177. Thyroid Histo/Path Flashcards
Normal Thyroid
- Embryology
- Anatomy (location)
- Histology
E: develops Day 24 from 1st pharyngeal arch endoderm, descends anterior to gut tube, connected to tongue by thyroglossal duct (obliterates week 7-10), descent/maturation to adult shape complete by W7, final location anterior to trachea below thyroid and cricoid cartilage
A: anterior neck from 5th cervical to 1st thoracic vertebra, 2 lobes connected by isthmus forming H or U shape, 2 pairs of parathyroid glands (4 total) in close proximity to thyroid, normal gland not palpable but moves with deglutition (swallowing/speaking b/c descended from tongue/hyoid bone)
H: inner true capsule forming numerous septae that make lobes/lobules
Lobule: 20-40 follicles - structural unit of gland, simple epithelial layer enclosing colloid-filled cavity
C-cells (parafollicular): <0.1% cells (minority), hard to ID without additional stains, synthesize/secrete calcitonin
Thyroid Nodule Prevalence
Thyroid Cancer Prevalence
Fine Needle Aspiration (FNA) Biopsy
- what is it
- advantages
- purpose
- indications
Nodule: VERY common, most found incidentally or on autopsy
Thyroid Cancer: FASTEST growing (increasing prevalence) cancer among men and women due to increased incidental dx’s, BUT death rate stable over time (not increasing with more dx)
FNA Biopsy: small thin needle removes cell from lesion/mass in body
Purpose: gives info about lesion etiology (neoplasia, infection, inflammation), determine if pt needs surgery and extent of surgery
Advantages: simple, safe, accurate, inexpensive
Indications: professional guidelines exist (size + US findings)
Bethesda system reports findings - categories based on malignancy risk based on clinical algorithm
Thyroglossal Duct Cyst
- prevalence
- what it is
- sx
- histo
- tx
MOST COMMON clinically significant congenital anomaly
Abnormal persistence of thyroglossal duct
sx: midline spherical cystic mass closely assoc with hyoid bone, moves with deglutition
Histo: lined by cuboidal/squamous epithelium, contains proteinaceous fluid, +/- follicles
Tx: surgical removal of cyst + mid-portion of hyoid bone (SISTRUNK procedure)
Chronic Lymphocytic (Hashimoto’s) Thyroiditis
- what is it
- pt population
- disease assoc
- gross
- histo
- cytology
autoimmune destruction of gland due to antibodies against TG and TPO = causes HYPOTHYROIDISM
Pt: 45-65yo women
Assoc: higher risk of developing other autoimmune disease, B-cell non-Hodgkin Lymphoma, Papillary Thyroid Carcinoma
Gross: diffusely enlarged gland (or solitary nodule in some cases)
Histo: extensive infiltration of parenchyma by small lymphocytes/plasma cells with germinal centers; follicles are atrophic, lined by regenerating Hurthle cells (metaplastic response of normally low cuboidal epithelium to ongoing injury)
Cyto: Hurthle cells + heterogeneous population of lymphoid cells
Graves’ Disease
- what is it
- pt population
- sx
- tx
- gross
- histo
MOST COMMON CAUSE of endogenous HYPERTHYROIDISM
caused by breakdown in self-tolerance to thyroid autoantigens (development of antibodies against TSH receptor)
Pt: peaks b/w 20-40 y.o.
Sx: Thyroid gland hyperplasia, opthalmopathy (proptosis), dermatopathy (skin changes)
tx: Radioactive Iodine/Drug Therapy (surgery if tx fails)
Gross: thyroid diffusely and symmetrically enlarged
Histo: papillary hyperplasia with tall follicular cells - papillary are broad-based, short, stubby, and lack nuclear features of papillary carcinoma (often confused with PTC)
Adenomatous (Colloid or Hyperplastic) Nodule
- what is it
- types of changes
- benign or malignant?
Goiter = enlarged thyroid gland
Spectrum of changes:
- hyperplastic stages: small follicle lumen, scant colloid, tall columnar epithelium, some papillae
- degenerative stage: fibrosis, hemorrhage, regeneration/repair, dystrophic calcification
- involutional stage: follicles distended with colloid (non-fx), lined by small cuboidal/flat epithelium
Multiple cycles of hyperplasia and involution lead to nodularity
70-75% nodules are hyperplastic
Vast majority are non-neoplastic (benign)
Follicular/Hurthle Cell Adenoma
- what is it
- gross
- histo
- distinguish from malignant potential
- tx
- cyto
5-10% of thyroid nodules
- clinically difficult to ddx from dominant nodules in hyperplastic gland, impossible to predict which are follicular carcinoma until removed
- use tumor capsule integrity to determine malignant potential: adenomas have thin, uniform, completely intact capsule
Gross: discrete solitary nonfx mass derived from follicular epithelium
Histo: uniformly sized follicles, surrounding fibrous capsule, compression of adjacent follicles
Tx: surgical removal of lobe (lobectomy)
Cyto: repetitive pattern of microfollicles and rosettes, single cell type, scant colloid, CANNOT distinguish follicular adenoma and carcinoma (FNA Dx: Follicular NEOPLASM)
Follicular/Hurthle Cell Carcinoma (FTC)
- key gross/histo signs of malignancy
- genetic testing for malignant potential
- Capsular invasion
- Vascular invasion
Genes: RAS mutations, PAX8-PPARG fusion gene commonly seen
Papillary Carcinoma (PTC)
- prevalence
- pt age/hx
- prognosis
- gene assoc
- gross
- histo
- tx
MOST COMMON MALIGNANT thyroid nodule (5-10% all nodules, 85% all malignant nodules)
Pt: 20-40yo, assoc w/radiation, non-fx mass, can initially present as cervical LN metastasis
Prognosis: GREAT!! even if mets to LNs still not very deadly
Gene: assoc w/ activation of MAPK pathway (test for RET rearrangements, RET-PTC fusion proteins, activating point mutations in BRAF)
Gross: varies depending on degree of fibrosis, encapsulation, cystic change = multifocal process (micro <1.0cm; macro >1.0cm)
Histo: atypical nuclear morphology (HALLMARK), hypochromasia (lighter), nuclear grooves, intranuclear inclusions, ovoid nucleus (orphan annie eyes), micronucleosis
TX: surgery - near total thyroidectomy
NIFTP (Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features)
- what is it
- malignant or benign?
- how is it dx
Encapsulated follicular variant of PTC = not considered malignant (low grade)
Clinically and genetically behaves more like follicular neoplasm
Only dx on excised specimen
Poorly Differentiated Carcinoma
- what is it
- histo
Thyroid cancer without obvious follicular or papillary pattern = implies lack of differentiation
Histo: insulae (nests), may find well-differentiated areas that look follicular or papillary
Medullary Carcinoma (MTC)
- what is it
- etiology
- tumor markers
- gross
- histo
- tx
Neuroendocrine neoplasm derived from C cells (5% all thyroid neoplasms)
Etiology: 75-80% sporadic, rest occur in setting of MENII or Familial tumors (FMTC)
Genetics: activating point mutations in RET proto-oncogene (warrants prophylactic total thyroidectomy)
Markers: serum calcitonin and CEA important for dx and recurrence monitoring
Gross: non-encapsulated (may have circumscribed border) usually in junction of middle and upper thirds of thyroid lobes (where C cells are most densely found), sporadic cases = solitary nodule; familial cases = bilateral/multicentricity
Histo: variable - polygonal/spindle-shaped cells form nests, trabeculae and follicles; acellular amyloid deposits (derived from altered calcitonin polypeptides) in stroma, calcitonin stain positive, familial MTC = multicentric C Cell hyperplasia
Tx: total thyroidectomy with LN dissection (re-tx resected parathyroid glands) = MOST EXPENSIVE SURGICAL Tx
Anaplastic (Undifferentiated) Carcinoma
- prevalence
- what is it
- dx
- histo
- mgmt
Rare <5% thyroid tumors
Most undifferentiated ca present with extensive local extension beyond thyroid
Mimics other tumors - including metastases
Dx: clinical hx, pathology stains to exclude mets, may see concurrent well-differentiated component
histo: high-grade carcinoma with no obvious follicular differentiation by histo or immunochemistry, variety of morphologic patterns, extreme cellular/nuclear pleomorphism (variation in size/shape), necrosis
Mgmt: mostly palliative (b/c quite disseminated), surgery +/- radio/chemo-tx to alleviate sx
Metastatic Tumors
- prevalence
- common sites
- histo
RARE
common sites: Kidney, Lung, Breast
Histo: “alien” pattern - think anaplastic ca or metastases
immunohistochemical stain help with comparison to primary tumor pathology
May be virtually impossible to distinguish from anaplastic carcinoma
Thyroid Lymphoma
- types
- mimics
Primary and MORE COMMONLY secondary in thyroid
Predominantly non-hodgkin lymphoma, B cell type
75% assoc with Hashimoto’s
Low Grade = MALT = difficult to distinguish from CLT (Hashimotos) - need flow cytometry to differentiate
High Grade = mimics anaplastic carcinoma, morphologically easier to dx
