Thyroid cancer in a patient with Lynch syndrome – case report and literature review

Abstract

Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1, MSH2, MSH6, and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient’s metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient’s known Lynch syndrome and her thyroid cancer. The thyroid cancer tissue showed normal expression of MSH2, suggesting that the tumor was not due to the oncogenic mutation of Lynch syndrome, and molecular analysis confirmed BRAF V600E mutation. Although in this case the thyroid cancer was sporadic, it raises the importance of considering cancer genetics in familial cancer syndromes when other cancers do not fit the criteria of the syndrome. Careful documentation of other malignancies in patients with thyroid cancer and their families would assist in better understanding of any potential association. Appropriate genetic testing will clarify whether a common pathogenic mechanism links seemingly unrelated cancers.

Autophagy-Related MicroRNA: Tumor miR-125b and Thyroid Cancers

“…We revealed gene and signaling components responsible for PTC manifestation. Lynch syndrome describing a familial cancer syndrome with four DNA mismatch repair genes mutations was found to be associated with PTC [ 74 ]. A high risk of familial adenomatous polyposis (FAP) was found in PTC patients [ 75 ].…”

“…MiR-125b targets a number of genes such as components of signaling cascades and transcriptional factors [ 10 ]. Most of them are universal and highlight the variety of oncogenic processes: cell motility [ 66 , 67 , 68 , 69 , 70 , 71 ], epigenetic regulation [ 69 ] as well as metabolic reprogramming [ 72 , 76 ], viruses [ 70 ], immune response [ 73 ] and familial genetic disorders [ 74 , 75 ]. It was again mentioned that the FOXo signaling cascade participation in PTC oncogenesis as well as in autophagy initiation [ 77 ].…”

Co-Occurrence of Familial Non-Medullary Thyroid Cancer (FNMTC) and Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Associated Tumors—A Cohort Study

“…On the contrary, the genetic basis for FNMTC susceptibility remains largely unknown ( 7 – 12 ), and FNMTC is not a typical part of the known LS spectrum of tumors. However, previous studies have presented TC as a rare LS-associated cancer in carriers of germline MMR gene mutations ( 51 ) and a handful of case reports document ATC and undifferentiated thyroid cancers ( 35 , 52 ) and PTC in LS patients ( 53 , 54 ), either with or without MSI in the analyzed tumors. However, none of the abovementioned studies have presented FNMTC as a part of the LS comorbidity.…”

Use of multikinase inhibitors/lenvatinib in patients with synchronous/metachronous cancers coinciding with radioactive‐resistant differentiated thyroid cancer

“…Nowadays, there are just a few reports of aDTC in the context of MPMN 50–54 and there is no definitive published clinical evidence supporting the use of MKIs in patients with MPMNs and aDTC. The usefulness of MKIs in patients with MPMNs (including DTC) has been described in some patients though, with comparable results to those in a non‐MPMN context 53,55–58 .…”

“…Additionally, other non-registrational studies have shown the potential efficacy of MKIs alone or given with other drugs in other advanced cancers, thus increasing their potential usefulness in scenarios associated with DTC and MPMN. 48,49 Nowadays, there are just a few reports of aDTC in the context of MPMN [50][51][52][53][54] and there is no definitive published clinical evidence supporting the use of MKIs in patients with MPMNs and aDTC. The usefulness of MKIs in patients with MPMNs (including DTC) has been described in some patients though, with comparable results to those in a non-MPMN context.…”