Primitive neuroectodermal tumors: Two genitourinary afflictions with varied presentations.

Primitive neuroectodermal tumor (PNET) is a rare disease with high malignant potential. It usually affects the skeletal system. Primary extraskeletal involvement of PNET is uncommon with few reported cases. PNET of the genitourinary system requires a very high index of suspicion for the diagnosis since the presentation of these tumors can be varied. We report two cases of PNET with varied presentations, affecting the genitourinary system.

INTRODUCTION

Primitive neuroectodermal tumor (PNET) predominantly affects children and adolescents and belongs to the Ewing's sarcoma family of tumors. This disease usually affects the skeletal system and primary extraskeletal involvement is uncommon.[1] PNET has been very rarely reported to affect the genitourinary system.[23] We report two cases of PNET affecting the genitourinary system, which had varied presentations.

CASE REPORTS

Case report: 1

A 16-year-old adolescent male presenting with priapism and dorsal penile swelling was treated elsewhere with open drainage of both corpora cavernosa and excision of the swelling. The swelling contained necrotic material which was diagnosed as PNET by histopathological examination [Figure 1] and confirmed by immunohistochemistry with Mic-2, and vimentin positive and negative for smooth muscle actin, Bcl-2, desmin, friend leukemia integration factor-1 (FLI-1), synaptophysin, chromogranin, and CD117/c-kit antigen. Fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (CT) scan was suggestive of subcentimetric bilateral lung metastases. Six courses of vincristine-based chemotherapy were administered followed by image-guided radiotherapy to the penis and lung metastases. The patient remained asymptomatic for a year, after which he again presented with multiple painful nodules in the penis. Magnetic resonance imaging (MRI) scan was suggestive of multiple heterointense masses involving both the corpora cavernosa extending along the entire length of the penis [Figure 1]. The patient was offered total penectomy and adjuvant chemotherapy. However, he refused penectomy and underwent further course of chemotherapy with 24 monthly cycles of vincristine, adriamycin, and cyclophosphamide. On follow-up MRI brain and spine scan done at 2 years, the patient showed the left frontoparietal brain metastasis. Salvage chemotherapy was initiated in the form of cisplatin, docetaxel, and actinomycin D. However, in another 3 months, the patient further developed diffuse lung metastasis and he succumbed to the disease.

Figure 1

Magnetic resonance image of primitive neuroectodermal tumor penis showing multiple hyperintense nodules (H and E, ×400) of primitive neuroectodermal tumor penis showing tightly sheeted round blue cells

Case report: 2

A 44-year-old male presented with two episodes of hematospermia and suprapubic pain during sexual intercourse for 3 months. He also had bowel discomfort while defecating. Ultrasonography of the abdomen was suggestive of hypoechoic lesion on the right side of prostate without internal vascularity. The patient's serum prostate-specific antigen was 0.82 ng/ml. CT urography was suggestive of the right seminal vesicle being replaced with 6 cm × 4 cm × 5.7 cm heterogeneously enhancing mass compressing upon surrounding structures and ureter, thereby causing the right hydroureteronephrosis. MRI findings further suggested that the mass invaded all the surrounding structures, including the prostate [Figure 2]. The patient underwent Trucut biopsy of the mass. Histopathology was suggestive of PNET of seminal vesicle, which was further confirmed by immunohistochemistry with vimentin, Ki67 (50%–55%), and Mic-2/CD99 positive and negative for CD34, CD45, smooth muscle actin, epithelial membrane Ag, desmin, , Bcl-2, FLI-1, prostate-specific Ag, synaptophysin, chromogranin, cytokeratin 7 and 20, carcinoembryonic antigen, and CD117/c-kit [Figure 2]. The patient is currently on neoadjuvant chemotherapy with vincristine, actinomycin D, and cyclophosphamide for the past 3 months. The initial follow-up with ultrasonography shows considerable regression in the tumor volume.

Figure 2

Computed tomography urography and magnetic resonance imaging demonstrating right seminal vesicle invasive mass; H and E staining demonstrating sheets of round blue cells with immunohistochemistry being positive for CD-99, vimentin, and Ki-67

DISCUSSION

The usual age of presentation of PNET of the penis is 15–30 years.[23] The patient usually presents with painless penile swelling; however, the presentation with priapism has not been reported yet. The histopathology generally demonstrates sheet of tightly arranged round cells, and immunohistochemistry will show high intracytoplasmic glycogen content, along with Mic-2 and vimentin positivity. Of the published cases of PNET of the genitourinary system, none of the immunohistochemical marker has proven to be specific for PNET. FLI-1, though found in about 50% of published PNET cases of other organs, it has not been reported to be positive in any case of genitourinary affliction of PNET. Thus, a concerted histopathological and immunohistochemical approach is prudent to arrive at the diagnosis of PNET accurately. However, other immunohistochemical markers such as desmin, smooth muscle actin, synaptophysin, and chromogranin do help in ruling out the other differential diagnosis. In the three cases of penile PNET published till date, all three have undergone total penectomy followed by vincristine-based chemotherapy for a variable duration. The average follow-up in these cases was around 2 years and all patients survived. For PNET affecting the other organs/skeletal system, the median survival rate reported has been 3–8 years. In our case, the patient presented with priapism and the diagnosis was incidentally made. Further, he refused penectomy and survived for 54 months after the first diagnosis. This may reiterate the primary role of surgical excision of genitourinary PNET due to its overtly aggressive nature to develop metastases.

Primary malignant tumors of seminal vesicle are extremely rare and only 100 such cases have been reported in the literature. Of these primary malignant tumors, only couple of cases of PNET of seminal vesicle have been reported so far in the literature.[45] Lower urinary tract symptoms especially hematospermia point to possible seminal vesicle pathology. It is also important to differentiate between primary tumor and a secondary metastatic spread to seminal vesicles, as the former is a localized disease with possibility of cure, while the latter is usually an advanced disease with dismal prognosis. It is evaluated further by imaging studies either CT or MRI. A TRUS-guided biopsy should suffice for histopathological diagnosis and immunohistochemistry. Management of this entity should be individualized. Seminal vesicle PNET generally responds well to vincristine-based chemotherapy like any other genitourinary PNET.

CONCLUSION

PNET of the seminal vesicle and penis is very rare malignancies and may present with varied locoregional symptoms. Even immunohistochemically, PNET of the genitourinary system is a diagnosis of exclusion as none of the markers seems to be specific. Primary excision seems to be the best option for localized disease, followed by vincristine-based chemotherapy. Overall, PNET of the genitourinary system seems to have an aggressive malignant potential.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.