Osteoclast-like giant cell variant of bladder urothelial carcinoma with poor response to neoadjuvant chemotherapy managed by robot-assisted radical cystoprostatectomy: A case report

Abstract

The osteoclast-like giant cell (OGC) variant of urothelial carcinoma is a rare histological entity characterized by an aggressive clinical course and diagnostic challenges.

We report the case of a 62-year-old who presented with a muscle-invasive locally advanced urothelial carcinoma of the bladder. the tumor was resistant to chemotherapy. A completely robot-assisted radical cystoprostatectomy (RARC) with an intracorporeal Bricker ileal conduit urinary diversion was successfully performed. Histopathological evaluation of the surgical specimen demonstrated a OGC variant of bladder carcinoma.

This case highlights the potential chemoresistance of the OGC variant to conventional platinum-based neoadjuvant regimens.

Highlights

• •A case of bladder osteoclast-like giant cell variant treated via completely robotic RARC.
• •The rare osteoclast-like giant cell variant showed severe chemoresistance to neoadjuvant therapy.
• •Histology post-chemotherapy revealed 95% viable tumor cells with extensive perineural invasion.
• •Intracorporeal Bricker diversion and extended PLND achieved optimal oncological margins ($pN0$).
• •Adjuvant immunotherapy is highlighted as a crucial option for chemoresistant aggressive variants.

1. Introduction

Urothelial carcinoma (UC) of the urinary bladder is notorious for its divergent differentiation and morphological variants. The 2022 World Health Organization (WHO) classification recognizes several subtypes,1, 2 among which the presence of osteoclast-like multinucleated giant cells (OGCs) represents an extremely rare entity.3, 4

Unlike sarcomatoid carcinomas or carcinomas with choriocarcinoma-like giant cells, the OGC variant is defined by a dual cell population: a malignant mononuclear epithelial component and a background of numerous benign, reactive multinucleated giant cells resembling bone osteoclasts.3, 5

Due to its rarity, the clinical behavior, optimal sequencing of therapy (neoadjuvant chemotherapy versus upfront surgery), and response to systemic agents remain poorly understood. We report a rare case of OGC variant bladder carcinoma that exhibited significant resistance to neoadjuvant chemotherapy and was subsequently treated with robot-assisted radical surgery.

2. Case presentation

A 62-year-old male, a former heavy smoker, presented to our urology department with recurrent gross haematuria and lower urinary tract symptoms. Baseline transabdominal ultrasound revealed a large, asymmetric, sessile bladder mass measuring 19 *41 mm arising from the mid-portion of the left lateral bladder wall.

The patient underwent a transurethral resection of the bladder tumor (TURBT). Histopathological examination confirmed a high-grade (G3) muscle-invasive urothelial carcinoma infiltrating the deep detrusor muscle pT2 G3. Secondary review of the initial TURBT specimen revealed only high-grade conventional muscle-invasive urothelial carcinoma without giant cells, likely due to sampling limitations and spatial intratumoral heterogeneity.

A staging thoraco-abdomino-pelvic computed tomography (CT) scan performed on August 4, 2025, demonstrated an irregular, circumferential-predominant thickening of the postero-lateral left bladder wall, measuring up to 13 mm in thickness and extending over 70 mm. The lesion exhibited clear signs of infiltration into the adjacent perivesical fat. There was no evidence of pelvic or retroperitoneal lymphadenopathy (N0). A technetium-99m methylene diphosphonate Tc-99m MDP bone scintigraphy on August 26, 2025, ruled out distant bone metastases (M0). The clinical stage was established as cT3a,N0,M0.

The patient fulfilled Galsky criteria for cisplatin eligibility, with an estimated glomerular filtration rate of 70 mL/min/1.73 m² and an ECOG performance status of 0. He was initiated on neoadjuvant systemic chemotherapy comprising four cycles of gemcitabine (1000 mg/m² on Days 1 and 8) and cisplatin (70 mg/m² on Day 1) every 21 days. Follow-up imaging was performed to assess therapeutic response. A interim CT scan in December 2025 noted persistent irregular thickening (12 mm) with early encasement of the left ureteral orifice and mild homolateral ureterohydronephrosis.

A post-chemotherapy evaluation CT scan on February 25, 2026, confirmed stable disease according to RECIST 1.1 criteria, with the left perivesical mass measuring 15 *14mm. However, significant local progression was noted at the left ureterovesical junction, causing a major worsening of the left-sided uretero-pyelo-caliceal dilatation. No distant or nodal progression was detected(Fig. 1).

Fig. 1.

Computed tomography (CT) images demonstrating primary tumor and upstream obstruction. Baseline axial unenhanced CT scan prior to chemotherapy showing initial left-sided hydronephrosis with renal pelvic dilatation(A). Follow-up axial unenhanced CT scan after chemotherapy showing progressive worsening of left ureterohydronephrosis with marked increase in renal pelvic dilatation (B). Baseline contrast-enhanced axial pelvic CT scan showing the primary infiltrating bladder wall mass prior to chemotherapy(C). Post-chemotherapy contrast-enhanced axial pelvic CT scan revealing persistent extensive circumferential tumor thickening, marked mural enhancement, luminal narrowing, and local disease progression(D).

Given the local encasement of the left ureter and the absence of metastatic disease, the patient was scheduled for radical surgery. On April 6, 2026, he underwent a completely robot-assisted radical cystoprostatectomy (RARC) combined with an extended bilateral pelvic lymph node dissection. Urinary diversion was performed entirely intracorporeally via a Bricker ileal conduit. The operative course was uneventful with no perioperative complications(Fig. 2).

Fig. 2.

Surgical specimen of a cystoprostatectomy.

Gross examination of the cystectomy specimen revealed a firm, whitish, multinodular mass measuring 5*4 *1 cm located on the left lateral bladder wall, located 1.5 cm from the prostate base and infiltrating microscopically into the perivesical fat.

Microscopic analysis demonstrated a striking lack of therapeutic response, with post-chemotherapy changes (fibrosis) estimated at only 5%, leaving 95% viable tumor cells (Fig. 3).

Fig. 3.

The tumor is poorly differentiated and composed of sheets of malignant mononuclear epithelial cells admixed with numerous osteoclast-like giant cells within a fibro-inflammatory stroma (A). The malignant mononuclear cells exhibit abundant cytoplasm and round to oval vesicular nuclei with moderate atypia (B). Reactive osteoclast-like giant cells are indicated by an asterisk (*) (B). The tumor infiltrates the muscularis propria (C) and extends into the perivesical adipose tissue (D). (Hematoxylin-eosin; A,×100; B,C,D, ×400).

Extensive perineural and perineural sheath invasion was identified. The tumor reached within 1 mm of the closest peripheral soft tissue surgical margin. Crucially, the prostate gland, seminal vesicles, vasa deferentia, and both left and right ureteral surgical margins were completely free of tumor invasion. The extended pelvic lymphadenopathy yielded 10 lymph nodes (5 left, 5 right), all of which were highly reactive but negative for metastatic disease. The final pathological stage was determined as ypT3a,pN0,pMx according to the AJCC 8th edition.

the mononuclear malignant cells demonstrated strong and diffuse positivity for GATA3 and cytokeratin 7 (CK7), confirming their carcinomatous urothelial origin, whereas the multinucleated osteoclast-like giant cells showed intense and diffuse cytoplasmic positivity for CD68 and were completely negative for cytokeratins and p53.

3. Discussion

The osteoclast-like giant cell (OGC) variant of bladder carcinoma is an exceptional morphological subtype. Histologically, it must be differentiated from other giant cell lesions. Immunohistochemical studies in literature typically show that the mononuclear cells are positive for epithelial markers (cytokeratines) confirming their carcinomatous nature, whereas the OGCs are of mesenchymal/monocytic origin, characteristically expressing histiocytic markers such as CD68(3, 4, 5).

A key finding in our case is the marked chemoresistance of this tumor variant. Despite completing a standard neoadjuvant chemotherapy regimen, histological evaluation revealed a nearly untouched tumor mass with 95% viable cells and negligible tissue fibrosis (5%). This clinical course strongly supports growing evidence that the OGC variant may not benefit from conventional cisplatin-based regimens.⁶ This underlines the crucial importance of early aggressive surgical intervention or the exploration of alternative upfront targeted approaches.

A key clinical dilemma in this case was the therapeutic management following the interim CT in December 2025. Despite the emergence of new left ureteral obstruction, the multidisciplinary tumor board elected to complete the planned four cycles of chemotherapy rather than proceeding to immediate surgery. This strategy was guided by the absence of distant metastases, preserved contralateral renal function, and the therapeutic objective of eradicating potential occult micrometastases before major extirpation. In retrospect, persistent local tumor growth and worsening hydronephrosis reflected primary chemo-refractoriness. This observation highlights that the development of de novo obstructive uropathy during neoadjuvant chemotherapy in rare urothelial variants should be interpreted as an alarming hallmark of chemo-refractory disease, prompting strong consideration of early abortive transition to definitive salvage radical cystectomy.

To the best of our knowledge, this report represents one of the first documented cases of an OGC variant of the bladder managed entirely via a minimally invasive, robot-assisted approach (RARC + Bricker). Although the tumor exhibited highly aggressive local features—including extensive perineural invasion and microscopic extension into the perivesical fat (ypT3a)—the 3D high-definition visualization and meticulous dissection capability of the robotic platform allowed for an oncologically sound resection.⁷ This is reflected by the negative margins on adjacent organs and the successful clearance of 10 pelvic lymph nodes (pN0),and the feasibility of a totally intracorporeal urinary diversion.⁸

Given the close soft tissue margin (1 mm), the adverse perineural features, and the lack of response to neoadjuvant chemotherapy, this patient represents an ideal candidate for adjuvant checkpoint inhibitor immunotherapy (e.g., Nivolumab), which has recently established a survival benefit in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery (ypT3/pN0). Although it could not be administered due to severe financial constraints, lack of insurance coverage/reimbursement, and limited availability in our regional setting.9, 10

4. Conclusion

The osteoclast-like giant cell variant of urothelial carcinoma is a highly aggressive entity with a propensity for rapid local invasion and potential resistance to standard neoadjuvant chemotherapy. Entirely robot-assisted radical cystoprostatectomy with intracorporeal Bricker diversion is a safe and feasible surgical approach that provides excellent local control. Close oncological follow-up and consideration for adjuvant immunotherapy are warranted for these high-risk patients.

CRediT authorship contribution statement

Abdelhakim Oukouhou: Writing – original draft. Mohamed Tetou: Writing – review & editing, Conceptualization. Saad Assila: Writing – original draft, Data curation. Abdessamad El Bahri: Supervision. Mohamed Alami: Supervision. Ahmed Ameur: Supervision.

Declaration of generative AI and AI-assisted technologies in the manuscript preparation process

Statement: During the preparation of this work the author(s) used [Gemini] in order to [text synthesis, language editing, and improving readability. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the published article.