Thyroid Medullary Carcinoma

Cell of origin:  C cells, secrete calcitonin

Clinical features:

1.    Neck mass

2.    Paraneoplastic syndrome (e.g. VIP, Cushing syndrome)

3.    Site of mets:

a.    Cervical, mediastinal lymph nodes

b.    Lung, liver, skeletal system

Prognosis

1.    Good prognostic factors – young age, female, familial, tumour size, confined to gland

2.    Poor prognosis – poor reactivity for calcitonin with increased reactivity for CEA

3.    5-yr survival 80%

Microscopic features:

1.    Single or multiple

2.    Polygonal, plasmacytoid, spindled cells arranged in nests and trabeculae

3.    Amyloid

Histologic variants:

1.    anaplastic or giant cell type

2.    oncocytic variant

3.    papillary variant

4.    mucinous or amphicrine medullary carcinoma

5.    clear cell variant

6.    small cell type – resemble small cell of lung or neuroblastoma

7.    pigmented (melanin-producing) variant

Electron Microscopy

-  membrane-bound electron-dense granules within cytoplasm

Sporadic vs. familial

1.    Sporadic 80%

a.    Adulthood (40-50’s)

b.    One lobe

2.    Familial 20% – MEN2A, MEN2B, familial medullary thyroid carcinoma (FMTC)

a.    Younger age (except FMTC), mean age 35, also see in children

b.    Bilateral, multicentric

c.    Multicentric C-cell hyperplasia

Screening:

-  relatives of MEN-2 patients (prophylactic thyroidectomy in those with germline RET mutations)

Oncogene:

- activating point mutations in RET

Thyroiditis

Hashimoto thyroiditis

Histologic classification of thyroiditis:

1.    Infectious thyroiditis

2.    Hashimoto thyroiditis, 3 histologic features:

a.    Extensive mononuclear inflammatory infiltrate (germinal centers)

b.    Hurthle cells

c.    Atrophic thyroid follicles

3.    Subacute granulomatous thyroiditis (De Quervain)

4.    Subacute lymphocytic (painless) thyroiditis

5.    Fibrous (Riedel) thyroiditis

6.    Palpation thyroiditis
Evidence for autoimmune etiology of Hashimoto thyroiditis:

-    Presence of antithyroid antibodies

-    Increased risk of developing other autoimmune diseases

-    Female predominance 10:1
Cytologic features of Hashimoto thyroiditis:

-    Mixed population of lymphocytes

-    Tingible-body macrophages

-    Lymphohistiocytic aggregates (i.e. germinal centers)

-    Hurthle cells
Clinical features of Hashimoto:

1.    Painless enlargement (symmetric, diffuse) of thyroid

2.    Hypothyroidism (may be preceded by transient thyrotoxicosis)

3.     Increased risk for developing other autoimmune disorders (e.g. type 1 diabetes, SLE, Sjogren syndrome)

4.    Increased risk for developing B-cell NHL
Prognosis

1.    Hypothyroidism – treat medically

2.    Subtotal thyroidectomy for large size and/or pressure symptoms
Associated neoplasms

1.    B-cell non-Hodgkin lymphoma

2.    Plasmacytoma within gland

3.    Not associated with increased risk for developing thyroid epithelial neoplasms but some evidence for an increased risk of papillary thyroid carcinoma

Thyroid Papillary Carcinoma Cytology

Fine Needle Aspiration

FNA features:

1.    Sheets, papillae, microfollicles

2.    Nuclear crowding/molding

3.    Nuclear changes – powdery chromatin, grooves, pseudoinclusions, membrane irregularity

4.    Psammoma bodies

5.    Nucleoli (small or large)

Thyroid Papillary Carcinoma

Clinical presentation

1.    Asymptomatic thyroid nodule (freely movable)

2.    Cervical nodal metastases

3.    Rare – hematogenous metastases

Microscopic findings

1.    Solitary or multifocal

2.    Well-circumscribed or infiltrative

3.    Nuclear changes – clearing, pseudoinclusions, grooves

4.    Psammoma bodies

Histologic variants

1.    Encapsulated variant

2.    Follicular variant

a.    Macrofollicular – rarest form

b.    Diffuse (multinodular) – worse prognosis

c.    Encapsulated follicular variant

3.    Diffuse sclerosing variant – worse prognosis

4.    Oncocytic variant

5.    Clear cell variant

6.    Tall cell and Columnar cell variant – worse prognosis

7.    Solid variant

8.    Cribriform-morular variant

9.    Papillary carcinoma with exuberant nodular fasciitis-like stroma

10.    Papillary carcinoma with spindle and giant cell carcinoma

11.    Papillary microcarcinoma (≤ 1 cm) – most common

Clinical course and prognosis:

-   10-yr survival > 95%

-   5-20% local or regional recurrences

-   10-15% distant mets

Prognostic factors:

1.    Age

2.    Extra-thyroidal extension

3.    Presence of distant metastases

Thyroglossal  Duct

Embryology:

Thyroid arises from the foramen cecum of the tongue and descends as part of the thyroglossal duct to the neck

Thyroglossal duct undergoes atrophy, leaving as a vestige the pyramidal lobe

Pathology:

1.    May get remnants of thyroid tissue (heterotopic thyroid) along path of descent (i.e. midline) from base of tongue to mediastinum

2.    Persistence of thyroglossal duct

a.    sinus tract or blind tubule

b.    thyroglossal duct cyst if tract is dilated

Thyroid Antibodies and Thyroid Disorders

1.    Anti-TSH (binds TSH receptor)

a.    Stimulates:  Thyroid-stimulating immunoglobulin (TSI) in Graves disease

b.    Blocks:  Hashimoto thyroiditis

2.    Anti-thyroglobulin:  Graves disease, Hashimoto thyroiditis

3.    Anti-thyroid peroxidise:  Graves disease, Hashimoto thyroiditis