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SurgPatho Thyroid 2018
SurgPatho Thyroid 2018
|2018
-‐ expressed in the normal lung (bronchial cells and
pneumocytes) and in most cases of lung carcinoma
ANATOMY
(including the small cell neuroendocrine type)
-‐ occasionally expressed in other sites, such as the
Normal adult thyroid gland is composed of: normal and neoplastic female genital tract, Wilms
• Two lobes joined by the isthmus, which lies across the trachea tumor, and Merkel cell tumor.
anteriorly, below the level of the cricoid cartilage
• It is endowed with a rich lymphatic network, not always evident Thyroglobulin – most widely used marker
in hematoxylin and eosin (H&E) sections but clearly evident with
the D2-40 immunostain.
• The lymph vessels coalesce in the subcapsular region to give rise CONGENITAL ABNORMALITIES
to collecting trunks that drain into the following nodes:
pericapsular;
-‐
-‐ internal jugular chain;
THYROGLOSSAL DUCT ANOMALIES
-‐ pretracheal, paratracheal, and prelaryngeal (the
pretracheal node located near the isthmus is sometimes • Result of a localized persistence of the thyroglossal duct
referred to as the Delphian node); • In form of a sinus tract connected to foramen cecum,
-‐ recurrent laryngeal nerve chain; supersternal notch or in form of blind tubular structure
-‐ retropharyngeal and retroesophageal • May accompany cyst formation due to secretion of lining cells
-‐ The anterosuperior mediastinal nodes are secondary to the • THYROGLOSSAL DUCT CYTS – prominent cystic changes
recurrent laryngeal nerve chain and pretracheal groups, • Most cases – clinically evident in childhood
but studies have shown that dye injected into the thyroid • Tx: surgical removal – include the middle 3rd of the hyoid bone
isthmus can also drain directly into them and the entire length of the sinus tract
HISTOLOGY MICRO
• Made up of round or oval follicles that vary considerably in Thyroglossal duct cyst
size -‐ Cyst: lined by pseudostratified ciliated / squamous epithelium
• With an average diameter of 200 m -‐ IHC: TTf 1 (+), thyroglobulin (-)
• Lined by a single layer of follicular cells whose shape ranges -‐ Subjacent stroma: mucous glands and thyroid follicles
from flattened to low columnar, depending on their degree of
activity • Secondary inflammation
• Cytoplasm has a pale acidophilic or amphophilic staining -‐ In cases accompanied by sinus tract
quality; the greater the activity of the cell, the greater its -‐ Epithelial lining may be absent as a result
amount -‐ Stroma infiltrated by inflammatory cells
• Follicular cells with abundant granular acidophilic cytoplasm
are referred to as Hürthle cells (a misnomer), Askanazy cells, • Thyroid tissue present can undergo malignant transformation:
oxyphilic cells, or oncocytes. -‐ Papillary carcinoma
• Divided by CT septae into lobules, each containing 20-40 § Prognosis is excellent after surgical removal. Does
follicles (Functional unit) not need to include thyroid gland.
-‐ Others: oncocytic (Hurthle cell) carcinoma and
C-cells undifferentiated (anaplastic) carcinoma
• Or parafollicular cells
• At the junction of the upper 3rd and middle 3rd of the lateral
lobes
• The number of C cells varies according to age; they are more HETEROTROPIC THYROID TISSUE
numerous in infancy and old age than in adults.
• Most adult glands contain no more than 10 C cells in a low-
• As a component of thyroglossal duct cyst, anywhere along the
power microscopic field.
course of the thyroglossal duct, or as a sole abnormality
• In old age, they may form nodular aggregates.
• Most frequent: base of the tongue à difficulty in swallowing and
• Ultrastructurally:
respiratory obstruction
-‐ contain numerous dense-core granules of neurosecretory
• Microscopic lingual (subclinical) thyroid seen in 10% of individuals
type
-‐ Not different microscopically from the main gland
-‐ argyrophilic with the Grimelius reaction;
-‐ Sometimes with capsule or follicles grow between skeletal
-‐ metachromatic with toluidine blue;
muscle
-‐ positive for lead hematoxylin;
-‐ in 70% of patients with grossly evident lingual thyroid there is
-‐ immunoreactive for calcitonin, katacalcin, calcitonin gene–
absence of the normal thyroid gland
related peptide, neuron-specific enolase (NSE),
• Other sites of heterotrophic thyroid
chromogranins A and B, secretogranin II, and synaptophysin
-‐ The anterior tongue
-‐ also immunoreactive for carcinoembryonic antigen (CEA),
-‐ Submandibular region
although less so than their neoplastic counterparts in
-‐ Larynx
medullary carcinoma
-‐ Trachea
-‐ Mediastinum (usually superior but sometimes posterior)
IMMUNOHISTOCHEMICAL STAIN
-‐ Heart
• Distant locations
Ttf-1
-‐ Wall of the duodenum, gallbladder region of the porta
• an extremely useful marker for all types of primary and
hepatis, adrenal gland, fallopian tube, vagina, and the
metastatic thyroid tumors (including medullary carcinoma),
ovary and other sites as a component of teratoma
except for anaplastic carcinoma
-‐ Is subject to the same diseases that can affect the main
-‐ not expressed in normal, hyperplastic, or
gland
adenomatous parathyroid tissue
Ø Inflammation, hyperplasia, and tumors
• May be associated with lymphocytic inflammation of the other • Enlargement of the thyroid gland is due to defects in the
organs synthesis of thyroid hormones
-‐ As parts of autoimmune polyendocrine syndromes: • Thyroid dyshormonogenesis – accounts 20% of cases of primary
Ø Addison’s disease (the combination being known as congenital hypothyroidism, 80% of thyroid dysgenesis
Schmidt syndrome) and • Mutations: steps of thyroid hormone synthesis
Ø Diabetes mellitus -‐ Defective iodide transport
-‐ Distinctive features of autoimmune polyendocrine -‐ Defective iodide organification
syndrome type II: -‐ Defects of thyroglobulin synthesis
Ø Chronic autoimmune thyroiditis -‐ Dehalogenation
Ø Addison’s disease,
Ø and type 1A diabetes MICRO
Ø Type I characterized by: -‐ Solid and microfollicular patterns
Ø Hypoparathyroidism -‐ In some cases, there are papillary and insular formations
Ø Addison’s disease is not typically associated with thyroid -‐ Fibrosis is a common finding
disease)
• Hashimoto thyroiditis (and other autoimmune thyroid diseases) GRAVES DISEASE (DIFFUSE TOXIC GOITER)
can also be associated with non-endocrine autoimmune
disorders like vitiligo, pernicious anemia, myasthenia gravis, • Graves ophthalmopathy (or orbitopathy) develops in 25%-30%
autoimmune gastritis, celiac disease, and hepatitis • Dermatopathy (pretibial myxedema) and so-called thyroid
acropathy – late manifestation
Complications: • Elevation of bound T4, free T4, or bound T3 levels
• Thyroid lymphoma, oncocytic (Hurthle cell) neoplasms, and • Increased radioactive iodine uptake in the presence of low TSH
papillary carcinomans levels
• Can have loss of heterozygosity (LOH) at tumor suppressor
ggene loci GROSS
• RET/PTC may provide a link between Hashimoto thyroiditis and • Mild to moderate symmetric diffuse enlargement
papillary carcinoma • Succulent and reddish
• Cut surface:
Treatment: -‐ Uniformly gray or red
• No treatment -‐ Long standing
• Hormone therapy -‐ Friable and dull yellow
• Subtotal thyroidectomy: size, pressure symptoms MICRO
• Markedly hyperplastic, with prominent papillary infoldings
• Columnar
R.B.
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E.
L.
3
• Aggregates of lymphoid tissue with germinal center formation -‐hemorrhage, edema, necrosis, calcification, bone
• T-cell type formation, and cystic degeneration (LARGER TUMORS)
• MICRO:
NODULAR HYPERPLASIA -‐ Patterns: singly or in combination
o Normofollicular (simple)
• AKA: multinodular hyperplasia, nodular or multinodular goiter, o Macrofollicular (colloid)
adenomatoid goiter, adenomatous hyperplasia o Microfollicular (fetal)
• Euthyroid o Solid / trabecular (embryonal)
• Large, cause tracheal obstruction and produce considerable -‐ Mitoses are rare or absent
disfigurement -‐ Muscular cushions - vessels in the capsule of adenomas
show thickening of the wall
GROSS -‐ May exhibit papillary or pseudopapillary structures-
• Enlarged, and its shape is distorted follicular adenomas with papillary hyperplasia
• One lobe being frequently larger than the other -‐ Hyperfunctioning (hot) adenomas- cellular, more
• Multiple nodules cytoplasm (Inc. N:C ratio)
• Hemorrhage, calcification, and cystic degeneration are o Activating mutations in gene TSH receptor
common (TSHR)/ Gsa subunit protein (GNAS)
o EIH1 gene mutations (20-30%)
MICRO -‐ Chromosomal abnormalities activating RAS mutations,
• Huge follicles lined by flattened epithelium and PAXS/PPARG rearrangement (same as follicular Ca)
• Conglomerate of small active follicles at one pole (so-called
Sanderson pollsters) SEVERAL VARIANTS: FOLLICULAR ADENOMA
• Benign papillary formations protruding toward the center of a
cystically dilated follicle 1. Oncocytic (Hurthle cell) Adenoma and Hyalinizing Trabecular
Adenoma
2. Atypical adenoma
-‐ pronounced cellular proliferation and less regular
cytoarchitectural patterns
3. Adenoma with bizarre nuclei
-‐ presence of huge hyperchromatic nuclei, usually in
clusters
4. Rare types:
-‐ clear cell changes (including the signet ring, mucin-
producing and lipid- rich types)
-‐ lipoadenomas or adenolipomas (adipose metaplasia of
the stroma)
-‐ adenochondromas (with cartilaginous metaplasia)
-‐ spindle cell and black adenomas (cytoplasmic pigment
ff minocycline therapy)
• most common type of thyroid carcinoma and the most • composed of entirely or almost entirely of follicles
common endocrine malignancy • a.k.a. “Lindsay tumor”
• Females > males • Dx: PTC like nuclei
• Initial Dx approximately 40-50 years • Infiltrative follicular variant Papillary Carcinoma
• History of irradiation exposure in 5% • Devoid of a fibrous capsule
• Increase in incidence of Hashimoto’s • Partial remnants of capsule identified
• With infiltrative growth margins
GROSS:
-‐ Microscopic to very large ENCAPSULATED FOLLICULAR VARIANT AND
-‐ High proportion <1cm NONINVASIVE FOLLICULAR THYROID NEOPLASM WITH
-‐ Solid, whitish, firm and clearly invasive
PAPILLARY-LIKE NUCLEAR FEATURES
-‐ 10-20% encapsulated
-‐ marked cystic changes in 10%
-‐ Sometimes papillary formations seen by naked eye • Surrounded by a capsule, follicular growth pattern (no
papillae),
NUCLEAR FEATURES (PTC- TYPE NUCLEI) nuclear alterations of papillary carcinoma
• Ground glass (optically clear) nuclei • “well- differentiated tumor of uncertain malignant potential
• Nuclear pseudoinclusions- invaginations of the cytoplasm (WDT- UMP)
sharply outlined (nuclear membrane bound) round • cytoarhitectureal alterations “incomplete/ focal” (+) galectin-3
acidophilic vacuoles and HBME-1 with questionable/ incomplete nuclear changes
• Nuclear grooves- infoldings of a redundant nuclear membrane that fall short of a diagnosis of papillary carcinoma
• Nuclear microfilaments- nuclear clearing due to accumulation • well- differentiated carcinoma, not otherwise specified (WDC-
of thread like fibrils NOS) – similar cases with invasion
• Mitoses- very scanty or absent • “noninvasive follicular thyroid neoplasm with papillary-like
nuclear features” (NIFTP)- to avoid overdiagnosis of CA
OTHER FEATURES: • Based on a 0-3 point scoring system conventional morphologic
• Extensive fibrosis- sharply outlined bands traversing the tumor features
• Psammoma bodies – ½ of cases, strongly suggests the diagnosis • If criteria met, the likelihood of the tumor recurring or
of papillary carcinoma, if found in non- neoplastic thryroid, metastasizing is less than 1%
chances are high (+) papillary CA near the vicinity • Encapsulated follicular variant of papillary carcinoma with
• Solid/ trabecular pattern in 20%, foci of squamous metaplasia in capsular and/or vascular invasion – when invasive
similar number
• Bland- looking spindle cell component
IHC
• (+) S- 100 protein- positive dendritic/ Langerhans cells and
macrophages
• (+) Thyroglobulin
• (+) pan- keratin, CAM 5.2, AE1/3 antibodies, with a CK 7
positive/ CK 20 negative profile, Low molecular weight CK19
• Vimentin (+)
• TTF-1 (+) PAX 8 (+) vs Lung adenocarcinoma PAX8 (-)
• Benign and malignant thyroid lesions
• (-) HBME-1, galectin -3, CK 19, CITED1, (-) CD 56
Primary tumor (p1) The most common causes of death are local recurrence and
pulmonary metastases
P1X cannot be assessed
P10 no evidence of primary tumor UNDIFFERENTIATED (ANAPLASTIC)
P11 Tumor size 2cm or less, limited to thyroid
P11a Tumor < 1cm in greatest dimension CARCINOMA
P11b Tumor 1-2 cm in greatest dimension
P12 Tumor >2cm to 4cm, limited to thyroid
P13 Tumor >4cm, limited to thyroid or any tumor • Undifferentiated (high grade) carcinoma of thyroid gland
extension • Also called carcinosarcoma, sarcomatoid carcinoma
P14a moderately advanced disease, tumor of any • Aggressive
size extending beyond they thyroid capsule to • Mortality rate approaches 100%
invade subcutaneous soft tissues, larynx, • Mean age of 65 years
trachea, laryngeal nerve • 20% have prior undifferentiated carcinoma
P14b very advanced disease , tumor invades • 20% have concurrent differentiated carcinoma (probably arises
prevertebral fasca or encases carotid artery or as anaplastic transformation)
mediastinal vessels • presents as a rapidly enlarging, bulky neck mass
• invades adjacent structures causing hoarseness, dysphagia,
Note: there is no category of carcinoma in situ to carcinoma of dyspnea
thyroid gland • highly necrotic and hemorrhagic solid tumor mass
CLINICAL
• Invades locally
• Metastases to cervical and mediastinal nodes, lung, liver and
bone
• Metastases may be the initial presentation of disease and usually
contain amyloid
LABORATORY
• High serum calcitonin and chromogranin A levels
• Calcitonin – monitors recurrence
Positive stains:
• Ttf-1
• Low molecular weight keratin
• Chromogranin A and b
• Synaptophysin
• Neuron specific enolase
• Calcitonin
• Congo red for amyloid
• CEA
• Progesterone receptors
EPITHELIAL TUMORS