Clinical Guidance

POT1 tumor predisposition (POT1-TPD) is associated with an increased risk for multiple cutaneous melanomas, sarcomas (particularly cardiac angiosarcomas), chronic lymphocytic leukemia (CLL), and gliomas. Additional cancers have been reported in individuals with a germline POT1 pathogenic variant. However, due to limited data it is unclear if these cancers are specifically associated with POT1 germline pathogenic variants. The general experience, however, is that there is a great diversity of tumor types within and between families. Cutaneous melanoma is the most commonly reported malignancy in individuals with POT1-TPD. The age of onset for first primary cutaneous melanoma ranges from 15 to 80 years .

Diagnostic Criteria

No consensus clinical diagnostic criteria for POT1 tumor predisposition (POT1-TPD) have been published.

Suggestive Findings

POT1-TPD should be suspected in an individual with the following:

• Multiple cutaneous melanomas

• One of the POT1-TPD core cancers and a first- or second-degree relative with a confirmed POT1-TPD core cancer. POT1-TPD core cancers include cutaneous melanoma, sarcoma, chronic lymphocytic leukemia, and glioma.

Management Guidelines

No clinical practice guidelines for POT1 tumor predisposition syndrome (POT1-TPD) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with POT1-TPD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. The majority of POT1-associated cancers are diagnosed in adulthood. Therefore, screening should generally begin at age 18 years (see .)

Surveillance Guidelines

There are no published guidelines for surveillance for individuals with POT1-TPD. Decisions regarding individual surveillance protocols should be based on the emerging phenotypic spectrum of POT1-TPD, as well as the affected individual's personal and family history. In addition, individuals should be educated regarding general signs and symptoms of malignant diseases and advised to seek medical attention with any concerning findings. Due to the similarity to Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome with tumors in multiple organ systems in certain families, it seems appropriate to employ screening similar to that used in LFS. Table 4. POT1 Tumor Predisposition: Recommended Surveillance