- Clinically, the term ‘goiter’ relates to an enlarged thyroid gland:
- A finding that is associated with various neoplastic and non-neoplastic disorders
- Goiter often presents as:
- A nodular and rarely as a diffuse process
- Most agree that the terms ‘colloid nodules,’ ‘multinodular goiter,’ ‘adenomatous goiter’ and ‘multinodular hyperplasia’:
- Often used by pathologists are not reflective of the underlying pathology besides the mere confirmation of clinical findings
- Molecular analyses of individual nodules
in such cases have revealed that a good proportion of goitrous nodules is:- Monoclonal and represents neoplastic
proliferations:- Making it impossible to distinguish between non-neoplastic and benign neoplastic follicular neoplasms i.e. adenomas on the basis of morphology alone (Mete & Asa 2012)
- Monoclonal and represents neoplastic
- In addition, most of the adenomatous nodules
encountered in patients with DICER1, PTEN and PTEN-like syndromes (Harrer et al. 1998a,b, Derwahl & Studer 2002):- Also represent multiple follicular adenomas (Wasserman et al. 2018, Cameselle-Teijeiro et al. 2021):
- Therefore, an umbrella term of ‘follicular nodular disease’ (FND):
- Has been proposed in the latest WHO classification, to avoid the above-mentioned issues (Baloch et al. 2022)
- Therefore, an umbrella term of ‘follicular nodular disease’ (FND):
- Also represent multiple follicular adenomas (Wasserman et al. 2018, Cameselle-Teijeiro et al. 2021):
- In the 2017 WHO classification scheme of thyroid
neoplasms:- Follicular adenoma was the only entity
included in the benign follicular cell-derived tumors:- However, in the fifth edition, ‘follicular adenoma with papillary architecture’ (previously termed as papillary adenomatous / hyperplastic nodule) is also included in the benign neoplasm category
- Follicular adenoma with papillary architecture:
- Is a well-demarcated and non-invasive, often encapsulated tumor with intra-follicular centripetal papillary growth, and the lesional cells lack nuclear features of papillary thyroid carcinoma (PTC) (Mete & Asa 2012, Baloch et al. 2022)
- These tumors are often associated with autonomous hyperfunction:
- May therefore appear as hot or warm nodules on radionuclide thyroid scan (Mete & Asa 2012)
- Molecular analyses have shown that these are driven by:
- TSHR, GNAS or EZH1 mutations and alterations that activate the protein kinase
A (PKA) pathway (Parma et al. 1993, Gozu et al. 2010)
- TSHR, GNAS or EZH1 mutations and alterations that activate the protein kinase
- These tumors may also occur in the setting of McCune–Albright and Carney complex syndromes:
- Both are PKA pathway-related conditions driven by GNAS and PRKAR1A mutations, respectively (Kamilaris et al. 2019, Nosé et al. 2022)
- Moreover, non-functional follicular adenomas with papillary architecture:
- Can harbor DICER1 mutations, and a subset of these have been reported in association with DICER1 syndrome (Wasserman et al. 2018, Cameselle-Teijeiro et al. 2021, Juhlin et al. 2021):
- Thus, the association between thyroid function and related tumor syndromes
makes the distinction between these tumors clinically significant
- Thus, the association between thyroid function and related tumor syndromes
- Can harbor DICER1 mutations, and a subset of these have been reported in association with DICER1 syndrome (Wasserman et al. 2018, Cameselle-Teijeiro et al. 2021, Juhlin et al. 2021):
- Furthermore, a diagnosis of oncocytic
follicular adenoma:- Requires >75% of tumor cells to exhibit oncocytic features (Baloch et al. 2022)
- Overall, oncocytic thyroid tumors represent a distinct entity of thyroid neoplasms, supported by specific genetic aberrations
including:- Mitochondrial DNA mutations and increased copy number alterations (Gopal et al. 2018, Doerfler et al.
2021, McFadden & Sadow 2021)
- Mitochondrial DNA mutations and increased copy number alterations (Gopal et al. 2018, Doerfler et al.
- Follicular adenoma was the only entity
Rodrigo Arrangoiz MS, MD, FACS, FSSO 