DICER1: Medical considerations for health professionals

Since its inception in 1987, the Registry has collected detailed information on family history and from this learned that some children with PPB or their relatives have developed other kinds of tumors (see Registry publications). In 2009, a linkage analysis by Dr. Ashley Hill showed germline loss of function in the DICER1 gene in 11 families with PPB. This critical finding brought the Registry one step closer to understanding the events underlying the familial manifestations of PPB and related tumors. Since that time, our understanding of this unique tumor predisposition continued to expand.

We have learned that most individuals with germline DICER1 pathogenic variation lead healthy lives, however thyroid nodules and lung cysts are common. In addition to PPB, DICER1-related tumors include renal tumors (most commonly cystic nephroma but also Wilms tumor and renal sarcoma), ovarian tumors (Sertoli-Leydig cell tumor, gynandroblastoma and sarcoma), certain eye and nasal tumors, rhabdomyosarcoma and other soft tissue neoplasms, thyroid cancer and certain brain tumors including intracranial sarcoma, pineoblastoma pituitary blastoma and others. Individuals with pathogenic DICER1 variation may also have thyroid nodules, macrocephaly or juvenile gastrointestinal polyps.

Importantly, preoperative assessment of the family history may provide clues to the diagnosis of these rare tumors, allowing the most appropriate surgical procedure to be undertaken. For example, a young child with a cystic lung lesion a family history of Sertoli-Leydig cell tumor suggests the preoperative diagnosis of PPB. The cystic lesion may represent PPB and care should be taken to avoid spillage of malignant cells.

A spectrum of conditions from thyroid nodules to lung cysts to Type III PPB may indicate underlying DICER1 variation. Testing guidelines and surveillance guidelines are available. Please contact the Registry for more information. The goal of testing and surveillance, is to detect PPB and other DICER1-related cancers in their earliest and most curable form.

PPB and other DICER1-related conditions are rare. International collaboration is the best way to improve outcomes for children and adults with these conditions. Meaningful data on these rare conditions can only be collected if we all work together. We encourage all treating physicians and families to consider participation in the Registry.

The Registry will work with families and physicians regarding informed consent, HIPAA consent, IRB processing and related issues as needed. Regardless of enrollment status, the Registry will work with families and physicians on any questions related to PPB and other DICER1-related cancers. Together we can find a cure.

Preoperative assessment of the individual and family history may provide clues to the diagnosis of these rare tumors, allowing the most appropriate surgical procedure to be undertaken. For example, a young child with a cystic lung lesion a family history of Sertoli-Leydig cell tumor (or thyroid nodules or other DICER1-related conditions) suggests the preoperative diagnosis of PPB. The cystic lesion may represent PPB and care should be taken to avoid spillage of malignant cells.

In girls and young women with an ovarian mass, preoperative findings of thyroid nodules, lung cysts or other individual or family history consistent with DICER1 variation or clinical features of male hormone production (deepening voice, acne, excess hair growth) may suggest the diagnosis of a DICER1-related tumor.

Tumor that has been removed for clinical reasons is of great utility in PPB research. If circumstances allow, enrollment in the Registry to allow sharing of clinical data and tumor tissue is strongly encouraged. We hope that by working together we can find more effective and less toxic treatments for these rare tumors.

Consultation for pathologists to review/confirm the diagnosis of PPB is provided by Registry pathologists at no charge. This is done through review of slides. This process also fulfills the need for central path review if the child is enrolled in the Registry. (Go here for the Pathology Consultation – Specimen Transmittal form). Pathologists and treating physicians are also asked to consider sending fresh or frozen tissue to the PPB/DICER1 Registry so that it can be used to improve our understanding of potential therapeutic targets.