Thyroid follicular nodules are quite common in general population, however only a small proportion is malignant. Follicular thyroid cancer (FTC) differs from adenoma (FA) by features of cellular atypia, angioinvasiveness and possibility of metastasis via blood. There is no possibility to determine with certainty whether the lesion is benign or malignant before surgery. Moreover, follicular patterned nodules are complex to be classified due to ambiguous nuclear features also at histological examination.
In addition, a clear molecular profile able to discriminate FA from FTC is missing. There is only a pathway hypothesis for progression from FA to FC that still requires confirmatory studies and there aren't evidences about a possible malignant potential in lesions morphologically diagnosed as adenomas.
Raman spectroscopy (RS) is an emerging method able to analyze composite molecular configurations, providing fingerprint information on biological structures of the analyzed samples. We recently used RS to investigate histological samples from human thyroid. While RS has allowed to distinguish healthy tissues from cancerous ones and to discriminate with high accuracy major categories of thyroid cancer (papillary, follicular, papillary/follicular), the analyzed FA were spread by the cluster analysis over the four categories (Benign, PTC, FTC, FV-PTC).
The aim of the present study is to perform a deeply examination of the 5 identified FA falling in the Raman malignant cluster by a combined approach including clinical, morphological, immunohistochemical and mutational analysis through next-generation sequencing (NGS), and to compare the results with paired methods applied to FAs that fall in the Raman benign cluster (n=5).
Results are expected to assess early molecular alteration likely related to ongoing malignant transformation, thus differentiating non-evolving benign tumors from the ones with identical morphology that may require surgical management.
Follicular patterned thyroid lesions are a diagnostic dilemma both at cytological and histological examinations. In addition, molecular analysis is not able alone to differentiate benign from malignant follicular patterned lesions. Indeed, a clear molecular profile able to identify FA and to differentiate this lesion from the malignant counterpart is missing. Most important, there is only a pathway hypothesis for progression from FA to FC that still requires confirmatory studies and there aren¿t evidences about a possible malignant potential in lesions morphologically diagnosed as adenomas.
In the last years, Raman spectroscopy was among a few emerging and innovative method able to analyze composite molecular configurations. RS is based on the scattering of monochromatic light, usually coming from a laser, when interacting with a molecular system. Thus, the resulting spectra provide fingerprint information on biological structures, even in complex systems, and may be used to integrate the traditional tools used for cancer diagnosis. For these characteristics, it has been recently applied on a variety of biological and medical samples to identify specific metabolic states of cells, tissues and bacteria, and to differentiate between healthy and cancer tissues.
We recently used RS to investigate histological samples from human thyroid. While RS has allowed to distinguish healthy tissues from cancerous ones and to discriminate with high accuracy major categories of thyroid cancer (papillary, follicular, papillary/follicular), the analyzed FA were spread by the cluster analysis over the four categories (Benign, PTC, FTC, FV-PTC).
We speculated that adenomas falling in the Raman malignant cluster could harbor early molecular alterations possibly related to ongoing malignant transformation. To prove this hypothesis, we plan to perform targeted-NGS of these tumors by using a novel assay that we recently developed (PMID: 32232767) for mutation detection in thyroid nodule aspirates and tissue.
Finally, genetic results will be integrated with clinical, sonographic, morphological and immunohistochemical analysis and comparison with paired methods applied to five FAs that fall in the Raman benign cluster will be performed.
Results are expected to assess early molecular alteration possibly related to ongoing malignant transformation, so allowing identifying pathways of malignant progression and to differentiate non-evolving benign tumors from the ones with identical morphology that may require surgical management.