Acute pancreatitis secondary to small-cell lung cancer metastasis: A case report and literature review

Abstract

BACKGROUND

Acute pancreatitis (AP) is commonly encountered in gastroenterology, with biliary and alcohol-related causes being predominant. Among less frequent etiologies, metabolic and drug-induced origin are the most prevalent. As an exception, non-pancreatobiliary malignancies may trigger AP, representing less than 1% of cases. We present a case of AP secondary to an uncommon oncologic etiology.

CASE SUMMARY

We describe the case of a 50-year-old male recently diagnosed with small-cell lung cancer (SCLC). The patient was admitted to the emergency department with acute abdominal pain and subsequently diagnosed with AP. He was hospitalized under the care of the gastroenterology service. During the etiological workup, metastatic pancreatic lesions were identified on imaging, which had not been observed on the initial cancer staging. Following resolution of the initial episode, oral intake was introduced, but the patient experienced recurrent abdominal pain and laboratory abnormalities consistent with new episodes of AP. This pattern repeated over the following days. After several episodes, and with suspicion of a metastatic origin, the case was discussed in multidisciplinary meeting. In agreement with the patient and given the need to initiate treatment for the primary tumor as well, chemotherapy was started. This treatment successfully alleviated symptoms, allowing dietary progression without complications and discharge from the hospital.

CONCLUSION

Oncologic treatment can be considered as part of the therapeutic approach in AP secondary to SCLC metastasis, especially chemotherapy.

Key Words: Acute pancreatitis; Small-cell lung cancer; Metastasis; Chemotherapy; Case report

Core Tip: Acute pancreatitis secondary to pancreatic metastases from small-cell lung cancer is an extremely rare entity, with few cases reported in the literature. This case highlights the importance of considering metastatic involvement in unexplained acute pancreatitis and reinforces the role of imaging for early diagnosis. Our findings suggest that targeted oncologic therapy, particularly chemotherapy, may be considered part of the first-line treatment in these situations. Further studies are needed to establish standardized management protocols and improve outcomes in this challenging clinical scenario.

INTRODUCTION

Acute pancreatitis (AP) is one of the most common conditions leading to hospitalization in gastroenterology services. The global incidence of AP ranges from 5 to 73.4 cases per 100000 inhabitants, with a prevalence of 76.2 cases per 100000 inhabitants[1,2]. This corresponds to an annual increase in AP incidence of approximately 3.07%[3]. Although most cases are not fatal, AP-related mortality is estimated at 1.4 to 1.6 cases per 100000 inhabitants, a non-negligible figure considering the high number of cases and the lack of data from many countries[2,4].

AP accounts for approximately 30% of hospital admissions in gastroenterology units, with nearly 300000 hospitalizations annually in the United States alone[5]. The leading cause, by far, is biliary etiology, responsible for 42% to 56% of AP episodes. Other major causes include alcohol consumption, hypertriglyceridemia (over 1000 mg/dL), hypercalcemia, and idiopathic cases. Less common etiologies include post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and atypical causes such as drug-induced AP[6-9]. Among these atypical cases, neoplasms represent a distinct subgroup.

Neoplastic AP is estimated to account for approximately 1% of all AP cases. The most frequently associated tumors include primary pancreatic, biliary, and ampullary neoplasms[9,10]. Anecdotally, case reports in the literature have described episodes of AP secondary to other types of tumors. These reports have included cases of various origins, such as pulmonary, adrenal, neuroendocrine, and renal tumors, as well as osteosarcomas[11-14].

Due to its exceptionally rare origin, we present a case of AP secondary to metastasis from small cell lung cancer (SCLC).

CASE PRESENTATION

Chief complaints

A 49-year-old Caucasian male presented with continuous epigastric pain radiating in a belt-like pattern, with no clear triggering factor.

History of present illness

The patient reported a 5-day history of symptoms and had attempted to manage the pain at home with morphine and fentanyl, without improvement, after consulting his primary physician. Three days prior to the hospital admission described in this case, he visited the emergency department with the same symptoms, where his analgesic regimen was adjusted due to normal laboratory test results. He denied alcohol consumption or dietary indiscretions.

History of past illness

The patient was diagnosed 2 weeks prior with stage IV SCLC with infiltration of major vessels, bilateral mediastinal lymphadenopathy, bone and adrenal metastases, and pleural effusion. Additionally, nonspecific lymphadenopathy was noted at the hepatic hilum. The diagnosis was established following persistent dorsal pain that failed to improve despite various conservative treatments. Magnetic resonance imaging (MRI) revealed a left mediastinal mass involving the main pulmonary artery and 40% of the descending aorta, as well as the previously mentioned pleural effusion and an expansive lytic lesion at the T7 Level.

His medical history was notable for a 30-year history of smoking, with a consumption of 30 cigarettes per day, as well as dyslipidemia, nephrolithiasis with recurrent renal colic, and hyperuricemia.

Personal and family history

The patient had no prior history of oncological disease.

Physical examination

On physical examination, the patient had a performance status of 3 due to dorsal metastases. The pain secondary to this lesion limited her mobility and caused her to spend a significant amount of the day in bed. The patient weighed 54 kg and was 162 cm tall. His blood pressure was 138/90 mmHg, and his heart rate was 94 beats per minute. He was afebrile and required oxygen via nasal cannula at 2 L per minute to maintain an oxygen saturation above 92%. Pulmonary auscultation revealed decreased breath sounds in the left hemithorax. The abdomen was mildly distended, with tenderness primarily in the epigastric region. Bowel sounds were present, with no abnormal noises. No abdominal guarding was observed.

Laboratory examinations

Upon presentation to the emergency department, laboratory tests revealed a leukocyte count of 27400 cells/mm³, with 95% neutrophils. Coagulation parameters were unremarkable, except for an elevated fibrinogen level of 707 mg/dL. Liver function tests showed a mild elevation of alanine aminotransferase (65 U/L) and an amylase level of 1077 U/L. C-reactive protein was elevated at 106 mg/L.

Once admitted to the ward, a comprehensive liver panel was performed, revealing only a mildly elevated gamma-glutamyl transferase of 74 U/L, with normal bilirubin levels. Other potential causes of AP were investigated, but corrected calcium levels (8.9 mg/dL), total cholesterol (128 mg/dL), and triglycerides (77 mg/dL) were all within normal ranges. Figure 1 presents a summary of the laboratory parameter trends observed during hospitalization and follow-up.

Figure 1 Summary of the analytical evolution during hospitalization for acute pancreatitis and follow-up after four cycles of chemotherapy. AP: Acute pancreatitis; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CRP: C-reactive protein; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; NSE: Neuron-specific enolase; ProGRP: Pro-gastrin-releasing peptide.

Imaging examinations

Given the recent whole-body computed tomography (CT) scan and the greater accessibility of ultrasound (US), an abdominal US was performed by an expert radiologist specialized in biliopancreatic pathology. This imaging study revealed multiple nodular lesions, most of them hypoechoic and approximately 2 cm in size, consistent with metastatic pancreatic lesions (Figure 2). No gallstones or abnormalities in the common bile duct were observed.

Figure 2 Ultrasound images showing some of the pancreatic metastases (arrows). The largest one, measuring 21.6 mm, is highlighted. A: Metastatic lesion was identified in the distal pancreatic body; B: Additional lesions were noted in the pancreatic tail region; C: The main lesion, located in the pancreatic body prior to measurement; D: Measurement of the largest lesion (21.6 mm).

Due to the short time elapsed since the initial SCLC diagnosis, the previously performed CT scan from 1 month earlier was reviewed. That scan had shown a single hypodense area between the body and tail of the pancreas, initially considered nonspecific (Figure 3). Given the patient's clinical progression, this lesion was retrospectively interpreted as pancreatic metastasis.

Figure 3 Images from computed tomography performed at the diagnosis of small cell lung cancer. A: Coronal section, showing the hypodense lesion classified as nonspecific (arrow); B: Axial section displaying the same lesion in this plane (arrow).

FINAL DIAGNOSIS

Based on the clinical presentation, laboratory results, imaging studies, and medical history, the diagnosis was mild AP secondary to metastasis from SCLC.

TREATMENT

Initially, conservative management was implemented, as with any case of mild AP. Several attempts were made to initiate oral intake once the pain subsided, but each time even a liquid diet was reintroduced, the pain reappeared.

Given the complexity of the clinical case and the inability to progress and the repeated recurrence of pain, the case was discussed in a multidisciplinary team meeting. Several options were considered. First, endoscopic US (EUS) with biopsy was proposed to confirm the suspected diagnosis prior to initiating treatment. Pancreatic MRI was also considered but ultimately dismissed as the radiologists deemed the US images conclusive for the etiological assessment. Given the need to initiate chemotherapy for the underlying SCLC, which had been delayed due to the current hospitalization and pending immunohistochemical results, this option was also evaluated. Concomitant radiotherapy was discussed but deferred in case abdominal pain persisted. All options were thoroughly discussed with the patient and his family. Along with all this information, the patient was also asked for permission to publish this clinical case due to its rarity and the limited evidence available in the literature. Informed consent was obtained. The patient declined invasive procedures unless strictly necessary; therefore, chemotherapy with carboplatin and etoposide at 80% of the standard dose was initiated. After the first cycle of treatment, the patient was able to advance with the diet without issues and was discharged after resolution of the condition.

OUTCOME AND FOLLOW-UP

After discharge, the patient did not experience any further episodes of AP. Four cycles of chemotherapy were received, along with radiotherapy for analgesic control of pain due to dorsal bone metastasis. A follow-up CT scan showed a partial response of the SCLC. Pancreatic lesions were resolved, revealing a pancreatic cystic lesion consisting of an asymptomatic pseudocyst (Figure 4). Due to the clinical response, Atezolizumab was added to treatment based on the IMpower133 trial[15].

Figure 4 Follow-up computed tomography. A cystic lesion at the level of the pancreatic head-uncinate process compatible with a pancreatic pseudocyst is observed. A: Axial view showing a cystic lesion; B: Coronal view showing a cystic lesion.

One month later, the patient was admitted due to bradyphrenia and paralytic ileus. Brain progression was diagnosed through MRI. The patient and family were informed about the disease progression. In agreement with them, a limitation of therapeutic effort was decided. The patient was discharged home after receiving whole-brain radiotherapy with an infusion pump for symptom control, and follow-up by the palliative care team. Eventually, the patient passed away at home. A timeline has been developed to summarize this section (Figure 5).

Figure 5 Timeline summarizing the most important events in clinical progression. CT: Computed tomography.

DISCUSSION

SCLC are highly aggressive tumors primarily associated with smoking. They are characterized by rapid growth and a high tendency to metastasize, which often results in an advanced stage at the time of diagnosis[16,17]. Fortunately, the decline in tobacco use in recent decades has led to a decrease in their incidence, dropping from 15.3 per 100000 people in the 1980s to 6.5 per 100000 people in 2019[18].

The ability of these tumors to metastasize is influenced by various factors, including the following: Their high proliferation rate and cellular plasticity, which allow them to change phenotypes and facilitate their spread; the expression of adhesion molecules that enable them to adhere to the vascular endothelium and extravasate into other tissues; evasion of the innate immune system, especially natural killer cells; and their intratumoral heterogeneity, which favors the dissemination of specific tumor subpopulations through the bloodstream[19,20].

Although it remains a tumor with poor prognosis, recent years have witnessed significant advances in its treatment, particularly with the incorporation of immunotherapy and the identification of novel molecular targets are offering renewed hope in the management of SCLC. The disease remains a significant clinical challenge due to its aggressive behavior and rapid development of treatment resistance.

The combination of chemotherapy with immune checkpoint inhibitors (ICIs) has shifted the treatment paradigm for extensive-stage SCLC (ES-SCLC). The combination of platinum–etoposide chemotherapy with ICIs, such as atezolizumab or durvalumab, has transformed the therapeutic landscape. This strategy has shown a significant improvement in overall survival, with an increase in median survival from 8.1 to 11.1 months (hazard ratio = 0.62, P < 0.001)[21]. Moreover, combinations such as carboplatin, etoposide, and atezolizumab have reported median overall survival rates of up to 35 months in certain studies[22]. These combinations currently represent the first-line standard of care for ES-SCLC[23,24].

In limited-stage disease (LS-SCLC), concurrent chemoradiotherapy remains the cornerstone of treatment, often followed by thoracic radiotherapy and prophylactic cranial irradiation in patients achieving complete response to initial therapy[19,25]. Recently, durvalumab has been explored as consolidation therapy after chemoradiation, showing long-term survival benefits[26]. Furthermore, ongoing clinical trials are evaluating the synergistic effects of immunotherapy and radiotherapy in both ES-SCLC and LS-SCLC[27].

Regarding second-line therapies, topotecan and amrubicin (the latter primarily used in Japan) remain traditional options. However, lurbinectedin, a transcriptional inhibitor with alkylating activity, has been recently approved for its efficacy in patients with relapsed metastatic SCLC, also demonstrating promising results in combination with immunotherapy[19,28,29].

In parallel, translational research is actively exploring novel therapeutic targets and personalized strategies. Notable approaches include inhibitors of aurora kinase A, cyclin-dependent kinase 7, and poly (ADP-ribose) polymerase, as well as agents targeting delta-like ligand 3 such as the bispecific T-cell engager tarlatamab[30-32]. In addition, emerging modalities such as antibody–drug conjugates and cellular therapies, including CAR-T cells targeting SCLC-specific antigens, are currently under preclinical and clinical investigation[33,34]. These novel strategies hold promises for expanding the therapeutic arsenal and improving outcomes for patients with SCLC.

The most common organs for metastasis are the brain, bone tissue, liver, adrenal glands, and lymph nodes[35]. Gastrointestinal tract metastases are rare but can occur in advanced stages, particularly in the stomach, where they may cause both nonspecific symptoms and upper gastrointestinal bleeding[36,37].

Pancreatic metastases are extremely rare, at least in the published scientific literature. In our literature search, we found only about 50 cases to date, including a case series of 14 patients[38]. This highly atypical situation means that clinical guidelines do not mention this condition, making its management particularly challenging. The different cases reported in our literature research have been summarized in Table 1.

Table 1 Summary of the literature search conducted.

Ref.	Year	Article type	Diagnosis	Treatment	Outcomes
Levine and Danovitch[55]	1973	Case report	SCLC with pancreatic metastasis	Conservative management	Resolution of AP with supportive care; SCLC diagnosis confirmed later
Yeung et al[56]	1979	Case report	SCLC with metastasis-induced AP	Conservative management	Resolution of AP after conservative treatment
Schmitt[57]	1985	Case report	Metastatic SCLC with pancreatitis and diabetes	Supportive care	Clinical presentation of both pancreatitis and diabetes
Allan et al[58]	1985	Case report	SCLC with associated AP	Conservative management	Resolution of AP with conservative therapy
Hall et al[59]	1987	Case report	Oat cell carcinoma with AP	Symptomatic treatment	Diagnosis of AP revealed metastatic SCLC
Noseda et al[40]	1987	Case report	AP as sole manifestation of SCLC	Conservative management	AP resolved with supportive care
Evans et al[60]	1988	Case report	Necrotizing pancreatitis and diabetes due to metastatic SCLC	Supportive care	Associated with disseminated disease
Chowhan et al[61]	1990	Case report	Metastasis-induced AP	Chemotherapy	Symptom resolution after treatment
Maclennan et al[62]	1993	Case report	SCLC-induced AP	Chemotherapy	Symptom resolution
Stewart et al[63]	1993	Case report	SCLC presenting as AP	Conservative management	Symptom resolution; SCLC diagnosis confirmed
Huang et al[64]	2005	Case report	AP and Budd-Chiari syndrome due to SCLC	Supportive and systemic therapy	Initial manifestation of SCLC
Tanaka et al[65]	2009	Case report	Metastasis-induced AP from SCLC	Conservative management	Resolution of AP
Wurm Johansson et al[41]	2012	Case report	Pancreatic metastases from SCLC causing AP	Conservative management	AP resolved; detected by EUS
Hussain et al[66]	2012	Case report	SCLC presenting as AP	Conservative management	Resolution of AP
Leung et al[67]	2013	Case report	SCLC metastasis-induced pancreatitis	Supportive care	AP resolved with management
Khan et al[68]	2014	Case report	SCLC with AP as initial manifestation	Conservative management	Improved with supportive care
Okutur et al[51]	2015	Case report	Metastasis-induced AP in SCLC	Chemotherapy (cisplatin and irinotecan) + radiotherapy	Resolution of AP; tumor control at 6 months
Hernanz et al[69]	2016	Case report	Pancreatitis as first manifestation of SCLC	Conservative management	Favorable outcome
Yu et al[38]	2019	Retrospective study	SCLC with AP due to metastases	Systemic chemotherapy vs supportive care alone	Chemotherapy improved survival
Zhang et al[50]	2023	Case report	Recurrent SCLC transformation with AP after adenocarcinoma surgery	Radiotherapy	Resolution of AP; tumor control at 6 months
Jing et al[46]	2024	Case report	Lung adenocarcinoma with SCLC transformation causing AP	Chemotherapy (etoposide + cisplatin)	Resolution of AP; transformation confirmed
Xiao and Gu[47]	2025	Case report	Refractory SCLC with pancreatic metastasis	Chemotherapy + PD-1 (albumin with paclitaxel + atezolizumab)	Resolution of AP; tumor control at 3 months

AP: Acute pancreatitis; EUS: Endoscopic ultrasound; PD-1: Programmed cell death protein 1; SCLC: Small-cell lung cancer.

In this case, as in the reviewed literature, the clinical presentation is indistinguishable from any other type of pancreatitis. That is, epigastric abdominal pain radiating in a belt-like fashion toward the back[5]. This makes it indistinguishable from other etiologies and requires the exclusion of other potential causes that could justify the origin of pancreatitis. The laboratory results do not provide any differences in behavior, except to rule out other potential causes such as endocrine-metabolic conditions. One possibility could be the request for tumor markers, but it is well known that they are not specific markers and, at a minimum, would require a baseline reference value for comparison[39]. Additionally, their request from the emergency department is not feasible, at least in our setting, and their elevation does not necessarily indicate solely pancreatic progression.

Once other potential causes were ruled out, and considering the limitations in performing additional tests as outlined later, imaging played a pivotal role in guiding the diagnostic process. In our patient, the performance of the US and its comparison with the previously performed CT scan was considered enough for establishing diagnosis. However, other tests may be required, as outlined in the literature. For example, the case presented by Noseda et al[40] required the use of ERCP for diagnosis[40]. Another report by Wurm Johansson et al[41] required the use of EUS to establish the diagnosis. The choice of one technique over the other will always depend on the clinical context, as well as the need for biopsy if there is diagnostic uncertainty and the necessity of performing therapeutic procedures.

Due to the unusual nature of this etiology of AP, its management is not addressed in the current clinical guidelines[5,42-45]. In the literature, only case reports are published with the management deemed most appropriate. According to our scientific literature research, there is only a retrospective case series of 14 patients in which chemotherapy plus palliative treatment was compared to palliative care alone. Although it lacks significant statistical power, this study showed that patients treated with chemotherapy had better outcomes[38]. The results align with most published clinical cases, in which chemotherapy treatment yields favorable results. However, the regimens used are often not detailed in the reported cases. The regimens employed are typically platinum-based, such as etoposide and cisplatin[46]; or irinotecan and cisplatin, with less optimal results but still considered a valid option in SCLC therapeutic schemes[35]. Recently, a report was published on a patient with platinum-refractory and resistant SCLC treated with albumin-paclitaxel combined with atezolizumab, showing promising results[47].

Radiotherapy has also been described as an adjunct to chemotherapy with promising results. Its use is documented in both SCLC treatment regimens and secondary metastases[35,48,49]. Although not commonly used, in cases of AP where low-dose radiotherapy has been combined with chemotherapy, as well as in subsequent consolidation treatment, positive results have been reported, including a reduction in lesion size[47,50,51].

In our case, we initially opted for a conservative management with absolute diet and analgesia. The response was rapid with the disappearance of pain. Once we attempted to reintroduce oral intake, pain and analytical alterations secondary to AP were observed. After several attempts, due to suspicion of the origin of the AP, a consultation with the oncology team was made. The case was discussed in a multidisciplinary committee. Two options were considered to confirm the diagnosis. One was a pancreatic MRI, but the US image was considered sufficient for diagnostic purposes. Another option was EUS with the intent to confirm the diagnosis. However, when this option was presented to the patient, it was rejected as they did not want to undergo invasive procedures unless absolutely necessary. Additionally, the anesthetist also assessed the case and commented that the anesthetic risk was very high, so unless it was essential for diagnosis and subsequent treatment, it would be better to avoid any invasive procedure.

Given the suspicion of AP secondary to pancreatic metastases and the need to initiate treatment for SCLC, chemotherapy with carboplatin + etoposide at 80% dose (100 mg/m²) was prescribed. The clinical response was rapid, allowing for the reintroduction of oral intake without new episodes of pain or any analytical worsening. After completing the first cycle of treatment, the patient was discharged home to continue with outpatient treatment.

If the patient had not responded, the consensus plan would have been to perform EUS to confirm the diagnosis of pancreatic metastases from a pulmonary origin. After confirmation, both radiotherapy and atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor approved for use in SCLC in combination with chemotherapy, would have been added. Atezolizumab was initiated later, so the plan would have been to advance this therapeutic option.

Other therapeutic options may be explored in the future for the management of these patients. The emergence and development of ICIs could be a possibility. In addition to atezolizumab, other PD-L1 inhibitors such as durvalumab, nivolumab, or pembrolizumab have been used in the management of SCLC[35,52]. Additionally, improvements in the precision and doses administered through stereotactic body radiation therapy may also serve as an alternative to conventional radiotherapy. It has not yet been used in this context. The number of pancreatic lesions, their location, and proximity to the pancreatic ducts would likely need to be considered to avoid potential side effects[49]. Lastly, the use of EUS in these situations may also prove highly beneficial in the future. The possibility of administering chemotherapy locally, along with the placement of fiducials to guide radiotherapy, and the development of devices that could enable the local application of radiotherapy are potential therapeutic options for the future[53,54].

CONCLUSION

AP secondary to metastases from SCLC is an extremely rare condition, and its management is not yet clearly defined. Oncological treatments, especially chemotherapy, may be considered among the therapeutic options for the management of these patients. However, further studies are needed to establish a standardized management protocol for this entity.

ACKNOWLEDGEMENTS

This article was sponsored by Virgen de la Luz Hospital and Chair of Artificial Intelligence by Bayer.