Pleuropulmonary blastoma-like peritoneal sarcoma: a newly described malignancy associated with biallelic DICER1 pathogenic variation

Kris Ann P Schultz, Alexander Nelson, Anne K Harris, Mike Finch, Amanda Field, Jason A Jarzembowski, Mercedes Wilhelm, William Mize, Portia Kreiger, Katrina Conard, Andrew Walter, Thomas Olson, Sarah Mitchell, Daniel V Runco, Allison Bechtel, Darren Klawinski, Scott Bradfield, Katie Gettinger, Douglas R Stewart, Yoav Messinger, Louis P Dehner, D Ashley Hill, Kris Ann P Schultz, Alexander Nelson, Anne K Harris, Mike Finch, Amanda Field, Jason A Jarzembowski, Mercedes Wilhelm, William Mize, Portia Kreiger, Katrina Conard, Andrew Walter, Thomas Olson, Sarah Mitchell, Daniel V Runco, Allison Bechtel, Darren Klawinski, Scott Bradfield, Katie Gettinger, Douglas R Stewart, Yoav Messinger, Louis P Dehner, D Ashley Hill

Abstract

Since the original description of pathogenic germline DICER1 variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be associated with DICER1 has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye, and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and DICER1-associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3-14 years). Primary sites of origin included the fallopian tube (four cases), serosal surface of the colon (one case), and pelvic sidewall (two cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB, and the remaining five had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic DICER1 variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of DICER1 pathogenic variation whose pathologic features are also recapitulated in DICER1-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli-Leydig cell tumors with heterologous elements. Tumors arising from the fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor DICER1 testing.

Conflict of interest statement

Conflict of Interest/Disclosure Statement: DRS provides telegenetics services for Genome Medical, Inc, in accordance with relevant National Cancer Institute policies. The other authors have no conflicts of interest to disclose. DAH is founder/investor in ResourcePath LLC.

Figures

Fig. 1:
Fig. 1:
Case 1 - Axial (A) computed tomography images demonstrate a heterogeneous low attenuation intraperitoneal lesion within the pelvis with peripheral areas of decreased attenuation and areas with higher attenuation consistent with solid components, embedded bowel or a combination.
Fig. 2:
Fig. 2:
A Shows a cystic and solid mass arising in the Fallopian tube with histologic patterns of embryonal RMS with a botryoid growth pattern and nodules of cartilage (Case 1). B Shows multi-locular peritoneal cysts, without a primitive cellular component, resembling type Ir “regressed” PPB (Case 2). C Shows a low power view of blastemal nodules on left and embryonal RMS on the right (Case 6). D Shows nodules of primitive blastemal cells with anaplasia in a solid mass (Case 7).
Fig. 3:
Fig. 3:
Case 4 - Axial (A) and coronal (B) computed tomography images demonstrate a heterogeneous low attenuation lobulated intraperitoneal mass with nonenhancing regions suggesting intratumoral necrosis extending from the level of the umbilicus to the lower pelvis in appearance to a type III PPB.

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