An autopsy case of prostatic rhabdomyosarcoma with DICER1 hotspot mutation

Abstract

Somatic hotspot DICER1 mutations, which frequently coexist with germline inactivating mutation (i.e., DICER1 syndrome), have been identified in various types of benign and malignant conditions. Herein, we report an autopsy case of prostatic rhabdomyosarcoma (RMS) with a hotspot DICER1 c.5125G>A (p.D1709N) mutation. A 26 year‐old man presented with a prostatic mass, hematuria, and urinary retention. He underwent total pelvic exenteration, colostomy, ileal conduit construction and partial urethrectomy. Five months postoperatively, he developed multiple metastases to the lungs, brain, iliopsoas muscles and bones. He died of respiratory failure, and autopsy was performed. Microscopically, the tumor was primarily composed of uniform primitive mesenchymal cells infiltrating to the prostate with cambium layer. Rhabdomyoblasts and anaplastic cells were focally observed. Immunohistochemically, tumor cells were positive for desmin, myogenin, PAX7, HMGA2. Multinodular goiter was detected at autopsy. Because the morphology is similar to pleuropulmonary blastoma and DICER1‐mutant RMS of the female genital tract, we tested and identified a hotspot DICER1 mutation with Sanger sequencing. Recognizing DICER1‐mutant tumor is important because of its frequent association with germline DICER1 inactivation and potential therapeutic implication. Further research is needed to clarify whether this case can be classified as embryonal RMS with anaplasia or ‘DICER1‐associated sarcoma’.

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

“…Nonetheless, as the clinical, histological and immunohistochemical findings are variable, these tumors can be diagnostically challenging. In particular, easily recognizable rhabdomyoblasts may be absent and an aberrant immunophenotype can occur, including diffuse keratin expression (current study, case 6) and positivity for S100, TLE1, SALL4, BCOR or loss of H3K27me3 [23,26,[37][38][39][40][41][42][43][44] (see for more details Table 4).…”

DICER1 Syndrome: A Multicenter Surgical Experience and Systematic Review

“…Overall survival rate was 85.7% at a three-year follow-up from DICER1 diagnosis, versus 92.9% reported in the literature. Among our cases, only an infant affected by ERMS died at the age of five after a three-year follow-up, while seven out of the 132 patients (7%) died in previous reports: three for PPB2 [27,28,86], one for pituitary blastoma [16], one for SLCT [29], one for ovarian tumors of the stroma and sex cords [30], one for RMS [31].…”

DICER1 syndrome with an intronic germline variant causing splice alteration

“…14,15 Additionally, an autopsy case of adult prostate ERMS with lung and bone metastases and a female case of a bladder tumor were also reported, although the germline status was not confirmed in these cases. 16,17 Regarding surveillance protocols for DICER1 syndrome, regular imaging tests for the early detection of male genitourinary tumors would (D and E) Histology of the prostate tumor unveils two distinct patterns: the first one is characterized by hypocellular proliferation of polygonal cells with eccentric nuclei and eosinophilic cytoplasm with an edematous stroma (D), whereas the other exhibits a solid proliferation of short spindle cells with nuclear enlargement and hyperchromasia (E). (F and G) Histology of the primary pleuropulmonary blastoma (F) and the first relapse (G) similar to that of the prostate tumor.…”