Familial 46, XY Disorder of Sexual Development identified in a Ph+BCR::ABL1P210+ Acute Lymphoblastic Leukemia septuagenarian female with RCBTB2::LPAR6 fusion gene: a case report.

Background: Familial 46, XY Disorder of Sexual Development (DSD) was discovered in a Ph+, BCR::ABL1P210+ Acute Lymphoblastic Leukemia (ALL) female with RCBTB2::LPAR6 fusion gene. Siblings developing 46, XY DSD are extremely rare. Patients with 46, XY DSD have much higher rates of gonadal cancers. Nevertheless, the incidence of hematologic malignancies in patients with DSDs has received little attention. RCBTB2::LPAR6 is a rarely reported fusion gene in ALL. Case presentation: Herein, we report a rare case of a newly diagnosed Ph+, BCR::ABL1P210+ ALL patient who was 77 years old and female by social sex. Whole Exome Sequencing (WES) and RNA sequencing revealed TET2 and NF1 mutations in addition to a rarely reported RCBTB2::LPAR6 fusion gene and 17 other genes with uncertain clinical significance. The patient was surprisingly found to have a male karyotype. On ultrasound, neither the uterus nor the ovaries were discernible. A detailed family and marital history revealed that the patient had undergone surgery at an early age for an unexplained inguinal mass. She had slow pubertal development, scanty menstruation, and few overtly feminine characteristics. She had three marriages, but none succeeded in getting pregnant. The patient had never sought therapy for infertility due to the inaccessibility of medical treatment and a lack of medical knowledge. Her sister, 73 years old and female by social sex, who had amenorrhea in adolescence and was unable to conceive, had the same experience. To our surprise, she also had a male karyotype. Conclusions: Due to the absence of long-term social attention and follow-up, studies on the incidence of hematologic malignancies in patients with 46, XY DSD are incredibly uncommon. Siblings developing 46, XY DSD is extremely rare. We report the oldest patient diagnosed with 46, XY DSD. There have not yet been any reports of familial 46, XY DSD with a concurrent diagnosis of Ph+BCR::ABL1P210+ ALL with a rarely reported RCBTB2::LPAR6 fusion gene.

Hematologic secondary malignancies among 102 Chinese patients with Waldenstrom's macroglobulinemia: a single-center case experience and literature review.

Waldenstrom's macroglobulinemia (WM) is a rare and indolent B-cell lymphoma. To investigate the type and survival of hematologic secondary malignancies (SMs) in Chinese patients with WM, we retrospectively reviewed the characteristics of 102 patients with WM from February 2002 to May 2023 in our center. Four men and two women were diagnosed with hematologic SMs. Of the six patients with hematologic SMs, one was diagnosed with acute myeloid leukemia (AML), one with multiple myeloma (MM), one with myelodysplastic syndrome (MDS), one with B-cell acute lymphoblastic leukemia (B-ALL), and two with diffuse large B-cell lymphoma (DLBCL). The median age was 65.5 years (56-74 years). The median interval time between diagnosis of WM and hematologic SMs was 39.5 months (10-117 months). Among those with WM with hematologic SMs, five died and one survived. Overall survival (OS) was just 33 months (12-119 months) on median. A total of 32 patients died and 64 survived in the group of WM without hematologic SMs, and the median OS was 82 months (3-250 months). This is the first study in the Chinese population on hematologic SMs in WM. The purpose of this study was to investigate the prognosis of hematologic SMs in WM in the Chinese population, as well as to compare the population's characteristics to those of other centers. We investigated the underlying causes further and presented a research strategy for our forthcoming investigation. We intend to investigate risk factors for SMs as well as more accessible screening methods.