Cystic hamartomata of lung and kidney: A spectrum of developmental abnormalities

Graham, John M.; Boyle, William; Troxell, Jeffrey; Cullity, G. J.; Sprague, P.; Beckwith, J. Bruce; Reynolds, James F.

doi:10.1002/ajmg.1320270107

Cited by 19 publications

(9 citation statements)

References 16 publications

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“…This type of dysplastic nephrogenesis appears to be characteristic of, but not unique to, BWS. Some cases of Perlman syndrome and the Weinberg Zumwalt association seem to exhibit similar features (9,10).…”

Section: Discussionmentioning

confidence: 90%

Hepatic Hemangioendotheliomas, Placental Chorioangiomas, and Dysmorphic Kidneys in Beckwith-Wiedemann Syndrome

Drut¹,

Drut²,

Toulouse³

1992

Pediatric Pathology

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A 4-month-old female, birth weight 3150 g, had a history of maternal eclampsia, multiple placental chorioangiomas, and persistent neonatal hypoglycemia. Macroglossia and enlarged kidneys were recorded. Autopsy revealed multiple hepatic hemangioendotheliomas (type 1), massive cardiomegaly, and bilateral nephromegaly. Both kidneys were lobulated with active glomerulogenesis and clusters of immature tubules and foci of dysplastic medullary ducts. The features suggest that the nephrogenesis was secondary to the persistence of actively branching nephron-inducing ducts. Nodular hyperplasia of the adrenal cortex (adrenoblastomatosis) was present. This report expands the list of tumors to be found in Beckwith-Wiedemann syndrome (BWS).

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Section: Discussionmentioning

confidence: 90%

Hepatic Hemangioendotheliomas, Placental Chorioangiomas, and Dysmorphic Kidneys in Beckwith-Wiedemann Syndrome

Drut¹,

Drut²,

Toulouse³

1992

Pediatric Pathology

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“…We have provided a bioinformatic link between deregulated microRNAs and key growth signalling pathways that provides a potential mechanism by which these mutations may cause tumour formation and overgrowth. While rare cases of nephromegaly34 and renal hamartomas35 have been associated with pulmonary cysts, none have been reported to develop Wilms tumour. We therefore suggest that these domain- and site-specific mutations are causal for a unique constellation of associated clinical features representing a novel syndrome.…”

Section: Discussionmentioning

confidence: 99%

Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain ofDICER1cause GLOW syndrome

et al. 2014

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Background Constitutional DICER1 mutations have been associated with pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig tumours and multinodular goitres, while somatic DICER1 mutations have been reported in additional tumour types. Here we report a novel syndrome termed GLOW, an acronym for its core phenotypic findings, which include Global developmental delay, Lung cysts, Overgrowth and Wilms tumour caused by mutations in the RNase IIIb domain of DICER1. Methods and results We performed whole exome sequencing on peripheral mononuclear blood cells of an affected proband and identified a de novo missense mutation in the RNase IIIb domain of DICER1. We confirmed an additional de novo missense mutation in the same domain of an unrelated case by Sanger sequencing. These missense mutations in the RNase IIIb domain of DICER1 are suspected to affect one of four metal binding sites located within this domain. Pyrosequencing was used to determine the relative abundance of mutant alleles in various tissue types. The relative mutation abundance is highest in Wilms tumour and unaffected kidney samples when compared with blood, confirming that the mutation is mosaic. Finally, we performed bioinformatic analysis of microRNAs expressed in murine cells carrying specific Dicer1 RNase IIIb domain metal binding site-associated mutations. We have identified a subset of 3p microRNAs that are overexpressed whose target genes are over-represented in mTOR, MAPK and TGF-β signalling pathways. Conclusions We propose that mutations affecting the metal binding sites of the DICER1 RNase IIIb domain alter the balance of 3p and 5p microRNAs leading to deregulation of these growth signalling pathways, causing a novel human overgrowth syndrome.

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“…Furthermore, there have been some reports concerning association between CCAM and renal dysgenesis [11,15]. These findings suggest that congenital cystic lesions in both lung and kidney might result from a common alteration at the early point of embryogenesis [13]. It might be more likely that CN or cystic renal lesions have a closer relationship not with PPB but with preceding cystic lung lesions.…”

Section: Discussionmentioning

confidence: 96%

“…CN has received little attention with respect to the association with lung cysts. A few reports, however, referred to the asso- ciation between lung cysts and CN or cystic renal lesions [12][13][14]. Furthermore, there have been some reports concerning association between CCAM and renal dysgenesis [11,15].…”

Section: Discussionmentioning

confidence: 99%

Synchronous occurrence of pleuropulmonary blastoma and cystic nephroma: Possible genetic link in cystic lesions of the lung and the kidney

Ishida

Kato

Kigasawa

et al. 2000

Med. Pediatr. Oncol.

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Pleuropulmonary blastoma (PPB) is among the rarest pediatric malignancies [1,2]. It has been postulated that PPB may serve as a marker for predisposition of childhood neoplasms in other family members [3]. Various types of neoplasms have been reported either as second neoplasms in already affected PPB patients or as a first neoplasm in the relatives. To date, there have been four PPB patients (two were siblings) whose relative(s) had cystic nephroma [3][4][5][6]. Two other patients who had both PPB and renal cystic lesions were recently reported [3,7]. We describe here an additional patient with a PPB and a synchronous cystic renal tumor and briefly comment on the etiology and the clinical significance of this association.A Japanese boy aged 1 year 10 months was referred to our center because of abdominal distension. The patient was born to nonconsanguineous, healthy Japanese parents at 39 weeks of gestation. Personal and family (firstand second-degree relatives) histories were unremarkable. Imaging studies demonstrated a large multilocular tumor of the left kidney ( Fig. 1a) and a large, solid and cystic tumor in the left thoracic cavity (Fig. 1b). Diagnosis on imaging studies was a left renal tumor with a large lung/pleural metastasis. At first, the left renal tumor was biopsied; the sample revealed multilocular cysts lined by cuboidal epithelia and intervening fibrocollagenous tissue (Fig. 2a). There was no blastemal element or atypical cytologic features, so the histologic diagnosis was cystic nephroma (CN). The left intrathoracic tumor was biopsied subsequently; the sample revealed diffuse growth of spindle-shaped to oval atypical cells with hyperchromatic nuclei beneath the cystically dilated respiratory epithelia (Fig. 2b). The stroma was occasionally myxoid. Some tumor cells were rich in eosinophilic cytoplasm positive for desmin and myoglobin (Fig. 2c). Histologic diagnosis was PPB with rhabdomyoblastic differentiation. The patient underwent chemotherapy employing ifosfamide (isophosphamide), carboplatin, and etoposide. The left intrathoracic tumor decreased to less than half the original size and was resected 7 months after the onset. The tumor was completely necrotic and was replaced by collections of foamy histiocytes. The patient is alive and well without recurrence of metastasis 8 months after the onset. The left renal tumor has remained almost unchanged during the clinical course. DISCUSSIONPleuropulmonary blastoma (PPB) usually occurs in patients under 5 years of age [1,2]. Recent studies have indicated that PPB may serve as a marker for predisposition of childhood neoplasms/dysplasias in other family members [3,4,7]. Although PPB is among the rarest pediatric malignancies, the incidence of familial disease is apparently high. Priest et al. [3] mentioned that an association between PPB and various types of other pediatric neoplasms/dysplasias was found in approximately 25% of the cases. Etiology of this newly recognized family cancer syndrome remains unknown.To date, there have been four cases of ...

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Cystic hamartomata of lung and kidney: A spectrum of developmental abnormalities

Cited by 19 publications

References 16 publications

Hepatic Hemangioendotheliomas, Placental Chorioangiomas, and Dysmorphic Kidneys in Beckwith-Wiedemann Syndrome

Hepatic Hemangioendotheliomas, Placental Chorioangiomas, and Dysmorphic Kidneys in Beckwith-Wiedemann Syndrome

Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain ofDICER1cause GLOW syndrome

Synchronous occurrence of pleuropulmonary blastoma and cystic nephroma: Possible genetic link in cystic lesions of the lung and the kidney

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