CASE REPORT Rare Plasmacytoid Urothelial Carcinoma of the Bladder: Two Case Reports Tuba Devrim1*, Fatih Ataç2, Canan Altunkaya1, Ayşe Özbek1, Gülhan Özdemir1, Merve Eryol1 Keywords: plasmacytoid; urothelial carcinoma; CD138; E-cadherin. Departments of Pathology1, and Urology2, Faculty of Medicine, Kırıkkale University, 71450, Kırıkkale, Turkey. *Correspondence: University of Kırıkkale, Faculty of Medicine, Department of Pathology, Kırıkkale, Turkey. Tel: +90 543 202 2088. Fax: +90 318 224 0786. E-mail: tubadevrim@gmail.com. Received July 2017& Accepted Plasmacytoid urothelial carcinoma is a rare and aggressive form of urothelial carcinoma characterized with de- layed presentation and poor prognosis. Very few cases of this carcinoma have been reported in the literature. Here, we report and discuss two cases of bladder plasmacytoid urothelial carcinoma of a 57-year-old male presented with renal colic, and a 33-year-old female presented with macroscopic hematuria. Pathologic examinations of the transurethral biopsies revealed urothelial carcinoma with plasmacytoid appearance. Subsequently, immunohis- tochemical evaluation showed positive expression of epithelial markers and CD138. Additionally, losing of the membranous expression of E-cadherin verified the diagnosis of plasmacytoid urothelial carcinoma. INTRODUCTION Plasmacytoid urothelial cancer (PUC) is an aggressive and quite uncommon form of urothelial carcinoma (UC).(1) It is characterized with late presentation and poor prognosis.(2) Microscopically, PUC reveals a plasmacytoid morphology appearing with eosinophilic cytoplasm and eccentric nuclei. It also shows a discohesive growth and often extends in the perivesical adipose tissue.(3) Additionally it may morphologically resemble plasmacytoma, lymphoma, or carcinoma variants, therefore the appropriate diagnosis in small biopsy samples is very important.(4) Figure 1. preoperative appearance of the Mass abdomen. A. abdominopelvic tomography. B. Cystoscopic appearance. Arrows indicate the mass located on the right side of the bladder Wall in both cases (Case 1: female, Case 2: Male). Case Report 86 Vol 16 No 01 January-February 2019 87 In the present study, we aimed to report and discuss two uncommon cases of bladder PUC of both sexes, which presented with renal colic or macroscopic hematuria to our hospital surprisingly at similar times. CASE REPORT Case 1: A 33-year-old female presented to our hospital with macroscopic hematuria. Case 2: A 57-year-old male patient presented to the urology outpatient department with a history of left re- nal colic. A solid lesion was observed in the right side wall of the bladder of the both cases in cystoscopy examina- tion (Figure 1) and incomplete transurethral resections (TUR) were performed. Therewithal, abdomino-pel- vic tomography revealed a mass which constituted a marked wall thickening and extension to the bladder perivesical adipose tissue (Figure 1). In both cases, microscopic evaluation of the TUR materials showed a high-grade tumor, arranged in discohesive cords and plasmacytoid features; in both cases penetrating the muscle. Immunohistochemically, tumors of both cases showed positivity for PANCK, CK7 and CD138, be- sides negativity for E-cadherin (Figure 2). In the light of these results, radical cystectomy and ileal loop oper- ations were performed. In the pathological evaluations of radical materials, the tumors morphologically resem- bled the previous TUR samples. Also, tumors of these materials infiltrated the perivesical fatty tissue. The conditions of the patients were consulted with the on- cology department and chemotherapies were planned. After radical cystectomy the male patient was evaluated for distant metastasis by thorax CT and bone scintigra- phy. However distant metastasis was not detected. The preoperative evaluation of the female patient for distant metastasis was performed by thoracic CT and eventu- ally no pathological formation was determined. Due to the right iliac LAP metastasis and perivesical spread de- termined in the male patient and the tumor infiltrating perivesical fatty tissue and vaginal anterior wall of the female patient, gemcitabine and cisplatin-based combi- nation chemotherapy was administered to both patients. The male patient was given 3 cycles of chemotherapy and there was no pathological involvement in the MR examination of the lower and upper abdomen. He was started to drug-free follow-up after taking the 4th cure chemotherapy. The female patient's 2nd cure chemo- therapy is completed. After 3 cycles of systemic chemo- therapy, upper and lower abdomen will be reevaluated with MR. If pathological formation is not found, treat- ment with 4 cycles of chemotherapy will be terminated and the patient will be followed up. DISCUSSION PUC of urinary bladder is an uncommon malignant ne- oplasm declared by recent World Health Organization (WHO) classification.(5) Chung et al. (2017) reported an 8-year retrospective search of the archive at their in- stitution identifying 22 patients with PUC. The median age of the cases were stated as 74 years (range 51-86) and only three of them were reported as female. Un- commonly, the 33-year-old female case presented in this study was a rare case both in terms of age and sex. Also, the researchers reported the percentage of mus- cle-invasive disease as 86%, and the distant metasta- ses as 9% among the presented PUC cases.(6) Muscle and perivesical adipose tissue invasion were present in the both cases of the present study. In the male case lymphovascular and perineural invasions of PUC were common and significant. Moreover, tumor metastasis was detected in 7 out of 22 lymph nodes detected. In an- other study of retrospective case series the rate of PUC was reported as 2.4%, which is the lowest rate among the UC variants. Futhermore, PUC was accounted for 7% of all deaths from UC at 1 year period.(7) In accord- ance with the literature, PUC cases of the present study were also late presented and unfortunately advanced pathological tumor stage was detected in the radical materials. The morphological similarity of PUC to other benign and malign lesions such as cystitis with plasma cell in- filtration, plasma cell-derived neoplasms, lymphomas, lymphoepitheliomas and metastatic carcinoma of the breast and stomach is the main cause of misdiagnosis.(8) PUC as the rare variant of UC should be considered in order to avoid misdiagnosis. In this regard, immunohis- tochemistry is an essential technique to make a correct diagnosis on small biopsies. CD138 expression is reported as an important marker for PUC. It can be observed in other malignant tumors, such as plasmacytomas, melanomas, rhabdomyosarco- mas, and other carcinomas as well as it can be posi- tively staining in all variants of UCs and various other epithelial tumors of the urinary tract.(9) Therefore, the pathological diagnosis should be based on the morpho- logical aspect and the differential diagnosis should be considered widely. Figure 2. Microscopic views of the tumor. Hematoxylin-eosin staining: A, B: the appearance of PUC as discohesive (A) or groups (B). Immunohistochemical stainings: C, D: CD138 positive stain- ing indicating PUC. E, F: CK7 positive staining in surface epithe- lium (E) and in PUC (E, F). G, H: E-cadherin positive staining in surface epithelium (G) and lost of membranose staining in PUC (G, H). Plasmacytoid Urothelial Carcinoma of Bladder-Devrim et al. Plasmacytoid Urothelial Carcinoma of Bladder-Devrim et al. Radical treatment must be provided to patients diag- nosed with PUC. This view is also supported by Ohtaka et al. (2016) treated PUC successfully with a combina- tion of radical cystectomy and adjuvant chemotherapy. Median overall survival of the PUC patients is lower than conventional urothelial carcinomas.(11) In this re- gard, current studies that express survival rates in wide series are limited. Cockerill et al. (2017) reported 46 patients with plasmacytoid carcinoma, 27 (59%) died of bladder cancer with a median survival of 1.7 years, and 10 patients died of other causes with a median follow up of 2.2 years. Of the 9 surviving patients, the median follow-up was reopted as 10.3 years. In conclusion, consideration of this rare variant by the pathologist is important for correct diagnosis and de- termining prognosis. Thus, the radical resection of this aggressive tumor variant, which is not predicted clini- cally and radiologically, provides a relatively prolonged survival of the patient. CONFLICT OF INTEREST There is no conflict of interest among the authors. REFERENCES 1. Keck B, Wach S, Stoehr R, et al. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy. BMC Cancer. 2013;13:71. 2. Wang Z, Lu T, Du L, et al. Plasmacytoid urothelial carcinoma of the urinary bladder: A clinical pathological study and literature review. Int. J. Clin. Exp. Pathol. 2012;5:601- 608. 3. Raspollini MR, Sardi I, Giunti L, et al. Plasmacytoid urothelial carcinoma of the urinary bladder: linicopathologic, immunohistochemical, ultrastructural, and molecular analysis of a case series. Human Pathology. 2011;42(8):1149-1158. 4. Nigwekar P, Tamboli P, Amen MB, Osunkoya AO, Ben-Dor D, Amin MB. 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