or tubular growth.
Adenoid-cystic carcinoma: Immunohistochemistry.
Positive:
− p63 (myoepithelial cells).
− CD117 (not specific).
Adenoid-cystic carcinoma vs. polymorphous low-grade adenocarcinoma.
PLGA:
− Very rarely involves major salivary glands.
− Cribriform architecture like that of AdCC is uncommon.
− Dual-cell population is not as conspicuous.
Acinic-cell carcinoma: Patterns of growth (4).
Solid, microcystic: Most common.
Papillary-cystic.
Follicular.
Acinic-cell carcinoma: Cytology (3).
Sheets of cells with coarsely granular or vacuolar cytoplasm.
Minimal cytologic atypia.
Variable mitotic activity.
Acinic-cell carcinoma: Special stain.
Tumor cell are PAS positive and diastase resistant.
Acinic-cell carcinoma: Predictors of aggressive behavior (7).
Stromal hyalinization. Cytologic atypia. High mitotic rate. Large size. Infiltrative borders. Neural invasion. Necrosis.
Acinic-cell carcinoma: Predictors of favorable outcome (4).
Tumor in minor salivary gland.
Encapsulation.
Lack of vascular invasion.
Lymphocyte-rich stroma.
Mammary-analogue secretory tumor: Definition.
Salivary-gland tumor with translocation involving ETV6.
Mammary-analogue secretory tumor: Histology.
Apocrine-like cells forming microcysts or sheets.
Bland, vesicular nuclei.
Mammary-analogue secretory tumor:
A. Immunohistochemistry.
B. Special stain.
A. Positive: S100 (not specific), mammaglobin.
B. PAS negative.
Mammary-analogue secretory tumor: Translocation.
t(12;15)(p13;q25) :: ETV6−NTRK3.
Polymorphous low-grade adenocarcinoma:
A. Site.
B. Epidemiology.
A. Minor salivary glands, esp. at the junction between the hard and soft palates.
B. Twice as common in females.
Polymorphous low-grade adenocarcinoma: Clinical appearance.
Rarely ulcerated.
Polymorphous low-grade adenocarcinoma: Cytology.
Bland; rare mitotic figures and necrosis.
Polymorphous low-grade adenocarcinoma: Stroma.
Collagenous or hyalinized.
Polymorphous low-grade adenocarcinoma: Architecture.
Variable architectural patterns, including cribriform.
However, cribriform structures mimicking those of adenoid-cystic carcinoma are rare.
Polymorphous low-grade adenocarcinoma: Infiltration (3).
Infiltrates soft tissues, sometimes bone.
Tendency toward perineural invasion.
Vascular invasion is less frequent.
Most common malignant tumor of the salivary glands in
A. Adults.
B. Children.
Both: Mucoepidermoid carcinoma.
Mucoepidermoid carcinoma: Clinical presentation.
Usually as a solitary painless mass.
Facial nerve involved in some cases.
Mucoepidermoid carcinoma: Associations (2).
Radiation.
Warthin’s tumor.
Mucoepidermoid carcinoma: Cells that line the cysts.
Mucous cells (mostly) and epidermoid cells.
Mucoepidermoid carcinoma: Morphology of most common cell type.
Intermediate cells are basaloid or appear less squamoid than the epidermoid cells.
Mucoepidermoid carcinoma: Clear cells (2).
Usually a minor component.
Contain glycogen rather than mucus.
Mucoepidermoid carcinoma: Grading.
1 (Low): Mostly cystic; focal cellular proliferation.
2 (Intermediate): Addition of invasive features.
3 (High): Solid; high-grade cytology.
Mucoepidermoid carcinoma: Translocation.
t(11;19) :: MAML−CTRC1.
Mucoepidermoid carcinoma vs. cystadenocarcinoma.
Cystadenocarcinoma:
- Fewer types of cells make up the cystic structures.
- Epidermoid cells are uncommon.
Mucoepidermoid carcinoma vs. necrotizing sialometaplasia (3).
Necrotizing sialometaplasia:
− Islands of cells have smooth outlines and a lobular distribution like that of normal salivary acini.
− No cysts.
− No intermediate-type cells.
Epidermoid-cell-rich mucoepidermoid carcinoma vs. squamous-cell carcinoma.
Squamous-cell carcinoma:
− More keratinization.
− No mucin in tumor cells.
High-grade mucoepidermoid carcinoma: Metastasis.
To lung, bones, brain.
Epithelial-myoepithelial carcinoma: Grade.
Low.
Epithelial-myoepithelial carcinoma: Cells.
Myoepithelial cells: More numerous; polygonal or spindle-shaped; clear cytoplasm.
Ductal: Cuboidal; eosinophilic cytoplasm.
Epithelial-myoepithelial carcinoma: Histology (3).
Myoepithelial cells surround ductal structures or form sheets or nests.
Fibrous bands may surround lobules of tumor.
Variable stroma.
Epithelial-myoepithelial carcinoma: Infiltration.
Occasional infiltration of soft tissues and perineural invasion.
Epithelial-myoepithelial carcinoma: Myoepithelial stains (3).
S100, p63, calponin.
Epithelial-myoepithelial carcinoma vs. adenoid-cystic carcinoma.
Adenoid-cystic carcinoma:
− Classic cribriform structures.
− Ductal cells are more basaloid and less conspicuous.
Epithelial-myoepithelial carcinoma: Histologic predictors of prognosis.
Histology has not been found to predict prognosis.
Carcinoma of salivary ducts:
A. Age group.
B. Clinical presentation.
A. Can affect young adults, but peak is in the 5th and 6th decades.
B. Rapidly enlarging mass that may involve the facial nerve.
Carcinoma of salivary ducts: Histology.
Resembles ductal carcinoma of the breast.
Carcinoma of salivary ducts: Immunohistochemistry (3).
Androgen receptor: Most cases.
EFGR: About half.
HER-2 is overexpressed in some cases.
Carcinoma of salivary ducts vs. salivary-gland adenocarcinoma, NOS.
Salivary-gland adenocarcinoma, NOS, lacks morphologic criteria of typical carcinomas of the salivary gland.
Carcinoma of salivary ducts vs. metastasis.
Metastatic carcinoma from breast or prostate: Clinical history may be required.
Carcinoma ex pleomorphic adenoma: Diagnosis.
Must contain areas of benign mixed tumor.
Carcinoma ex pleomorphic adenoma: Histology of the malignant component.
Resembles salivary-gland adenocarcinoma, NOS.
High-grade nuclei and many mitotic figures.
Carcinoma ex pleomorphic adenoma: Infiltration (3).
May remain within capsule: Known as encapsulated mixed tumor, noninvasive mixed tumor, or mixed tumor in situ.
May breach capsule and infiltrate adjacent soft tissue.
May invade vessels and surround nerves.
Carcinoma ex pleomorphic adenoma: Prognosis (2).
Encapsulated tumors: Same prognosis as that of benign mixed tumor.
Invasive tumors: Distant metastasis can occur.
Carcinoma ex pleomorphic adenoma vs. carcinosarcoma.
Carcinosarcoma: The mesenchymal component is also malignant.
Carcinosarcoma of the salivary gland: Histology of the sarcomatous component (2).
Usually predominates.
Usually chondrosarcoma, but other types of sarcoma have been reported.
Carcinosarcoma of the salivary gland: Histology of the carcinomatous component.
Most often high-grade ductal adenocarcinoma, but other types of carcinoma have been reported.
Metastatic carcinosarcoma of the salivary gland:
A. Route.
B. Site.
A. Hematogenous.
B. Most often to the lungs.
Metastatic carcinosarcoma of the salivary gland: Histology.
Sarcomatous; the carcinomatous component may also be present.
Small-cell (undifferentiated) neuroendocrine carcinoma of the salivary gland: Clinical presentation.
Rapidly growing, painless mass.
Small-cell neuroendocrine carcinoma of the salivary gland vs. metastatic small-cell neuroendocrine carcinoma of the lung.
Similar histology.
Salivary tumor is negative for TTF-1 by IHC.
Lymphoepithelial carcinoma of the salivary gland:
A. Epidemiology.
B. Association.
A. More common in natives of the Far North.
B. EBV.
Lymphoepithelial carcinoma of the salivary gland:
A. Epithelial component.
B. Lymphoid component.
A. Undifferentiated malignant cells with vesicular nuclei and pink cytoplasm; may resemble amelanotic melanoma.
B. Benign; dense infiltrate; may form germinal centers.
Lymphoepithelial carcinoma of the salivary gland: Ancillary studies (3).
ISH for genomes of EBV.
IgA anti-VCA.
IgG anti-EBNA.
Lymphoepithelial carcinoma of the salivary gland vs. large-cell undifferentiated carcinoma.
Large-cell undifferentiated carcinoma: No lymphoid stroma.
Lymphoepithelial carcinoma of the salivary gland vs. metastatic nasopharyngeal carcinoma.
Requires clinical correlation.
Lymphoma of the salivary gland: Most common origin of primary tumors.
De novo, i.e. not arising from a benign lymphoid process.
Lymphoma of the salivary gland: Frequent association in young men.
HIV.
Lymphoma of the salivary gland: Most common types (2).
Follicular lymphoma.
Diffuse large B-cell lymphoma.
Metastasis to the salivary glands: Most common origins (5).
SCC of head and neck.
Malignant melanoma.
Carcinomas of lung, kidney, breast.
Undifferentiated tumors of the base of the skull: Most helpful immunohistochemical markers (4).
Cytokeratin.
Synaptophysin.
Desmin.
Melanocytic marker.
Ewing’s sarcoma / PNET: Positive immunohistochemical markers (2).
CD99.
Synaptophysin / chromogranin.
Which type of rhabdomyosarcoma can be positive for cytokeratin?
Alveolar rhabdomyosarcoma.
Sinusitis: Most frequently involved sinus.
Maxillary.
Chronic sinusitis: Important complication.
Mucocele (pseudocyst) may be mistaken clinically for a malignancy.
Allergic fungal sinusitis: Agents (3).
Aspergillus spp.
Curvularia spp.
Dematiaceous fungi.
Allergic fungal sinusitis: Gross pathology.
Thick secretion that resembles putty or clay.
Allergic fungal sinusitis: Histology.
“Tidal wave” layering of mucus and eosinophils.
Charcot-Leyden crystals sometimes.
Hyphae are uncommon.
Myospherulosis: Etiology.
Packing the nose with petrolatum.
Myospherulosis:
A. Histology.
B. Importance.
A. Large spaces that contain brown spherules representing altered erythrocytes.
B. Spherules may be confused with Prototheca.
Rhinoscleroma:
A. Etiology.
B. Geography.
A. Klebsiella rhinoscleromatis.
B. Central America, India.
Rhinoscleroma: Histology (2).
Lymphoplasmacytic infiltrate.
Foamy macrophages (Mikulicz cells) filled with bacteria.
Rhinosporidiosis: Agent.
Rhinosporidium seeberi.
Rhinosporidiosis: Histology.
Spherules (300 μm) containing endospores (2-9 μm).
Dense lymphoplasmacytic infiltrate.
Rhinosporidiosis: Special stains (3).
PAS, GMS, mucicarmine.
Nasal polyp: Associations in children.
Cystic fibrosis.
Hurler’s syndrome.
Nasal polyp: Histology (4).
Respiratory epithelium.
Thickened basement membrane.
Myxoid stroma containing inflammatory cells.
Vascular proliferation sometimes.
Respiratory epithelial adenomatous hamartoma: Age group.
Sixth decade.
Respiratory epithelial adenomatous hamartoma: Histology.
Adenoma-like proliferation of pseudostratified, ciliated glands.
Thick basement membrane surrounds glands.
Some glands show connection to the surface.
Glial heterotopia:
A. Definition.
B. Variant histology.
A. Mature glial tissue without connection to the CNS.
B. Gemistocytic change in astrocytes.
Nasopharyngeal angiofibroma: Site.
Posterolateral wall or roof of the nasopharynx or posterior nasal cavity.
Nasopharyngeal angiofibroma: Stromal cells (2).
Stellate or spindled.
Many mast cells.
Nasopharyngeal angiofibroma: Immunohistochemistry (3).
Positive:
- β-Catenin (nuclear).
- Androgen receptor.
- Vascular markers.
Nasopharyngeal angiofibroma vs. hemangiopericytoma.
Hemangiopericytoma: Stromal cells are positive for smooth-muscle actin.
Nasopharyngeal angiofibroma vs. solitary fibrous tumor.
Solitary fibrous tumor: Stromal cells are positive for CD34.
Nasopharyngeal angiofibroma: Prognosis.
Malignant transformation rarely occurs.
Nasopharyngeal lobular capillary hemangioma: Site.
Nasal cavity, frequently the septum.
Sinonasal papilloma: Epidemiology.
Twice as common in men.
Sinonasal papilloma:
A. Most common type.
B. Least common type.
A. Inverted papilloma.
B. Cylindrical-cell papilloma.
Sinonasal papilloma: Possible microbiological association.
HPV types 6 and 11.
Inverted sinonasal papilloma: Sites (2).
Lateral nasal wall.
Paranasal sinuses.
Inverted sinonasal papilloma: Histology.
Deeply invaginated nests of benign squamous epithelium.
Intact basement membrane.
Intraepithelial microabscesses.
Exophytic sinonasal papilloma:
A. Synonym.
B. Site.
A. Fungiform papilloma.
B. Nasal septum.
Exophytic sinonasal papilloma: Histology.
Nonkeratinized squamous or transitional epithelium lines true papillae.
Cylindrical-cell sinonasal papilloma:
A. Synonym.
B. Sites (2).
A. Oncocytic papilloma.
B. Lateral nasal wall; paranasal sinuses.
Cylindrical-cell sinonasal papilloma: Histology.
Similar to that of inverted papilloma, but may be either endophytic or exophytic.
Sinonasal papilloma: Prognosis.
Malignant transformation is most likely in inverted (10-15%) and cylindrical-cell types.
Dysplasia, if seen, should be graded.
Sinonasal squamous-cell carcinoma: Sites (3).
Maxillary sinus.
Nasal cavity.
Ethmoid sinus.
Sinonasal squamous-cell carcinoma: Risk factors (5).
Smoking.
Ni, Cr, Ra.
Isopropanol.
Sinonasal squamous-cell carcinoma: Subtypes.
Conventional SCC.
Verrucous, basaloid, spindle-cell carcinomas.
NUT midline carcinoma: Histology.
High-grade undifferentiated cells and areas of necrosis.
Widely infiltrative and destructive.
NUT midline carcinoma:
A. Immunohistochemistry.
B. Genetics.
A. Positive: NUT (nuclear protein in testis).
B. Rearrangement involving NUT gene on 15q14.
NUT midline carcinoma: Prognosis.
Death in 7 months.
Sinonasal undifferentiated carcinoma: Epidemiology.
Three times more common in males.
Sinonasal undifferentiated carcinoma: Histology.
Sheets, trabeculae, or nests of cells.
Extensive necrosis.
Sinonasal undifferentiated carcinoma: Cytology.
Undifferentiated cells with a high N:C ratio and a single prominent nucleolus.
Many mitotic figures.
Sinonasal undifferentiated carcinoma: Immunohistochemistry.
Positive: Pancytokeratin, CK 7.
Negative: CK 5/6.
Rare: Focal synaptophysin / chromogranin.
Sinonasal undifferentiated carcinoma vs. nasopharyngeal carcinoma.
Nasopharyngeal carcinoma:
− Lymphoid infiltrate (absent in SNUC).
− Often positive for EBV.
Sinonasal undifferentiated carcinoma: Prognosis.
Death within 2 years.
Nasopharyngeal carcinoma, keratinizing type:
A. Association with EBV.
B. Epidemiology.
C. Prognosis.
A. Weaker.
B. Older patients.
C. Worse.
Nasopharyngeal carcinoma, keratinizing type: Histology.
It is a keratinizing squamous-cell carcinoma.
Nasopharyngeal carcinoma, non-keratinizing type:
A. Association with EBV.
B. Most common clinical presentation.
A. Stronger.
B. Unilateral cervical lymphadenopathy.
Nasopharyngeal carcinoma, non-keratinizing type:
A. Epidemiology.
B. Geography.
A. Three times more common in males.
B. Southeast Asia, North Africa.
Nasopharyngeal carcinoma, non-keratinizing type: Environmental risk factors (4).
Nitrosamines.
Salted fish.
Smoking.
Formaldehyde.
Nasopharyngeal carcinoma, non-keratinizing type: Histologic subtypes.
Undifferentiated (lymphoepithelial carcinoma).
Non-keratinizing SCC.
Nasopharyngeal carcinoma, non-keratinizing SCC: Histology.
Resembles non-keratinizing SCC in other sites.
Desmoplastic stroma.
Nasopharyngeal carcinoma, undifferentiated: Growth patterns.
Regaud’s type: Well-defined tumor nests in fibrous stroma.
Schminke’s type: Sheets of cells obscured by lymphoid infiltrate.
Nasopharyngeal carcinoma, undifferentiated: Cytology (3).
Vesicular nuclei, large nucleolus.
Many mitotic figures.
Necrosis may be extensive.
Nasopharyngeal carcinoma, undifferentiated: Inflammatory component.
Usually lymphoid, but eosinophils can predominate.
Nasopharyngeal carcinoma, undifferentiated: Stroma.
Usually not desmoplastic.
May contain amyloid.
Nasopharyngeal carcinoma: Immunohistochemistry.
Positive: CK 5/6, 34βE12.
Detection of EBV in nasopharyngeal carcinoma:
A. Best method.
B. Presumptive method.
A. ISH for Epstein-Barr−encoded RNA (EBER).
B. IgA anti-VCA or IgG anti-EA.
Nasopharyngeal carcinoma: Treatment.
Radiation:
- Chemotherapy may be added.
- Keratinizing SCC is less responsive.
Sinonasal adenocarcinoma: Sites (2).
Nasal cavity, sinuses.
Sinonasal adenocarcinoma: Histologic types (3).
Enteric.
Non-enteric.
Salivary.
Sinonasal adenocarcinoma, enteric type:
A. Histogenesis.
B. Risk factors.
A. Respiratory epithelium.
B. Woodworking, leather, some chemicals.
Sinonasal adenocarcinoma, enteric type: Histology.
Intermediate- or high-grade tumor resembling colonic adenocarcinoma.
May contain intestinal metaplasia without atypia.
Sinonasal adenocarcinoma, enteric type: Immunohistochemistry.
Positive: Cytokeratin; often CDX2 (nuclear).
Tumors gain colonic-type markers (e.g. CK20) as they come to resemble the colon histologically.
Sinonasal adenocarcinoma, enteric type, vs. metastatic colonic carcinoma.
Requires clinical correlation.
Sinonasal adenocarcinoma, enteric type: Mutated genes.
RAS, TP53.
Sinonasal adenocarcinoma, non-enteric type:
A. Histogenesis.
B. Risk factors.
A. Seromucinous glands.
B. None known.
Sinonasal adenocarcinoma, non-enteric type, low-grade: Histology.
Bland tumor resembling benign seromucinous glands.
Back-to-back glands, or papillary formations.
Sinonasal adenocarcinoma, non-enteric type, high-grade: Histology.
More solid growth.
More pleomorphism.
More mitotic activity.
More necrosis.
Sinonasal adenocarcinoma, non-enteric type: Immunohistochemistry.
Positive: CK7.
Variable: S100.
Sinonasal adenocarcinoma, salivary type: Histology.
Identical to tumors arising from the salivary glands.
Adenoid-cystic carcinoma in the most common.
Sinonasal adenocarcinoma, salivary type: Immunohistochemistry.
Positive: CK7.
Variable: S100.
Nasopharyngeal papillary adenocarcinoma:
A. Age group.
B. Prognosis.
A. Children and adults.
B. Cured by resection.
Nasopharyngeal papillary adenocarcinoma:
A. Histology.
B. IHC.
A. Nuclei resemble those of papillary thyroid carcinoma.
B. Positive for TTF-1; negative for thyroglobulin.
Teratocarcinoma: Histology.
Composite malignancy of several lineages, including carcinoma, neuroblastoma, sarcoma, and sometimes germ-cell tumor.
Olfactory neuroblastoma: Age group.
Peaks at 15 years and 55 years.
Olfactory neuroblastoma: Histology (3).
Small round blue cells form rosettes (Homer Wright and Flexner-Wintersteiner).
Fibrillary stroma.
May contain ganglion cells.
Olfactory neuroblastoma: Immunohistochemistry (3).
Positive: Neuroendocrine markers.
Variable: Cytokeratin.
S100 highlights sustentacular cells.
Olfactory neuroblastoma: Electron microscopy.
Dense-core neurosecretory granules.
Olfactory neuroblastoma: Sites of metastases.
Cervical lymph nodes, lung.
Most common sarcoma of the head and neck:
A. In children.
B. In adults.
A. Embryonal rhabdomyosarcoma.
B. Alveolar rhabdomyosarcoma.
Embryonal rhabdomyosarcoma: Subtypes (2).
Botryoid.
Spindled.
Embryonal rhabdomyosarcoma, botryoid subtype: Histology (2).
Small blue cells in abundant myxoid stroma.
Subepithelial “cambium” layer consisting of more compacted cells.
Embryonal rhabdomyosarcoma, spindled subtype: Histology (3).
Fairly uniformed spindled cells.
Rare rhabdoid cells.
Occasional rhabdomyoblasts.
Embryonal rhabdomyosarcoma: Mutation.
Loss of heterozygosity in 11p.
Alveolar rhabdomyosarcoma: Typical histology (3).
Nests of incohesive small round blue cells.
Many mitotic figures.
Fibrous stroma.
Alveolar rhabdomyosarcoma: Variant histology (2).
Solid pattern.
Clear cells.
Alveolar rhabdomyosarcoma: Mutations (2).
t(2;13) :: PAX3−FKHR.
t(1;13) :: PAX7−FKHR.
Rhabdomyosarcoma: Aberrant expression of IHC markers (2).
Alveolar rhabdomyosarcoma:
- Cytokeratin (up to 50%).
- Neuroendocrine markers.
Sinonasal melanoma: Histologic clue to diagnosis.
Melanocytes located at the base of the respiratory epithelium or exhibiting pagetoid spread.
Sinonasal melanoma: Mutations (2).
In contrast to melanoma of the skin:
- Mutation of CD117.
- Infrequent mutation of BRAF.
Western sinonasal lymphomas: Most common type.
Diffuse large B-cell lymphoma.
Non-Western sinonasal lymphomas:
A. Most common type.
B. Gender predilection.
A. NK/T-cell lymphoma, angiocentric.
B. Three times more common in males.
NK/T-cell lymphoma, angiocentric: Histology (3).
Small and medium-sized cells.
Prominent necrosis, karyorrhexis, inflammation.
Vascular invasion and angiocentricity.
NK/T-cell lymphoma, angiocentric: IHC (3,2).
Positive: CD2, CD43, CD56.
Negative: CD3, CD57.
NK/T-cell lymphoma, angiocentric: Additional study.
ISH for EBV.
Metastases to the sinonasal region: Most common sources (3).
Kidney.
Melanoma.
Breast.
Leukoplakia: Sites of greatest risk for dysplasia.
Floor of mouth.
Ventrolateral aspect of tongue.
Labial mucosa.
Oral squamous papilloma: HPV types (6).
2, 4, 6, 11, 13, 32.
Oral squamous papilloma: Associated syndrome.
Cowden’s syndrome.
Oral squamous papilloma vs. condyloma acuminatum (2).
Condyloma acuminatum:
- More conspicuous HPV effect.
- Broader papillary fronds.
Squamous-cell carcinoma of the oropharynx:
A. Most common site.
B. Clinical presentation.
A. Tonsil.
B. Neck mass in 30%; dysphagia, sore throat, otalgia.
Oral Kaposi’s sarcoma: Most common site.
The palate.
Peripheral giant-cell granuloma: Histology.
Granulation tissue with
- Giant cells.
- Acute and chronic inflammation.
- Metaplastic bone sometimes.
Granular-cell tumor: Granules.
Lysosomes.
Periapical cyst:
A. Synonym.
B. Sites.
A. Radicular cyst.
B. Maxillary incisors, mandibular molars.
Periapical cyst: Radiography.
Round or flask-shaped radiolucency with a radiopaque margin.
Periapical cyst: Histology (3).
Lined by stratified squamous epithelium that is chronically inflamed.
Cholesterol clefts.
Rushton (hyaline) bodies in 10% of cases.
Periapical cyst vs. odontogenic keratocyst.
Odontogenic keratocyst: No inflammation.
Dentigerous cyst: Site.
Third molars (most often).
Encases the crown of an unerupted tooth.
Dentigerous cyst: Radiography.
Unilocular radiolucency.
Dentigerous cyst: Histology.
Lined by stratified squamous epithelium that is uninflamed (unless infected).
Odontogenic keratocyst:
A. Synonym.
B. Sites.
A. Keratocystic odontogenic tumor.
B. Posterior mandible, posterior maxilla.
Odontogenic keratocyst: Radiography.
Unilocular or multilocular radiolucency.
Odontogenic keratocyst: Histology.
Lined by stratified squamous epithelium that has
- No inflammation.
- A corrugated surface.
- Palisaded basal cells.
Odontogenic keratocyst: Associated syndrome.
Nevoid-basal-cell-carcinoma (Gorlin’s) syndrome.
Ameloblastoma:
A. Most common site.
B. Associations (2).
A. Posterior mandible.
B. Impacted 3rd molars; odontogenic keratocyst.
Ameloblastoma: Radiography.
Multilocular, “soap-bubble” radiolucency.
Ameloblastoma: Clinicopathologic forms (3).
Unicystic, multicystic: Younger patients.
Peripheral: Older patients, extraosseous.
Ameloblastoma, follicular pattern: Histology.
Nests of epithelial cells with reverse polarity (nuclei away from the basement membrane).
Centers of nests contain loose stellate epithelium and microcysts.
Ameloblastoma, plexiform pattern: Histology.
Cytologically similar to the follicular pattern, but arranged in anastomosing cords.
Ameloblastoma, acanthomatous pattern: Histology.
Follicular nests with squamous metaplasia.
Ameloblastoma, desmoplastic pattern: Histology.
Dense stroma that may contain osteoid.
Ameloblastoma: Relevance of histology to prognosis (2).
Presence or absence of infiltration is the most important prognostic factor.
Histologic pattern does not matter.
Ameloblastic fibroma: Histology.
Benign mixed tumor with epithelial (odontogenic) and mesenchymal (dental papilla−like) components.
Calcifying epithelial odontogenic tumor:
A. Synonym.
B. Most common site.
A. Pindborg’s tumor.
B. Posterior mandible.
Calcifying epithelial odontogenic tumor:
A. Association.
B. Radiography.
A. Impacted tooth (half of cases).
B. Poorly demarcated, multilocular radiolucency that contains granular opacities.
Calcifying epithelial odontogenic tumor: Cytology (3).
Polyhedral cells with much pink cytoplasm and intercellular bridges.
Pleomorphic nuclei with large nucleoli.
No mitosis, necrosis, or inflammation.
Calcifying epithelial odontogenic tumor: Stroma (3).
Concentric calcifications (Liesegang’s rings).
Amyloid-like matter.
Little fibrosis.
Adenomatoid odontogenic tumor:
A. Age group.
B. Most common site.
A. Second decade.
B. Maxilla; anterior portions of jaws, esp. canines.
Adenomatoid odontogenic tumor: Radiography.
Well-defined radiolucency with or without an impacted tooth.
Adenomatoid odontogenic tumor: Histology (4).
Thick fibrous capsule.
Odontogenic epithelium forms sheets, strands, and duct-like structures.
Little fibrous stroma.
Small calcifications.
Cementoblastoma: Most common sites.
Mandibular 1st molar and premolars.
Cementoblastoma: Radiography.
Well-defined radiopacity attached to the tooth root and surrounded by a thin radiolucent zone.
Cementoblastoma: Histology (3).
Thick trabeculae of mineralized osteoid-like tissue displaying cementoblastic rimming.
Loose fibrovascular tissue between the trabeculae.
Radiating columns of uncalcified matrix at the periphery.
Chondrosarcoma of the jaw: Most common sites.
Maxilla.
Base of skull.
Chondrosarcoma: Histologic subtypes (3).
Conventional.
Mesenchymal.
Dedifferentiated.
Chondrosarcoma, conventional subtype: Histology.
Invasive lobules of cartilage.
Mild to severe atypia.
Chondrosarcoma, conventional subtype: Criteria of a grade 3 lesion.
Peripheral spindling
- or -
More than 2 mitotic figures per 10 hpf.
Chondrosarcoma, mesenchymal subtype: Histology.
Two components:
− Clearly recognizable hyaline cartilage.
− Small round blue cells.
Chondrosarcoma, dedifferentiated subtype: Histology.
Two components:
− Conventional chondrosarcoma (often grade 1).
− High-grade spindle cells or epithelioid cells.
Chondrosarcoma vs. chondroblastic osteosarcoma.
Chondroblastic osteosarcoma:
− Lacelike osteoid.
− Atypical osteoblasts.
Chondrosarcoma, grade 1 vs. enchondroma (3).
Enchondroma:
− Less cellular.
− No binucleate chondrocytes.
− No necrosis.
Chondrosarcoma vs. chondroid chordoma (2).
Chondroid chordoma:
− Contains foci of conventional chordoma in addition to chondroid areas.
− Expresses cytokeratin, EMA, Brachyury marker.
Chondrosarcoma: Relevance of grade to metastasis (3).
Grade 1: Very few tumors metastasize.
Grade 3: About 70% metastasize.
A metastasis is often of higher grade than the primary tumor.
Osteosarcoma of the jaw: Associations (3).
Radiation, fibrous dysplasia, Paget’s disease.
Most cases arise de novo.
Osteosarcoma of the jaw:
A. Age group.
B. Locations within the bone.
A. Third and fourth decades.
B. Medullary, periosteal.
Osteosarcoma of the jaw: Radiography.
Radiolucent or radiopaque.
Sunburst pattern is classic.
Osteosarcoma of the jaw: Most common histologic type.
Chondroblastic: Malignant-appearing chondroid areas with focal deposition of malignant osteoid.
Osteosarcoma of the jaw: Less common histologic types (3).
Fibroblastic: Resembles fibrosarcoma or MFH but contains focal osteoid.
Osteoblastic: Predominance of malignant, lacelike, variably mineralized osteoid.
Telangiectatic: Resembles aneurysmal bone cyst but consists of very pleomorphic cells.
Osteosarcoma of the jaw vs. ossifying fibroma:
Ossifying fibroma:
− Bland cells.
− Radiologically and histologically well circumscribed.
Oral squamous-cell carcinoma, HIV-associated: Most common sites (2).
Oropharynx.
Tonsils.
HPV in squamous-cell carcinoma of the oropharynx:
A. Frequency.
B. Prognosis.
A. 30-70% of tumors.
B. Better; more responsive to radiation.
Oral squamous-cell carcinoma: Genetics (2).
Overexpression of TP53 in 30-50% of cases.
Non-diploid tumors are more aggressive.
Oral verrucous carcinoma: Most common sites (2).
Buccal mucosa.
Gingiva.
Oral verrucous carcinoma: Risk factor.
Chaw.
Metastases to the oral cavity: Most common primary sites.
Lung.
Kidney, breast, skin.
Laryngeal nodule: Synonyms (2).
Vocal-cord nodule.
Singer’s nodule.
Laryngeal nodule: Most common site.
Anterior third of the vocal cord.
Laryngeal nodule: Histology.
Covering: Stratified squamous epithelium.
Stroma: Collagenous and vascular (telangiectatic form) or edematous (gelatinous form).
Laryngeal nodule: Possible confounding histologic features (2).
Florid papillary endothelial hyperplasia.
Amyloid-like matter.
Contact ulcer of the vocal cord: Typical site.
Posterior commissure of the vocal cord.
Contact ulcer of the vocal cord: Histology.
Exuberant granulation tissue, with ulceration of the overlying squamous epithelium.
Laryngeal amyloidosis:
A. Most common site.
B. Typical composition.
A. False cords.
B. Immunoglobulin light chains.
Laryngeal papilloma: Clinical types.
Juvenile: Typically multiple; often recurs.
Adult: Typically solitary; infrequently recurs.
Laryngeal papilloma: HPV types.
6, 11.
Laryngeal papilloma: Risk factors for malignancy (3).
Dysplasia.
Previous irradiation.
Solitary lesion.
Squamous cell carcinoma of the larynx: Association with HPV.
Present in less than 5 percent of cases.
Squamous cell carcinoma of the larynx: Sites.
Glottic (esp. anterior vocal cord): Most common.
Supraglottic.
Subglottic.
Squamous cell carcinoma of the larynx: Subtypes (5).
Keratinizing.
Non-keratinizing.
Verrucous.
Basaloid.
Spindle-cell (sarcomatoid).
Squamous cell carcinoma of the larynx: Relevance of site to prognosis.
Glottic: Best.
Supraglottic.
Subglottic: Worst.
Squamous cell carcinoma of the larynx: Relevance of subtype to clinical behavior (2).
Non-keratinizing: Tends to spread along mucosal surface.
Basaloid: Typically poor prognosis.
Neuroendocrine tumors of the larynx: Types.
Carcinoid.
Atypical carcinoid.
Neuroendocrine carcinoma.
Atypical carcinoid of the larynx:
A. Frequency.
B. Definition.
A. More common than typical carcinoid.
B. 2-10 mitotic figures per 10 hpf or small foci of necrosis.
Carcinomas of the trachea: Most common (2).
Squamous-cell carcinoma: Lower third.
Adenoid-cystic carcinoma: Upper third.