Thyroid nodule pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

[Pathogen name] is usually transmitted via the [transmission route] route to the human host. Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell. On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. [Disease name] is transmitted in [mode of genetic transmission] pattern. [Disease/malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells]. Development of [disease name] is the result from multiple genetic mutations. Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3]. The progression to [disease name] usually involves the [molecular pathway]. The pathophysiology of [disease name] depends on the histological subtype.

Pathogenesis

• Pathogenesis is the mechanism by which a certain factor causes disease (pathos = disease, genesis = development). The term can also be used to describe the development of the disease, whether it is acute, chronic, or recurrent. It can also be used to describe whether the disease causes inflammation, malignancy,necrosis etc.

Genetics

• Some diseases are genetic, and have particular inheritance patterns, and express different phenotypes.
• The effect that genetics may have on the pathophysiology of a disease can be described in this section.

thyroid-stimulating hormone (TSH) stimulation cascade related

Associated Conditions

• Conditions associated with the disease can be detailed in this section.

Gross Pathology

• Gross pathology refers to macroscopic or larger scale manifestations of disease in organs, tissues and body cavities. The term is commonly used by pathologist to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.
• This section is a good place to include pictures. Search for copyleft images on The Pathology Wiki [1] and Ask Dr. Wiki [2].

Microscopic evaluation

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Cytology classification		Referred to	FNA	Surgical biopsy	May be seen in:	FNA cytology
Follicular lesions	Benign (macrofollicular)	Adenomatoid adenoma Hyperplastic adenoma Colloid adenoma	+		Normal thyroid tissue Sporadic nodular goiter Monoclonal macrofollicular tumors Hyperplastic nodules Colloid adenomas (most common)	May have areas of cystic degeneration with cellular debris and hemosiderin-laden macrophages Cellular characteristics: Small and flat Uniform in size Non-crowded Smeared colloid is seen in the background Follicle size may vary, with a few microfollicles interspersed among the macrofollicles, especially if the sample was obtained from an area close to the capsule of the lesion Colloid: May smear across the slide or occasionally aggregated into droplets due to disruption of follicles during FNA Stains blue on a Papanicolaou stain May be abundant in the background of macrofollicular lesions
	Follicular neoplasm/microfollicular	Cellular adenoma Indeterminate adenoma Trabecular adenoma		+	Follicular adenomas Follicular carcinomas Follicular variant of papillary cancer Occasionally from autonomously functioning thyroid nodules	Well-developed microfollicles Crowding of cells May form clusters and clumps Scant colloid Varying nuclear atypia Varying cellular pleomorphism Follicular carcinoma: Focal microscopic invasion Cellular or trabecular adenomas: Lesions with less definite or no follicle formation May show vascular or capsule invasion
	Follicular lesion of undetermined significance (FLUS)		+		common, especially in nodular goiters.	FLUS: the lesion has approximately equal number of macrofollicular fragments and microfollicles AUS: cells with mild nuclear atypia Mostly due to compromised speciemens: Poor fixation or obscuring blood (FLUS)
	Atypia of undetermined significance (AUS)
	Hürthle cells	Oncocytes Askanazy cells Oxyphil cells	+		Focal Hürthle-cell change: Degenerating macrofollicular lesions Hashimoto's thyroiditis	Large polyclonal cells Oxyphil cytoplasm Considered benign if there is no evidence of vascular or capsular invasion Considered malignant if invasion is present Hürthle-cell cancer Follicular cancer Oxyphil cell type cancer
Papillary cancer		The follicular variant of papillary cancer		+	Epithelioid giant cells Papillary cancer Degenerating areas of macrofollicular nodules Subacute granulomatous thyroiditis Psammoma bodies Papillary carcinoma Benign thyroid lesions	Large cells and nuclei  Ground glass appearance of cytoplasm  Nuclei appearance: Clefts  Grooves  Holes  Intranuclear cytoplasmic inclusions = Orphan Annie eyes  Small nucleoli  Psammoma bodies Small laminated calcifications Sticky colloid Colloid "stick" to debris and cell clusters, instead of smearing across the slide Epithelioid giant cells Can also be seen in: Degenerating areas of macrofollicular nodules Subacute granulomatous thyroiditis
Medullary cancer				+	Medullary cancer	Spindle-shaped cells Frequently pleomorphic cells without follicle development Supporting stroma may frequently stains for amyloid Red cytoplasmic granules Eccentrically placed nuclei Slightly granular Cytoplasm that may be configured as a tear drop or cytoplasmic tail
Anaplastic thyroid cancer			+ Large needle biopsy if needed		Anaplastic thyroid cancer	Spindle cells Pleomorphic giant cell Squamoid Mitosis Numerous mitotic figures Atypical mitoses Extensive necrosis.

Papillary thyroid carcinoma:

Criteria for papillary thyroid carcinoma:

1. Nuclear inclusion (really pseudoinclusions):
   1. Edge of inclusion must be sharp (nuclear membrane-like).
   2. Size: at least 1/4 of the nucleus.
   3. Round, regular.
   4. Within epithelial cell.
   • Additional criteria:^[22] Inclusion center should match cytoplasm.
2. Nucleoli (micro or macro).
3. Nuclear grooves.
   • No universal criteria; some believe grooves should go from edge-to-edge, i.e. across the nucleus.
4. Nuclear enlargement.
5. Changes in chromatin - patterns:
   • Granular.
   • Washed-out.

Additional features:

• Papillary architecture (not commonly seen).
  • Clump of epithelial cells with attached fibrous tissue "tail" - that has a smooth edge.
• Cellular/nuclear membrane overlapping; cells do not respect one another (very common).
• +/-Psammoma bodies (uncommon - but helpful if seen).

Follicular thyroid neoplasm

Features:^[10]

1. Hypercellular lesion.
2. 3-dimensional clusters of cells.
3. Nuclear overlap/crowding.
4. +/-Microfollicles, numerous.
   • Microfollicles are defined as: <15 cells forming at least two thirds of a circle.
5. +/-Atypia marked.

Hurthle cell neoplasm

1. Single cells or sheets of oncocytic cells.
   • 3-D clusters.
   • +/-Transgressing vessels - cluster of oncocytes surrounding vessels.
2. Oncocytic cells:
   • Well-defined cellular borders.
   • Finely granular abundant cytoplasm.
   • Nucleoli, may be prominent.

Medullary thyroid carcinoma

Features:^[10]

1. Single or loosely cohesive cells.
   • Spindle cell morphology common.
2. Abundant eosinophilc granular cytoplasm - key feature
3. Salt and pepper chromatin - key feature; no nucleoli.
4. Nucleus eccentric and round/oval - plasmacytoid appearance.
5. Amyloid - acellular, amorphous material may be present; cotton candy-like.
   • May be confused with fibrin...
     • Fibrin = fluffy edge vs. amyloid = sharp border. (???)
     • Fibrin - associated with PMNs/has PMNs within it.
   • Amyloid cannot be definitively differentiated on morphologic grounds from colloid.
   • Described by Halliday et al. as:^[27]
     • Romanowsky type staining: "amorphous, irregular, waxy basophilic to metachromatic clump".
     • Pap staining: "cyanophilic-organophilic clumps of material + occasional prominent fissures".

Anaplastic thyroid carcinoma

Features:

• Nuclear atypia - marked.
• Spindle cell morphology common.
• Nucleolus.
• Usually scant cellularity.^[30]
• Necrosis very common.

Microscopic Pathology

• Microscopic pathology is the disease process as it occurs at the microscopic level.
• This section is a good place to include pictures. Search for copyleft images on The Pathology Wiki [3] and Ask Dr. Wiki [4].
• Both polyclonal and monoclonal nodules appear similar on fine needle aspiration (FNA) (macrofollicular) and are benign 8426623
• Thus, the diagnosis of follicular cancer in situ does not exist, because vascular or capsular invasion is required to make the diagnosis of follicular cancer. 8420446