A 71-year-old elderly patient presenting with 1 month long painless intermittent macroscopic hematuria, and a history of the frequency with intermittency was admitted to our outpatient clinic. The patient was an ex-smoker (50 pack/year), also had diabetes and chronic kidney disease. He was on routine surveillance for an incidental tubulo-villous adenoma found on sigmoid colon by our general surgery department. Patient had no history of a previous radiotherapy or neurofibromatosis disease.
On physical examination there was no remarkable finding during the inspection. No skin lesions (neurofibromas, café-au-lait spots) were noted. On digital rectal examination, prostate was found to be moderately enlarged with no stiffness or irregularities. On blood samples collected at admission the PSA level was at normal range 2.46 ng/ml (0 to 4) and the patient had elevated BUN and creatinine levels; 69 mg/dl and 1.30 mg/dl respectively. In the collected urine sample patient had microscopic hematuria (33 erythrocyte/hpf).
A urinary ultrasound scan was conducted revealing a diverticulum with a 45x35mm diameter harboring a suspicious papillary projection with a dimension of 30x20 mm on posterior bladder wall. A prompt cystoscopy was performed revealing one papillary lesion with a 30x30 mm diameter on the prementioned diverticulum wall and another 10x10 mm lesion on the right posterolateral bladder wall. TURBT was performed on both lesions. Since one of the lesions was located on the diverticulum wall the resection had been performed superficially. On pathological evaluation, both resection materials were found to be non-invasive low-grade papillary urothelial carcinoma (Fig. 1).
After the initial procedure, patient’s hematuria regressed. Patient then underwent a routine control cystoscopy session 3 months after the primary resection. Suspicious papillary projections on both old resection sites and one in proximity to the right ureteric orifice were identified. Complete resection was performed this time with respective deep resection biopsies. On pathological examination, both lesions had non-invasive low-grade papillary urothelial carcinoma. In addition to this finding, the tissue sample resected near the right ureteric orifice was found to have atypical mesenchymal cell infiltration in the lamina propria. The cells stained positive with S100, SOX-10 and vimentin suggesting these cells can have a neural origin (Fig. 1). The blood sample was sent to our genetic department for NF-1 mutation analysis but it was not detected on fluorescent in situ hybridization (FISH).
A re-TURBT was planned 2 weeks after, for the proper reassessment of the tumor but due to in adherence of the patient, it could have been performed 4 months later. The patient had weight loss and intermittent hematuria with clot passage during the time span. On cystoscopic examination, suspicious bladder wall irregularities including diffuse solid lesions protruding into the bladder lumen were observed in a 5x5 cm area extending from one lateral wall to the other, including the bladder trigone. An incomplete resection could have been performed due to the tumor size. Microscopically, the tumor comprised a relatively uniform but clearly atypical population of epithelioid cells and a smaller proportion of fascicle-forming spindle cells. The epithelioid tumor cell population showed a multilobular growth pattern, with lobules, nests and cords surrounded by fibrous and focal myxoid stroma. The polygonal tumor cells had round vesicular nuclei, prominent nucleoli and abundant palely eosinophilic to amphophilic cytoplasm. Mitotic rate was 42/10HPF and atypical mitotic figures were seen. Necrosis was present. The background was occasionally infiltrated with neutrophils. The tumor was highly dedifferentiated and was in concordance with grade 3 sarcoma according to FNCLCC(Fédération Nationale des Centres de Lutte Contre le Cancer) sarcoma grading system (15). Immunohistochemically, the tumor cells showed strong and diffuse staining for S100, SOX10, vimentin, p16 and focal staining for CK7, EMA, collagen type 4 (Fig. 2). There was no expression of the melanocytic markers, Myo-D1, desmin, CD34, SMA, myogenin, CD117, GATA3 or ALK. No loss of INI1 expression was observed. Ki67 proliferative index was determined as 10%. The pathological diagnosis was in concordance with high-grade eMPNST. This time a sample had also been sent to the molecular pathology laboratory for BRAFv600 mutation analysis for evaluating the availability of novel systemic treatment agents, yet it wasn’t detected.
A full body FDG-PET scan was performed to rule out distant metastases and for local staging. On abdominopelvic cross-sectional images, an intrapelvic mass was bordering the posterior bladder wall and causing compression and distortion of pelvic structures. No distinctive border could be identified between the mass and the bladder wall. Increased FDG uptake on both the right external iliac and right common iliac lymph nodes was noted. An isolated paracaval lymph node just above the right iliac bifurcation also had increased FDG uptake. On cross-sectional thoracal images a nodular lesion on right upper lobe of the lung with a 14x13mm diameter was observed. The lesion also had nuclear material uptake making it a candidate for metastases of the primary lesion (Fig. 3).
The patient was discussed in a multidisciplinary uro-oncology meeting with the participation of urology, oncology, pathology, and radiation oncology departments. It had been decided to perform a radical cystoprostatectomy and extended lymph node resection for providing local disease control. The patient underwent radical cystoprostatectomy with ileal loop repair and bilateral ilioinguinal lymph node dissection. During the surgery, no notable adhesions, stiff tissues, or pathologic bodies along the perivesical spaces, rectovesical borders, and retropubic area were noted. These perioperative findings indicated that the tumor anatomically originated from the bladder rather than the pelvic plexuses. There were no operation-related complications during the hospital stay. The patient was discharged 7 days after the surgery following the drain removal.
Through the pathologic examination of the cystoprostatectomy specimen, full-thickness infiltrating eMPNST into the bladder wall was seen. There was also a heterologous component (mature bone) in the focal area within the tumor, no other peripheral nerve sheat associated tumor types(schwannoma, neurofibroma or perineuroma) were noted. In addition, acinar adenocarcinoma (Gleason score 3 + 3 = 6) was detected incidentally in the prostate. eMPNST metastases detected in two right pelvic lymph nodes.
An intravenous contrast-enhanced CT scan was performed 3 months after the cystectomy. The lesion located on the apical portion of the right lung was found to be increased in diameter (13x14 mm) and another nodular lesion with contrast uptake was added to the inferior lobe of the right lung (6x6 mm). Patient could not receive any additional systemic therapy due to frailty. The patient passed away 4 months after the cystectomy and 12 months after the initial diagnosis due to emerging type 1 respiratory failure causing cardiac arrest after ICU admission.