Pathology Review Flashcards
Endocrine / Neuroendocrine
a. Paracrine:
- Release / Transport: Local
- Action: Local cells
- Example: Cytokines
b. Synaptic:
- Release / Transport: Local
- Action: Local neuron/muscle
- Example: Neuromuscular
junction
c. Endocrine / Neuroendocrine:
- Release / Transport: into capillary
- Action: remote
- Names used interchangably
d. Architecture
• Nested
• Ribbon-like / trabecular
e. Cytology • Nucleus • Monomorphic (minimal variability) • “Salt-and-pepper” chromatin • Cytoplasm • Granular to vacuolated (granularity=neurosecretory vesicles)
Thyroid
a. Divided into lobules, each composed of 20-40 follicles
b. Follicles
• Follicular cells: cuboidal to low columnar epithelium
• Colloid: thyroglobulin (iodinated precursor of active
thyroid hormone)
c. Under influence of TSH, thyroid follicular epithelial cells convert thyroglobulin into thyroxine (T4) and lesser amounts of triiodothyronine (T3)
d. C-cells (aka parafollicular cells)
• Synthesize and secrete calcitonin
Diffuse hyperplasia (Graves disease)
a. Most common cause of endogenous hyperthyroidism
b. F»_space; M
c. Peak incidence 20 to 40 years
d. Association with HLA-DR3
e. Triad of manifestations:
• Thyrotoxicosis – diffusely enlarged hyper-functioning thyroid
• Infiltrative ophthalmopathy with resultant exophthalmos (~40%)
• Localized infiltrative dermopathy (pretibial myxedema) (minority of cases)
f. Breakdown of self-tolerance to thyroid autoantigens (most importantly TSH
receptor) –> multiple autoantibodies:
• Thyroid-stimulating immunoglobulin (TSI) —> binds TSH receptor –> hormone
release —> thyrotoxicosis
• Thyroid-growth-stimulating immunoglobulins (TGI) —> epithelial proliferation
• TSH-binding inhibitor immunoglobulins (may actually inhibit thyroid cell
function - may explain why sometimes spontaneous episodes of
hypothyroidism)
Diffuse hyperplasia (Graves disease)
Autoantibodies
a. Breakdown of self-tolerance to thyroid autoantigens (most importantly TSH
receptor) –> multiple autoantibodies:
b. Thyroid-stimulating immunoglobulin (TSI) —> binds TSH receptor –> hormone
release —> thyrotoxicosis
c. Thyroid-growth-stimulating immunoglobulins (TGI) —> epithelial proliferation
d. TSH-binding inhibitor immunoglobulins (may actually inhibit thyroid cell
function - may explain why sometimes spontaneous episodes of
hypothyroidism)
Diffuse hyperplasia (Graves disease)
Clinical Findings
*important slide
a. Infiltrative ophthalmopathy
1. Lymphocytic infiltration of retro-orbital space (T-cells)
2. Inflammatory edema / swelling of extraocular muscles
3. Accumulation of extracellular matrix components (e.g. hydrophilic
glycosaminoglycans)
4. Increased number of adipocytes
b. Infiltrative dermopathy (pretibial myxedema)
1. Deposition of glycosaminoglycans
2. Lymphocyte infiltration
Chronic lymphocytic (Hashimoto) thyroiditis
a. Most common cause of hypothyroidism in iodine-sufficient areas of the world
i. F»_space; M
ii. Peak incidence: 45 to 65 years
b. Gradual thyroid failure from autoimmune destruction of thyroid gland
c. Breakdown in self-tolerance to thyroid autoantigens
d. Anti-thyroid antibodies
• Anti-thyroglobulin
• Anti-thyroid peroxidase
• Anti-microsomal
e. Genetics: increased susceptibility with
polymorphisms in immune regulationassociated genes
• CTLA4 (cytotoxic T lymphocyte-associated antigen-4)
• PTPN22 (protein tyrosine phosphatase-22)
Chronic lymphocytic (Hashimoto) thyroiditis
Histology
• Diffuse, symmetrically enlarged
gland
• Mononuclear inflammatory
infiltrate (lymphocytes) +/-
germinal center formation
• Atrophic follicles with oncocytic
metaplasia
Other thyroiditis…
a. Subacute granulomatous (de Quervain) thyroiditis
i. Triggered by viral infection (usually history of URI)
ii. Self-limited, painful
b. Riedel thyroiditis (IgG4 related disease)
i. Fibrosing inflammatory process; extends beyond capsule into surrounding tissue
ii. Fibrosis, lymphoplasmacytic infiltrate (enriched with IgG4 plasma cells), obliterative phlebitis
iii. Hard/fixed mass clinically – can simulate a thyroid neoplasm
Diffuse and multinodular goiter
a. Goiter = abnormal growth of thyroid gland
i. Endemic (iodine deficient) or sporadic
ii. Impaired synthesis of thyroid hormone–> compensatory ↑ TSH–> hypertrophy and
hyperplasia of follicular cells and gland enlargement
iii. Functional outcome: normal, decreased or increased thyroid hormone production
• Euthyroid - increased mass overcomes hormone deficiency
• Hypothyroid - can’t overcome impairment (or congenital biosynthetic defect)
• Hyperthyroid - hyperfunctioning (toxic) nodule (~10%)
b. FNA if rapid growth, pain, unusual firmness in one area, U/S detected nodules with
indeterminate or suspicious features
c. Risk of malignancy in long-standing goiters low (but not zero)
Follicular adenoma
- Benign neoplasm derived from follicular epithelium
- Usually solitary
- Circumscribed proliferation of follicles with well-defined, intact capsule
• Majority nonfunctional although small percentage produce thyroid hormones
(so-called toxic adenoma)
• NOT usually precursor of follicular carcinoma
Follicular carcinoma
a. 5-15% of thyroid carcinomas
b. Diagnosis based on capsular OR vascular invasion
c. Architecture = sheets of follicles
d. No special nuclear features
• No PTC nuclear features allowed
• If PTC nuclear features, instead classified as PTC, follicular variant
e. 10-year survival:
• Minimally invasive (>90%)
• Widespread capsular and vascular invasion (~50%)
Papillary thyroid carcinoma
a. Most common thyroid cancer (>85% of thyroid carcinoma)
b. Solitary or multifocal
c. Diagnosis based on nuclear features:
• Nuclear clearing
• Nuclear pseudoinclusions
• Nuclear grooves
d. Architecture classically papillary (with fibrovascular cores) but may also be follicular (among
many other variants); cribriform-morular variant associated with FAP
e. Psammoma bodies / calcifications common
f. Local lymph node metastasis = common; 10-year survival ~98%; Bad prognostic indicators: elderly, distant metastasis (not just local nodes), invasion into adjacent soft tissue
Anaplastic carcinoma
a. <5% of thyroid carcinomas
b. Highly aggressive malignancy with extensive infiltration of soft tissues
c. Majority patients older with history of thyroid disease
d. Approximately quarter with history of well-diff. thyroid carcinoma (e.g. PTC, FC) and another quarter with concurrent well-diff. thyroid carcinoma in resection specimen
e. Presents as rapidly enlarging neck mass
f. Aggressive local growth and compromise of vital neck structures
g. Median survival - ~ 3 months
Medullary carcinoma
a. 5% of thyroid carcinomas
b. Nests / trabeculae of neuroendocrine cells (fine, stippled chromatin)
c. Amyloid (calcitonin-derived)
d. Genetics :
• Sporadic – RET activating mutations (70-80%)
• Familial (MEN-2A, 2B) – RET
- More often multifocal
- Often associated with C-cell hyperplasia
- Prophylactic thyroidectomy
Parathyroid
a. Derived from developing pharyngeal pouches that also give rise to thymus
b. Located in close proximity to upper and lower poles of right and left thyroid
lobes (also anywhere along path of descent of pharyngeal pouches)
c. Activity of parathyroid glands controlled by level of free (ionized) calcium in
bloodstream
d. Parathyroid hormone effects:
• Increased renal tubular reabsorption of calcium
• Increased urinary phosphate excretion (lowering serum phosphate levels)
• Increase conversion of vitamin D to active dihydroxy form in kidneys
(increased GI calcium absorption)
• Enhanced osteoclastic activity (bone resorption)
e. Cellular components
• Chief cells (PTH hormone production)
• Oxyphil cells
f, Cellularity (variable – age, body habitus and health status play a role)
• ~75% cellularity
• ~25% stromal adipose
Parathyroid - HYPERparathyroidism
a. Primary Hyperparathyroidism (95% sporadic; 5% familial)
b. Symptoms
• Asymptomatic (MAJORITY)
• Other: Fractures, nephrolithiasis, cardiac disease, depression, etc.
-also possible GI isssues for “Groans:
Parathyroid - Adenoma
a. Definition: Single gland disease cured long term after excision of abnormal gland
b. Other • Single abnormal gland and three other pathologically documented normal glands • Single abnormal gland fulfilling IOPTH criteria post-excision
c. Enlarged (average 500 mg)
d. Hypercellular nodule (+/- capsule with rim of normal)
• Chief cell
• Oxyphil
e. Pattern subtypes
• Follicular
• Lipoadenoma
Parathyroid - Hyperplasia
a. Definition: Multi-gland disease
• Synchronous or metachronous (can be reason for surgical failure)
• Equal four gland involvement rare (2-3 glands)
• Usually large glands (combined weight ~1000 mg)
b. Enlarged, hypercellular (sometimes encapsulated)
Parathyroid
Adenoma VS Hyperplasia = Clinical distinction
Path sign out
• Enlarged, hypercellular parathyroid gland
• Size: __ cm
• Weight: __mg
Parathyroid - Carcinoma
a. RARE
b. Clinical presentation • Ca2+ >14 mg/dL (Ref range: 8.6 – 10.3 mg/dL) • PTH > 5x normal • Palpable mass • Adherent to surrounding tissue
c. Definitive pathologic criteria • Metastasis (but rare) • Angiolymphatic invasion • Perineural invasion • Invasion into surrounding structures (thyroid, skeletal muscle, vessel walls) • Extension through capsule
d. Histology
• Larger than adenomas (2000 – 10000 mg)
• Firm/fibrous tan white
• Often adherent to surrounding tissue (e.g. thyroid)
e. Prognosis Typically indolent disease
• Outcome based on age, completeness of excision, and presence of metastases
• Major morbidity and mortality from uncontrolled hypercalcemia
f. Mutation of HRPT2 (CDC73) tumor suppressor gene (chromosome 1, parafibromin) implicated in pathogenesis of parathyroid carcinoma
• HPT-JT (hyperparathyroidism-jaw tumor syndrome): AD, ossifying fibromas of jaw, cystic renal lesions, uterine tumors, parathyroid neoplasia (~15% develop
carcinoma)
• Sporadic parathyroid carcinoma
