DRCT is a rare but aggressive tumor, which is usually located intra-abdominally and in the pelvis but can be found in the retroperitoneum, thorax, and central nervous system. The tumor is most often seen in young males aged 8 to 38 years, but has been described in females. Patients typically present with abdominal pain or abdominal mass, and may have ascites. Prognosis is poor.

The specimen is often cellular with tumor cells in loosely cohesive groups or tighter clusters, without any distinct architecture. The presence of sphere-like clusters without a stromal core is a helpful feature, although this can morphologically mimic adenocarcinoma in fluids [9, 10]. Sporadic single cells and rosettes may also be seen. The cells have a high N/C ratio with minimal cytoplasm and occasional cytoplasmic vacuoles. The nuclei are round to oval with moderately granular chromatin and may show nuclear molding. Nucleoli can be prominent or inconspicuous. The background is typically hemorrhagic or necrotic. Despite the characteristic alternating round cell and stromal components observed on histology, metachromatic stromal fragments are seldom seen in the effusions, although scattered spindle cells may be present.

DRCT exhibits polyphenotypic immunostaining for epithelial (AE1/AE3, CK5/CK6, EMA, and/or others), muscle (desmin), and neural (NSE, synaptophysin, and/or others) markers. WT1 is usually positive, while FLI1 is negative. DRCT is characterized by a recurrent translocation t(11;22)(p13; q12) with fusion of the EWSR and WT1 genes which can be demonstrated by cytogenetics or reverse transcriptase-polymerase chain reaction (RT-PCR). An EWSR translocation can also be identified by fluorescence in situ hybridization (FISH), although this is not specific for DRCT . Electron microscopy shows intermediate filaments located near the nucleus.

The differential diagnosis includes other round cell tumors, and immunostains and FISH and/or RT-PCR studies are critical for establishing a correct diagnosis. Nephroblastoma or Wilms’ tumor has cytological features of tubules, blastema, and stroma, which are more prominent than in DRCT , but both are positive for epithelial markers and WT1. DRCT stains with antibodies to the carboxy terminus of WT1, whereas dual immunoreactivity for the carboxy and amino terminuses is seen in Wilms tumor. Neuroblastoma occurs in a younger age group, has neuropil, and lacks metachromatically staining stromal fragments but similar to DRCT can demonstrate rosettes and positive immunostaining for neuroendocrine markers. Rhabdomyosarcomas tend to have dense cytoplasm and hyperchromatic nuclei, may show evidence of rhabdomyoblastic differentiation , such as more abundant eccentric cytoplasm or strap cells, and are immunoreactive for myogenin and myoD1, in addition to desmin. Of note, aberrant staining for epithelial and neuroendocrine markers occurs in a minority of rhabdomyosarcomas and may lead to diagnostic confusion; however, in contrast to DRCT , rhabdomyosarcomas lack EWSR1 translocations. Ewing sarcoma/primitive neuroectodermal tumor (PNET) is typically negative for desmin, cytokeratin, EMA, and WT1, and has EWSR1 translocations that involve partners other than WT1. Lymphoid malignancies are characterized by lack of cellular cohesion, the presence of lymphoglandular bodies, and positivity for lymphoid markers. A less common tumor in the differential diagnosis includes extramedullary ependymoma of the myxopapillary type that may arise in the sacrum or abdominopelvic region and is positive for GFAP and S100. Small cell carcinomas and mesotheliomas are rare in the pediatric age group.

DRCT overlaps cytomorphologically with other small round cell tumors of childhood. Thus, it is essential to use a panel of immunostains, in addition to FISH and/or RT-PCR to exclude other small round cell tumors of childhood and arrive at the correct diagnosis. RT-PCR has an advantage over the break-apart FISH probe for EWSR1, in that the EWSR1-WT1 translocation detected by RT-PCR is specific for DRCT , whereas the break-apart probe for EWSR1 is positive in a variety of tumors, including Ewing/PNET (EWSR1-FLI1 and EWSR1-ERG), extraskeletal myxoid chondrosarcoma (CHN-EWSR1), clear cell sarcoma (EWSR1-ATF1), and desmoplastic small round cell tumor (EWSR1-WT1) [6].

PPB is a rare intrathoracic neoplasm that occurs predominantly in children under the age of 4 years, but is the most common tumor seen in the cancer predisposition syndrome associated with germline DICER1 mutations. It may be cystic, solid and cystic, or solid and, except for purely cystic tumors, follows an aggressive course. It is distinct from pulmonary blastoma. Patients present with respiratory symptoms, including cough, dyspnea, hemoptysis, and/or recurrent pneumonia, and some develop pleural effusions. Radiologically, these tumors can appear as low-attenuation masses in the pleural cavity with some high-attenuation areas, which can mimic an empyema [8].

PPB shows varying proportions of primitive blastema and sarcomatous elements and, in cystic lesions, benign epithelium. Lipoblastic, chondroblastic, and rhabdomyoblastic differentiation of the sarcomatous component has been described. The blastema is negative, on immunostaining, for CD99. Cytogenetic studies often show gains in chromosome 8q, and molecular studies reveal germline mutations in DICER1 in approximately 50–70 % of patients with PPB .

The differential diagnosis includes other small round cell tumors of childhood, malignant teratoma, synovial sarcoma, rhabdomyosarcoma, and infantile fibrosarcoma. Cases of pleuropulmonary blastoma can mimic an empyema of the pleural space on radiological imaging and thus awareness of this entity is important [11].