The First Korean Siblings With Adult-Onset 4H Leukodystrophy Related to Nonsynonymous POLR3B Mutations.

Objectives: 4H leukodystrophy is a rare autosomal recessive hypomyelinating disorder characterized by several combinations of motor dysfunction, abnormal dentition, and ophthalmic and endocrine abnormalities. To date, only a single Korean case report of pediatric leukodystrophy caused by the POLR1C sequence variation has been published, while there are no reports on the POLR3B, POLR3A, or POLR3K variants. Methods: Genetic tests of Korean sibling pairs with primary amenorrhea due to normosmic isolated hypogonadotropic hypogonadism and cognitive or behavioral symptoms were performed by whole-exome sequencing (WES). The WES results were validated by direct Sanger sequencing. Results: We identified biallelic variations in the POLR3B gene of p.Tyr685* and p.Tyr746Cys, which have not been associated with 4H leukodystrophy. Both sequence variants lie in the hybrid-binding domain of the protein RPC2. The protein structure analysis predicted that cysteine substitution of the phylogenetically conserved amino acid tyrosine can cause destabilization. Discussion: The siblings reported are the first POLR3B-related hypomyelinating leukodystrophy cases in Korea. Our report expands the mutational spectrum of 4H leukodystrophy and suggests that it is mandatory to consider its diagnostic possibility in adult patients presenting with primary amenorrhea and mild cognitive or behavioral symptoms.

Erratum: Oh, E., et al. Cryopreserved Human Natural Killer Cells Exhibit Potent Antitumor Efficacy against Orthotopic Pancreatic Cancer through Efficient Tumor-Homing and Cytolytic Ability (Running Title: Cryopreserved NK Cells Exhibit Antitumor Effect). Cancers 2019, 11, 966.

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Pituitary Blastoma in a 19-Year-Old Woman: A Case Report and Review of Literature.

BACKGROUND: Pituitary blastoma is a malignant neoplasm of the pituitary gland that was recognized by the World Health Organization in 2017. It is commonly diagnosed in children before 24 months of age. Here, we report the first case of a young adult patient who was diagnosed with pituitary blastoma with increased levels of growth hormone instead of adrenocorticotropic hormone and provide a review of the literature. CASE DESCRIPTION: A 19-year-old woman presented to our hospital with visual disturbance. She had a medical history of Wilms' tumor and multinodular goiter. The brain imaging showed a 3.2 × 2.5 × 1.8-cm solid sellar and suprasellar cystic mass that upwardly displaced the optic chiasm. She had an elevated level of growth hormone but a normal level of adrenocorticotropic hormone, cortisol, and prolactin. The mass was subtotally removed through the left pterional craniotomy. The pathologic examination suggested a pituitary blastoma. Thereafter, the patient was treated with chemotherapy and radiotherapy. At 4-year follow-up postsurgery, her overall well-being is good. CONCLUSIONS: Although in this case the patient was a young adult, pituitary blastoma should be taken into consideration when children have an enhanced sellar and suprasellar mass with peripherally located cysts.

Cryopreserved Human Natural Killer Cells Exhibit Potent Antitumor Efficacy against Orthotopic Pancreatic Cancer through Efficient Tumor-Homing and Cytolytic Ability (Running Title: Cryopreserved NK Cells Exhibit Antitumor Effect).

Pancreatic cancer is known to be highly aggressive, and desmoplasia-induced accumulation of extracellular matrix (ECM), which is a hallmark of many pancreatic cancers, severely restricts the therapeutic efficacy of both immunotherapeutics and conventional chemotherapeutics due to the ECM functioning as a major physical barrier against permeation and penetration. In the case of cell-based immunotherapeutics, there are several other bottlenecks preventing translation into clinical use due to their biological nature; for example, poor availability of cell therapeutic in a readily usable form due to difficulties in production, handling, shipping, and storage. To address these challenges, we have isolated allogeneic natural killer (NK) cells from healthy donors and expanded them in vitro to generate cryopreserved stocks. These cryopreserved NK cells were thawed to evaluate their therapeutic efficacy against desmoplastic pancreatic tumors, ultimately aiming to develop a readily accessible and mass-producible off-the-shelf cell-based immunotherapeutic. The cultured NK cells post-thawing retained highly pure populations of activated NK cells that expressed various activating receptors and a chemokine receptor. Furthermore, systemic administration of NK cells induced greater in vivo tumor growth suppression when compared with gemcitabine, which is the standard chemotherapeutic used for pancreatic cancer treatment. The potent antitumor effect of NK cells was mediated by efficient tumor-homing ability and infiltration into desmoplastic tumor tissues. Moreover, the infiltration of NK cells led to strong induction of apoptosis, elevated expression of the antitumor cytokine interferon (IFN)-γ, and inhibited expression of the immunosuppressive transforming growth factor (TGF)-ß in tumor tissues. Expanded and cryopreserved NK cells are strong candidates for future cell-mediated systemic immunotherapy against pancreatic cancer.

Use of preoperative mammography, ultrasonography, and MRI to predict nipple areolar complex involvement in breast cancer.

OBJECTIVE: To identify the predictive factors of cancer invading into the nipple. METHODS: Patients with breast cancer undergoing mastectomy between May 2009 and March 2019 were reviewed retrospectively. Of these, those with breast cancer within 2 cm of the nipple areolar complex on ultrasonography were included in this study. Clinicopathological data of the primary tumor and imaging findings from mammography, ultrasonography, and MRI were compared between cases with and without nipple involvement by cancer. RESULTS: In total, 156 of the 821 patients identified were included in the analysis. Of them, 29 had nipple involvement by cancer. Univariate analysis revealed that the following imaging results were significantly associated with nipple involvement: perineural invasion, lymphovascular invasion, lymph node metastasis; relation type between the tumor and the nipple on ultrasonography; periareolar skin thickening on mammography; and short tumor-nipple distance, continuous enhancement between the nipple and tumor, skin enhancement, and nipple enhancement on MRI. However, on multivariate logistic regression analysis, only invasion type of tumor on ultrasonography and nipple enhancement and short tumor-nipple distance on MRI were significantly correlated with nipple involvement by cancer. CONCLUSION: Imaging findings on preoperative mammography, ultrasonography and MRI are effective predictors for nipple involvement by cancer. ADVANCES IN KNOWLEDGE: Preoperative mammography, ultrasonography, and MRI help predict nipple involvement by breast cancer.

Prediction of Residual Malignancy After Excisional Biopsy for Breast Cancer With Suspicious Microcalcifications: Comparison of Mammography and Magnetic Resonance Imaging.

BACKGROUND: Whether surgery should be performed after excisional biopsy based on mammography or magnetic resonance imaging (MRI) findings has not been evaluated for breast cancer with suspicious microcalcifications on mammography. This study investigated the ability of mammography and MRI to predict residual malignancy after excisional biopsy for suspicious microcalcifications and whether background parenchymal enhancement (BPE) influences the diagnostic performance of MRI. PATIENTS AND METHODS: Fifty-one patients with breast cancer who underwent excisional biopsy for suspicious microcalcifications between January 2009 and February 2019 were enrolled in this single-center retrospective study. Two expert readers independently evaluated the ability of mammography and MRI to predict residual malignancy at the surgical site. The diagnostic value of mammography and MRI was evaluated using histopathology as the standard. RESULTS: Thirty-two patients had residual malignancy. The average overall sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve for residual malignancy were 78.1%, 42.1%, 69.4%, 42.1%, 62.7%, and 0.601 for mammography and 81.2%, 57.8%, 76.4%, 57.8%, 73.5%, and 0.696 for MRI; the respective values for residual malignancy were 88.8%, 57.1%, 72.7%, 57.4%, 76.5%, and 0.73 in the low BPE group and 71.4%, 60%, 83.3%, 57.4%, 65.7%, and 0.657 in the high BPE group. CONCLUSIONS: MRI is more accurate than mammography for prediction of residual malignancy after excisional biopsy for breast cancer with suspicious microcalcifications. However, the BPE of MRI influences diagnostic performance, so careful assessment is needed in patients with moderate or marked BPE.