Multiple endocrine neoplasia type 2 (MEN2) is caused by germline mutations in the RET gene. Medullary thyroid carcinoma (MTC) with MEN2 has almost complete penetrance. MTC has a high frequency of postoperative recurrence. Hereditary MTC arises at a young age. Moreover, the risk of hereditary MTC increases with age.

Prophylactic thyroidectomy for MTC during early childhood in patients with MEN2 is recommended worldwide. Prophylactic thyroidectomy in patients with MEN2 is considered to be the best approach for avoiding recurrence; however, thyroidectomy during early childhood has a higher frequency of postoperative complications. Previous studies, including ours, reported that prophylactic thyroidectomy may decrease recurrence and postoperative complications in pediatric patients with MEN2. Prophylactic thyroidectomy is total thyroidectomy without lymphadenectomy when the lesion is considered to be limited to the thyroid. Therefore, prophylactic thyroidectomy has achieved a lower frequency of postoperative complications in early childhood.

In Japan, prophylactic thyroidectomy is not covered by the national health insurance system, which, in combination with the difficult balance between preventing recurrence and postoperative complications, results in most children not undergoing prophylactic resection. Hence, early calcitonin level-based thyroidectomy that is not based on age may reduce postoperative complications and improve the prognosis of pediatric patients with MEN2 in Japan due to large heterogeneity in the age of onset and aggressiveness of MTC.

DICER1 syndrome is a cancer predisposition syndrome that is associated with an increased risk of rare tumors in children, adolescents, and young adults. DICER1 was identified as an RNase III endoribonuclease in 2001 and demonstrated to be a causative gene for familial pleuropulmonary blastoma in 2009. Since then, numerous tumors have been reported as being associated with DICER1. These include ovarian sex cord–stromal tumors, cystic nephroma, cervical embryonal rhabdomyosarcoma, multinodular goiter, and several recently defined tumors. This paper provides an overview of DICER1 syndrome, including a pattern of germline and somatic pathogenic variants, an update on DICER1-associated tumors, and proposed recommendations for genetic testing and surveillance.

Since 2012, breast surgeons at our facility have performed “pre-counseling” to give an overview of HBOC to patients suspected HBOC. If they request further detailed information about genetic testing for BRCA genes, we arrange genetic counseling in genetic medicine. The first half was from 2012 to 2015, and the second half was from 2016 to 2018. Eligible criteria in the first half were following: Among relatives including proband 3 or more women with breast cancer, ovarian cancers patients and patients with bilateral breast cancer or young breast cancer < 40 years. In the second half, the eligible criteria were expanded to include bilateral breast cancer and young breast cancer < 40 years regardless of family history. In the second half, the content of overview of HBOC was revised. Whether the price of genetic testing was expensive or not, depend on proband’s way of thinking. Providing appropriate medical management is strongly recommended for patients with positive results in genetic testing. Pre-counseling were 31 cases in the first half and 14 cases in the second half. The rate of genetic testing for BRCA genes were 6% (2 of 31 patients received precounseling) and 36% (5 of 14). Revised explanation in the second half may have acted on the rate of genetic testing effectively.

Hereditary breast and ovarian cancer (HBOC) is associated with a significantly increased risk of breast and ovarian cancer. Risk-reducing salpingo-oophorectomy (RRSO) has proven to reduce the incidence of ovarian/fallopian tube cancer as well as the cancer-specific and overall mortality. According to the National Comprehensive Cancer Network (NCCN) guidelines, RRSO is generally recommended for women aged 35–40 years with BRCA1 pathogenic mutations, who have already given birth. In patients with BRCA2 pathogenic mutations, RRSO can be delayed until 40–45 years of age.

Of the 78 women who underwent RRSO, occult cancer was observed in three women (3.8%), two were BRCA1 (44 and 73 years old) and one was a BRCA2 (47 years old) pathogenic mutation carrier. Although MRI was performed for these three women one month before RRSO, there was no evidence of malignancy, and serum level of CA-125 was not elevated. These three women were diagnosed with stage I.

The age of all three women diagnosed with ovarian cancer was higher than that recommended in the NCCN guidelines. RRSO at a recommended age in the NCCN guidelines is considered to be appropriate for Japanese women.

The differential diagnosis for oral and acral pigmented macules is important because it includes Peutz-Jeghers syndrome (PJS), which is associated with important systemic findings. We report a patient with typical PJS, and three patients with related diseases, LaugierHuntziker-Baran syndrome (LHBS) and McCune-Albright syndrome (MAS), and highlight the key dermatological findings for the differential diagnosis. Notable findings included the mucocutaneous pigmented macules exhibiting a freckle-like shape in PJS and a lenticular shape in LHBS. Pigmented nail streaks were uncommon in PJS, but common in LHBS. On dermoscopic examination for acral macules, a parallel ridge pattern was observed in both PJS and LHBS. In MAS, oral mucosal pigmentation is uncommon, but occasionally develops with a freckle-like shape during childhood. These clinical features may aid in the diagnosis of PJS among patients who present with oral and acral pigmented macules.

MPA therapy is widely administered to patients with early-stage endometrial cancer and atypical endometrial hyperplasia (AEH) who desire a fertility-preserving treatment modality. We examined the relationship between MMR protein expression and the effects of MPA therapy, risk of relapse, prognosis, and familial history in 21 patients. We observed MMR deficiency in 7 patients (MLH1: 4, PMS2: 5, MSH2: 2, and MSH6: 2). All patients with lymph node metastasis or who died had MLH1 deficiency. In 13 of 21 patients, we performed MPA therapy for fertility preservation and confirmed MMR deficiency in 2. After the initial treatment, ovarian cancer developed in 2 patients, one of whom had Peutz-Jeghers syndrome. Due to the small sample size of this study, we found no significant association between MMR deficiency and the effects of MPA therapy or the risk of relapse. Many young patients with endometrial tumors may have inherited diseases, although not necessarily with MMR deficiency. Therefore, clinical assessment considering their past history and family history should be performed prior to each treatment. Our findings will serve as a catalyst for future studies with larger sample sizes.

Object: To elucidate the clinical features of colorectal cancer patients who underwent MSI analysis for the purpose of Lynch syndrome screening.

Methods: Retrospectively, the medical records of 31 colorectal cancer patients who fulfilled the revised Bethesda guidelines and underwent tumor microsatellite instability (MSI) analysis were reviewed.

Results: Of 5 items of the revised Bethesda guidelines, the most frequent was “colorectal cancer diagnosed in a patient who is less than 50 years of age”, which was fulfilled by 16 patients. The second most frequent item was the “presence of synchronous, metachronous colorectal, or other Lynch syndrome-associated tumors, regardless of age”, which was fulfilled by 15 patients. Eight patients (25.8%) had MSI-high tumors and 23 had MSS.

Conclusion: Lynch syndrome is highly related to the family history and associated tumors; therefore, the establishment of genetic counselling and a medical treatment system for hereditary tumors across clinical departments is a present issue.

Patients suspected of hereditary breast and ovarian cancer (HBOC) are referred to the Clinical Genetics Unit from the department of Obstetrics and Gynecology and department of Surgery, of our institution. Pre-counseling is initially provided, after which genetic counseling is provided to those who request it. However, there are patients who do not desire genetic counseling even among those at high risk for HBOC. The purpose of the present study was to clarify the background factors associated with genetic counseling for HBOC by comparing those who received genetic counseling with those who did not. Patients undergoing preoperative or postoperative adjuvant chemotherapy often did not receive genetic counseling. Pre-treatment patients and those receiving treatment were considered to lack the time, financial resources, or mental strength to undergo such counseling. Observing treatment progress, and repeating guidance on genetic counseling, may be effective to increase the number of the patients who undergo such counseling.

Hereditary breast and ovarian cancer syndrome (HBOC) has a high lifetime morbidity of breast and ovarian cancers based on BRCA1/2 pathogenic variants. Properly selecting patients and diagnosing HBOC by genetic counseling and genetic testing will enable surveillance and preventive intervention for not only patients, but also their family members. Risk reduction salpingo-oophorectomy (RRSO) is the only highly recommended ovarian cancer prophylaxis for carriers of BRCA1/2 pathogenic variants. The gynecology department of our hospital performed laparoscopic RRSO for HBOC as a clinical study, "Evaluation of risk-reduction surgery for hereditary breast and ovarian cancer syndrome", after approval from our ethics review committee in January 2017. We analyzed issues from our experience of RRSO at this hospital, and examined HBOC cases in which RRSO was not performed and follow-up is ongoing.

Contralateral risk-reducing mastectomy is a prophylactic treatment for breast cancer patients with hereditary breast and ovarian cancer syndrome (HBOC). Patients can elect to undergo this treatment based on the biological characteristics of BRCA-related breast cancer in order to reduce anxiety about secondary cancer development. In recent years, risk-reduction surgery has been reported to reduce the risk of developing new primary breast cancer by >90% and improve overall survival. As of 2020, prophylactic surgery is covered by public health insurance in Japan based on evidence of its efficacy and safety for the treatment of patients with hereditary breast and ovarian cancer. As BRCA1/2 genetic testing is also now covered by health insurance, the number of patients diagnosed with HBOC is expected to increase. Currently, the number of elderly breast cancer patients is increasing due to the aging population and progress in drug treatment. Therefore, it is necessary to respond to the needs of patients of a wide age range. Based on this background, we report a case of contralateral risk-reducing mastectomy for an elderly patient with HBOC who developed unilateral breast cancer.