Synchronous medullary carcinoma of the pancreas and non-ampullary duodenal adenocarcinoma

ABSTRACT

Synchronous primary malignancies involving the pancreas and duodenum are rare and distinguishing them from direct extension or metastatic spread may be difficult in the periampullary region. We report a 73-year-old man who initially presented with upper gastrointestinal bleeding and was later investigated for weight loss, abdominal pain, dyspepsia, and abnormal liver biochemistry. Preoperative imaging and biopsy identified poorly differentiated adenocarcinoma involving the pancreatic and duodenal region, but the relationship between the lesions remained uncertain. Following pancreaticoduodenectomy, two macroscopically separate tumor sites were identified. Histological examination showed that the pancreatic tumor had features of medullary carcinoma, including syncytial growth, pushing borders, marked lymphocytic infiltration, and mismatch repair deficiency. In contrast, the duodenal tumor showed glandular differentiation, infiltrative invasion, and desmoplastic stroma, but also deficient mismatch repair. Lymph node involvement was seen with the pancreatic tumor but not the duodenal lesion. This case suggested that synchronous primary tumors should remain in the differential diagnosis when adjacent periampullary lesions show discordant pathological features, and that definitive classification may require integration of gross examination, morphology, selected immunohistochemistry, mismatch repair status, and nodal disease pattern on the resection specimen. The underlying diagnosis of Lynch syndrome provides a novel pathogenesis for these genetically related yet distinct tumors. This diagnosis was important not only for understanding tumor pathogenesis but also for ongoing surveillance and family counselling.

INTRODUCTION

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor long-term survival and includes several recognized histological variants [1]. Medullary carcinoma of the pancreas (MCP) is a rare PDAC subtype whose pathogenesis and clinical course remain incompletely understood [2-4]. It is characterized by syncytial growth, poor gland formation, prominent tumor-infiltrating lymphocytes and pushing borders, and has been associated with microsatellite instability (MSI), mismatch repair (MMR) deficiency and, in some reported series, wild-type KRAS status [2-4]. Recognition of this phenotype is clinically relevant because MMR deficiency/MSI may prompt consideration of an underlying inherited or somatic mismatch repair abnormality, including Lynch syndrome, although this requires correlation with family history and molecular or germline testing [2-4]. MCP has been suggested to have a better prognosis than conventional PDAC, but reported outcomes remain variable and overall survival remains poor [2-4].

Duodenal adenocarcinoma is also uncommon. Due to the close anatomical relationship between the pancreas, duodenum, ampulla and distal bile duct, periampullary tumors may be difficult to classify as direct extension, metastatic disease or synchronous primaries, thereby affecting staging, prognosis and interpretation of tumor biology. Tumors arising in the second part of the duodenum are frequently managed surgically in a similar framework to other periampullary malignancies because of their proximity to the pancreatic head, distal bile duct and ampulla [5,6].

Synchronous primary malignancies involving the pancreas and duodenum are rare, and their recognition before resection may be particularly challenging when adjacent lesions show overlapping radiological or biopsy appearances [7-11]. We report a case of synchronous medullary carcinoma of the pancreas and duodenal adenocarcinoma, highlighting the morphological, immunohistochemical and mismatch repair features that supported two distinct primary tumors.

CASE PRESENTATION

A 73-year-old man first presented in March 2022 with significant upper gastrointestinal bleeding, coffee-ground vomiting, and melaena. Oesophago-gastro-duodenoscopy (OGD) showed Barrett esophagitis and a benign-looking, non-obstructing tumor in the duodenal bulb. Duodenal biopsy showed a tubular adenoma with low-grade dysplasia. Repeat OGD and duodenal biopsy in May 2022 showed a large duodenal adenoma at the D1/D2 junction, involving approximately 50% of the circumference; biopsy showed histologically a tubulovillous adenoma with low-grade dysplasia (Figure 1).

Fig. 1.

Initial duodenal biopsy at D1/D2 junction. A tubulovillous adenoma with low grade dysplasia. No carcinoma is seen. (HE, ×10 magnification).

In February 2023, he presented with weight loss, abdominal pain, early satiety, dyspepsia, night sweats, and a palpable left upper quadrant mass. He had no jaundice or right-sided abdominal tenderness. Fecal immunochemical tests and chest X-ray were unremarkable. Blood tests showed marked microcytic anemia (Hb 85 g/L, MCV 67 fL, HCT 0.28 L/L), elevated C-reactive protein (CRP 117 mg/L), hypoalbuminemia (albumin 29 g/L), deranged liver biochemistry (ALT 95 U/L, AST 56 U/L, total bilirubin 22 µmol/L) and remarkably high alkaline phosphatase (ALP 1746 U/L). Contrast-enhanced chest-abdomen-pelvis CT showed a large (63 × 46 mm) tumor in the head of pancreas (Figure 2A, 2B) invading and obstructing the duodenum, causing gastric outlet obstruction, and intrahepatic and extrahepatic duct dilatation.

Fig. 2.

Chest-abdomen-pelvis CT. (A) A large tumor (blue and yellow lines) within the head of pancreas radiologically reported to be invading duodenum. (B) A pancreatic head lesion (blue and yellow lines) obstructed the duodenum, with associated intrahepatic and extrahepatic biliary duct dilation.

Endoscopic ultrasound (EUS) with OGD found a 25mm rounded smooth mass adjacent to the duodenal wall. The pancreas appeared stranded and lobular. A slightly hypoechoic area was noted at the ampullary end of the common bile duct (CBD). Pancreatic core needle biopsy initially reported lymphoid aggregates in keeping with origin from a lymph node, with poorly differentiated malignant cells forming sheets surrounded by intratumoral lymphocytes (shown in Figure 3A). IHC staining was CK7 positive, CA19.9 focally positive, and synaptophysin negative, with Ki-67 index of 75% (Figure 3B-D). The lesion was thereby interpreted as metastatic adenocarcinoma of duodenal origin. Repeat pancreatic core needle biopsy later showed a poorly differentiated adenocarcinoma (Figure 4A) with focal CA19-9 positivity and negative synaptophysin expression (Figure 4B). Duodenal mucosal biopsy from the D2 region showed low-grade dysplasia with fragments of poorly differentiated invasive adenocarcinoma (Figure 5). IHC showed BerEp4 positivity and negative synaptophysin expression.

Fig. 3.

Core needle biopsy from tissue initially reported as an undefined lymph node in pancreatic mass adjacent to duodenal wall. (A) Tumor cells forming sheets (arrows) and surrounding intratumoral lymphocytes. (H&E, ×40 magnification); (B) CK7 positivity. (IHC, CK7, ×20 magnification); (C) Focal CA19-9 positivity. (IHC, CA19-9, ×20 magnification); (D) High proliferative index, with over 95% of tumor cells in the upper one-third area; lymphoid cells were seen in the lower two thirds area. (IHC, Ki-67, ×20 magnification).

Fig. 4.

Core needle biopsy from the pancreas. (A) Sheets of tumor cells with no desmoplastic stroma or glandular structures (blue arrow). Lymphoid aggregates are seen together with pancreatic tissue. (HE, ×20 magnification); (B) Focal CA19-9 positivity. (IHC, CA19-9, ×20 magnification).

Fig. 5.

Duodenal biopsy from the D2 region. (A) Moderately–to-poorly differentiated adenocarcinoma. Obvious glandular structures are seen. (HE, ×20 magnification); (B) Another area of the tumor showing glandular structures with surrounding stroma rich in plasma cells. (HE, ×40 magnification).

In March 2023, he was admitted with malignant duodenal obstruction and upper gastrointestinal bleeding. CT showed an increase in size of the pancreatic head mass to 66 × 52 mm, with 180° contact with the superior mesenteric vein (SMV), worsening gastric outlet obstruction, increased intrahepatic and extrahepatic duct dilation, and enlarged peripancreatic nodes. He was referred to the hepatopancreatobiliary (HPB) multidisciplinary team (MDT) and received neoadjuvant FOLFIRINOX chemotherapy because the tumor was considered borderline resectable. He also underwent duodenal stenting for his gastric outlet obstruction during this admission. In April 2023, he was admitted again for percutaneous transhepatic cholangiography and common bile duct stenting for biliary drainage.

He was first reviewed in the oncology clinic in April 2023. Blood tests at that time showed persistent marked microcytic anemia (Hb 80 g/L, MCV 69.5 fL, HCT 0.28 L/L), hypoalbuminemia (albumin 28), deranged liver functions (ALT 61 U/L, AST 48 U/L, total bilirubin 35µmol/L), elevated alkaline phosphatase (ALP 769 U/L), mildly elevated CA19-9 (CA19-9 44 U/mL), and normal CEA (CEA 2 ng/mL). During chemotherapy, CA19.9 decreased from 44 U/mL to 25 U/mL before the sixth cycle. After completion of six cycles of induction FOLFIRINOX chemotherapy in July 2023, restaging CT showed mild regression of the pancreatic head mass and an inseparable portocaval node measuring 58 × 32 mm, now with less than 90° contact with the SMV. Following further HPB MDT referral, the mass was considered operable.

In September 2023, pancreaticoduodenectomy (Whipple procedure) was performed with curative intent.

The resection specimen included pancreas, duodenum, and gallbladder. Lymph nodes were submitted from the pancreatic and duodenal sites (20 each).

Pathological examination of the pancreaticoduodenectomy specimen (Figure 6) demonstrated two distinct tumor sites. Tumor 1 was located in the pancreas and measured 80 mm in maximum diameter. Tumor 2 was located in the duodenum, measured 20 mm in maximum diameter, and was ulcerated in appearance. The bile duct measured 80 mm in length and was dilated. Two stents were found, one in the ampulla and one in the duodenum. Multiple polyps were identified, the largest measuring 15 mm, and located 20mm from the proximal duodenum.

Fig. 6.

Macroscopic examination of the specimen from Whipple procedure demonstrating 2 tumor sites of medullary carcinoma of pancreas (Red arrow) and duodenal adenocarcinoma (Blue arrow) were seen. The irregular nodular outline of MCP was noted (Green arrow).

Histologically, tumor 1 was in keeping with a medullary carcinoma of the pancreas (MCP), staging pT3N2M0V1G3R1. It was composed of neoplastic cells with pleomorphic and prominent nuclei, relatively abundant amphophilic cytoplasm, and a syncytial growth pattern. The architecture was predominantly nested with focal necrosis and pushing expansile borders (Figure 7). A very prominent lymphocytic reaction was present, with nested groups of lymphocytes staining very positively with CD3, CD8 and CD20 (Figure 8). IHC (Figure 9) showed focal positive staining of CA19.9, positive staining of CEA, CD10, EMA and CK7, negative staining of CK20, and MUC2. The Ki67 proliferative index was high (>90%). MMR IHC showed isolated loss of PMS2 expression with retained nuclear staining of MLH1, MSH2, and MSH6 (Figure 10), supporting MMR deficiency. Out of 20 lymph nodes, 12 were involved. Lymphovascular invasion was present, but perineural invasion and distant metastasis were not identified.

Fig. 7.

Tumor 1, medullary carcinoma of pancreas. Sheets of tumor cells (areas encircled in red) surrounded by lymphoid stroma with intratumoral lymphocytes. (HE, ×20 magnification).

Fig. 8.

Tumor 1, medullary carcinoma of pancreas with prominent lymphocytic reaction. (A) Positive CD3 staining of intratumoral lymphocytes. (IHC, CD3, ×20 magnification); (B) Positive CD8 staining of peritumoral and intratumoral lymphocytes. (IHC, CD8, ×20 magnification); (C) Positive CD20 staining seen densely in peritumoral lymphocytes and sparsely in intratumoral lymphocytes. (IHC, CD20, ×20 magnification).

Fig. 9.

Tumor 1, medullary carcinoma of pancreas. Positive – CK7 (A), CEA (B), CD10 (C, staining for lymphocytes), EMA (D) (IHC, CK7 / CEA / CD10 / EMA, ×20 magnification) IHC focally positive – CA19-9 (E) (IHC, CA19-9, ×20 magnification) IHC negative – CK20 (F), MUC2 (G) (IHC, CK20 / MUC2, ×20 magnification) High Ki67 proliferative index in tumor cells (H) (IHC, Ki-67, ×20 magnification).

Fig. 10.

Tumor 1, medullary carcinoma of pancreas with loss of PMS2 expression. (A) MLH1 (IHC, MLH1, x 20 magnification); (B) MSH2 (IHC, MSH2, x 20 magnification) (C) MSH6 (IHC, MSH6, x 20 magnification); (D) PMS2, negative in the tumor and positive in surrounding lymphocytes (IHC, PMS2, x 20 magnification).

Histologically, tumor 2 was a poorly differentiated non-ampullary duodenal adenocarcinoma, staging pT3N0M0V1G3R0. The carcinoma arose on a background of tubulovillous adenoma, from which the prior duodenal biopsies were likely taken (Figure 1). The neoplastic cells showed glandular formation, an infiltrative invasion pattern, and desmoplastic stroma (Figure 11). The lymphocytic reaction was much less prominent than in tumor 1, and lymphocytes were not seen infiltrating solid areas of neoplastic cells. IHC (Figure 12) showed focal CK7 positivity, dot-like focal MUC2 positivity, and positive staining of CD10, EMA, CEA, with negative staining for CK20 and CA19.9. MMR protein expression was also lost, similar to that seen in tumor 1 (Figure 13). The Ki67 proliferative index was also high. None of the duodenal lymph nodes were involved. Intramural venous, lymphatic, and perineural invasions were present, but distant metastasis was not identified.

Fig. 11.

Tumor 2, duodenal adenocarcinoma. (A) H&E at ×20 magnification – glandular structures can be seen (blue arrows); (B) H&E at ×20 magnification – tumor arising from duodenum, infiltrating the muscle layer, including perimuscular tissue (areas encircled in red). Residual foci of tubulovillous adenoma are seen adjacent to the carcinoma.

Fig. 12.

Tumor 2, duodenal adenocarcinoma – IHC staining showing focal positive – CK7 (A) (IHC, CK7, x 20 magnification), positive – CEA (B), CD10 (C, staining adenocarcinoma cells), EMA (D) (IHC, CEA / CD10 / EMA, ×20 magnification), negative – CA19.9 (E), CK20 (F) (IHC, CA19-9, CK20, ×20 magnification), weak focal positive – MUC2 (G) (IHC, MUC2, ×20 magnification), and high Ki67 proliferative index, approximately 90% (IHC, Ki-67, ×20 magnification).

Fig. 13.

Tumor 2, duodenal adenocarcinoma with loss of PMS2 expression, except in surrounding lymphocytes. (A) MLH1 (IHC, MLH1, x 20 magnification); (B) MSH2 (IHC, MSH2, x 20 magnification); (C) MSH6 (IHC, MSH6, x 20 magnification); (D) PMS2, negative in the tumor and positive in surrounding lymphocytes (IHC, PMS2, x 20 magnification).

All involved lymph nodes, including common hepatic artery lymph nodes, contained neoplastic cells with morphological and architectural features consistent with tumor 1 and were therefore interpreted as metastatic spread from the MCP.

Because the MCP infiltrated into the duodenum and came into close contact with the duodenal adenocarcinoma, the findings were interpreted as synchronous primary tumors with a collision-type interface (Figure 6).

Following the diagnosis of MMR-deficient MCP, the patient was referred to clinical genetics for assessment of possible Lynch syndrome. A pathogenic PMS2 variant was subsequently identified, leading to a diagnosis of Lynch syndrome. Molecular analysis for KRAS, BRAF, and NRAS variants was also performed on the MCP block and identified an activating KRAS variant (G12V). BRAF and NRAS had no detected variants.

Postoperative abdominopelvic CT in October 2023 showed ileus and a persistent intra-abdominal collection despite drain insertion. In January 2024, restaging CT after completion of FOLFIRINOX chemotherapy showed a persistent intra-abdominal collection, new increased soft tissue density posterior to portal vein, and multiple enlarged para-aortic and superior mesenteric lymph nodes, raising suspicion of tumor recurrence.

Following HPB MDT advice, repeat CT was performed in April 2024, showing local recurrence measuring 65 × 49 mm encasing the splenic artery, common hepatic artery, and proximal left gastric artery. The previously enlarged para-aortic nodes had increased to 87 × 94 × 52 mm and engulfed the retroperitoneal nodes. Because the recurrence was inoperable, he was managed by oncology with palliative chemotherapy using gemcitabine and nab-paclitaxel from May 2024.

Following palliative chemotherapy, he had multiple admissions for increasingly uncontrolled abdominal pain and was managed conservatively by oncology and palliative care teams. In September 2024, he was admitted with uncontrolled abdominal pain secondary to advanced pancreatic cancer and ascites. After palliative care review, fast-track discharge with anticipatory medications was arranged. The patient, unfortunately, died later that month.

DISCUSSION

Multiple primary malignancies are defined as two or more histologically distinct tumors arising in the same patient, with synchronous lesions diagnosed simultaneously or within six months. Although pancreatic cancer may coexist with other primary malignancies, synchronous tumors of the pancreaticoduodenal region are rare and often difficult to detect preoperatively. In our case, the synchronous carcinoma was identified only on examination of the resected specimen. A large surgical series reported double primary tumors in 8.4% of resected pancreatic cancers, most commonly involving the stomach, colorectum, lung, or thyroid rather than the duodenum [10].

The coexistence of duodenal adenocarcinoma and pancreatic malignancy is exceptionally rare. Previous reports have described synchronous pancreatic ductal adenocarcinoma with duodenal MALT lymphoma, collision tumors involving pancreatic ductal adenocarcinoma and peri-pancreatic MALT lymphoma, collision carcinoma of the bile duct and pancreas, and three separate synchronous periampullary and pancreatic tumors identified after pancreaticoduodenectomy [11-14]. A further report described synchronous adenocarcinomas of the esophagogastric junction, duodenum, and pancreas [9]. In contrast, the present case involved pancreatic medullary carcinoma and a distinct primary duodenal adenocarcinoma, confirmed by macroscopic, morphological, and immunohistochemical assessment. To our knowledge, this specific combination has not previously been reported in the English literature.

The principal diagnostic challenge was distinguishing synchronous primary tumors from local extension or metastatic spread. Preoperative imaging suggested a pancreatic head tumor invading and obstructing the duodenum, while initial biopsy interpretation was complicated by the poor differentiation and cytological similarity of the sampled lesions. Definitive distinction was achieved only after pancreaticoduodenectomy, which revealed two macroscopically separate tumors. Correlation with preoperative imaging demonstrated that the presumed intra-pancreatic lymph node represented a second primary tumor. The pancreatic lesion exhibited features of medullary carcinoma. In contrast, the duodenal tumor showed glandular differentiation, infiltrative growth, and desmoplastic stroma. These distinct morphological features supported the diagnosis of two independent primary tumors rather than direct tumor extension.

IHC and MMR findings further supported the diagnosis of synchronous tumors. The pancreatic lesion showed focal CA19-9 and CK7 positivity, with loss of PMS2 and retained MLH1, MSH2, and MSH6 expression, consistent with an MMR-deficient medullary carcinoma phenotype and mirroring the MMR profile of the duodenal adenocarcinoma. The duodenal tumor demonstrated focal MUC2 positivity, gland-forming morphology, and a less prominent lymphoid infiltrate. Similarities in IHC profiles were expected given the patient's underlying genetic abnormality. Nodal involvement further indicated the pancreatic tumor as the biologically dominant malignancy. Collectively, the gross, microscopic, immunohistochemical, MMR, and nodal findings supported synchronous independent primaries with a collision-type interface rather than a single tumor with contiguous extension.

The medullary phenotype of the pancreatic tumor was clinically significant because it suggested an MMR-deficient carcinoma rather than simply a rare histological subtype. On preoperative biopsy, poorly differentiated sheet-like tumor cells and a prominent lymphoid background made interpretation of the pancreatic, nodal, and duodenal lesions challenging; however, retrospective review demonstrated features consistent with medullary carcinoma. Examination of the resection specimen raised suspicion for MCP, a tumor known to be associated with MMR deficiency, prompting MMR immunohistochemistry [15]. This revealed an MMR-deficient MCP with isolated PMS2 loss and an MMR-deficient duodenal adenocarcinoma. The isolated PMS2 loss prompted investigation for an underlying hereditary cancer syndrome, and a pathogenic PMS2 variant was subsequently identified, confirming Lynch syndrome. This diagnosis is important not only for understanding tumor pathogenesis but also for ongoing surveillance and family counselling.

Comparison with previously reported pancreatic medullary carcinomas demonstrates both similarities and differences. The pancreatic tumor in this case demonstrated characteristic MCP features, including poorly differentiated syncytial or sheet-like growth, pushing borders, minimal gland formation, and a prominent lymphoid infiltrate [2-4]. These findings closely resemble the MCPs described by Yago et al. and Verocq et al., both of which exhibited sheet-like or syncytial growth patterns with dense lymphocytic infiltration [2,3]. However, unlike these isolated MCPs, the present tumor was in close proximity to a separate duodenal adenocarcinoma, creating a collision-type interface and posing a diagnostic challenge in distinguishing synchronous primaries from local tumor extension.

Immunophenotypically and molecularly, the pancreatic tumor showed features consistent with previously reported MCPs, including expression of ductal/epithelial markers and absence of MUC2 expression [2,3]. Tumor analysis identified an activating KRAS variant together with isolated PMS2 loss. While some MCPs have been reported as KRAS wild-type, KRAS mutations occur in a subset of cases [4], and therefore KRAS activation does not exclude MCP when characteristic morphology and an MMR-deficient phenotype are present. The MCP demonstrated focal CA19-9 and CK7 positivity, CK20 and MUC2 negativity, whereas the duodenal adenocarcinoma showed focal CK7 and MUC2 positivity, absent CA19-9 and CK20 expression, and the same pattern of isolated PMS2 loss with retained MLH1, MSH2, and MSH6. This MMR profile differed from previously reported MCPs, including a microsatellite-stable KRAS-mutant MCP reported by Yago et al. and an MSH2/MSH6-deficient, KRAS- and TP53-mutant MCP reported by Verocq et al. [2,3]. The shared PMS2 deficiency in both tumors was particularly significant, as it prompted clinical genetics assessment and led to identification of a pathogenic PMS2 variant, confirming Lynch syndrome. Although the coexistence of KRAS activation and MMR deficiency has been described in Lynch syndrome-associated colorectal cancers [16,17], it remains poorly reported in pancreatic medullary carcinoma because of the rarity of this entity.

The metastatic behavior of the present case was also different from several previously reported MCPs. Yago et al. described a small pT1aN0M0 MCP without lymphovascular invasion or lymph node metastasis, while Verocq et al. reported a pT1cN0 MCP without lymphovascular or perineural invasion [2,3]. By contrast, the present pancreatic MCP was pT3N2M0 with lymphovascular invasion, R1 resection status, and 12 of 20 pancreatic lymph nodes involved. All involved lymph nodes showed morphology consistent with MCP, while the duodenal adenocarcinoma was pT3N0M0 with no duodenal lymph node involvement. This metastatic pattern supports the pancreatic MCP as the biologically dominant tumor and distinguishes this case from a single pancreatic carcinoma with non-specific duodenal extension.

Comparison with reported synchronous pancreatic and periampullary malignancies further highlights the rarity of this case. Previous reports have described synchronous esophagogastric junction adenocarcinoma, duodenal adenocarcinoma, and conventional pancreatic ductal adenocarcinoma, as well as pancreatic ductal adenocarcinoma with duodenal MALT lymphoma [9,11]. Other reported collision or synchronous tumors have involved pancreatic ductal adenocarcinoma, peri-pancreatic MALT lymphoma, bile duct carcinoma, ampullary carcinoma, neuroendocrine tumors, and other periampullary combinations [12-14]. Similar to these cases, the present case demonstrates the diagnostic challenge of distinguishing adjacent pancreaticoduodenal tumors from local extension or metastatic disease. However, it is distinct in that the pancreatic component was MCP with MMR deficiency and confirmed Lynch syndrome rather than conventional PDAC. Furthermore, the metastatic pattern supported MCP as the biologically dominant tumor, with nodal metastases attributable to MCP and no evidence of duodenal nodal involvement. Despite resection and systemic therapy, the patient developed local recurrence and progressive nodal disease, resulting in death approximately one year after pancreaticoduodenectomy, further supporting MCP as the primary determinant of clinical outcome.

Clinically, this case highlights the importance of careful evaluation of adjacent periampullary lesions. Their proximity can lead to the assumption of a single locally advanced malignancy and may obscure the possibility of synchronous primaries. Although preoperative investigations may suggest local invasion, pathological examination of the resection specimen remains the gold standard for distinguishing true synchronous primary tumors from contiguous spread. This distinction has implications for staging, interpretation of nodal disease, hereditary cancer assessment, management, prognosis, and understanding of tumor biology.

CONCLUSION

This case highlights a rare synchronous combination of medullary carcinoma of the pancreas and primary duodenal adenocarcinoma. Although preoperative imaging and biopsy suggested a single pancreatic malignancy with apparent local spread, examination of the pancreaticoduodenectomy specimen demonstrated two separate tumors with distinct morphological and immunohistochemical profiles. The case emphasizes that synchronous primary malignancy should remain in the differential diagnosis when adjacent periampullary lesions show discordant pathological features, and that definitive classification may require integrated assessment of gross findings, morphology, selected immunohistochemistry, MMR status, and nodal disease pattern on the resection specimen. The underlying diagnosis of Lynch syndrome provides a novel pathogenesis for these genetically related yet distinct tumors. This diagnosis is important not only for understanding tumor pathogenesis but also for ongoing surveillance and family counselling.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

Informed written consent was obtained from the patient and signed by him and a member of the surgical team on 24/01/2024. The patient was deceased at the time of publication. Consent forms are available at reasonable request.

Funding

The author(s) declared that financial support was not received for this work and/or its publication.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.