Diagnostic decision through molecular testing

Gabriela Colichio

The histopathological diagnosis has been used as a standard for the diagnosis of many diseases, including cancer. However, in some circumstances, this type of diagnosis cannot be used and, in recent years, technical advances in molecular tests have unveiled genetic variants in many cases of tumors, determining the final diagnosis and leading to the adoption of this technique in clinical practice.

Next-Generation Sequencing (NGS) is an important technique for genomic detailing of cancers. This technology, through whole genome sequencing or whole exome sequencing, has generated an increase in the understanding of genomic variations in cancers, including point mutations, insertions or deletions.

Therefore, to show the importance of molecular testing in diagnostics, Cap Today together with the Association for Molecular Pathology, released this year a publication with examples of clinical cases in which molecular tests were relevant and decisive.

A 52-year-old woman with a medical history of an intrauterine tumor. A new CT scan showed a new pelvic mass and the MRI confirmed it, with concern for invasion of the bladder. The patient underwent a biopsy and on histological examination, the pelvic tumor invaded some areas and presented nodules in the adipose tissue. Subsequently, immunohistochemistry was performed and showed positive results for some types of cancers, but the result remained inconclusive. After performing some tests, the NGS was performed and 40% of the tumor revealed two pathogenic variants that supported the final diagnosis of Leiomyosarcoma.

The second patient is a 72-year-old woman with a history of shortness of breath for a few months, morning cough and difficulty swallowing, a thyroid nodule was found that compressed the trachea. Papillary thyroid carcinoma was indicated with aspiration of the thyroid, with inconclusive biopsy. The tumor showed large areas of necrosis and immunohistochemistry was performed indicating anaplastic thyroid carcinoma. NGS was performed for definitive confirmation and the patient underwent radiotherapy and chemotherapy. The sequencing performed showed about 10% of the tumor identified with a pathogenic variant, and based on this variant, the decisive diagnosis of anaplastic thyroid carcinoma was made.

The NGS can bring important information about several genes, through only a small DNA sample. Large-scale genomic research and NGS technological innovation have revealed many details of somatic and germline mutations in tumors, allowing the classification of subcategories of tumor types based on genetic changes. This test is very important to investigate genomic mechanisms, including therapy-related signaling pathways. With this new information, new drugs and targeted therapies are being administered to patients.

These two clinical case studies are part of several cases that have shown that the NGS can assist in the definitive diagnosis of tumors when morphological and immunohistochemical tests alone are not enough.

Therefore, molecular cytopathology can refine diagnoses in cases with a high level of diagnostic uncertainty, assisting in the treatment and resulting in an improvement in the patient’s quality of life.


[1] Garakani, Kiavash et al. AMP case report: NGS as the tiebreaker in tumors with similar morphology and equivocal immunophenotype. Cap Today, p. 1-4, 2020. 

[2] GARZIERA, Marica et al. New challenges in tumor mutation heterogeneity in advanced ovarian cancer by a targeted next-generation sequencing (NGS) approach. Cells, v. 8, n. 6, p. 584, 2019.

[3] SURREY, Lea F. et al. Clinical utility of custom-designed NGS panel testing in pediatric tumors. Genome medicine, v. 11, n. 1, p. 1-14, 2019.

[4] WAKAI, Toshifumi et al. Next-generation sequencing-based clinical sequencing: toward precision medicine in solid tumors. International journal of clinical oncology, v. 24, n. 2, p. 115-122, 2019.

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