The synchronous occurrence of primary malignant neoplasms with diverse histogenesis in the gastrointestinal tract is a rare event, but relevant from a clinical and pathological point of view. Gastric adenocarcinoma is the most common type of gastric cancer, often related to risk factors such as Helicobacter pylori infection, tobacco consumption and inadequate diet. The prognosis depends on factors such as the level of invasion and the presence of metastases, both assessed by TNM pathological staging. Patients with late diagnosis have a worse prognosis, with high mortality rates [1,2].

Mantle cell lymphoma (MCL) represents an uncommon and aggressive non-Hodgkin’s B-cell neoplasm, accounting for approximately 5% of lymphoma cases. It originates from B cells in the mantle zone and is characterized by the t(11;14) genetic translocation, which leads to the overexpression of cyclin D1, an essential protein in cell cycle control [3-5]. Gastrointestinal involvement by MCL occurs in approximately 20% to 30% of cases, being more common in the small intestine, while primary presentation in the stomach is less frequent [5].

The coexistence of gastric adenocarcinoma and MCL in the same patient, synchronously, is extremely rare. Studies of isolated cases in the medical literature indicate that these tumors can coexist in different regions of the stomach, intestine or even in the same location, creating significant diagnostic challenges [2,3,5]. The discovery of both tumors may be incidental, during the investigation of one of the gastric lesions, as occurred in the present case.

A 74-year-old male patient was referred for medical evaluation due to gastrointestinal symptoms, including marked weight loss (24 kg in one month) and abdominal discomfort. He had a significant medical history, including diabetes mellitus, systemic arterial hypertension, and chronic kidney disease on regular hemodialysis treatment for seven years. The patient was also a former smoker, with a history of smoking from 7 to 57 years of age.

Upper digestive endoscopy examination revealed a 2 cm ulcerated lesion in the gastric antrum, which was confirmed by biopsy as moderately differentiated tubular adenocarcinoma. Given the invasive nature and the postero-antral-pyloric location of the lesion and the patient’s clinical condition, as he was undergoing hemodialysis, it was decided to perform a total gastrectomy with Roux-en-Y reconstruction. The surgery was performed successfully, and lymph nodes from the regions of the lesser and greater gastric curvature were removed to evaluate the presence of metastases. The pathological staging of the adenocarcinoma was pT1bN1. MCL was detected only in the perigastric lymph nodes, with no direct involvement of the gastric mucosa. Preoperatory computed tomography (CT) scan did not show masses or enlarged lymph nodes.

The macroscopic examination showed an ulcerated and infiltrative lesion, measuring 2.1×2.0 cm and 0.6 cm thick, located on the posterior wall of the stomach. The neoplasm infiltrated to the submucosal layer, without evidence of perforation or serosal involvement. Other findings included chronic gastritis with intestinal metaplasia, and areas of epithelial dysplasia in the gastric mucosa adjacent to the neoplasia. Macroscopic evaluation of the lymph nodes showed the presence of areas suggestive of metastases in 2 of 47 regional lymph nodes. Microscopic findings confirmed gastric adenocarcinoma, Lauren’s intestinal type, invasive to the submucosa (Fig. 1A and B). In the immunohistochemical analysis, there was no overex-pression of HER-2.

During the histopathological examination of the regional lymph nodes, an unexpected discovery was made. The areas suggestive of metastasis seenduring the macroscopic evaluation showed histopathological characteristics compatible with atypical lymphoid proliferation (Fig. 1C and D), suggestive of lymphoma, raising the hypothesis of the coexistence of two independent neoplasms, a rare and clinically relevant finding.

The immunohistochemistry was performed using the Dako Autostainer Link 48 (Dako) automated platform and EnVision FLEX/HPR detection system (Dako). The following antibodies were used: CD20 (L26, Dako IR604), CD3 (Polyclonal, Dako IR503), CD10 (56C6, Dako IR648), BCL-2 (124, Dako IR614), Ki-67 (MIB-1, Dako IR626), Cyclin D1 (EP12, Dako IS152), CD5 (4C7, Dako IR082), CD138 (MI15, Dako IS642), Kappa/Lambda (Polyclonal, Dako IR506/507). Positive and negative controls were adequate. Detection was performed using DAB chromogen (Dako).

This analysis was crucial for the differential diagnosis, with neoplastic B lymphocytes showing positivity for Cyclin D1, CD20 and BCL-2 and negativity for CD10 (Fig. 2). The Ki-67 proliferation marker indicated a low proliferation rate in the MCL (less than 10% of lymphocytes), suggesting a less aggressive biological behavior. Furthermore, positivity for cyclin D1 (Clone EP12 Dako - Code IS152), a diagnostic marker for MCL [2], was essential to differentiate this condition from other B-cell lymphomas. Table 1 presents the antibodies used in the diagnosis of MCL in this case, detailing their expression and interpretation.

In the postoperative period, a CT scan was performed, which showed no lymphadenopathy or residual neoplasia, reinforcing the absence of evident metastatic disease at the time of evaluation.

Thus, the present case illustrates the rare coexistence of gastric adenocarcinoma and MCL, neoplasms with distinct biological characteristics and different therapeutic approaches.

The synchronous coexistence of gastric adenocarcinoma and MCL is a rare clinical situation, with few cases reported in the literature [2,5,6]. Most cases of primary gastric lymphoma are of the mucosa-associated lymphoid tissue (MALT) lymphoma subtype, with MCL being less common. When MCL affects the gastrointestinal tract, it tends to involve the small intestine and colon, making the stomach an even more unusual location for this neoplasm [6,7]. Synchronous presentation of gastric adenocarcinoma and MCL is exceptionally rare. The main histological differential diagnosis of MCL is with MALT lymphoma and follicular lymphoma. In the present case, the negativity for CD10 and CD5, combined with positivity for cyclin D1 and BCL-2, supports the diagnosis of CD5-negative MCL. The exclusion of follicular lymphoma was based on positivity for cyclin D1, as well as CD10 negativity. Fluorescence in situ hybridization (FISH) for the t(11;14) translocation was not performed. According to the essential WHO criteria, the diagnosis of MCL requires compatible morphology (classic or variant), expression of B-cell lineage markers such as CD20 and usually CD5, and either cyclin D1 positivity by immunohistochemistry or detection of CCND1 gene rearrangement by FISH [8]. In the present case, cyclin D1 expression was positive, which, together with the morphological and immunophenotypic findings, confirmed the diagnosis of MCL without the need for additional FISH analysis. In cases where cyclin D1 is negative, FISH becomes necessary to identify translocations involving CCND2 or other related genes.

There were no clinical or laboratory signs suggesting lymphoma preoperatively, reinforcing the critical role of immunohistochemistry. The pathological staging of the adenocarcinoma was pT1bN1, and initial management consisted of clinical follow-up due to the indolent nature of the MCL and complete resection of the carcinoma.

The literature suggests that the pathophysiology of the coexistence of adenocarcinoma and lymphoma in the gastrointestinal tract is not yet completely elucidated but may involve a common inflammatory response or predisposing genetic factors. Recent studies suggest that both adenocarcinoma and gastric lymphomas may be associated with Helicobacter pylori infection, although the role of this agent in the genesis of MCL is less clear than in MALT lymphoma [1,7]. In the present case, the absence of gastric involvement by the lymphoma, since it was restricted to the perigastric lymph nodes, suggests a distinct evolution for each neoplasm, reinforcing the hypothesis that the two arose independently.

This case highlights the need for diagnostic vigilance even in patients with confirmed gastric carcinoma, as synchronous hematolymphoid neoplasms may be present in regional lymph nodes without prior clinical or endoscopic evidence. Recognizing these entities is essential, as they can significantly alter oncological staging, impact prognosis, and require important modifications in therapeutic strategy.

The diagnosis of MCL was confirmed by immunohistochemistry, which demonstrated positivity for CD20, cyclin D1 and BCL-2, typical markers of this lymphoma. Among these markers, cyclin D1 is the most valuable for the diagnosis MCL. Its overexpression indicates rearrangement of the bcl-1 gene, which occurs due to the t(11;14) translocation in 70% of cases [2]. The low expression of Ki-67, a cell proliferation marker, indicated a less aggressive biological behavior for the lymphoma. The same happened with adenocarcinoma, which, as its invasion is limited to the submucosa, tends to have a more favorable prognosis [9].

The simultaneous presence of these two neoplasms in the same patient poses major diagnostic and therapeutic challenges, requiring multidisciplinary management. While gastric adenocarcinoma is often treated with total or partial gastrectomy, the management of MCL may include chemotherapy and immunotherapy, among others. The early and accurate identification of these synchronous neoplasms is crucial for therapeutic planning, especially in cases where the aggressive behavior of one of the neoplasms can influence the overall prognosis [1,3,5].

The therapeutic approach in these cases must be focused on managing the most aggressive neoplasm, with the worst prognosis. In the present case, surgery was sufficient to remove the adenocarcinoma. MCL diagnosed in the perigastric lymph nodes, after postoperative evaluation, can be complemented with adjuvant treatment [9].

The case demonstrates the simultaneous presence of gastric adenocarcinoma and MCL, two neoplasms with distinct biological characteristics that require different therapeutic approaches. Total gastrectomy surgery was effective in the treatment of gastric adenocarcinoma, while MCL, with low proliferation, was identified only after immunohistochemical analysis of the lymph nodes, demonstrating the importance of this method in identifying coexisting pathologies. Thus, this case underscores the need for detailed histopathological investigation even in patients with confirmed gastric adenocarcinoma, as the presence of synchronous lymphomas in the lymph nodes can significantly alter prognosis and therapeutic management. The absence of clinical or laboratory signs suggestive of lymphoma further highlights the importance of thorough immunohistochemical analysis.