Identification of BRAF, CCND1, and MYC mutations in a patient with multiple primary malignant tumors: a case report and review of the literature

Abstract

Background: Multiple primary malignant tumors (MPMTs), usually associated with worse malignant behavior and prognosis comparing to a single primary tumor, and have recently been found to have an increasing incidence globally. However, the pathogenesis of MPMTs remains to be clarified. Here, we report a unique case of the coexistence of malignant melanoma (MM), papillary thyroid carcinoma (PTC), and clear-cell renal cell carcinoma (ccRCC) along with our perceptions on its pathogenesis.

Case presentation: The case reported is of a 59-year-old male patient with unilateral nasal obstruction as well as a renal occupying lesion. Positron emission tomography-computed tomography (PET-CT) revealed a palpable mass of 32 × 30 mm on the posterior and left walls of the nasopharynx. In addition, an isodense nodule was observed in the right superior renal pole, approximately 25 mm in diameter, as well as a slightly hypodense shadow in the right leaf of the thyroid, approximately 13 mm in diameter. Nasal endoscopy and magnetic resonance imaging (MRI) confirmed the existence of a nasopharyngeal neoplasm. Afterward, biopsies of the nasopharyngeal neoplasm, thyroid gland and kidney were performed, and the patient was diagnosed with MM, PTC, and ccRCC according to the pathological and immunohistochemical results. Moreover, mutation of BRAF^V600E was detected in bilateral thyroid tissues, and amplification of both CCND1 and MYC oncogenes were detected in the nasopharyngeal melanoma. After chemotherapy, the patient is now in good overall condition.

Conclusions: This is the first reported case of a patient with the co-existence of MM, PTC and ccRCC undergoing chemotherapy with a favorable prognosis. Herein, we suggest that such a combination may be non-random, as for mutation of BRAF^V600E might account for the co-occurrence of PTC and MM, while mutations of CCND1 and MYC cause the coexistence of MM and ccRCC. This finding may provide valuable guidance on the diagnosis and treatment of such disease, as well as the prevention of developing a second or third tumor for patients with a single primary.

Keywords: Clear-cell renal cell carcinoma; Genetic linkage; Malignant melanoma; Multiple primary malignant tumors; Papillary thyroid carcinoma.

Fig. 1

PET-CT scan findings of the loss of left pharyngeal recess and a palpable mass formed by incrassated soft tissue on posterior and left walls of the nasopharynx, of which the FDG metabolism increased

Fig. 2

PET-CT scan findings of an isodense nodule in the right superior renal pole, approximately 25 mm in diameter

Fig. 3

A slightly hypodense shadow in the right leaf of the thyroid was revealed

Fig. 4

A nodule in the inferior lobe of left lung, 12 × 10 mm in size

Fig. 5

Multiple patchy shadows with low density in the liver

Fig. 6

Bone destructions in the left frontoparietal suture

Fig. 7

PET-CT scans revealed bone destructions in multiple vertebral bodies and appendix

Fig. 8

The result of nasal endoscopy. The arrow points towards the gigantic tumor-like neoplasm in nasopharynx

Fig. 9

a Pathological results of the neoplasm in nasopharynx. Haematoxylin–eosin (H&E) staining of biopsy samples (× 100) magnification. b Immunohistochemical staining results of the neoplasm in nasopharynx showed HMB45 ( +) c Ki67 (10%) d MelanA ( +)