Large Malignant Testicular/Paratesticular Tumors in Adolescence: Assessment of Gross Tumor Size in a Vulnerable Age Group.

OBJECTIVE: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence. METHODS: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed. RESULTS: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups. CONCLUSION: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.

CD8 cytotoxic T-cell infiltrates and cellular damage in the hypothalamus in human obesity.

Rare cases of paraneoplastic obesity in children suggest sporadic obesity might also arise from an adaptive immune cell-mediated mechanism. Since the hypothalamus is a central regulator of feeding behavior and energy expenditure, we quantified lymphocytic inflammation in this region in a cohort of obese and non-obese human post-mortem brains. We report that CD8-positive cytotoxic T-cells are increased in hypothalamic median eminence/arcuate nucleus (ME/Arc) and bed nucleus of the stria terminalis in 40% of obese compared to non-obese patients, but not in other hypothalamic nuclei or brain regions. CD8 T-cells were most abundant in individuals with concurrent obesity and diabetes. Markers of cytotoxic T-cell induced damage, activated caspase 3 and poly-ADP ribose, were also elevated in the ME/Arc of obese patients. To provoke CD8 cytotoxic T-cell infiltrates in ventromedial region of hypothalamus in mice we performed stereotactic injections of an adeno-associated virus expressing immunogenic green fluorescent protein or saline. AAV but not saline injections triggered hypothalamic CD8 T-cell infiltrates associated with a rapid weight gain in mice recapitulating the findings in human obesity. This is the first description of the neuropathology of human obesity and when combined with its reconstitution in a mouse model suggests adaptive immunity may drive as much as 40% of the human condition.

A Congenital Tongue Mass.

A 13-month-old male presents with a firm left anterior tongue mass noted since birth that has increased proportionally with the child's growth. What is your diagnosis?

Clinical consequences of a 30-day interval between antibody identifications.

BACKGROUND: While studies have shown that antibody detection may be delayed if an antibody identification (ABID) is not performed every 3 days, little data exist on the potential major risk of an acute hemolytic transfusion reaction (aHTR). STUDY DESIGN AND METHODS: At our institution, if no change in the screen, or a positive crossmatch, ABIDs are performed every 30 days. Between January 1, 2015 and May 31, 2019, all new antibodies detected within 28 days of a prior transfusion were identified. Testing results and patient charts were reviewed for evidence of hemolysis. The $211 patient charge was used to determine the cost for ABIDs performed during the studied time period. RESULTS: For 36 patients, a new clinically significant alloantibody was detected within 28 days of an antigen-positive transfusion. Only one of these patients had a history of prior alloimmunization and put at possible risk due to the ABID policy. For this patient, while there was less than the expected increment to an antigen-positive unit, there was no clinical or laboratory evidence of an aHTR. During this same time, 6095 ABIDs were performed, at a cost of approximately $1.29 million, and 72,665 red cell transfusions occurred. CONCLUSION: With an ABID every 30 days, only one patient, over 4.5 years, was put at potential risk for hemolysis from one transfusion (0.001% of the total units transfused during the time period). While antibody detection may be delayed, performing ABIDs every 30 days saves money and medical laboratory scientist time and should be balanced against potential patient harm.

Ex vivo paracrine properties of cardiac tissue: Effects of chronic heart failure.

BACKGROUND: Cardiac regenerative responses are responsive to paracrine factors. We hypothesize that chronic heart failure (HF) in pediatric patients affects cardiac paracrine signaling relevant to resident c-kit(+)cluster of differentiation (CD)34- cardiac stem cells (CSCs). METHODS: Discarded atrial septum (huAS) and atrial appendages (huAA) from pediatric patients with HF (huAA-HF; n = 10) or without HF (n = 3) were explanted and suspension explant cultured in media. Conditioned media were screened for 120 human factors using unedited monoclonal antibody-based arrays. Significantly expressed (relative chemiluminescence >30 of 100) factors are reported (secretome). Emigrated cells were immunoselected for c-kit and enumerated as CSCs. RESULTS: After culture Day 7, CSCs emigrate from huAA but not huAS. The huAA secretome during CSC emigration included hepatocyte growth factor (HGF), epithelial cell-derived neutrophil attractant-78 (ENA-78)/chemokine (C-X-C motif) ligand (CXCL) 5, growth-regulated oncogene-α (GRO-α)/CXCL1, and macrophage migration inhibitory factor (MIF), candidate pro-migratory factors not present in the huAS secretome. Survival/proliferation of emigrated CSCs required coculture with cardiac tissue or tissue-conditioned media. Removal of huAA (Day 14) resulted in the loss of all emigrated CSCs (Day 28) and in decreased expression of 13 factors, including HGF, ENA-78/CXCL5, urokinase-type plasminogen activator receptor (uPAR)/CD87, and neutrophil-activating protein-2 (NAP-2)/CXCL7 candidate pro-survival factors. Secretomes of atrial appendages from HF patients have lower expression of 14 factors, including HGF, ENA-78/CXCL5, GRO-α/CXCL1, MIF, NAP-2/CXCL7, uPAR/CD87, and macrophage inflammatory protein-1α compared with AA from patients without HF. CONCLUSIONS: Suspension explant culturing models paracrine and innate CSC interactions in the heart. In pediatric patients, heart failure has an enduring effect on the ex vivo cardiac-derived secretome, with lower expression of candidate pro-migratory and pro-survival factors for CSCs.

Heart cells with regenerative potential from pediatric patients with end stage heart failure: a translatable method to enrich and propagate.

Background. Human cardiac-derived progenitor cells (hCPCs) have shown promise in treating heart failure (HF) in adults. The purpose of this study was to describe derivation of hCPCs from pediatric patients with end-stage HF. Methods. At surgery, discarded right atrial tissues (hAA) were obtained from HF patients (n = 25; hAA-CHF). Minced tissues were suspended in complete (serum-containing) DMEM. Cells were selected for their tissue migration and expression of stem cell factor receptor (hc-kit). Characterization of hc-kit(positive) cells included immunohistochemical screening with a panel of monoclonal antibodies. Results. Cells, including phase-bright cells identified as hc-kit(positive), spontaneously emigrated from hAA-CHF in suspended explant cultures (SEC) after Day 7. When cocultured with tissue, emigrated hc-kit(positive) cells proliferated, first as loosely attached clones and later as multicellular clusters. At Day 21~5% of cells were hc-kit(positive). Between Days 14 and 28 hc-kit(positive) cells exhibited mesodermal commitment (GATA-4(positive) and NKX2.5(positive)); then after Day 28 cardiac lineages (flk-1(positive), smooth muscle actin(positive), troponin-I(positive), and myosin light chain(positive)). Conclusions. C-kit(positive) hCPCs can be derived from atrial tissue of pediatric patients with end-stage HF. SEC is a novel culture method for derivation of migratory hc-kit(positive) cells that favors clinical translation by reducing the need for exogenously added factors to expand hCPCs in vitro.