Microscopic description:

On low power, scattered cores of bladder tissue infiltrated by tumor cells are seen. On high power, majority of the tumor shows high grade, pleomorphic tumor cells with hyperchromatic nuclei resembling mononuclear and multinuclear giant cells are arranged in diffuse sheets and nests. The nests of tumor cells are separated by prominent desmoplastic stroma. Frequent mitoses and rare pockets of lymphocytic inflammation was seen. About 10% of the area shows relatively uniform cells with eosinophilic cytoplasm, low grade cytology and rare mitotic figures suggesting presence of conventional component of urothelial carcinoma. The tumor invades lamina propria and muscularis propria.

No component of prostatic adenocarcinoma, osteoclast giant cells, intra-nuclear inclusions, pigment or spindle cell component seen.

Based on these histopathological features, the tumor is consistent with a diagnosis of pleomorphic giant cell carcinoma of bladder.

Discussion:

Pleomorphic giant cell carcinoma of bladder is a rare and aggressive neoplasm that has histologic appearance similar to giant cell carcinoma of lung.

Primary pleomorphic giant cell carcinoma of bladder should be differentiated from osteoclast rich undifferentiated carcinoma and other bladder tumors with osteoclast type or trophoblastic giant cells.

Patients usually present with hematuria, dysuria and increased frequency.

Age range 55 to 88 years (mean 67 years).

Histologically, mononuclear or multinuclear giant cells with abundant pale eosinophilic, amphophilic or basophilic cytoplasm are seen arranged in sheets or aggregates. Tumor shows high mitotic rate and necrosis. Few tumors can also show intracytoplasmic vacuoles.

The architectural pattern of growth varied from infiltrating pleomorphic tumour with bizarre giant cells to solid expansile nests with occasionally discohesive cells. A rare hypocellular sclerosing pattern may also be recognised. The proliferating anaplastic cells are giant and bizarre and occasionally multinucleated, with frequent typical or atypical.

Differential diagnosis of prostate and urothelial carcinoma may result following transurethral resection of the bladder neck or prostate with extensive undifferentiated tumor. Studies have demonstrated uniform positivity for CK 8/18 and AE1/AE3, with many demonstrating positivity for CAM 5.2, CK7, CK20, uroplakin III and GATA binding protein 3 (GATA3). β-human chorionic gonadotrophin (β-hCG) is typically negative.

Diagnosis is usually rendered on Transurethral resection of bladder tumor (YURBT) specimens or cystectomy specimens.

Most patients present with T3 stage at diagnosis.

Differential diagnosis includes metastatic pleomorphic giant cell carcinoma of prostate, osteoclast rich undifferentiated carcinoma, sarcomatoid carcinoma, metastatic melanoma and giant cell carcinoma of lung.

Patients show poor prognosis and aggressive clinical course.

Treatment includes cystoprostatectomy with or without neo-adjuvant chemotherapy.

Probability of recurrence and progression at 1 year is 24% and 17% respectively.

European association of Urology guidelines suggest follow-up with cystoscopy and cytology every three months for a period of two years, every six months thereafter until five years and then yearly. Annual upper tract imaging with computed tomography-intravenous urography (CT-IVU) or IVU is also recommended.

References:

Lopez-Beltran A, Henriques V, Montironi R, Cimadamore A, Raspollini MR, Cheng L. Variants and new entities of bladder cancer. Histopathology. 2019 Jan;74(1):77-96. doi: 10.1111/his.13752. PMID: 30565299.

Samaratunga H. Pleomorphic giant cell carcinoma of the urinary bladder. Pathology. 2014;46doi:10.1097/01.Pat.0000454233.75372.31

Samaratunga H, Delahunt B, Egevad L, et al. Pleomorphic giant cell carcinoma of the urinary bladder: an extreme form of tumour de-differentiation. Histopathology. Mar 2016;68(4):533-40. doi:10.1111/his.12785

Wijesinghe HD, Malalasekera A. Giant Cell Urothelial Carcinoma of Bladder. Case Rep Urol. 2021 Jul 15;2021:8021947. doi: 10.1155/2021/8021947. PMID: 34327036; PMCID: PMC8302384.

CASE IMAGES