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].

classification		Referred to	FNA cytology
FOLLICULAR LESIONS	Benign (macrofollicular) cytology		Macrofollicular Adenomatoid/hyperplastic nodules Colloid adenomas (most common) Nodular goiter Lymphocytic thyroiditis Granulomatous thyroiditis
	Follicular neoplasm/microfollicular cytology
	Follicular lesion of undetermined significance (FLUS)		Mostly due to compromised speciemens: Poor fixation or obscuring blood (FLUS) Common cytology in nodules, especially in nodular goiters.
	Atypia of undetermined significance (AUS)
	Hürthle cells	Oncocytes Askanazy cells Oxyphil cells	large, polyclonal cells with abundant oxyphil cytoplasm benign if there is no evidence of vascular or capsular invasion on pathologic examination of the excised nodule, and malignant (Hürthle-cell cancer or follicular cancer, oxyphil cell type) if invasion is present.
			Focal Hürthle-cell change can be seen in both degenerating macrofollicular lesions and Hashimoto's thyroiditis
PAPILLARY CANCER		The follicular variant of papillary cancer	papillary structure, with or without follicles, and little or no colloid  occasional cases, only follicular development is seen
MEDULLARY CANCER			Atypical cells
Follicular neoplasm			Microfollicular nodules Hurthle cell lesions
Suspicious for a follicular neoplasm			Suspicious for Hurthle cell neoplasm
Malignant			PTC (most common) MTC Anaplastic carcinoma High-grade metastatic cancers

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