Collision metastasis refers to the coexistence of metastatic deposits from two independent primary tumors with distinct histological features at the same anatomical site (1). The simultaneous presence of prostatic adenocarcinoma in radical cystectomy specimens for bladder cancer is not uncommon. However, reports in the literature of simultaneous metastasis of urothelial carcinoma and prostatic carcinoma in a single lymph node are extremely rare. To our knowledge, only seven cases have been recorded. Among these cases, six were identified during radical cystoprostatectomy with pelvic lymphadenectomy, while one was detected during right nephroureterectomy with periureteral lymph node dissection. This study reports a case of lymph node collision metastasis involving both urothelial carcinoma and prostatic adenocarcinoma. As far as we know, this is the first case from China.

Historically, different authors have had slightly varying definitions of “collision tumors”, with one point of difference being whether a transitional pattern is allowed to exist in the collision area. In 1961, Dodge (1) proposed that a “collision tumors” refers to two tumors independently originating from different sites, which need to meet the following conditions: the presence of two separate tumor regions with distinct histological characteristics; if both types of tumors metastasize, they should exhibit clearly distinguishable growth patterns in the metastatic lesions, and there should be no transitional areas between them. In 1980, Spagnolo and Heenan (2) proposed that the diagnosis of “collision tumors” should be based on two essential criteria: anatomically, the two components must originate from distinct sites; and there should be at least some degree of histological separation between the closely adjacent components. The observation of transitional patterns at the collision zone is permissible, as they hypothesized that during tumor progression, the two components may invade each other, consequently forming an intermediate zone with hybrid histopathological features. In 2009, Satter et al. (3) defined collision tumors as: “two independent neoplasms that occur in close proximity to one another, yet maintain sharply distinct boundaries.” In their 2020 review on the types, pathogenesis, and diagnostic challenges of collision tumors, Bulte et al. (4) endorsed the definition proposed by Satter et al.

Possible explanations for collision metastases of malignant tumors within the same lymph node include: (i) Certain cancers, such as prostate cancer, tend to have high incidence and lengthy disease progression, often presenting subtle symptoms. This long timeline provides ample opportunity for a second primary tumor to emerge and spread to the same lymph node (5, 6). (ii)Some researchers have proposed the “altered tumor microenvironment” hypothesis: the first metastatic tumor may modify the local microenvironment to facilitate colonization and growth of a second tumor (7), this mechanism may similarly apply to lymph node collision metastases. (iii)Gasparinho et al. (8) documented a case of metastatic collision within a lymph node involving both breast carcinoma and rectal neuroendocrine carcinoma. They subsequently proposed the “chemokine-guided migration” hypothesis, suggesting that malignancies with comparable chemokine receptor expression profiles may exhibit tropism toward specific lymph nodes or organs, potentially resulting in collision metastases.

The incidental detection of prostate cancer in radical cystoprostatectomy specimens represents a relatively common clinical phenomenon. Baio et al. (9) conducted a single-center retrospective study that analyzed data from 303 patients with urothelial carcinoma of the bladder who underwent radical cystoprostatectomy (excluding patients with a preoperative diagnosis or clinical suspicion of prostate cancer). Among these, 69 patients (22.7%) were found to have prostate cancer. Wu et al. (10) conducted a population-based cohort study involving 14,199 bladder cancer patients who underwent radical cystoprostatectomy. Among these patients, 4,096 (28.8%) were incidentally diagnosed with prostate cancer. Notably, 89.9% of these prostate cancer cases were localized (stage T1-2).

However, the phenomenon of collision metastases within the same lymph node from coexisting bladder and prostate cancers is exceptionally rare. To our knowledge, there are only seven documented cases of collision metastases involving urothelial carcinoma and prostatic adenocarcinoma in the literature (Table 1). These tumors may display similar morphological features and cannot be clearly differentiated solely through HES staining. Consequently, immunohistochemistry is necessary for distinguishing between poorly differentiated prostatic adenocarcinoma and urothelial carcinoma. Among the seven cases, PSA antibodies were used in six cases, a combination of CK7 and CK20 antibodies in three, and GATA3 antibody in two. In our specific case, staining with PSA, CK7, CK20, and GATA3 antibodies successfully differentiated the two tumor components in the lymph node. However, staining with the P504S antibody showed positive results in both tumor components. Langner et al. (17) demonstrated P504S expression in 127 of 261 urothelial carcinomas (48.7%), with its positivity rate showing positive correlation with tumor stage and grade. In this case, we observed more intense P504S antibody staining in the prostatic adenocarcinoma metastatic foci compared to the bladder carcinoma foci within the same lymph node (Figure 1I).

Among seven reported cases in literature, most cases did not mention postoperative treatment and follow-up data. In our case, the liver metastases responded effectively to Disitamab Vedotin treatment, supporting the notion that the tumor originated from urothelial carcinoma. However, the bone metastases progressed after treatment, suggesting that they might not be derived from urothelial carcinoma. The efficacy of Disitamab Vedotin in treating HER2-overexpressing urothelial carcinoma has been clinically validated. Sheng et al. (18) performed a pooled analysis of two Phase II clinical trials, involving 107 patients with HER2-positive locally advanced or metastatic urothelial carcinoma whose disease had progressed despite at least one prior systemic chemotherapy regimen. These patients received Disitamab Vedotin treatment at a dose of 2 mg/kg every two weeks. The overall confirmed objective response rate was 50.5% (95% CI, 40.6% to 60.3%). Among these patients, there were 48 cases each with liver metastases and bone metastases. However, the analysis did not address the “dissociated responses” of these two types of metastases during the course of treatment.

Anti-HER2 therapy demonstrates limited efficacy and lacks robust evidence in metastatic prostate cancer, primarily due to inconsistent outcomes and inadequate clinical responses (19, 20). The presence of osteoblastic lesions and a SUV max of 14.33 on ¹⁸F-PSMA-PET/CT suggests that the bone metastases may originate from prostate cancer.

In the present case, the patient was diagnosed with two distinct malignant neoplasms requiring systemic therapy: urothelial carcinoma and prostate cancer. The disease progression was characterized by initial nodal collision metastases, followed by the subsequent development of multiple metastatic lesions in the liver and bones. However, these two malignancies have distinct first-line standard treatment regimens. Specifically, for urothelial carcinoma, the recommended first-line options include Enfortumab Vedotin plus Pembrolizumab or platinum-based chemotherapy (e.g., cisplatin plus gemcitabine). In contrast, for metastatic prostate cancer, the standard first-line therapeutic strategies consist of antibody-drug conjugate (ADC) combined with novel hormonal therapy, as well as triple therapy regimens comprising ADT plus docetaxel and darolutamide/abiraterone. The ideal therapeutic strategy for such patients is to identify a drug combination that exerts efficacy against both tumor components while exhibiting non-overlapping or minimally overlapping toxicity profiles. This approach aims to maximize therapeutic benefits while controlling toxicities within a manageable range. Chen et al. (21) reported a case of collision carcinoma involving lung adenocarcinoma and prostate cancer. Specifically, the postoperative pathological stage of lung adenocarcinoma was pT1N2M0 with an EGFR exon 19 deletion mutation, while the prostate cancer was complicated by multiple metastases to the lungs, lymph nodes, and bones. Both adjuvant chemotherapy and targeted therapy are recommended as first-line treatment options for the patient’s lung cancer. The patient initially initiated treatment for prostate cancer with a regimen consisting of goserelin acetate combined with abiraterone acetate. Concurrently, ibandronate sodium was administered for anti-bone metastasis therapy. Targeted therapy with osimertinib (80 mg, once daily) was initiated three weeks after lung cancer surgery. Following the operation, the patient underwent regular re-evaluations and maintained treatment with the aforementioned regimen. The tumors were well-controlled, with no evidence of recurrence observed. Sellman et al. (15) identified a case of collision metastasis involving bladder urothelial carcinoma and prostatic adenocarcinoma in a pelvic lymph node following radical cystoprostatectomy. They elected to promptly initiate adjuvant hormonal therapy combined with a chemotherapy regimen consisting of Cisplatin and Gemcitabine. During the initial follow-up period, no evidence of disease progression was observed. In the present case, a platinum-containing regimen was administered for the high-grade urothelial carcinoma, while ADT was initiated for the management of prostate cancer. Upon disease progression, a HER2-targeted antibody-drug conjugate (ADC) combined with a PD-1 inhibitor was administered to control liver metastases derived from urothelial carcinoma. Concurrently, novel hormonal therapy agents and denosumab were added to treat bone metastases originating from prostate cancer. Considering the patient’s tolerability, taxane-based chemotherapy was not utilized. Clinical follow-up data demonstrated that the patient currently maintained favorable disease control with a high quality of life.

To further understanding “collision metastasis” in lymph nodes, we conducted comprehensive searches across multiple databases including PubMed, China National Knowledge Infrastructure, Chinese Medical Journal Full-text Database, and Wanfang Database. We categorized and analyzed 32 reported cases of lymph node collision metastasis. Literature reports describing the coexistence of metastatic tumors and lymphoproliferative disorders within the same lymph node were excluded, as these cases ought to be classified as inter-tumor metastasis (Table 2). The most frequently involved sites were pelvic lymph nodes (9/32 cases, 28.1%) and cervical lymph nodes (10/32 cases, 31.3%). Regarding primary malignancies, prostate cancer accounted for 17 cases (53.1%), while thyroid cancer comprised 10 cases (31.3%), including 3 cases (9.4%) demonstrating collision metastases between two distinct histological subtypes of thyroid carcinoma.

The present study has the following limitations: the follow-up duration of the case is relatively short, resulting in a lack of survival data; in addition, the hepatic and osseous metastatic lesions of this patient lack pathological evidence and are solely based on limited inferences derived from imaging findings and treatment responses, which inherently entails uncertainty.

When markedly distinct histological morphologies are observed in lymph node metastases, the possibility of collision metastases must be considered to avoid missing a second tumor type. Immunohistochemical staining serves as a crucial tool for differentiating various collision tumors. Lymph node collision metastases represent a special type of lymph node metastasis. Research into their molecular mechanisms may yield novel insights into tumor lymph node metastasis and advance our understanding of the competitive metastatic mechanisms among different cancer types within the tumor microenvironment.