A case report of a collision tumor composed of pancreatic ductal adenocarcinoma and peri-pancreatic mucosa-associated lymphoid tissue lymphoma

Collision tumors are composed of two distinct tumor components. Most tumors are described in neurosurgery, dermatology, and urology. In visceral surgery, most collision tumors are noted in the stomach, such as the gastrointestinal stromal tumor (GIST) and adenocarcinoma. Collision tumors composed of pancreatic ductal adenocarcinoma and malignant lymphoma occurring in the pancreas have not been previously described in the scientific literature. In this case report, we describe a unique patient with a collision tumor composed of pancreatic ductal adenocarcinoma and peri-pancreatic mucosa-associated lymphoid tissue (MALT) lymphoma occurring in the pancreas.

An 82-year-old woman visited the emergency room of Himeji St. Mary’s Hospital complaining of dizziness. She had a gastric ulcer and had undergone distal gastrectomy 40 years previously. There were no abnormal findings on head computed tomography (CT) scanning and otorhinological examination, excluding blood examination showing an increase in hepatobiliary enzymes level, CA 19–9, and DUPAN-II (Table 1). After admission, the sIL-2 receptor was revealed to be high at 1710 U/mL.

Abdominal contrast-enhanced CT showed a large homogeneous low-density lesion, 13 × 9 × 5 cm in size, widely spreading from the peri-pancreatic head to the hepatic hilus, the hepatoduodenal ligament, the duodenum, and root of the mesenteric vessels. Intrahepatic duct and common hepatic duct were dilated, but the lower bile duct was obstructed by the lesion’s central part. The main pancreatic duct of the pancreatic head was also obstructed by the lesion’s central part. The portal vein and superior mesenteric vein went through the lesion’s peripheral part but were neither involved nor narrowed. The duodenal wall was thickened, but the duodenum lumen was not narrowed. The peripheral part had a slightly low density in the early phase and homogeneous isodensity in the late phase. However, the central part revealed a lower density in the early phase and a heterogeneous high density in the late phase (Figs. 1 and 2).

Contrast-enhanced MRI showed that the peripheral part had a low signal in the early phase and a slightly low signal in the late phase. In contrast, the central part revealed a low signal in the early phase and a heterogeneous high signal in the late phase (Fig. 3).

Diffusion-weighted imaging (DWI, b = 800 s/mm²) showed a very high signal in the peripheral part and a relatively lower signal in the central part (Fig. 4a). The peripheral part revealed high-cell density and was considered as malignant lymphoma due to the markedly low diffusion. However, the central part seemed to be a different kind of tumor from the peripheral part. Positron emission tomography (PET) showed a strong accumulation of fluorodeoxyglucose (FDG) on the central part, suggesting a high-grade malignant tumor (Fig. 4b).

This is the first case report of a collision tumor composed of pancreatic ductal adenocarcinoma and MALT lymphoma occurring in the pancreas. A PubMed search of “collision tumor” showed 1742 studies to date. Most tumors are described in neurosurgery, dermatology, and urology. In visceral surgery, most collision tumors are described in the stomach such as GIST and adenocarcinoma. In addition, a PubMed search for “collision tumor” and “adenocarcinoma” and “malignant lymphoma” yielded 64 hits, of which 43 cases were eligible. The most common site was the stomach (n = 22), followed by the colon (n = 11), lymph nodes (n = 4), mammary gland (n = 3), liver (n = 2), and duodenal papilla (n = 1). There is no eligible case colliding in the pancreas. Dasanu et al. reported a collision tumor of pancreatic adenocarcinoma and mantle cell lymphoma, but the collided tumor was found in the liver and composed of metastatic liver cancer from pancreatic adenocarcinoma and mantle cell lymphoma diagnosed Ann Arbour stageIVB [1]. Therefore, this case was not eligible as a collision tumor occurring in the pancreas.

Furthermore, a PubMed search on “pancreatic ductal adenocarcinoma” and “collision tumor” revealed that there are only nine publications about collision tumor consisting of pancreatic ductal adenocarcinoma and other tumors colliding in the pancreas (Table 2).

Six of nine are neuroendocrine tumors of the pancreas [2‐7], and others are comprised of a retroperitoneal liposarcoma [8], a bile duct carcinoma [9], and a gastric stromal tumor [10]. The frequency of collision with neuroendocrine tumors might be explained by the fact that neuroendocrine tumors are frequent secondary solid tumors arising from the pancreas. The chief complaints in these nine cases were abdominal pain (n = 4), weight loss (n = 4), and others (n = 1). The most common preoperative diagnosis was suspected pancreatic carcinoma (n = 5), and others were pancreatic neuro-endocrine tumor (P-NET), GIST, and liposarcoma (n = 1 each). Therefore, only one case had a preoperative diagnosis of collision tumor. The disposition of the site was the head (n = 4), body (n = 1), and tail (n = 4). CA19-9 was elevated in six cases. All patients underwent pancreatectomy: pancreaticoduodenectomy (n = 3), distal pancreatectomy (n = 5), and total pancreatectomy (n = 1). A collision tumor was diagnosed after surgery and was found by chance in eight other cases than the one diagnosed preoperatively. On the other hand, a collision tumor with malignant lymphoma in the pancreas has not been reported previously; therefore, the present case is the first case of a collision tumor composed of pancreatic ductal adenocarcinoma and malignant lymphoma occurring in the pancreas.

With regard to image diagnosis, each tumor exhibited typical findings. Contrast-enhanced CT revealed that the peripheral part had a slightly low density in the early phase and homogeneous iso-density in the late phase. However, the central part revealed a lower density in the early phase and a heterogeneous high density in the late phase. Thus, each tumor presented the typical features of malignant lymphoma and pancreatic ductal adenocarcinoma, respectively. Contrast-enhanced MRI showed that the peripheral part had a low signal in the early phase and a slightly low signal in the late phase. In contrast, the central part revealed a low signal in the early phase and a heterogeneous high signal in the late phase. Moreover, contrast-enhanced MRI demonstrated typical patterns for each tumor. DWI (b = 800 s/mm²) showed a very high signal in the peripheral part and a relatively lower signal in the central part. The peripheral part revealed high-cell density and was considered as malignant lymphoma due to the markedly low diffusion. However, the central part seemed to be a different kind of tumor from the peripheral part, indicating a pancreatic ductal adenocarcinoma. Furthermore, the portal vein and SMA in the peripheral lesion were uninvolved and penetrating the tumor, indicating typical findings of malignant lymphoma. Leite et al. also reported that the envelopment of adjacent vessels without evidence of obstruction is suggestive of lymphoma [11]. In contrast, the main pancreatic duct and common bile duct were involved and obstructed, indicating typical findings of pancreatic ductal adenocarcinoma. Moreover, high uptake on the central part by FDG-PET suggested pancreatic ductal adenocarcinoma.

MALT lymphoma arises from the mucosa-associated lymphoid tissue of the gastrointestinal tract, salivary glands, lungs, and thyroid glands. According to Tanaka et al., the gastrointestinal tract tumors mostly arise from the stomach (76.9%) and colon/rectum (16.5%), but rarely arise in the duodenum (3.6%), small intestine (2.4%), and esophagus (0.6%) [12]. This disease is a lymphoid tumor with low-grade malignancy, representing characteristic histopathological features, such as centrocyte-like cells with positive B cell surface markers, lymphoepithelial lesions, lymph-follicular proliferation, and infiltration of plasma cells [13]. Differential diagnosis for marginal zone B cell lymphoma mainly depends on immunohistochemistry, including at least CD20, CD10, CD5, CD23, cyclin D1, immunoglobulin D, and SOX11 [14]. In the present case, immunohistochemical staining revealed that infiltrating lymphoid cells were diffusely positive for CD20 and BCL2, while CD3-positive cells were negative. These CD20-positive cells were negative for CD5, cyclin D1, SOX11, CD10, and BCL6, with a low level of Ki67-labeling index. Finally, the lesion was diagnosed as a MALT lymphoma.

Primary pancreatic lymphoma (PPL) is a rare disease [15], encountered in only 0.5% of patients undergoing endoscopic ultrasound-guided fine needle aspiration of solid pancreatic masses [16]. Behrns et al. defined the diagnostic criteria of PPL as follows: mass predominantly located within the pancreas, with grossly involved lymph nodes confined to the peripancreatic region, no palpable superficial lymphadenopathy, no hepatic or splenic involvement, no mediastinal nodal enlargement on chest radiography, and a normal white blood cell count [17]. In our case, the tumor had spread widely, mainly to the pancreatic head, hepatic portal region on the head side, from the transverse part of the duodenum to the transverse mesocolon on the tail side, further right of the duodenal descending limb on the right side, and to the afferent loop for gastrojejunostomy on the left side. Therefore, it does not exactly match the first definition of Behrns et al. However, the fact that the central lesion was the pancreatic head cannot be ruled out based on images. Our case met other definitions.

Pancreatic MALT lymphomas are extremely rare in PPL. In a PubMed search for “pancreas” and “MALT lymphoma,” pancreatic MALT lymphoma was reported in only two cases to date [18, 19] (Table 3).

Both were asymptomatic, relatively large pancreatic head masses found incidentally during screening for diabetes mellitus and follow-up of gallbladder polyps. Hypoechoic areas were detected in both cases, of which the lesions were not enhanced on contrast CT in Case 1 but Case 2. Case 2 showed high-signal intensity on diffusion-weighted MRI. Ga scintigraphy and FDG-PET showed increased uptake in Cases 1 and 2, respectively. The diagnosis in both cases was malignant lymphoma that was diagnosed as MALT lymphoma using endoscopic ultrasound-guided fine-needle aspiration biopsy and laparotomy biopsy in Cases 1 and 2, respectively. Remissions were achieved by radiotherapy in Case 1 and R-CHOP therapy in Case 2.

Determining the origin of the MALT lymphoma in the present case has been controversial since it was not known whether it originated from the pancreatic head or duodenum. CT and MRI showed a large iso-dense tumorous lesion mainly located in the pancreatic head and expanding to peripancreatic tissues, including the duodenal wall and hepatoduodenal ligament. Therefore, a pancreatic head origin may be possible. On the other hand, histopathological examination of the resected specimen revealed that lymphoepithelial lesions were focally seen in the duodenal mucosa, but not in the pancreas. Moreover, MALT lymphomas usually arise from the mucosa-associated lymphoid tissue of the gastrointestinal tract, and the lymphoma originating from the duodenum can easily invade the fatty tissue of the pancreatic head; thus, a duodenal origin may also be possible. Considering these, the origin of MALT lymphoma in the present case remains unknown.

It is difficult to make a preoperative diagnosis of a collision tumor. In only one of the nine reported cases, a collision tumor of pancreatic ductal adenocarcinoma and NET was diagnosed by preoperative endoscopic ultrasound-guided needle biopsy. In this case, a collision tumor could be suspected because preoperative contrast CT showed distinct characteristics of both tumors, and a definitive pathological diagnosis could be made by preoperative endoscopic ultrasound-guided needle biopsy. Also, in our case, CT, MRI, US, and PET-CT could clearly distinguish heterogeneous tumor lesions, and a preoperative diagnosis of a collision tumor could be made based on percutaneous ultrasound-guided needle biopsy. However, in the other eight cases, collision tumor had not been suspected at all because the two components were not clearly distinguished in preoperative images, or the one element was too small. When obtaining inconsistent findings on CT or MRI for the diagnosis of tumor lesions, we must also consider the presence of a collision tumor. It is also critical to make a definitive diagnosis by needle biopsy when determining the treatment strategy.

This is the first report of a surgically resected collision tumor of pancreatic ductal adenocarcinoma and MALT lymphoma originating from the peri-pancreatic head. We were able to preoperatively diagnose it using percutaneous echo-guided needle biopsy and multiple imaging modalities, which provided beneficial information in considering the treatment strategy for the tumor. A needle biopsy is useful when inconsistent findings are observed on diagnostic CT and MRI of tumor lesions since there is the possibility of a collision tumor.