Malignant Peripheral Nerve Sheath Tumor in Cowden Syndrome

Abstract

Malignant peripheral nerve sheath tumor is a rare malignancy, accounting for 3% to 10% of all soft-tissue sarcomas. We describe a previously healthy 48-year-old man who was diagnosed as having a high-grade malignant neoplasm involving the facial nerve in the right petrous canal after a 4-year history of deafness. The tumor was resected; histologic appearance and immunophenotype, including patchy but strong positivity for S100 protein, indicated a diagnosis of malignant peripheral nerve sheath tumor. A PTEN mutation, c.1003C>T p.(Arg335Ter), was subsequently identified as the cause of Cowden syndrome in another family member (a nephew) with dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), and genetic testing in the proband's daughter indicated that he was an obligate carrier of the mutation. Sequencing of the tumor showed homozygosity for c.1003C>T, confirming the presence of a germline mutation and implying loss of the second allele. With the exception of Lhermitte-Duclos disease, tumors of the nervous system are not a prominent feature of Cowden syndrome, and this is the first report of malignant peripheral nerve sheath tumor in Cowden syndrome. Sequencing results in the tumor lend evidence to PTEN gene inactivation being implicated in tumorigenesis in this case, suggesting causality rather than chance association.

Nonreceptor Protein Kinases and Phosphatases Necessary for Auditory Function

“…Heterozygous knockout Pten +/− mice have inner ear abnormalities [61] while the inner ear specific homozygous knockout mice are deaf [62] and have supernumerary hair cells [63]. In humans, some patients with Cowden syndrome have a hearing loss due to PTEN variants [64].…”

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Challenges and opportunities in genetic counseling for hereditary endocrine neoplasia syndromes

“…It can be tempting to assume that a rare tumor is due to a pathogenic variant in a gene associated with a rare condition, especially in the setting of endocrine neoplasia. For examples, several tumors have been reported to occur in a patient with a diagnosis of Cowden syndrome, including a pancreatic neuroendocrine tumor, atypical lung carcinoid, malignant peripheral nerve sheath tumor, and Ewing sarcoma (Chandhanayingyong et al 2015, Taylor et al 2015, Neychev et al 2016, Tsunezuka et al 2016. Certainly, individuals with hereditary tumor predispositions can coincidentally develop sporadic tumors.…”

PTEN hamartoma tumour syndrome: case report based on data from the Iranian hereditary colorectal cancer registry and literature review

“…Reporting cases with different characteristics can help improve national and international approaches to early diagnosis of affected patients and their family members, who are at increased risk of developing several cancers in their lifetime. Previous case reports have highlighted clinical or skin symptoms associated with PHTS, such as papillomatous skin lesions, macrocephaly, gingival hypertrophy and blood vessel problems [12][13][14][15][16][17][18][19]. CS-related hamartoma polyps in various parts of the body have been reported [6,17], including a 16-year-old Iranian female with pathognomonic cutaneous features of CS, who was evaluated for the PTEN gene through testing by the polymerase chain reaction (PCR) [19].…”

“…Previous case reports have highlighted clinical or skin symptoms associated with PHTS, such as papillomatous skin lesions, macrocephaly, gingival hypertrophy and blood vessel problems [12][13][14][15][16][17][18][19]. CS-related hamartoma polyps in various parts of the body have been reported [6,17], including a 16-year-old Iranian female with pathognomonic cutaneous features of CS, who was evaluated for the PTEN gene through testing by the polymerase chain reaction (PCR) [19]. However, there are no reports from Iran of breast cancer associated with PHTS.…”