Context - DICER1-associated sarcomas are rare. These are currently described under a wide variety of appellations; morphologic characterizations in reported cases and sites of occurrence have also been disparate. Design – We aimed to review pediatric sarcomas associated with DICER1-mutation reported at our center, along with literature review, to identify histologic hallmarks for diagnosis. Results - A 12 year old girl with intracranial sarcoma mimicking mesenchymal chondrosarcoma, a 16 year old girl with broad ligament sarcoma mimicking fibrosarcoma and a 5 month old girl with vaginal sarcoma mimicking embryonal rhabdomyosarcoma showed DICER1-mutation. All three tumors though seemingly diverse, had an uncanny resemblance, comprising of a primitive mesenchyme-like spindle cell component with rhabdomyoblastic differentiation on immunohistochemistry. Primitive blastema, chondroid differentiation and foci of anaplasia mimicking pleuropulmonary blastoma histology were variably present. One case showed primitive neuroblastic differentiation. Though the constellation of features reported in literature is quite varied, rhabdomyoblastic differentiation has been ubiquitously reported in tumours across sites. Molecular testing showed gain of chromosome 8 in 2 cases. All 3 cases responded to alternating Vincristine, doxorubicin and cyclophosphamide / Cisplatin, etoposide and ifosfamide (VDC/PEI) backbone followed by maintenance chemotherapy. Conclusion - We highlight this morphologic hallmark of rhabdomyoblastic differentiation with or without chondroid differentiation, in primitive appearing pediatric sarcomas, especially of female genital tract and brain, which should raise a flag to test for DICER1 pathogenic variation. This is crucial in low / middle income countries where sequencing is not done routinely. Timely diagnosis can ensure appropriate treatment and implementation of surveillance protocols for those with germline mutation.

Pleuropulmonary blastoma (PPB) is the most common primary lung tumor of childhood and is associated with somatic or germline DICER1 variants. Recurrent PPB, especially with brain metastases, are difficult to treat and survival is poor. Comprehensive genomic analyses of PPB have been limited in number and depth. The cases presented here identified additional oncogenic drivers from tumor sequencing that could be modulating tumor progression and response to therapy outside of known DICER1 mutations highlighting the need for upfront genomic analysis on all patients with PPB.