A case report of urothelial carcinoma with combined micropapillary and plasmacytoid morphology in the urinary bladder

A case of combined micropapillary and plasmacytoid urothelial carcinoma (UC) of the urinary bladder is presented for a 74‐year‐old male who was admitted to the hospital with gross hematuria and multifocal papillary bladder tumors. Abdominal computed tomography showed a large enhancing mass on the left lateral and anterior wall of the urinary bladder, which was highly suspicious for extravesicular extension and focal extension of the anterior lesion to the pubic bone. In voided urine, cancer cells were scattered as micropapillae or nests as well as single cells on the low power view. On a higher power view, micropapillae or nests were composed of pleomorphic, high grade tumor cells with an inverted nuclear arrangement and with acinar structures occasionally identified. Single cells were discohesive and large with a thick cytoplasm and eccentrically located nuclei. Histologically, the tumor from the resected bladder showed diffusely infiltrating micropapillae or nests with a surrounding halo and dense singly‐scattered plasmacytoid cells. Immunohistochemically, the cancer cells were positive for cytokeratin‐7 and cytokeratin‐20 but negative for S‐100, leukocyte common antigen, and vimentin. At the time of radical cystectomy, severe adhesions and peritoneal metastases were found and the surgery was discontinued. The patient received systemic chemotherapy, but died of bladder cancer 14 months after surgery. Diagn. Cytopathol. 2016;44:124–127. © 2015 Wiley Periodicals, Inc.     

Microcystic urothelial cell carcinoma with neuroendocrine differentiation arising in renal pelvis. Report of a case

Microcystic urothelial cell carcinoma is a rare variant of urothelial cell carcinoma which occurs in the bladder and, rarely, in the renal pelvis. Neuroendocrine differentiation is uncommon in pure urothelial carcinoma and is more frequently found in neoplasms with glandular differentiation. We report a case of microcystic urothelial cell carcinoma arising in renal pelvis and showing focal neuroendocrine differentiation. A 55-year-old man with a history of non-small cell cancer of the lung presented with abdominal pain and hematuria. Imaging studies and gross examination revealed a partially cystic mass in the left kidney. Microscopic examination disclosed invasive carcinoma with prominent microcystic features, with microcysts lined by low columnar and flat cells. Immunohistochemical analysis confirmed the urothelial histotype (positive for thrombomodulin, p63 and high-molecular-weight cytokeratins) and disclosed focal neuroendocrine differentiation.     

Recently described and unusual variants of urothelial carcinoma of the urinary bladder

Urothelial carcinoma (UC) of the urinary bladder has a great propensity to undergo divergent differentiation. The resulting subtypes are morphologically unique and have significant prognostic and therapeutic differences. While squamous and glandular subtypes are the most common, a number of other well characterised morphological subtypes were described in the 2004 World Health Organization Classification. More recently additional variants of UC have been described, while others have been more fully characterised. In this review we report the details of recently described and selected unusual variants of UC. Specifically, the pathological and clinical details are discussed, relating to large nested and nested variant of UC, large cell undifferentiated carcinoma, lymphoepithelioma-like carcinoma, osteoclast rich undifferentiated carcinoma, pleomorphic giant cell carcinoma, UC with syncytiotrophoblastic giant cells, lipid cell variant of UC, micropapillary UC, UC with abundant myxoid stroma and plasmacytoid UC.     

Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications

An increasing number of histologic variants of urothelial carcinoma have been recognized in recent years. It is important for surgical pathologists to be aware of these morphological variants that, on occasion, may lead to misinterpretation as benign. Some also require a specific therapeutic approach. In this article, we review the most common histologic variants of urothelial carcinoma of the bladder. Emphasis is placed on clinical significance and differential diagnosis.     

A case of urothelial carcinoma,lipid cell variant

The lipid cell variant of urothelial carcinoma is a rare variant of urinary bladder cancer, comprised of lipoblast‐like cells. In this report, we describe a case of the lipid cell variant of aggressive urothelial carcinoma. A 78‐year‐old man was admitted to the hospital because of gross hematuria. On cystoscopy, an ulcerative lesion, non‐papillary architecture, was observed in the lateral wall of the bladder. Transurethral resection was performed. Histopathological findings of the bladder tumor indicated neoplastic cells forming irregular solid nests and sheets. Lipoblast‐like neoplastic cells that had eccentric nuclei and cytoplasmic vacuoles were observed, not only in the resected specimen, but also in urine samples. On mucin histochemistry, the tumor cell cytoplasm contained no neutral or acidic mucus. The lipoblast‐like cells were positive for cytokeratins (AE1/AE3, CK7) and adipophilin, known as a protein associated with neutral lipid synthesis. In general, it is difficult to prove the existence of intracytoplasmic lipid in formalin‐fixed paraffin‐embedded materials. This is the first report in which the presence of lipid in vacuoles of the lipid cell variant has been verified by immunohistochemistry.     

Plasmacytoid urothelial carcinoma of the urinary bladder: A case report and immunohistochemical study

We report a rare case of plasmacytoid urothelial carcinoma (PUC) of the urinary bladder. A 50-year-old man complained of pollakiuria and urinary incontinence. MRI detected a bladder tumor invading the rectum and bilateral hydroureteronephrosis. Radical cystectomy with partial resection of the rectum was performed, and ileus due to peritoneal dissemination occurred 2 years after surgery. He died of the disease 42 months after the initial presentation. Histologically, urothelial carcinoma in situ with a focal invasive urothelial carcinoma (IUC) component and widely spread PUC was observed. There was no lymph node metastasis. PUC cells had eccentrically placed nuclei and eosinophilic cytoplasm resembling plasmacytoma cells, and proliferated with a single-cell infiltrative pattern to the outside of the bladder. IUC cells with intracytoplasmic lumina were focally intermingled with PUC cells. Immunohistochemically, PUC cells were positive for cytokeratin 7, epithelial membrane antigen, and CA19-9, but negative for cytokeratin 20, E-cadherin, p63, and lymphoid markers. The Ki-67 labeling index of PUC cells was 9.3%. IUC containing intracytoplasmic lumina showed intermediate features of conventional IUC and PUC morphologically and immunohistochemically. PUC is a distinct entity of bladder cancer with a high propensity for invasion and poor prognosis.     

EGFR expression in urothelial carcinoma of the upper urinary tract is associated with disease progression and metaplastic morphology

EGFR represents a promising therapeutic target in urothelial cancer (UC). Our study aimed to investigate the clinicopathological significance of EGFR in upper urinary tract UC. EGFR was immunohistochemically assessed (EGFR pharmDX kit(TM)) in 268 consecutive tumours using a tissue microarray technique and correlated with other histopathological parameters as well as patient outcome. EGFR immunoreactivity was observed in 140/253 (55%) evaluable UCs and was associated with high tumour stage (47% pTa/pT1 vs 66% pT2-pT4; p=0.003) and high tumour grade (45% low grade vs 67% high grade; p<0.001). In addition, EGFR expression was associated with metaplastic squamous and/or glandular differentiation (p<0.001). EGFR staining intensity was 1+ in 49%, 2+ in 31%, and 3+ in 20% of cases. EGFR 3+ staining intensity was associated with the occurrence of metastatic disease by univariate analysis (p=0.016). Multivariate analysis, however, proved only pT stage >1 (p<0.001) and high tumour grade (p<0.001) to be independent predictors of patient outcome. In conclusion, EGFR was significantly associated with advanced disease and metaplastic squamous and/or glandular differentiation. Since UCs with metaplastic morphology have been shown to be more resistant to conventional radiotherapy or chemotherapy, the strikingly strong EGFR expression in these tumours may offer a new perspective for affected patients.     

Nested variant of urothelial carcinoma of the renal pelvis

The nested variant of urothelial carcinoma is an uncommon form of urothelial carcinoma with distinctive histopathologic features. The majority of cases of this unusual type of urothelial carcinoma have been described in the urinary bladder, with examples of this neoplasm involving the upper urinary tract being extremely limited. The present report details the clinical and pathologic features of an unusual case of a nested variant of urothelial carcinoma occurring in the renal pelvis of a 71-year-old woman. The tumor was characterized by a nested pattern of growth and relatively bland cytologic features, and presented with locally advanced disease at the time of nephroureterectomy. Although rare, awareness that the nested variant of urothelial carcinoma may occur at this particular site is important so as not to confuse this unusual form of urothelial carcinoma with other pathologic lesions of the renal pelvis.     

Invasive urothelial carcinoma with chordoid features of the ureter: a rare entity and review of literature

Invasive urothelial carcinoma (UC) is characterized by some histologic variants that can sometimes lead to diagnostic difficulty. In addition to those described by the World Health Organization. Recently invasive urothelial carcinoma with chordoid features (UCC) has been described as a distinct entity and there are relatively few reported cases in the English-language literature. To date 13 cases of UCC have been reported in 2 case series, respectively in 2009 and 2015. We report the 14^th case in an 80-year-old female, and to the best of our knowledge this is the second case report of UCC in the ureter. She was admitted to our hospital with macroscopic haematuria and unspecific left lower abdominal pain. Computed tomography scan revealed a soft tissue nodule in the middle of the left ureter. The left nephroureterectomy was performed. Morphologically, 85% areas had acellular myxoid stroma was associated with the neoplastic cells. The neoplastic cells had scant eosinophilic cytoplasm and were arranged into cords closely mimicking chordoma or extraskeletal myxoid chondrosarcoma. 15% areas was typical invasive urothelial carcinoma, and focal areas had transition phenomenon between them. Immunohistochemically, the tumor cells were positive for CK, 34βE12 and p63, but were negative for S100, AFP, CD34, Syn and CgA. The final histopathological diagnosis was UCC of the ureter.     

Micropapillary component of urothelial carcinoma detected in transurethral resection of bladder tumor (TUR-BT) tissues: a case report

A case of urothelial carcinoma (UC) containing a micropapillary carcinoma (MPC) component in the urinary bladder of an 83-year-old man is reported. The MPC component of UC has been reported to be a variant featuring poor prognosis and rapid progression. In the present case, a characteristic MPC component with micropapillary growth, in association with a fine meshwork-like stroma, was observed in less than 10% of fragmented cancer tissues of UC, G3, obtained by transurethral resection of a bladder tumor (TUR-BT). Lymphatic invasion was also detected. UC cancer cells had invaded the prostatic glands and replaced the original epithelial cells. The unique "insideout" feature of the MPC component was immunohistochemically obvious on staining with antibody to epithelial membrane antigen (EMA). On immunohistochemical study, cancer cells of both UC and MPC components were positive for pancytokeratin AE1/AE3 and cytokeratins 7 and 20. Carcinoembryonic antigen (CEA) and CAM5.2 were only focally positive in UC cells. MIB-1(Ki-67) labeling index was high, at 80%-90%, in cancer cells of UC. This was a case of UC, G3 with invasion to the muscularis propria layer of the urinary bladder and also to the prostate. MPC and MPC components in cancers should be recognized as a marker of poor prognosis, even when detected in less than 10% of UC within TUR-BT tissues, as in the present case.     

CD24 expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression

Expression of the mucin-like adhesion molecule CD24 has been implicated in the progression of several types of cancer and has been identified as new prognostic factor. We evaluated CD24 expression in 268 consecutive cases of upper urinary tract urothelial carcinoma with respect to associations with tumour stage, grade, angioinvasion and infiltrative growth pattern using a tissue microarray technique and correlated data with patient outcome. CD24 expression was demonstrated in 161/259 (62%) evaluable tumours and was associated with high tumour stage [77/139 (55%) pTa/pT1 vs 84/120 (70%) pT2–pT4; P = 0.02] and high tumour grade [68/139 (49%) low vs 93/120 (78%) high grade; P < 0.001] as well as presence of angioinvasion (P = 0.002) and infiltrative pattern of invasion (P = 0.007). Patients with CD24-positive tumours tended to have a higher risk of disease progression (P = 0.065). Multivariate analysis, however, proved pT stage >1 [P < 0.001, risk ratio (RR) = 5.87, 95% confidence interval (CI) = 2.88–11.95] and high tumour grade (P < 0.001, RR = 3.30, 95% CI 1.75–6.22) as only independent predictors of metastatic disease. In conclusion, CD24 expression in upper urinary tract urothelial cancer is associated with advanced tumour stage and high tumour grade as well as histopathological features indicative of aggressive tumour behaviour, but it lacks independent impact on patient outcome.     

Synchronous clear cell renal cell carcinoma and clonal plasmacytoid cell infiltration: A case report and literature review

Recent studies of tumor microenvironments have revealed that clonal B cells reacting to tumor-derived antigens play an important role in anti-tumor immunity. We report a case of a 72-year-old Japanese man with a complaint of fever for 1 month. Computed tomography revealed a 48 mm mass in his right kidney. The patient underwent a right nephrectomy and histology revealed clear cell renal cell carcinoma (ccRCC) of Fuhrman Grade 4 with rhabdoid morphology. Focally, marked plasmacytoid cell infiltration was detected in the carcinoma. These plasmacytoid cells were immunohistochemically positive for immunoglobulin (Ig) G, and kappa light chain restriction was confirmed using mRNA in situ hybridization. Programmed death-ligand 1 (PD-L1) immunostaining and RNA in situ hybridization of transforming growth factor beta (TGF-β) revealed that both PD-L1 and TGF-β were highly expressed in the area with clonal plasmacytoid cell infiltration. The patient developed bone metastasis 3 months after surgery, and plasmacytoma was not detected during the observation period. We identified a potential link between an immunosuppressive microenvironment and clonal B cell proliferation. The latter posed a differential diagnosis problem between reactive and neoplastic clonal B cell proliferation vis-à-vis a plasmacytoma complicating carcinoma.     

Papillary carcinoma of thyroid: A 30-yr clinicopathological review of the histological variants

Many histological variants of PTC have been described and some are known to have prognostic significance. However, their relative frequencies and associated clinicopathological features in a large cohort of patients with PTC treated at a single institution have seldom been documented. We reclassified 1035 malignant thyroid tumors treated in a 30-yr study period, into variants of PTC according to current histological criteria and analyzed their features. Six hundred and fifty two patients (153 men; 499 women) with PTC were identified. PTC accounted for 72.8% of primary thyroid cancers. Conventional papillary carcinoma (n=300) accounted for 46% of PTC and papillary microcarcinoma 27.8% (n=181). The frequencies of the common histological variants were follicular (17.6%, n=115), tall cell (4%, n=26), and diffuse sclerosing (1.8%, n=12). Uncommon histological variants including solid (n=5), diffuse follicular (n=5), papillary carcinoma with focal insular component (n=3), columnar cell (n=2), papillary carcinoma with fasciitis-like stroma (n=2), and oncocytic (n=1) were also noted. Histological variants of PTC had different age presentation, tumor size, frequencies of lymph node metastases, calcification, metaplastic bone, and psammoma bodies, when compared with conventional PTC. We conclude that a high prevalence of different variants of PTC with distinct clinico-pathological features can be documented. Recognition of these histological variants may be important for better management of patients with PTC.