Primary bladder adenocarcinoma versus metastatic colorectal adenocarcinoma: a persisting diagnostic challenge

Abstract

Aim: This study attempted to distinguish primary bladder adenocarcinoma (PBA) from metastatic colonic adenocarcinomas (MCA), which is a difficult diagnostic and clinical problem.

Methods: Twenty-four cases of bladder adenocarcinomas (12 primary & 12 metastatic colorectal) were included in the study with urothelial carcinoma (UC) and colonic adenocarcinoma (CA) as controls. A panel of immunohistochemical (IHC) stains along with fluorescence in-situ hybridization (FISH), using the UroVysion probe set, was performed.

Results: The majority of the PBAs presented with advanced disease. Enteric histologic subtype was the most common morphological variant. Strong nuclear with cytoplasmic-membranous staining of β-catenin was seen in 75% of MCA and only 16.7% PBA (<10% staining cells). Although abnormal nuclear staining with E-cadherin was seen in both PBA and MCA, it was more frequent in former. CK-7, CK-20, villin and CDX-2 stains were not helpful in distinguishing the two entities. FISH did not reveal any unique differences in chromosomal abnormality between the two groups.

Conclusion: Although there was a statistically significant difference in β-catenin and E-cadherin staining between two groups, we did not find any IHC or FISH marker that was specific for PBA. Distinction between PBA and MCA remains a diagnostic problem and clinical correlation is vital before rendering a diagnosis.

Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1393156268152357.

Figure 1

a: Primary bladder adenocarcinoma, enteric type. Moderately differentiated malignant glands are seen with dirty luminal necrosis. Elongated, enlarged and hyperchromatic nuclei with prominent stratification line the malignant glands. (Hematoxylin & eosin, x100). b: Primary bladder adenocarcinoma, mucinous type. Scattered small groups of tumor cells with intracytoplasmic mucin are seen in a background of abundant mucinous material (Hematoxylin & eosin, x200). c: Primary bladder adenocarcinoma, signet ring cell type: Tumor comprised of diffuse sheets of signet ring cells infiltrating the bladder wall (Hematoxylin & eosin, x200). d: Cystitis cystica involving the surface urothelium with underlying invasive primary bladder adenocarcinoma (Hematoxylin & eosin, x100). e: Extensive cystitis glandularis, intestinal type seen adjacent to a focus of invasive primary bladder adenocarcinoma (not seen in this image) (Hematoxylin & eosin, x40). f: Metastatic colorectal adenocarcinoma. Moderately differentiated, infiltrating malignant glands with morphological features similar to primary bladder adenocarcinoma see in a (Hematoxylin & eosin, x100).

Figure 2

a: Primary bladder adenocarcinoma. Strong cytoplasmic membranous staining with β-catenin (DAB chromogen, x100). b: Metastatic colorectal adenocarcinoma. Strong nuclear staining in addition to cytoplasmic staining with β-catenin (DAB chromogen, x100). c: Primary bladder adenocarcinoma. Strong nuclear staining with e-cadherin in addition to weaker cytoplasmic staining pattern. This pattern was more frequent in this group of tumor in contrast to metastatic colorectal adenocarcinoma (DAB chromogen x200). d: Metastatic colorectal adenocarcinoma. Prominent cytoplasmic membranous staining with e-cadherin. Note the absence of nuclear staining (DAB chromogen, x200).

Figure 3

a: Primary bladder adenocarcinoma demonstrating apical brush border staining with villin. Very similar staining pattern was also seen in metastatic colorectal adenocarcinoma. (DAB chromogen, x100). b: Primary bladder adenocarcinoma demonstrating strong diffuse nuclear staining with CDX-2. Metastatic colorectal adenocarcinoma demonstrated same staining pattern. (DAB chromogen, x100). c: Primary bladder adenocarcinoma shows strong cytoplasmic staining with CK7. Overall, it was infrequently seen in glandular bladder tumors, however slightly more frequently in primary than metastatic adenocarcinomas. (DAB chromogen, x100). d: Primary bladder adenocarcinoma shows diffuse strong cytoplasmic positivity for CK20. This was also seen in majority of metastatic colorectal adenocarcinoma. (DAB chromogen, x100).

Figure 4

Primary bladder adenocarcinoma. FISH using UroVysion probe set demonstrates complete loss of yellow signal in some cells (homozygous loss 9p21) and single chromosome 3 gain in fewer cells (>2 red signals) (Red – CEP3, Green – CEP7, Aqua – CEP17 and Yellow – LSI 9p21, x600).

Figure 5

Primary bladder adenocarcinoma. FISH using UroVysion probe set demonstrates a polysomy pattern with more than 2 red, green and aqua signals. (Red – CEP3, Green – CEP7, Aqua – CEP17 and Yellow – LSI 9p21, x600).