Diagnosis of PTEN mosaicism: the relevance of additional tumor DNA sequencing. A case report and review of the literature.

BACKGROUND: PTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by pathogenic variants in the tumor suppressor gene phosphatase and tensin homolog (PTEN). It is associated with an increased risk of muco-cutaneous features, hamartomatous tumors, and cancers. Mosaicism has been found in a few cases of patients with de novo PHTS, identified from blood samples. We report a PHTS patient with no variant identified from blood sample. Constitutional PTEN mosaicism was detected through sequencing of DNA from different tumoral and non-tumoral samples. CASE PRESENTATION: Our patient presented clinical Cowden syndrome at 56 years of age, with three major criteria (macrocephaly, Lhermitte Duclos disease, oral papillomatosis), and two minor criteria (structural thyroid lesions, esophageal glycogenic acanthosis). Deep sequencing of PTEN of blood leukocytes did not reveal any pathogenic variants. Exploration of tumoral (colonic ganglioneuroma, esophageal papilloma, diapneusia fibroids) and non-tumoral stomach tissues found the same PTEN pathogenic variant (NM_000314.4 c.389G > A; p.(Arg130Gln)), with an allelic frequency of 12 to 59%, confirming genomic mosaicism for Cowden syndrome. CONCLUSIONS: This case report, and review of the literature, suggests that systematic tumor analysis is essential for patients presenting PTEN hamartoma syndrome in the absence of any causal variant identified in blood leukocytes, despite deep sequencing. In 65 to 70% of cases of clinical Cowden syndrome, no pathogenic variant in the PTEN is observed in blood samples: mosaicism may explain a significant number of these patients. Tumor analysis would improve our knowledge of the frequency of de novo variations in this syndrome. Finally, patients with mosaicism for PTEN may not have a mild phenotype; medical care identical to that of heterozygous carriers should be offered.

Rapidly developing leptomeningeal carcinomatosis following anterior skull base surgery: a case report.

Leptomeningeal carcinomatosis is rare in evolution of head and neck cancers. Prognosis is poor and treatment is through supportive care. We report an atypical rapid post-operative leptomeningeal carcinomatosis after skull base resection for an ethmoidal adenocarcinoma. The anterior skull base resection was near-total and we suspect a seeding of subarachnoid space either before surgery, either during surgical extirpation or from the residual intracranial nodule. It is the first description of rapid LMC after surgery (less than 1 month). Post-operative MRI diagnosed the LMC through the detection of contrast enhancing leptomeningeal nodules at bilateral second and eighth cranial nerves and at bilateral interpedoncular area. A strong index of suspicion along with clinical and radiological correlation is essential to arrive at a correct diagnosis. Otolaryngologists should be aware of the possibility of leptomeningeal carcinomatosis, before or after surgery, in a patient presents with an appropriate constellation of neurologic symptoms and a history of cancer.