Primary pancreatic lymphoma (PPL) constitutes a rare malignancy, with an incidence rate of less than 2% among extranodal non-Hodgkin lymphomas in populations with good immunocompetent (1). The World Health Organization (WHO) has defined PPL as predominantly lymphomatous proliferation centered within the confines of the pancreas. However, involvement of contiguous lymph nodes within the pancreatic region and the possibility of distant dissemination remain plausible (2, 3), with potential associations to immunodeficiency as an underlying etiological factor. Owing to its rarity and a lack of distinct clinical manifestations, PPL poses a considerable diagnostic challenge prior to histopathological assessment, frequently leading to misdiagnoses akin to other pancreatic space-occupying lesions, such as pancreatic carcinoma (4).

Functional imaging stands as a pivotal achievement in the realm of medical imaging, enabling the simultaneous provision of metabolic and anatomical insights. Foremost among these modalities, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has emerged as a widely embraced functional imaging technique. It assumes a pivotal role in discerning differential diagnoses, facilitating staging procedures, and monitoring the trajectory of lymphomas (5, 6). However, owing to the infrequent occurrence of PPL, there exists a dearth of literature detailing the distinctive ¹⁸F-FDG PET/CT features pertinent to PPL. Notably, no comprehensive systematic review has hitherto encapsulated the value of ¹⁸F-FDG PET/CT in the context of PPL.

We report two PPL cases that underwent assessment via 18F-FDG PET/CT and discuss the potential utility of ¹⁸F-FDG PET/CT in the realm of PPL through a literature review. It is pertinent to underscore that this retrospective study has been carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association. This study has been approved by the Medical Ethics Committee of Qilu Hospital of Shandong University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

We present two cases of primary pancreatic lymphoma diagnosed with ¹⁸F-FDG PET/CT assistance in this article. For further investigation, we conducted an exhaustive literature review encompassing publications until July 2023, sourced from PubMed, Embase, and Web of Science databases. The predetermined inclusion criteria comprised the following aspects: Publications authored in the English language. Works involving human subjects. Cases of PPL that were accompanied by ¹⁸F-FDG PET/CT examination data.

The systematic search of the literature, a cumulative total of 19 articles (including 23 instances of PPL) (7–25) met the stipulated inclusion criteria. Incorporating our own two cases, the collective review encapsulated a total of 25 instances of PPL (including 31 lesions). The data assimilation process encompassed a spectrum of aspects, including age, gender, presenting symptoms, pathological findings, treatment modalities, prognosis, laboratory examination results, as well as morphological and PET imaging attributes of the respective cases. We conducted a comprehensive analysis of the data in the literatures and a descriptive statistical analysis of the counting data recorded in the literature. Data sets exhibiting a normal distribution were represented statistically in the format of mean ± standard deviation, whereas those deviating from the norm were expressed in the format of M (P25, P75).

The clinical manifestations of primary pancreatic lymphoma lack specificity, the clinical datas of our PPL cases are summarized in Table 1. Among the cases, a predominant male preponderance was evident, exhibiting a male-to-female ratio of 2.125:1. A total of 24 cases were documented with clinical symptoms, with gastrointestinal symptoms, particularly abdominal pain, prevailing as the most commonly reported clinical manifestation (15 out of 24 cases, 62.5%). All cases in our study were subjected to pathological confirmation, and DLBCL emerged as the principal subtype (40%). Our results are consistent with previous studies (26, 27).

Past investigations revealed laboratory evaluations often disclose abnormal liver function and escalated pancreatic enzyme levels, whereas elevated tumor markers assume less prevalence. Remarkably, certain patients showcase an increase in CA199 (4, 26, 28, 29). Aberrant liver function might be attributed to a sizable mass situated at the pancreatic head, causing obstructions within the common bile duct. In Our cases, sixteen cases possessed recorded laboratory test results, as detailed in Table 2, 80% (4 out of 5) of our cases characterized by irregular liver function had lesions located within the pancreatic head. And three cases evidenced elevated tumor markers (including CEA, CA199, and CA125), two cases demonstrated heightened levels of pancreatic enzymes (lipase and amylase).

In the realm of treatment, chemotherapy represents the primary modality for PPL (30). Solely relying on surgical intervention typically yields inferior prognoses compared to cases treated exclusively with chemotherapy. Consequently, surgery is better positioned as a diagnostic or palliative strategy (26, 31, 32). The post-chemotherapy prognosis for PPL is generally promising (26, 33), while advanced age (≥60 years), female gender, unmarried status, higher staging, and absence of chemotherapy emerge as adverse prognostic indicators for PPL (31, 32). Relapses within PPL predominantly manifest at distant sites, with pancreatic relapses being comparatively infrequent. Remarkably, a risk of central nervous system (CNS) relapse is also underscored (26, 32). In our cases, a Eighteen cases underwent chemotherapy, with the rituximab-combined CHOP regimen (R-CHOP) standing out as the prevailing therapeutic approach. Only one patient succumbed to septic shock 5°weeks post-diagnosis, while the remaining cases continue to exhibit vitality.

¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) offers the dual advantage of functional and morphological imaging. On CT scans, discerning a relatively sizeable mass in the pancreatic head devoid of pancreatic duct dilation reinforces the suspicion of PPL. Notable features include a pancreatic duct that generally remains either normal or exhibits mild displacement and constriction and invasive pancreatic masses infiltrating the pancreatic borders, along with enlarged lymph nodes below the renal vein level. Furthermore, untreated PPL seldom demonstrates calcification or necrosis. Bile duct dilation attributed to obstruction predominantly characterizes PPL situated at the pancreatic head (34, 35). The prevailing CT characteristics gleaned from the PPL cases incorporated within this study correspond with localized, substantial, low-density masses, with only three instances featuring mild pancreatic duct dilation. A substantial proportion (19 out of 25 cases, 76%) exhibited solitary lesions, while the remaining six cases demonstrated the presence of dual lesions. Notably, no preferential localization for lesions emerged, with 17 lesions situated in the pancreatic head and neck region, and 14 lesions located within the body and tail of the pancreas. The lesion dimensions were relatively expansive, with the median of maximum diameter recorded in 21 cases is 4.30 (3.15, 7.80) cm. Moreover, two cases of pancreatic head lesions engendered intrahepatic bile duct dilation, aligning seamlessly with prior investigations. The morphological imaging findings for the array of PPL cases are meticulously compiled within Table 3.

The most distinctive PET hallmark of PPL resides in the conspicuous hypermetabolic lesion discernible within the pancreas. Among the accumulated cases, a total of 16 lesions featured the documentation of the maximal standardized uptake value (SUVmax), yielding an average SUVmax of 14.37 ± 7.95, with a range spanning from 4.10 to 28.00. Furthermore, eleven instances evidenced the involvement of contiguous lymph nodes, of which five cases exhibited evidence of distant dissemination, encompassing lymph nodes in various locations including the splenic hilum, left kidney hilum, lower esophageal region, left supraclavicular region, and left internal mammary region. Notably, one case disclosed FDG uptake within the left adrenal gland, attributed to tumor invasion. The PET imaging findings for the array of PPL cases are meticulously compiled within Table 4.

The versatility of ¹⁸F-FDG PET/CT extends to its ability to discern glycometabolic changes within lesions prior to observable anatomical alterations, rendering it an invaluable asset for baseline assessment and the assessment of lymphoma treatment efficacy (5, 6, 36). In our study, two instances (9, 20) unveiled smaller pancreatic lesions that evaded detection via CT and MRI, accompanied by comparatively lower FDG uptake than their larger counterparts. Notably, among our cases, ten subjects underwent post-treatment ¹⁸F-FDG PET/CT evaluations, uncovering two cases of recurrence within the pancreas and peripancreatic lymph nodes. Following a change in chemotherapy regimen, subsequent scans signaled remission. The remaining cases indicated a state of remission on ¹⁸F-FDG PET/CT scans post-treatment.

¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT)’s significance in staging diverse lymphoma categories, particularly DLBCL, is profound. Moreover, for indolent lymphomas, ¹⁸F-FDG PET/CT emerges as a pivotal tool for identifying histological transformations from low-grade indolent lymphomas to more aggressive high-grade forms (36). One of the rationale behind ¹⁸F-FDG PET/CT’s superior staging potential compared to contrast-enhanced CT lies in its heightened sensitivity in detecting bone marrow involvement. Nevertheless, consensus remains elusive regarding whether diffuse FDG uptake in bone marrow should be construed as a definitive marker of bone marrow involvement (37). Prior investigations have suggested that diffuse bone marrow uptake in DLBCL signifies an elevated likelihood of bone marrow invasion. Conversely, diffuse bone marrow uptake in Hodgkin lymphoma (HL) is more likely indicative of bone marrow inflammatory changes (38). Nonetheless, as these studies feature relatively modest sample sizes, further research is warranted to elucidate this matter. An illustrative case within our study exhibited mild diffuse hypermetabolism in the thoracic vertebrae, despite normal findings from a bone marrow biopsy.

According to the WHO’s classification, PPL can indeed entail contiguous region lymph node involvement and distant spread, while the core of the lesion resides within the pancreas. Our study underscores that PPL commonly involves contiguous region lymph nodes, but distant spread is less prevalent. The distinction between PPL and secondary pancreatic lymphoma hinges on the status of lesions beyond the pancreas, with ¹⁸F-FDG PET/CT emerging as pivotal in this regard. ¹⁸F-FDG PET/CT effectively detects the primary lesion and distant spread of PPL, proficiently demarcating it from secondary pancreatic lymphoma. Compared with the ¹⁸F-FDG PET/CT findings of PPL, there are more lesions in other parts of secondary pancreatic lymphoma and higher uptake of FDG. Intriguingly, the pancreatic lesions in secondary pancreatic lymphoma are similar to those of PPL, characterized predominantly by sizeable hypermetabolic masses (39).

The precise differentiation between PPL and pancreatic carcinoma assumes paramount importance. Given the relatively favorable prognosis associated with PPL following chemotherapy (26, 33), accurate distinction from pancreatic carcinoma holds potential to avert unnecessary surgical interventions. At times, PPL proves elusive to traditional diagnostic techniques like computed tomography (CT) or magnetic resonance imaging (MRI). Of the cases assimilated within this study, 14 instances garnered a preliminary diagnostic conclusion via traditional imaging (CT or MRI) prior to pathological confirmation. Regrettably, a mere three cases received a lymphoma diagnosis, yielding a diagnostic accuracy of 21.4%, and predominantly manifesting as misdiagnoses spanning pancreatic cancer or malignant pancreatic masses. Pancreatic carcinoma exhibits a higher prevalence among males, with its zenith incidence occurring beyond the age of 70 years (40). In accordance with extant literature reports (27), PPL also displays a male predilection, yet its onset is characteristically earlier than that of pancreatic carcinoma, with a median age of 67. Additionally, a study (41) uncovered elevated CA199 levels in instances of pancreatic carcinoma (406.81 ± 352.09), while liver function (ALT, AST, ALP, etc.) and pancreatic enzymes were generally in a normal range. This stands in contrast to the laboratory findings in cases of PPL. Through an exhaustive scrutiny of antecedent literature (42, 43) including 230 instances of pathologically confirmed pancreatic carcinoma, it is established that pancreatic carcinoma predominantly manifests as hypoattenuated lesions during CT enhancement scans, occasionally displaying isodensity. The typical maximum diameter of isodensity pancreatic carcinoma lesions seldom exceeds 2 cm, while their hypoattenuated counterparts demonstrate an average maximum diameter of approximately 3 cm. Moreover, characteristic imaging attributes of pancreatic carcinoma encompass pancreatic ductal truncation, dilation of pancreatic ducts, and cholangiectasis (42, 44). Contrasting with the PPL cases expounded within this exposition, it becomes evident that PPL lesions generally exhibit relatively greater dimensions. Notably, the dilation of the bile duct and pancreatic duct is a rarity in PPL cases; however, akin to pancreatic carcinoma, both maladies predominantly showcase hypoattenuated lesions upon contrast-enhanced CT imaging.

As per antecedent investigations, both pancreatic carcinoma and PPL predominantly exhibit hypermetabolic lesions on ¹⁸F-FDG PET/CT scans. In the study by Moon (45), the SUVmax of 21 pancreatic carcinoma lesions registered at 6.8 ± 3.0, with a range spanning 2−12. An examination by Zhang et al. (41) on 40 patients with pancreatic carcinoma unveiled an average SUVmax of 7.30 ± 3.21 for 40 pancreatic carcinoma lesions. In a study conducted by Lee et al. (46) encompassing 87 cases of pancreatic carcinoma, the median SUVmax for pancreatic carcinoma lesions was 4.4, oscillating between 2.1 and 17.3. Drawing from the aforementioned investigations, when juxtaposed against the SUVmax value of PPL documented within our discourse (14.37 ± 7.95), it becomes apparent that the SUVmax of pancreatic carcinoma cases tends to be lower in comparison to those of PPL cases. Furthermore, the metastatic dissemination patterns for these two conditions deviate. Predominantly, pancreatic adenocarcinoma metastasizes to the liver, subsequently to the peritoneum, abdominal lymph nodes, and harbors a notable likelihood for lung metastasis. As a rule, pancreatic adenocarcinoma engages in multi-organ metastasis (47). In our analysis, PPL demonstrates a scarcity of distant dissemination, with sporadic instances of distant lymph node metastasis, thereby markedly diverging from the distant metastatic mode typified by pancreatic adenocarcinoma.

In summation, ¹⁸F-FDG PET/CT, functioning as a non-invasive functional imaging modality, assumes a pivotal role in diagnosing, initially assessing, and gauging the efficacy of treatment for PPL. Concurrently, the amalgamation of ¹⁸F-FDG PET/CT image attributes with clinical profiles and laboratory analyses possesses the potential to furnish more insightful information, facilitating the discrimination between PPL and pancreatic carcinoma.

Primary pancreatic lymphoma (PPL) constitutes a rare malignancy, with an incidence rate of less than 2% among extranodal non-Hodgkin lymphomas in populations with good immunocompetent. Owing to its rarity and a lack of distinct clinical manifestations, PPL poses a considerable diagnostic challenge prior to histopathological assessment, frequently leading to misdiagnoses akin to other pancreatic space-occupying lesions, such as pancreatic carcinoma.

¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has emerged as a widely embraced functional imaging technique. It assumes a pivotal role in discerning differential diagnoses, facilitating staging procedures, and monitoring the trajectory of lymphomas. However, owing to the infrequent occurrence of PPL, there exists a dearth of literature detailing the distinctive ¹⁸F-FDG PET/CT features pertinent to PPL.

The purpose of this article is to explore the potential value of ¹⁸F-FDG PET/CT in the diagnosis and treatment framework of PPL. By reporting two cases and literature review, a total of 25 cases (including 31 lesions) assessed by ¹⁸F-FDG PET/CT before treatment were included. The results of this study reveal that ¹⁸F-FDG PET/CT has important value in the diagnosis of PPL and the differential diagnosis between PPL and pancreatic carcinoma, and can effectively evaluate the therapeutic effect of PPL.

The original contributions presented in this study are included in this article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving humans were approved by the Medical Ethics Committee of Qilu Hospital of Shandong University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

JW: Conceptualization, Writing – original draft, Writing – review & editing. YZ: Conceptualization, Data curation, Writing – original draft, Writing – review & editing. HL: Formal Analysis, Investigation, Methodology, Writing – review & editing. JZ: Formal Analysis, Investigation, Methodology, Writing – review & editing. XL: Project administration, Supervision, Writing – original draft, Writing – review & editing.