Page 560 - Concise Pathology for Exam Preparation ( PDFDrive )

20 Endocrinology 545

6. Adenoma with papillae
7. Clear cell and signet-ring adenoma

Q. Differentiate between an adenomatous nodule and a follicular
adenoma.

Ans. Differences between an adenomatous nodule and a follicular adenoma are tabulated
in Table 20.1.

TABLE 20.1. Differences between an adenomatous nodule and a follicular adenoma

S. No. Features Adenomatous nodule Follicular adenoma
1 Nodules Multiple Solitary
2 Encapsulation Poor Good
3 Size of follicles within the nodules Variable Uniform
4 Morphology of adjacent thyroid Similar Architecture is different within
and outside the nodule
5 Compression of adjacent gland Not present Present

Q. Classify malignant lesions of thyroid. Describe the pathogenesis,
clinicopathological features and prognosis of various thyroid
malignancies.

Ans. Malignant lesions (carcinoma) of thyroid are mostly seen in adults (papillary carcinoma
may be seen in children). Females more commonly affected than males.
Subtypes
• Papillary carcinoma (.85%)
• Follicular carcinoma (5–15%)
• Medullary carcinoma (,5%)
• Anaplastic carcinoma (5%)
Pathogenesis
Contribution from genetic and environmental factors:
1. Genetic factors
• Genetic abnormalities in the three follicular epithelium-derived malignancies are
observed in two major pathways; namely, mitogen-activated protein (MAP) kinase
pathway and phosphatidylinositol 3-kinase (PI3K/AkT) pathway.
• In normal cells, these pathways are transiently activated by binding of soluble growth
factor ligands to extracellular domain of receptor tyrosine kinases resulting in autophos-
phorylation of the cytoplasmic domain of the receptor allowing intracellular signal
transduction.
• In thyroid carcinoma, gain of function mutations along these pathways lead to continuous
activation, promoting carcinogenesis. Examples include:
(a) Follicular carcinoma
• Abnormalities in PI3K/AKT signalling pathway due to:
NRAS (most common)
- RAS mutations HRAS
KRAS
- Mutations in PTEN tumour suppressor.
• Formation of PAX8-PPAR (peroxisome proliferator-activated receptor) gamma
1 fusion product due to translocation (2; 3) (q13; p25), which is a nuclear hormone
receptor and induces terminal differentiation of cells.
(b) Papillary carcinoma (PTC)
MAP kinase pathway is the major pathway involved in PTC and abnormalities in
this pathway can occur by the following mechanisms:
• Rearrangements of the tyrosine kinase receptors (TKRs), RET or NTRK1 (neutro-
philic tyrosine kinase receptor 1) due to inversion of chromosome 10 or a reciprocal
mebooksfree.com