Prolonged Remission in Multiple Relapsed MLL-rearranged Infant B-ALL with Inotuzumab OzogamicinAkhila Lattupally MD1, Adonis Lorenzana MD1, Gregory Anthony Yanik MD2, Danielle Bell MD1,31. Ascension St. John Children’s Hospital, Detroit, Michigan, United States.2. C.S. Mott Children’s Hospital – University of Michigan, Ann Arbor, Michigan, United States.3. Children’s Hospital of Michigan, Detroit, Michigan, United States.Corresponding Author: Akhila Lattupally MDAddress: 22101 Moross Rd, PB2, Suite 70, Detroit, Michigan 48236Phone: 469-468-7978Fax: 313-343-4756Email:Akhila.Lattupally@ascension.orgWord Count: Main text: 841 wordsNumber of Tables: 0 Number of Figures: 0 Number of Supporting Information Files: 0Running Title: Remission in Infant ALL with Inotuzumab Ozogamicin.Keywords: Infant Leukemia, ALL Relapse, Immunotherapy
Sickle cell disease is the most prevalent inherited blood disorder in the world, with significant morbidity and mortality. Patients often have recurrent painful vaso-occlusive episodes, and the American Society of Hematology gives a conditional recommendation for the use of regional anesthesia for acute sickle cell pain management. This scoping review summarizes the current evidence and identifies gaps for future research. Our screening process is outlined, and articles that mentioned the use of regional anesthesia for acute sickle cell crises were included. We present and interpret our results and highlight opportunities for future investigation.
Acute Lymphoblastic Leukemia of the Central Nervous System Presenting with Rapid Weight GainConnor P. Hall1 and Alan D. Friedman11Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USACorrespondence: Alan D. Friedman, MDJohns Hopkins UniversityCRB I, Rm. 253 1650 Orleans St. Baltimore, Maryland 21231 Phone: 410-955-2095; Fax: 410-955-8897 Email: email@example.comWord Count: 863Number of Figures: 1Running Title: Rapid Weight Gain in ALLKey Words: acute lymphoblastic leukemia/ relapse/ weight gain/ central nervous systemAbbreviations:
Primary pancreatic tumors in children are rare with an overall age-adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm followed by pancreatoblastoma. This manuscript describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow up.
The most common pediatric extragonadal pelvic cancers include germ cell tumors, sacrococcygeal teratomas, and rhabdomyosarcomas (arising from the urinary bladder, prostate, paratesticular tissues, vagina, uterus, and perineum). This manuscript describes the radiological and nuclear medicine features of these entities and provides consensus-based recommendations for the assessment at diagnosis, during and after treatment.
Pediatric thyroid cancer is rare in children, however incidence is increasing. Papillary thyroid cancer and follicular thyroid cancer are the most common subtypes, comprising about 90% and 10% of cases respectively. This manuscript provides consensus imaging recommendations for evaluation of pediatric patients with thyroid cancer at diagnosis and during follow-up.
Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element’s categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), ten were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.
Background: Desmoid tumor (DT) is rare and challenging, often affects head neck (HN) region in children, and its appropriate treatments are under discussed. This study aimed to retrospectively evaluate long-term effectiveness and safety of 125I seed brachytherapy for pediatric DT in HN. Procedure: Seven pediatric patients with median age of 3 years old suffered from DT in HN treated with 125I brachytherapy from January 2008 to June 2018 were included. Among which, 5 underwent sole brachytherapy and the others combined with surgery under a prescription doses ranging from 10 000 cGy to 12 000 cGy. The rate of local control (LC), complete response (CR) and partial response (PR) were calculated after evaluation by radiological and pathological means. The radiation-associated toxicities were also evaluated Results: The LC rate was 7/7 during the follow-up time ranging from 43 to 135 months and with a mean of 57 months. No recurrent lesion was found in the patients receiving surgery combined with brachytherapy. In patients treated with sole brachytherapy, the radiological PR rate and CR rate were 4/5 and 1/5, respectively. In those reaching radiological PR, 3/4 were pathological CR. Slight acute radiation-associated toxicities were observed in all patients, and no late or severe acute toxicity was observed. Conclusion: 125I brachytherapy is effective and safe in the management of pediatric DT in HN as sole modality or combined with surgery in long term.
Background: Irinotecan and temozolmide achieve objective responses in patients with Ewing sarcoma which recurrences after initial therapy. Optional dose schedules have not been defined. Procedure: We reviewed published series of patients treated with irinotecan and temozolomide for Ewing sarcoma which recurred after initial therapy. We compared objective response rates for patients who received 5 day irinotecan treatment schedules to response rates for patients who achieved 10 day irinotecan treatment schedules. Results: Among 94 patients treated with a 10 day irinotecan schedule there were 48 objective responses (51%). Among 218 patients treated with a 5 day irinotecan schedule there were 65 responses (30%). Conclusion: When we use irinotecan to treat Ewing sarcoma we should administer 10 days of treatment.
Relapsed or refractive pediatric B-Acute Lymphoblastic Leukemia (B-ALL) patients have high rates of toxicities and relapse, and novel therapy is needed. We present a case of a 5-year-old male with high-risk B-ALL that was refractive to several re-induction regimens. He was put into MRD-negative remission after re-induction with chemotherapy plus overlapping rituximab, inotuzumab ozogamicin and blinatumomab, termed Mini-Hyper-CVD plus CRIB. This was well tolerated, and he received his transplant and engrafted with no significant infections, toxicities, or sinusoidal obstruction syndrome. This is the first reported use in pediatrics of a condensed sequential immunotherapy/chemotherapy regimen in a pediatric leukemia patient.
Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High-risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost-efficient estimates of anti-tumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish-based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water-soluble chemicals. Under optimized temperature conditions, embryonal RMS-xenografts were established in zebrafish embryos at 3 hours post fertilization (hpf). In proof-of-principle experiments, chemotherapy drugs with established clinical anti-RMS efficacy (vincristine, dactinomycin) and the MEK inhibitor trametinib were shown to significantly reduce the cross-sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost-effective solution for pre-clinical candidate drug testing.
Juxtaglomerular cell tumor with pulmonary metastases: A case report and review of the literatureHideki Sakiyama1, Satoru Hamada1,2, Tokiko Oshiro1,2, Nobuyuki Hyakuna1,2 Masaaki Kuda3, Tomoro Hishiki4, Hajime Aoyama5, Naoto Kuroda6, Kenji Yorita7, Naoki Wada8, Takako Yoshioka9, Yuhki Koga10, Koichi Nakanishi1,21) Department of Pediatrics, University of the Ryukyus Hospital, Uehara, Nishihara, Okinawa, Japan2) Department of Child Health and Welfare, Graduate School of Medicine, University of the Ryukyus, Uehara, Nishihara, Okinawa, Japan3) Department of Digestive and General Surgery Graduate School of Medicine, University of the Ryukyus, Uehara, Nishihara, Okinawa, Japan4) Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan5) Department of Pathology, Heartlife Hospital, Okinawa, Japan6) Department of Internal Medicine, Kinro Hospital, Kochi, Japan7) Department of Diagnostic Pathology, Japanese Red Cross Kochi Hospital, Kochi, Japan8) Department of Pathology and Oncology, Graduate School of Medicine, University of Ryukyus, Uehara, Nishihara, Okinawa, Japan9) Department of Pathology, National Center for Child Health and Development, Tokyo, Japan10) Department of Pediatrics, Graduate School of Medical Science, Kyusyu University, Fukuoka, JapanCorrespondence: Satoru Hamada,Department of Pediatrics, Faculty of Medicine, University of Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0125, Japanshamada@med.u-ryukyu.ac.jpTo the Editor: Juxtaglomerular cell tumor (JGT) is a relatively rare, benign renin-producing tumor that causes hypertension, hyperaldosteronism, and hypokalemia due to excessive renin secretion. Here, we report a case of malignant JGT with pulmonary metastases. A 7-year-old male patient was referred to the hospital for proteinuria found during a school medical checkup. An ultrasound examination revealed a tumor on the right kidney. His blood pressure was 170/120 mmHg, and plasma renin activity was high at 30 ng/mL/hr. Computed tomography (CT) revealed a mass of 3.4 cm diameter on the right kidney with multiple pulmonary metastases, which was suggestive of nephroblastoma. He underwent right nephrectomy, resulting in a return of blood pressure and plasma renin activity to normal levels (reference range, 0.2–2.3 ng/mL/hr). Gross examination of the tumor revealed a 3.2 × 3.2 × 10-cm yellowish-white mass with necrosis in the mid pole of the kidney. Most of the tumor was covered with a fibrous membrane that partially extended into the normal tissue. Histology revealed a mesenchymal neoplasm with a blastemal component that was suggestive of nephroblastoma. No vascular invasion was observed within the analyzed area (Supplemental Figures S1, S2). Subsequently, he received chemotherapy according to the DD-4A regimen of the National Wilms Tumor Study Group. The immunophenotype demonstrated renin and CD34 positivity (Supplemental Figures S3, S4). This led to a definitive diagnosis of JGT, which was consistent with the clinical feature of hypertension. Chemotherapy was stopped at week 6, at which point CT revealed unchanged metastatic lung lesions. He then underwent a two-stage surgical resection for bilateral lung metastases, and total resection was achieved. Pathologically, the metastatic lung lesions were consistent with the resected renal tumor. Because no reports of effective chemotherapy for malignant JGT were found, we followed-up this patient without administering adjuvant chemotherapy. He showed no evidence of disease after a 2-year follow-up. Targeted DNA sequencing using FoundationOne® CDx detected six genetic mutations:NOTCH3 T272M, BRAF D22N, MAP3K1 L78P, CDKN2BA56D, DAXX E451del, and ERBB4 P3L in the primary tumor.JGT is a rare benign tumor that is more common in relatively young adults. JGT causes various clinical symptoms, such as headache, nausea, dizziness, weakness, hypertension, and proteinuria.1,2JGT is generally curable by surgical resection, and tumor removal results in the improvement of hyperreninemia and clinical symptoms.1 Immunohistochemically, the diagnosis is confirmed by renin positivity in the cytoplasm. In addition, CD34, CD117, vimentin, and ACTA2 are often positive.2,3Although JGT is generally considered benign, eight malignant or pathologically atypical cases have been reported in the literature (Table).3–10 Six were adult cases, and one was a pediatric case. In all cases, the tumor diameter was relatively large (>5 cm). Pathologically, seven of eight showed either vascular invasion or mitotic figures, and among these cases, four had distant metastasis: case 1 demonstrated bilateral lung metastases 6 years after nephrectomy,4 case 4 demonstrated bilateral lung metastases at initial diagnosis,9 case 6 demonstrated multicentric synchronous disease in the liver and spleen,7 case 8 succumbed to hepatic and bone metastases 10 months after nephrectomy.3 In our case, complete metastasectomy of the bilateral pulmonary nodules was achieved after nephrectomy. Thus, he was in remission at 2 years without adjuvant chemotherapy.Ours is the first reported case of pediatric malignant JGT with multiple pulmonary metastases. Although most patients with malignant JGT present with a large tumor that is pathologically characterized by vascular invasion, our case had a relatively small-sized tumor with no vascular invasion or nuclear atypia. Few reports have described genetic abnormalities in JGT. Targeted DNA sequences in our case revealed six gene mutations although the significance of these mutations in the pathogenesis of malignant JGT is unclear. A previous study reported that the NOTCH3 receptor is highly expressed in reninoma in mice.11 Dysregulation of NOTCH3 signaling plays a role in soft tissue tumor pathogenesis.12 Therefore, the NOTCH3 mutation in our case might have been involved in this malignant transformation. In addition, NOTCH3 signaling has shown to contributed to chemoresistance to doxorubicin13, which was consistence with the clinical feature of an ineffective for metastatic lung lesions after chemotherapy including doxorubicin. JGT is generally considered to be a benign tumor, but malignant cases have recently been reported. Our patient was successfully treated with complete pulmonary metastasectomy after primary tumor resection without adjuvant chemotherapy. Pulmonary metastasectomy represents an effective approach in the treatment of JGT-related lung metastases alone. However, no established reports on the prognosis and treatment of malignant JGT exist; thus, additional case reports are needed.Conflict of Interest StatementThe authors declare that there is no conflict of interest.1. McVicar M, Carman C, Chandra M, Abbi RJ, Teichberg S, Kahn E. Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases. Pediatr Nephrol 1993;7:404-412.2. Kuroda N, Gotoda H, Ohe C, et al. Review of juxtaglomerular cell tumor with focus on pathobiological aspect. Diagn Pathol 2011;6:80.3. Zhou J, Zheng S, Zhang Y, et al. Juxtaglomerular cell tumor: clinicopathologic evaluation in a large series emphasizing its broad histologic spectrum. Pathol Int 2020;70:844-856.4. Duan X, Bruneval P, Hammadeh R, et al. Metastatic juxtaglomerular cell tumor in a 52-year-old man. Am J Surg Pathol 2004;28:1098-1102.5. Beaudoin J, Périgny M, Têtu B, Lebel M. A patient with a juxtaglomerular cell tumor with histological vascular invasion. Nat Clin Pract Nephrol 2008;4:458-462.6. Shera AH, Baba AA, Bakshi IH, Lone IA. Recurrent malignant juxtaglomerular cell tumor: a rare cause of malignant hypertension in a child. J Indian Assoc Pediatr Surg 2011;16:152-154.7. Cucchiari D, Bertuzzi A, Colombo P, et al. Juxtaglomerular cell tumor: multicentric synchronous disease associated with paraneoplastic syndrome. J Clin Oncol 2013;31:e240-e242.8. Munakata S, Tomiyama E, Takayama H. Case report of atypical juxtaglomerular cell tumor. Case Rep Pathol 2018;2018:6407360.9. Huang PW, Lin YC, Wu KF, Sheng TW, Su PJ. Juxtaglomerular cell tumor with lung metastases in a young male patient. J Cancer Surviv . 2019;6(3):128.10. Hagiya A, Zhou M, Hung A, Aron M. Juxtaglomerular cell tumor with atypical pathological features: report of a case and review of literature. Int J Surg Pathol 2020;28:87-91.11. Martini AG, Xa LK, Lacombe M-J, et al. Transcriptome analysis of human reninomas as an approach to understanding juxtaglomerular cell biology. Hypertension 2017;69:1145-1155.12. Raimondi L, Ciarapica R, De Salvo M. Inhibition of Notch3 signalling induces rhabdomyosarcoma cell differentiation promoting p38 phosphorylation and p21(Cip1) expression and hampers tumour cell growth in vitro and in vivo. Cell Death Differ 2012;19:871-881.13. Xiu M, Wang Y, Li B, et al. The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies. Front Mol Biosci. 2021;14:694141.Figure legendsFigure S1. Neoplastic cells with an ovoid shape proliferate in a solid sheet growth pattern, 40×.Figure S2. Neoplastic cells display rare mitotic activity and mild nuclear atypia, 200×.Figure S3. Neoplastic cells show CD34 labeling, 200×.Figure S4. Renin is diffusely distributed in the tumor cytoplasm, 200×.
In this study, we reported a patient who presents with multicentric reticulohistiocytosis (MRH)-like clinical feature, but the histology is not compatible with it. Like our patient, a couple of patients described previously also had the dilemma that they could not be classified appropriately into any current histiocytosis entity. Considering the clinical and pathological features together, all these patients had a similar clinical profile: xanthomatous rash, erosive arthritis and histopathological findings showing xanthomized histiocytes. Therefore, we propose a new disease entity - xanthomatous erosive arthritis (XEA), to accommodate these patients that cannot be classified appropriately into the current system.