Pleuropulmonary blastoma (PPB) and other DICER1-associated high-grade malignancies are morphologically, genetically and epigenetically related - A comparative study of 4 PPBs and 6 sarcomas.

DICER1-related tumors occur hereditary or sporadically, with high-grade malignancies sharing clinicopathological and (epi)genetic features. We compared 4 pleuropulmonary blastomas (PPBs) and 6 sarcomas by mutation analysis, whole transcriptome sequencing and methylation profiling. 9/10 patients were female. PPB patients were 0-4 years. 3/4 were alive; 2 without disease. One patient died of metastatic disease (median follow-up, 16 months). Sarcoma patients were 16-56 years. Locations included: uterine cervix/corpus (3/1), soft tissue back/shoulder (1) and paravertebral (1). 5/6 patients were alive; 2 developed metastases: intracranial (1) and lung and kidney (1) (median follow-up, 17 months). The deceased patient previously had a PPB and a Sertoli-Leydig cell tumor. Histologically, tumors showed atypical primitive-looking cells with incomplete rhabdomyoblastic differentiation and cartilage (n = 5). Immunohistochemistry demonstrated desmin- (n = 9/10), myogenin- (n = 6/10) and keratin positivity (n = 1/1). Eight cases harbored biallelic DICER1 mutations with confirmed germline mutations in 4 cases. Two cases showed a monoallelic mutation. By RNA expression- and methylation profiling, distinct clustering of our cases was seen demonstrating a close relationship on (epi)genetic level and similarities to embryonal rhabdomyosarcoma. In conclusion, this study shows overlapping morphological, immunohistochemical and (epi)genetic features of PPBs and DICER1-associated high-grade sarcomas, arguing that these neoplasms form a spectrum with a broad clinicopathological range.

Sexual quality of life of adolescents and young adult breast cancer survivors.

BACKGROUND: With increasing survival rates of adolescents and young adults (AYAs) with breast cancer, health-related quality of life (HRQoL) becomes more important. An important aspect of HRQoL is sexual QoL. This study examined long-term sexual QoL of AYA breast cancer survivors, compared sexual QoL scores with that of other AYA cancer survivors, and identified factors associated with long-term sexual QoL of AYA breast cancer survivors. MATERIALS AND METHODS: Data of the SURVAYA study were utilized for secondary analyses. Sexual QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). Descriptive statistics were used to describe sexual QoL of AYA cancer survivors. Linear regression models were constructed to examine the effect of cancer type on sexual QoL and to identify factors associated with sexual QoL. RESULTS: Of the 4010 AYA cancer survivors, 944 had breast cancer. Mean sexual QoL scores of AYA breast cancer survivors ranged from 34.5 to 60.0 for functional domains and from 25.2 to 41.5 for symptom-orientated domains. AYA breast cancer survivors reported significantly lower sexual QoL compared to AYA survivors of other cancer types on all domains. Age, time since diagnosis, relationship status, educational level, chemotherapy, hormonal therapy, breast surgery, body image, and coping were associated with sexual QoL of AYA breast cancer survivors. CONCLUSIONS: AYA breast cancer survivors experience decreased sexual QoL in the long term (5-20 years) after diagnosis and worse score compared to AYA survivors of other cancer types, indicating a clear need to invest in supportive care interventions for those at risk, to enhance sexual well-being.

Psychological impact of lymphoma on adolescents and young adults: not a matter of black or white.

PURPOSE: The purpose of the study is to examine differences in perceived impact of cancer (IOC) between adolescents and young adults (AYAs; 18-35 years at cancer diagnosis), adults (36-64 years) and elderly (65-84 years) with a history of (non-)Hodgkin lymphoma. Furthermore, to investigate the association of socio-demographic, clinical and psychological characteristics with IOC; and the association between IOC and health-related quality of life (HRQoL) among AYAs only. METHODS: This study is part of a population-based PROFILES registry survey among lymphoma patients diagnosed between 1999 and 2009. Patients (n = 1.281) were invited to complete the IOCv1 and EORTC-QLQ-C30 questionnaires. Response rate was 67 % (n = 861). RESULTS: AYA lymphoma survivors scored higher on the positive IOC summary scale, compared to adult and elderly patients (p < 0.001), while no significant differences were observed for negative IOC. Among AYAs, females, survivors with a partner, and survivors with elevated psychological distress levels scored significantly higher on the negative IOC summary scale. The negative IOC summary scale was negatively associated with all EORTC QLQ-C30 functioning scales (ß ranging from -0.39 to -0.063; p < 0.05). The positive IOC summary scale was negatively associated with the EORTC QLQ-C30 subscale 'Emotional functioning' (ß = -0.24; p < 0.05). CONCLUSION: AYA, adult and elderly with a history of (non-)Hodgkin lymphoma experienced different types of IOC in terms of positive and negative aspects. IMPLICATIONS FOR CANCER SURVIVORS: Although AYAs experience a more positive IOC compared to older survivors, some AYAs experience more negative IOC and may require developmentally appropriate interventions to address their specific concerns.

High prevalence of late adverse events in malignant bone tumour survivors diagnosed at adult age.

BACKGROUND: Late treatment-related adverse events are particularly prevalent in survivors of childhood bone cancer because of the combination of cytotoxic drugs, major surgery and radiotherapy. Existing studies for late toxicity in survivors of Ewing's sarcoma (ES) and osteosarcoma (OS) diagnosed at adult age have focused on specific sequelae. We investigated a broad spectrum of potential late effects in these patients. METHODS: Relapse-free OS and ES patients aged ≥ 16 at diagnosis and treated at the Radboud University Medical Centre (1982-2007) were invited for systematic late toxicity screening. This included history taking, physical examination, echocardiogram, bone densitometry, audiogram, and serum and urine screening for renal toxicity and infertility. Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: In 24 survivors (63% male, mean age at screening 45.7 years, mean follow-up 10.9 years, 70% OS) we found a median of eight adverse events. Frequent findings included abnormal gait, osteoporosis, pain, left ventricular systolic dysfunction, obesity and nephropathy. The maximum grade of any adverse event was mild in four (17%), moderate in 11 (46%), severe in six (25%), and disabling in three cases (13%). There was a trend towards more events in patients diagnosed at an older age. CONCLUSION: The incidence of late adverse events in this study of survivors of bone tumours diagnosed at adult age is higher than in any previously published childhood cancer survivorship study. Older patients seem to be particularly at risk. Our findings underscore the need for systematic screening of late effects in bone cancer survivors of adult age at diagnosis.

Autotransplantation of cryopreserved ovarian tissue in cancer survivors and the risk of reintroducing malignancy: a systematic review.

BACKGROUND The risk of recurrent oncological disease due to the reintroduction of cancer cells via autotransplantation of cryopreserved ovarian tissue is unknown. METHODS A systematic review of literature derived from MEDLINE, EMBASE and the Cochrane Library was conducted. Studies on follow-up after autotransplantation; detection of cancer cells in ovarian tissue from oncological patients by histology, polymerase chain reaction or xenotransplantation; and epidemiological data on ovarian metastases were included. RESULTS A total of 289 studies were included. Metastases were repeatedly detected in ovarian tissue obtained for cryopreservation purposes from patients with leukaemia, as well as in one patient with Ewing sarcoma. No metastases were detected in ovarian tissue from lymphoma and breast cancer patients who had their ovarian tissue cryopreserved. Clinical studies indicated that one should be concerned about autotransplantation safety in patients with colorectal, gastric and endometrial cancer. For patients with low-stage cervical carcinoma, clinical data were relatively reassuring, but studies focused on the detection of metastases were scarce. Oncological recurrence has been described in one survivor of cervical cancer and one survivor of breast cancer who had their ovarian tissue autotransplanted, although these recurrences may not be related to the transplantation. CONCLUSIONS It is advisable to refrain from ovarian tissue autotransplantation in survivors of leukaemia. With survivors of all other malignancies, current knowledge regarding the safety of autotransplantation should be discussed. The most reassuring data regarding autotransplantation safety were found for lymphoma patients.

Systemic sclerosis: new insights in autoimmunity.

The strong female predilection of systemic sclerosis, especially in women after their childbearing years, and the clinical and histopathological similarities with chronic graft-versus-host disease make systemic sclerosis an interesting subject of debate. Recent studies concerning the pathogenesis of this disease demonstrated the persistence of fetal cells in the maternal circulation in a majority of female patients. How or whether microchimerism is involved in the pathogenesis of systemic sclerosis remains to be elucidated. The present paper reviews the recent findings on the subject.

Survival of donor cells 25 years after intrauterine transfusion.

Persistence of donor leukocytes in the circulation of recipients of intrauterine transfusion (IUT) has been observed up to 5 years after birth. The aim of this study was to determine whether transfusions with nonirradiated, nonleukocyte-depleted donor blood during the fetal period resulted in long-term immunomodulation of the recipient. Twenty-four surviving IUT recipients between 1966 and 1976 were tested for autoimmune disease and autoantibodies at follow-up. Ten had sex-mismatched donors and were therefore informative for chimerism studies using fluorescence in situ hybridization (FISH). Seven female recipients could be tested for chimerism using a Y- chromosome-specific polymerase chain reaction (PCR) because they received at least 1 IUT from a male donor. Nine recipients could be studied for cytotoxic T-lymphocyte precursor (CTLp) and helper T-lymphocyte precursor (HTLp) frequencies because the original donors were available for testing. All surviving IUT recipients were in good health at the time of the examination, and routine laboratory testing revealed no abnormalities. None of the IUT recipients were chimeric as determined by FISH analysis, but Y-chromosome-specific sequences were detected by PCR in 6 of the 7 women. However, the CTLp and HTLp frequencies of the IUT recipients against the donors were comparable to those of the controls. The current study provides evidence that IUT can result in the persistence of donor cells in the recipient for a period longer than 20 years but that it is not associated with immunotolerance or with signs of chronic antigenic stimulation. (Blood. 2000;95:2709-2714)