Mother-to-infant cancer transmission during birth: 2 reports from Japan

Study design

• The 2 cases were incidentally discovered during an analysis of the results of routine next-generation sequencing testing in the prospective gene-profiling TOP-GEAR trial.
• Funding: Japan Agency for Medical Research and Development; Ono Pharmaceutical; others.

Key points

• Genetic analyses and other evidence indicated that lung cancers in both boys developed after aspiration of uterine cervical cancer tumor cells into lungs during passage through the birth canal.
• Tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and single-nucleotide polymorphisms alleles with tumors from the mothers. 
• Tragically, both mothers who were diagnosed with cervical cancer after the births died while their offspring were still infants.
• In the first case, a 23-month-old toddler was diagnosed with neuroendocrine carcinoma of the lung.
  • Following 2 unsuccessful chemotherapy regimens, the toddler was enrolled in a clinical trial of nivolumab.
  • The response continued for 7 months, with no appearance of new lesions. 
  • Lobectomy was performed to resect a single remaining nodule, and there was no evidence of disease recurrence at 12 months post lobectomy.
• In the second reported case, a 6-year-old boy was diagnosed with mucinous adenocarcinoma in the left lung.
  • The tumor grew very slowly, which is rare for cervical adenocarcinoma.
  • Mucinous adenocarcinoma is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother.
  • The boy received chemotherapy and experienced a partial response, but there was a recurrence in the left lung 3 months later.
  • Following additional chemotherapy, he underwent total left pneumonectomy and was subsequently disease-free.