Primitive neuroectodermal tumor of the prostate in a 58-year-old man:A case report

lNTRODUCTlON

Primitive neuroectodermal tumor(PNET)is an extremely rare neural crest tumor with a poor prognosis that mainly affects children and adolescents.The clinical,morphological,and immunophenotypic characteristics of PNET are similar to Ewing’s sarcoma,and the two are thought to be related.Histologically,PNET is characterized by small round and oval cells.CD99,an antigen encoded by the

gene,is present on the surface of most PNET cells,and therefore represents a useful diagnostic marker for PNET[1].

PNET is divided into central PNET and peripheral PNET according to its location.Peripheral PNETs have occurred in the kidney,bladder,prostate,and adrenal gland,often revealing an infiltrative mass with an ill-defined and necrotic region on imaging[2].PNET of the prostate is extremely rare,with significant malignant potential.We here present the oldest prostatic PNET patient reported to date.Clinicopathological features of 18 cases reported since 2003,including ours,are reviewed.

CASE PRESENTATlON

Chief complaints

A 58-year-old man presented with a 2-year history of dysuria without obvious inducement.

History of present illness

The patient had dysuria without obvious cause accompanied by urinary hesitancy,which was progressively worsening.The pelvic ultrasound showed a cystic-solid mass.During 3 mo before admission,the patient had also presented with constipation and occasional pain.

History of past illness

The patient had no prior urologic history or significant medical history.

Personal and family history

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Physical examination

The examination revealed a softly distended tympanitic abdomen with tenderness near the pubic symphysis.

Laboratory examinations

Combinations of surgery,chemotherapy,and radiotherapy can form an effective treatment strategy for prostatic PNET.The commonly recommended chemotherapy drugs include vincristine,doxorubicin,cyclophosphamide,etoposide,and ifosfamide[18,20].In the 18 cases that we summarize,adjuvant or neoadjuvant chemotherapy was administered in all cases of prostatic PNET except for one case without detailed treatment strategy.In two cases in the literature,the patients underwent radical surgery combined with chemotherapy and radiotherapy[1,21].Our patient and five others were treated by radical surgery combined with chemotherapy[5,8,12,22,23],four patients received chemotherapy alone[3,4,14,16],and in other cases,the patients adopted single radical resection or chemoradiotherapy.Although standard treatment has not been established,a multimodal approach is recommended.Follow-up information was available for 13 patients and our case.In general,during an average followup period of approximately 18 mo(median period: 13 mo;range: 2 to 84 mo),patients with combination therapy had longer survival than patients with monotherapy.

Imaging examinations

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FlNAL DlAGNOSlS

The final diagnosis was prostatic PNET with cystic degeneration.Histopathology of the surgical specimens showed strongly staining small round cells(Figure 3A).Immunohistochemistry analysis showed strong positivity for CD99 and positivity for vimentin and synaptophysin(Figure 3B-D).

TREATMENT

The patient underwent robot-assisted laparoscopic resection.An insufflation needle was inserted from the edge of the umbilicus and a longitudinal incision of about 1 cm was made at 2 cm from the upper edge of the umbilicus.A large cystic-solid mass was observed in the rectum and bladder space which adhesions to the surrounding prostate and rectum.The neoplasm had a vascularized appearance.The cystic fluid was extracted with an aspirator and the tumor was removed gradually and completely.The resected cystic-solid tumor measured about 8 cm × 7 cm.Histological examination and immunohistochemical staining ultimately confirmed the PNET.After surgery,the patient received adjuvant chemotherapy based on an alternating VEC(vincristine,etoposide,carboplatin)and IE(ifosfamide,etoposide)regimen.Chemotherapy was repeated every 3 wk for up to six cycles as tolerated.

OUTCOME AND FOLLOW-UP

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The authors have read the CARE Checklist(2016),and the manuscript was prepared and revised according to the CARE Checklist(2016).

DlSCUSSlON

PNET is an extremely rare malignancy that is aggressive and has a poor prognosis[3].In 2003,Colecchia

[1]were the first to report PNET of the prostate,and besides the present case,only 17 cases of prostatic PNET have been reported to date.We review 18 cases including ours and summarize the clinicopathological features in Table 1.

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In the published cases,the patients were mainly young adults(median age: 29 years;range: 20 to 58 years).Our 58-year-old patient is the oldest patient described thus far.Patients with prostatic PNET may present with dysuria,hematuria,pelvic discomfort,constipation,and hematochezia[3-5].In these 18 cases,ten(56%)had dysuria,six(33%)were accompanied with pelvic discomfort or pain,and three(17%)presented with hematuria.Prostatic PNET should be suspected when young men present with dysuria.Although PSA is an essential serum marker for the diagnosis of prostate cancer,with a positive detection rate reaching 82%[6],the PSA values in all 18 patients with prostatic PNET were within normal limits(0 to 4 ng/mL).Approximately 44% of patients had distant metastases,with the lung as the most common site,accounting for 75% of all metastases,followed by the bone(25%),liver(12.5%),and meninges(12.5%).Distant metastasis is known as the most unfavorable prognostic factor for Ewing's sarcoma[7].Therefore,the search for metastasis must be emphasized in patients with prostatic PNET as the early detection of metastasis is crucial.

Imaging examination is beneficial in diagnosis,clarifying the internal structure,and assessing local invasion and distant metastasis.In 14 cases,including ours,the average size of the tumor was 8.5 cm(range: 2.6 to 14.4 cm).PNET of the prostate has been described as an ill-defined aggressive soft tissue mass with hemorrhage,necrosis,and cystic degeneration;as a multilobulated mass with heterogeneous enhancement;and as a mass replacing the prostate on CT and MRI[8,9].MRI generally shows the lesionto be hypointense on T1WI and iso- to hyperintense on T2WI,and contrast-enhanced T1WI shows heterogeneous enhancement[8,10-12].MRI is sensitive to evaluate local tumor invasion.In nine reported cases,there was compression or involvement of the bladder;five of these had distant metastases[5,8,13-15].There was compression or involvement of the rectum in six cases,two of which had metastases to distant sites[8,15].Four tumors were in close association with seminal vesicles but without metastases[5,8,16,17].Additionally,there was one lesion that invaded the left ureter and bladder with bilateral hydroureteronephrosis[16].In general,the imaging examination is useful to identify the relationship with adjacent tissues and distant metastasis,but preoperative diagnosis based on imaging alone is challenging.

The final diagnosis of a PNET involving the prostate relies on histopathological features.Under the light microscope,PNET is a mass of undifferentiated small round cells,which are arranged closely in a flaky,lobulated,or nest-like pattern.The characteristic small round cells of PNET are reactive to anti-CD99 antibody(Mic-2),and more than 90% of PNETs have demonstrated a translocation between the long arms of chromosomes 11 and 22,and are positive for the

fusion gene[18].The translocation can be confirmed by molecular techniques such as fluorescence

hybridization and reverse transcriptase-polymerase chain reaction[4].At present,the diagnosis scheme proposed by Schmidt

[19]has been extensively adopted,including the presence of Homer-Wright rosettes and/or the expression of at least two neural markers.Among 18 cases of prostatic PNET,89% were immunohistochemically positive for CD99,44% for vimentin,28% for synaptophysin,28% for CD56,and 22% for NSE.Molecular analyses in eight cases showed translocations of the chromosomes or

fusion.However,molecular techniques were not used to detect chromosomal translocations in our case.Identification of translocation may be crucial,as some translocation types are associated with a poor prognosis.

The serum prostate specific antigen(PSA)level was 0.82 ng/mL,the cytokeratin-19 fragment level was 6.79 ng/mL,and the other tumor markers including neuron specific enolase(NSE),alpha fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199 were all within normal ranges.

CONCLUSlON

PNET of the prostate shows aggressive biological behavior and is often overlooked in the differential diagnosis due to its rare occurrence.It should be considered in young men with the complaint of dysuria to contribute to early diagnosis.The appropriate therapeutic schedule is radical surgery as early as possible,and combined chemotherapy or radiotherapy,which could be helpful to improve prognosis.Further studies and longer-term follow-up await.

ACKNOWLEDGEMENTS

We thank the pathology department of The First Hospital of Shanxi Medical University for providing pathological information and the assistance of the patient.

FOOTNOTES

Tian DW reviewed the literature and contributed to manuscript drafting;Wang XC interpreted the imaging findings and contributed to manuscript drafting;Zhang H and Tan Y revised the manuscript.

The better she felt about herself, the prouder she grew of Loren and Lance. She started bringing them to visit with her coworkers, who showered them with kindness. It was time for her and her boys to leave their house, cut ties with the father and move on with their lives.

National Natural Science Foundation of China,Nos.81971593,81771824,81971592,and 82071893;and Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province,No.20200003.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

There was complete remission of the tumor after radical surgery and chemotherapy.At the most recent follow-up visit(34 mo),the patient was alive and well,and there was no recurrence.

The authors declare that they have no conflict of interest to disclose.

Contrast-enhanced computed tomography(CT)showed a mass between the bladder and rectum with cystic and necrotic components and heterogeneous enhancement(Figure 1A).Magnetic resonance imaging(MRI)of the pelvis confirmed a large cystic-solid mass measuring 10.7 cm × 10.8 cm × 8.1 cm near the prostate and compressing the rectum and bladder(Figure 1B-H).The lesion appeared isointense to slightly hyperintense on T1-weighted imaging(WI)and was heterogeneously hyperintense on T2WI.The solid portion of the tumor was hyperintense on diffusion-WI and correspondingly hypointense on the apparent diffusion coefficient maps.The mass showed prominent heterogeneous enhancement in the arterial phase and continuous enhancement in the venous and delayed phases.These findings initially suggested prostatic cystadenoma.However,prostate cancer could not be excluded considering the patient's age.At repeat CT examination 2 mo after surgery and the first cycle of chemotherapy,there was no evidence of residual or recurrent tumor(Figure 2).

One Easter Sunday, all the kids arrived with big eyes and big stories about what the Easter Bunny had brought. While all of the kids shared their stories with delight, one young boy, whom I will call Bobby, sat sullenly1. One of the teachers, noticing this, said to him, And what did the Easter Bunny bring you? He replied, My mom locked the door on accident so the Easter Bunny couldn t get inside.

There was no personal or family history.

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China

He placed the biggest and best-looking peach on the small plate in front of the girl, and then took the flawed peach and began to remove the skin. When he had half the skin off the peach he ate that side, neither of them talking, both of them just being there, and not being excited or anything—no plans, that is.

Da-Wei Tian 0000-0002-1770-5627;Xiao-Chun Wang 0000-0002-3216-5710;Hui Zhang 0000-0002-0565-0411;Yan Tan 0000-0002-7529-9807.

It takes an almighty17 pile of gall18 for a man to sit up and say what is going on in another man s mind, don t it? I mean one way or another. When Doc Eaton told me that story he didn t bother to point out any moral. By the way, he don t do any preaching any more. He s been a congressman19 from New Jersey20 for years and years. But I guess the story has a moral, all right. Always sort of tickled21 me, like it must have tickled Doc s rich parishioner.

Zhang H

Wang TQ

Zhang H

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