The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

Purpose: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. Methods The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder primarily affecting children, typically presenting as self-limiting skin lesions. However, extracutaneous JXG (extra-JXG) or systemic JXG (sJXG) can involve various organs, including the central nervous system (CNS), leading to high morbidity and mortality, especially in cases of CNS involvement. Treatment approaches for CNS–JXG, including surgical resection, chemotherapy, and radiation therapy, lack consensus, with reports of relapsed or refractory cases being rare. Here, we present the case of a 2-year-old girl with refractory extra-JXG involving the CNS, characterized by multiple intracranial lesions.Initial chemotherapy with prednisolone and vinblastine showed no response, and second-line therapy, including cytarabine and vincristine combined with surgical resection, was also ineffective. However, a 6-cycle third-line chemotherapy regimen incorporating vincristine and carboplatin led to a positive response, with stable disease status, and normal growth and neurodevelopment observed. Our findings suggest that combined chemotherapy with carboplatin and vincristine is a feasible and well-tolerated treatment strategy for patients with CNS–JXG.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langer‑ hans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature.This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in highrisk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects.MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults.Further research is required to determine the optimal treatment duration and strategies for managing therapy inter‑ ruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histio‑ cytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder primarily affecting children, typically presenting as self-limiting skin lesions. However, extracutaneous JXG (extra-JXG) or systemic JXG (sJXG) can involve various organs, including the central nervous system (CNS), leading to high morbidity and mortality, especially in cases of CNS involvement. Treatment approaches for CNS–JXG, including surgical resection, chemotherapy, and radiation therapy, lack consensus, with reports of relapsed or refractory cases being rare. Here, we present the case of a 2-year-old girl with refractory extra-JXG involving the CNS, characterized by multiple intracranial lesions.Initial chemotherapy with prednisolone and vinblastine showed no response, and second-line therapy, including cytarabine and vincristine combined with surgical resection, was also ineffective. However, a 6-cycle third-line chemotherapy regimen incorporating vincristine and carboplatin led to a positive response, with stable disease status, and normal growth and neurodevelopment observed. Our findings suggest that combined chemotherapy with carboplatin and vincristine is a feasible and well-tolerated treatment strategy for patients with CNS–JXG.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langer‑ hans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature.This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in highrisk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects.MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults.Further research is required to determine the optimal treatment duration and strategies for managing therapy inter‑ ruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histio‑ cytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder primarily affecting children, typically presenting as self-limiting skin lesions. However, extracutaneous JXG (extra-JXG) or systemic JXG (sJXG) can involve various organs, including the central nervous system (CNS), leading to high morbidity and mortality, especially in cases of CNS involvement. Treatment approaches for CNS–JXG, including surgical resection, chemotherapy, and radiation therapy, lack consensus, with reports of relapsed or refractory cases being rare. Here, we present the case of a 2-year-old girl with refractory extra-JXG involving the CNS, characterized by multiple intracranial lesions.Initial chemotherapy with prednisolone and vinblastine showed no response, and second-line therapy, including cytarabine and vincristine combined with surgical resection, was also ineffective. However, a 6-cycle third-line chemotherapy regimen incorporating vincristine and carboplatin led to a positive response, with stable disease status, and normal growth and neurodevelopment observed. Our findings suggest that combined chemotherapy with carboplatin and vincristine is a feasible and well-tolerated treatment strategy for patients with CNS–JXG.