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

Abstract

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 ...

Pulmonary cysts in early childhood and the risk of malignancy

“…33,[64][65][66][67][68][69][70] Considering all sources of cases, 33 cases of PPB-associated cystic nephroma are known. In five children, PPB, cystic nephroma and small bowel polyps with intussusception have occurred; small bowel polyps have also been diagnosed in other PPB children or family members.…”

2009 update on the classification of renal epithelial tumors in adults

“…Adult cases present after age 30 with female predominance. Some are associated with pleuropulmonary blastoma 87 . Non‐random X chromosome inactivation supports its neoplastic nature 16,46,78 …”

“…Some are associated with pleuropulmonary blastoma. 87 Non-random X chromosome inactivation supports its neoplastic nature. 16,46,78 Mixed epithelial and stromal tumor of kidney is a rare renal neoplasm composed of a mixture of stromal solid areas and epithelial (mostly cystic) elements previously reported as cystic hamartoma of renal pelvis or adult mesoblastic nephroma (Fig.…”

“…It describes categories and entities based on pathological and genetic analyses 2 . Since this is a rapidly expanding field, a number entities and morphologic variants of the main tumor categories have recently been described; 1,3–43 these may be important in patients' prognoses and differential diagnoses, and therefore, are important in patients' clinical management 2,5,44–91 . This review gives an overview on recent developments in the classification of adult epithelial kidney tumors.…”

Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

“…PPB cases can occur within a family environment but PPB has not been described as a well-defined component of a familial childhood cancer/constitutional disease [ 1 , 4 ].…”