A case of primary pancreatic lymphoma with splenic invasion improved significantly after treatment with R-CHOP chemotherapy

Introduction

Primary pancreatic lymphoma (PPL) is an extremely rare type of extranodal malignant lymphoma originating from the pancreatic parenchyma. It accounts for approximately 0.6% of all malignant extranodal lymphomas and less than 0.5% of all pancreatic neoplasms (1,2). Diffuse large B-cell lymphoma (DLBCL) is the most prevalent histological subtype (3,4). PPL typically manifests as abdominal pain and may be accompanied by clinical symptoms such as jaundice, nausea, vomiting, and ascites (5,6). It is generally aggressive, with potential involvement of non-lymphatic structures, including adjacent blood vessels, the spleen, liver, and bone marrow (2). Due to the similarity in clinical symptoms and imaging findings between PPL and pancreatic ductal adenocarcinoma (6) or pancreatic adenocarcinoma (7), it is often misdiagnosed, leading to changes in treatment. Therefore, accurate identification and treatment of this condition are crucial. Previous studies have focused on the cytopathological diagnosis of PPL (6,8), surgical treatment, and prognosis (5). However, few comprehensive analyses of PPL with the involvement of other organs, generalized lymphadenopathy, changes in patients’ chemotherapy regimens, or assessment of treatment efficacy have been conducted. In this report, we describe a case of PPL involving the spleen, leading to a splenic mass, with significant improvement observed after 4 months of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. The aim of this report is to enhance clinicians’ understanding of the disease, provide a reference for accurate diagnosis and precise treatment, and offer valuable insights into the clinical decision-making regarding surgical resection in patients with PPL.

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the relevant institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A 70-year-old female, who had undergone cholecystectomy several years prior to admission due to gallstones, was admitted to the Gansu Provincial Hospital with more than 20 days of intermittent distending pain in the upper abdomen without any obvious trigger, which had worsened over the previous 5 days. The initial biochemical test results showed elevated levels of carbohydrate antigen 125 (CA-125, 91.2 U/mL), β2-microglobulin (β2-MG, 4.1 mg/L), interleukin-6 (25.1 pg/mL), neuron-specific enolase (27.54 ng/mL), and procalcitonin (0.088 ng/mL). Liver function tests revealed a slight decrease in alanine aminotransferase (6 U/L) and albumin levels (31.5 g/L), while renal function remained normal. Complete blood count testing indicated a decrease in lymphocyte count (0.58×10⁹/L), hemoglobin level (108.0 g/L), and hematocrit level (33.5%), with an increase in mean platelet volume (14 fL) and plateletcrit (0.290%). Lipid metabolism results showed an elevated triglyceride level (2.00 mmol/L) and reduced high-density lipoprotein level (0.71 mmol/L), along with an increased erythrocyte sedimentation rate (79 mm/h). Lactate dehydrogenase (1,134 U/L), C-reactive protein (78.0 mg/L), and homocysteine (45 µmol/L) levels were significantly elevated.

Additionally, the patient underwent contrast-enhanced abdominal computed tomography (CT) and magnetic resonance imaging (MRI) (Figure 1A,1B). Abdominal MRI revealed a diffuse mass in the body and tail of the pancreas, encasing the celiac trunk and its branches, the superior mesenteric artery, bilateral renal arteries, and the splenic artery. The tumor measured approximately 10.89 cm × 7.42 cm × 6.62 cm, with diffusion-weighted imaging (DWI) showing significant restriction of the mass, with moderate enhancement observed on contrast-enhanced scans. The pancreatic duct was clearly visible without dilation or destruction. Additionally, multiple masses of varying sizes were observed in the spleen, with the largest measuring approximately 8.42 cm in diameter. The boundaries between the splenic and pancreatic masses were unclear. Multiple enlarged lymph nodes were visible in the fat spaces around the lesion, as well as near the retroperitoneum and abdominal aorta. The abdominal CT revealed multiple low-density masses in the body and tail of the pancreas and in the spleen, with mild enhancement on contrast scans, and the biological behavior of the other masses was similar to that on MRI findings. Contrast-enhanced soft tissue CT of the neck and superficial lymph node ultrasound results showed slightly enlarged and structurally abnormal lymph nodes in right cervical lymph node region III, the left supraclavicular fossa, and the axillary lymph nodes.

Figure 1 Imaging findings and pathological diagnosis of the patient before and after treatment. (A) Abdominal contrast-enhanced CT before treatment. (B) Abdominal MRI before treatment. (C) Histopathology of fine-needle aspiration (hematoxylin-eosin staining, 200×). (D) The abdominal contrast-enhanced CT after treatment shows significant reduction of the pancreatic mass and a shrunken splenic mass. Blue arrow: pancreas mass; orange arrow: spleen mass. CT, computed tomography; MRI, magnetic resonance imaging.

Due to the patient’s severe abdominal and lower back pain, analgesic treatment was administered, along with symptomatic treatments including antispasmodics, bowel regulation, and fluid replacement. The next morning, an endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreas was performed under local anesthesia. Based on the biopsy pathology and immunohistochemical (IHC) results, the diagnosis was pancreatic DLBCL (Figure 1C). The IHC results were as follows: CD3 (−), CD20 (diffuse+), Bcl-2 (+), Bcl-6 (+), CD10 (−), MUM-1 (−), cyclin-D1 (−), CD5 (−), CD138 (−), CD45 (+), CgA (−), S-100 (−), Syn (−), vimentin (+), Ki-67 (80%), c-Myc (+30%), and SOX-11 (−). Cytology brushing indicated highly nuclear heterogeneous cells in the pancreatic smear.

After contraindications to chemotherapy were excluded and the patient’s financial situation comprehensively assessed, the patient received the R-CHOP regimen. The Cotswold-modified Ann Arbor classification was used to stage the case of DLBCL, and based on the examination results, the patient was classified as stage IVB (9). An ultrasound-guided fine-needle aspiration tissue biopsy was performed on the splenic mass, and pathological consultation at the Gansu Provincial Cancer Hospital confirmed DLBCL of the spleen. The IHC results were as follows: CD3 (−), CD20 (+), Bcl-2 (+), Bcl-6 (+), CD10 (−), MUM-1 (−), cyclin D1 (−), CD5 (−), CD138 (−), CD45 (+), CD10 (−), CgA (−), S-100 (−), Syn (−), vimentin (+), Ki-67 (80%), c-Myc (+30%), SOX-11 (−), and Pax-5 (+). Due to the patient’s intolerable pain, bucinnazine, morphine, oxycodone, and acetaminophen tablet were administered based on the patient’s condition.

After a few days of chemotherapy, the patient’s pain was significantly relieved, but there was no noticeable change in the enlargement of the pancreas, spleen, and lymph nodes. The patient requested to be discharged. After discharge, the patient was followed up once a week. If there was an indication of bone pain, fever, or elevated white blood cell count, the patient was advised to return to the hospital promptly for treatment. In addition, the patient was hospitalized a total of five times between discharge and marked recovery (with an average hospital stay of 2.5 days per admission). During the hospital stays, the R-CHOP regimen was used for treatment, the course of therapy proceeded smoothly, and the results were remarkable. A re-examination enhanced CT scan showed that the size of the pancreas and enlarged lymph nodes had shrunk significantly, with the spleen mass decreasing to 2.41 cm (Figure 1D) and the patient’s clinical symptoms being markedly improved.

Discussion

PPL is a rare malignant tumor of the pancreas, with DLBCL being the most common histological type, most frequently occurring in the pancreatic head of elderly men (5). PPL is often difficult to distinguish from pancreatic cancer, which can damage the bile duct or pancreatic duct and shows low enhancement on contrast-enhanced scans, possibly related to the lower blood supply of pancreatic cancer. Behrns et al. (10) reported that PPL with jaundice is extremely rare. In the case we encountered, the patient also did not exhibit signs of jaundice. Additionally, a literature review by Luo et al. (11) indicated that approximately 26% of PPL cases present with an upper abdominal mass during physical examination, which is less common in pancreatic cancer. Since the clinical features of PPL and pancreatic cancer overlap and are not specific, distinguishing between the two is crucial for treatment and prognosis.

Laboratory markers for PPL also lack specificity. CA19-9 is significantly elevated in pancreatic cancer but remains generally normal in PPL, with only slight increases in cases of biliary obstruction (12-14). β2-MG is an important biochemical marker for the diagnosis and differential diagnosis of PPL, with its elevated level often indicating poor prognosis (15,16). Furthermore, studies have shown that CA-125 has the ability to evaluate the treatment efficacy and prognosis of PPL (17). In this case, the patient presented with elevated CA-125 and β2-MG levels, while LDL levels were normal. CT and MRI imaging can help inform the diagnosis of PPL, but cannot fully differentiate PPL from pancreatic cancer (7). CT can assess the aggressiveness of pancreatic masses, blood supply, and systemic metastasis. MRI, with its high resolution and multiparametric capabilities, can evaluate the relationship between the tumor and adjacent organs, as well as tumor metabolism. On imaging, PPL appears as a homogeneous soft-tissue mass isodensity or isosignal within the pancreatic parenchyma. PPL occurring in the head of the pancreas may involve the common bile duct and duodenum (18). In addition, the presence of calcification is often used to rule out PPL (16). Multiple enlarged lymph nodes are commonly visible in the retroperitoneum and para-aortic regions, some of which may coalesce into masses. PPL may envelop nearby vessels, showing the “arterial encasement sign” or “vascular floating sign”. The pancreatic duct is typically not dilated or disrupted (16,19). DWI and apparent diffusion coefficient images show pronounced restriction of the tumor, which may be related to the high cell density and limited movement of water molecules in lymphoma (20). In our case, the mass was primarily located in the body and tail of the pancreas, accompanied by spleen involvement leading to the formation of multiple splenic masses, and the other imaging findings were consistent with the above description. Laboratory tests and imaging examinations provide important clues for the diagnosis of PPL, but their value for the differential diagnosis of pancreatic tumors remains limited. Therefore, histological analysis through pathological biopsy has become a key means to differentiating pancreatic tumors. Studies have shown that endoscopic ultrasound-guided fine-needle aspiration biopsy can provide information for the diagnosis of PPL. Combining flow cytometry and IHC staining results can improve the diagnostic accuracy of PPL (6,21).

Surgical resection is a common curative treatment for pancreatic masses, but the treatment of PPL remains controversial. The R-CHOP chemotherapy regimen has become a standard treatment for DLBCL due to its high efficacy and complete remission rate (22,23). Lamrani et al. (24) conducted a retrospective analysis of four patients with PPL and found that R-CHOP chemotherapy provides a good therapeutic effect for patients with PPL. In our case, the same chemotherapy regimen also demonstrated strong curative effect for pancreatic and splenic DLBCL.

Conclusions

PPL lacks specific clinical features and biochemical markers. Imaging examinations, fine-needle aspiration histology, and IHC tests are key methods and important preliminary steps for the diagnosis, and subsequent treatment, of PPL. In addition, since chemotherapy may cause certain side effects for patients, in clinical practice, liposomal doxorubicin can be administered for prevention after a comprehensive assessment of the patient’s financial situation. Here, we report a case of primary pancreatic DLBCL involving the spleen and causing multiple splenic DLBCL lesions, with significant improvement following R-CHOP treatment. Our experience may help deepen clinicians’ understanding of the disease and provide a new opportunity for the noninvasive treatment for patients.

Acknowledgments

We sincerely thank Dr. Zhaokun Wei from the Department of Radiology at Gansu Provincial Hospital for his assistance and support in image acquisition and Dr. Ling Wang from the Department of Pathology at Gansu Provincial Hospital for her explanations and encouragement in pathological analysis.

Footnote

Funding: This work was supported by the Scientific Research Fund of Gansu Provincial Hospital (Nos. 23GSSYF-4 and 23GSSYA-2).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1804/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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