In any malignancy, metastatic disease is the primary cause of cancer morbidity and mortality [1]. The metastatic process involves both the intrinsic properties of tumour cells and complex interactions between tumour cells and the microenvironment. This leads to the formation of discontinuous secondary masses away from the primary site [1]. Metastatic cells acquire additional properties that are hallmarks of metastasis beyond those required to become neoplastic: motility and invasion, ability to modulate the secondary site or microenvironment, plasticity, and colonisation of secondary tissues [2]. Tumour cells from a metastatic focus acquiring metastatic capabilities and disseminating to another site is a rare phenomenon [3].

We present two cases of patients with metastatic renal cell carcinoma and gastric carcinoma, respectively. The unusual route of metastasis leading to further metastasis in regional nodal basins of metastatic foci is discussed. The mechanism of spread, incidence of metastasis from metastasis, prognostic significance, and the role of surgery in managing metastasis and lymph nodes in such scenarios are elaborated.

This case report aims to highlight the possibility of lymph node involvement in regional nodal basins of metastatic foci and offers several points for discussion: the mechanisms of hilar and axillary lymph node involvement in renal cell carcinoma (RCC) and gastric cancer, respectively; the incidence of such lymph node metastasis; the prognostic significance; and the role of surgery in the management of metastases and lymph nodes in these scenarios [3, 4].

A key question in this context is the mechanism of lymph node metastasis (LNM) occurring alongside metastatic foci, but in the absence of disease in other lymph node basins. The most plausible explanation is the concept of “re-metastasis”, which refers to locoregional spread of metastatic tumor cells from an existing metastatic site [3, 4]. For example, in the first case, hilar lymph node involvement likely represents lymphatic spread from the lung metastasis. Another, albeit rarer, explanation is that circulating tumour cells (CTCs) seed the lymph nodes in addition to the lung metastasis. Both of these explanations align with the fundamental models of metastasis—the linear progression model and the parallel progression model [2, 3].

According to these models, this unusual route of metastasis from a metastatic focus can be enumerated in both cases. Hilar lymph node involvement in lung metastasis from RCC is believed to arise from the metastatic focus itself, as there are no other nodal basins involved in the spread from the primary tumour. Similarly, axillary lymph node involvement in gastric adenocarcinoma may be explained through the same principle.

The diagnosis of breast metastasis from gastric signet ring cell carcinoma is a rare clinical entity posing diagnostic and therapeutic challenges. In this case, the breast lesion and axillary lymph node involvement were confirmed as metastatic adenocarcinoma of gastric origin, based on histopathology and immunohistochemistry. Although 3 of 17 axillary nodes were positive, raising the possibility of secondary spread from breast metastasis, it is critical to distinguish this, as it impacts staging, treatment, and prognosis significantly. Comprehensive immunophenotypic profiling, which included negative expression of breast markers such as ER, PR, HER2, and GATA3 alongside gastric cancer markers, helped exclude both primary breast carcinoma and secondary nodal spread from it [5, 6]. Such metastatic patterns emphasize the complexity of these cases and highlight the need for high clinical suspicion and thorough pathological evaluation to ensure accurate diagnosis.

Another important issue is the prognostic implication of metastatic lymph nodes from metastatic foci and the role of lymphadenectomy along with metastasectomy. Lymphadenectomy is not routinely performed with metastasectomy, making it difficult to determine the incidence and prognostic value of lymph node metastases in such contexts from existing literature. Data on breast metastasis from gastric signet ring cell carcinoma are limited, with only around 60 cases reported worldwide [5, 6, 8].

In lung metastasis from RCC, there is ongoing debate whether mediastinal lymphadenectomy should be performed during renal cell carcinoma lung metastasectomy. Existing evidence is derived from studies where lymph nodes were dissected based on preoperative imaging findings of enlarged or metabolically active nodes, or were inadvertently removed during metastasectomy [4, 9]. A summary of relevant data from these studies is provided in Table 1 (Ref. [9, 10, 11, 12, 13]), adapted from Stephane Renaud, 2013 [4].

In most of the aforementioned studies, lymph node involvement (LNI) was detected in approximately 30% of cases where lymphadenectomy was performed based on radiological suspicion [4]. Therefore, omitting lymphadenectomy risks failure to achieve complete resection and increases the likelihood of loco-regional recurrence. These studies consistently conclude that LNI is a significant independent prognostic factor for survival [4, 9].

Despite the poor prognosis associated with LNI, surgery remains the best potentially curative treatment option for RCC with metastases. Consequently, a systematic total mediastinal lymphadenectomy is recommended, even if preoperative imaging does not suggest lymph node invasion [9]. This approach is likely to improve loco-regional control and provide essential staging and prognostic information [14, 15]. However, current literature is limited and primarily based on low-level evidence, warranting further studies to confirm these recommendations.

Regarding our second case, although breast cancer incidence worldwide is approximately 2.1 million per year, metastasis to the breast is unusual. Only 0.5 to 2% of patients present with breast metastases, primarily originating from melanoma, lymphoma, lung, and ovarian cancers, with gastrointestinal tumours being among the least common sources [5, 16]. While systemic treatment is considered the primary intervention, its role remains controversial [17]. Prognosis for patients with breast metastases has improved recently due to advances in anticancer therapies. Conversely, available data suggest that surgery plays an unclear role, may not significantly improve survival, and is generally considered palliative. These patients face a poor prognosis, with mortality rates exceeding 80% within the first year [6, 8, 18]. Further research is necessary to elucidate the role of surgery, including lymphadenectomy, in managing such cases.

Several inherent limitations must be considered when interpreting this report and the accompanying review of the literature. First, the incredibly low global incidence of these specific metastatic pathways—such as breast metastasis from gastric signet ring cell carcinoma—restricts the available data to isolated case reports and small, retrospective series [5, 7]. This introduces significant publication bias, as unusual presentations with unique surgical outcomes are more likely to be documented than standard presentations. Second, the current medical literature lacks standardized, prospective clinical trials evaluating the survival benefit of systematic lymphadenectomy during metastasectomy in these rare cohorts. Much of the analyzed data regarding RCC lung metastasectomy relies on low-level evidence where lymph node dissections were not uniformly performed, introducing heavy selection bias based on varied preoperative imaging and individual surgeon preferences [4, 9].

These cases highlight the rare but significant phenomenon of secondary metastasis, where metastatic lesions themselves spread to regional lymph nodes. Recognizing this metastatic pattern is important for accurate staging, prognosis, and treatment planning. Careful pathological and immunohistochemical evaluation is essential to distinguish metastasis-from-metastasis versus primary or initial metastatic disease, influencing management strategies.

In renal cell carcinoma, lymph node metastasis during lung metastasectomy is an adverse prognostic factor, supporting consideration of systematic lymphadenectomy for better local control and staging. However, in the case of breast metastasis from gastric cancer, surgery remains mainly palliative with limited survival benefit, emphasizing the need for individualized multidisciplinary care.

Overall, awareness of re-metastasis pathways and thorough clinical evaluation can help optimize oncologic outcomes in complex metastatic scenarios. Further research is needed to clarify the therapeutic role of lymphadenectomy in these uncommon presentations.