Case Report: Pancreatic toxoplasmosis: role of endoscopic ultrasound in diagnosis

1 Introduction

Toxoplasmosis is a globally distributed zoonotic infection caused by Toxoplasma gondii, a protozoan parasite belonging to the class Conoidasida, order Eucoccidiorida, and family Sarcocystidae (1). Toxoplasmosis is typically acquired through ingestion of T. gondii oocytes from contaminated soil, water, or food, as well as through consumption of undercooked meat. Following infection, the parasite can disseminate systematically (2). According to the Centers for Disease Control and Prevention, over 40 million people are estimated to be infected with T. gondii in Indonesia (3). The global seroprevalence for T. gondii infection is approximately 25.7%, with the greatest contributors being Africa (61.4%), followed by Oceania (38.5%) and South America (31.2%). On the other hand, lower rates were observed in the United States/Canada (17.5%) and Asia (16.4%) (4).

In immunocompetent individuals, toxoplasmosis is typically asymptomatic or presents as a mild, self-limiting illness characterized by fever and lymphadenopathy. In immunocompromised individuals, particularly those with Human Immunodeficiency Virus (HIV), latent T. gondii may reactivate and result in focal or disseminated disease. The most common manifestation in this population is toxoplasmic encephalitis (TE), especially in those with CD4 count <100 cells/μL and who are not receiving prophylaxis (5, 6). Extracerebral manifestations—including pneumonitis, myocarditis, chorioretinitis, and pancreatitis—are far less common and often under-recognized (7).

Pancreatic toxoplasmosis is exceedingly rare, with only a limited number of cases reported in the literature, highlighting its rarity and diagnostic challenge. It can clinically and radiologically mimic neoplastic lesions of the pancreas, leading to potential misdiagnosis and delayed treatment. Definitive diagnosis typically requires histopathological or cytological confirmation through tissue sampling.

Herein, we present a rare case of pancreatic toxoplasmosis in a 48-year-old male patient. The patient was initially suspected to have a pancreatic malignancy. However, the diagnosis was ultimately established via endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB), which identified T. gondii organisms. This case emphasizes the importance of considering infectious etiologies, such as toxoplasmosis, in the differential diagnosis of pancreatic masses.

2 Case report

A 48-year-old male patient was referred to our hospital for evaluation of pancreatic nodules. He had been hospitalized at another institution with a three-week history of progressively worsening headaches, right-sided hemiparesis, dizziness, cognitive decline, and intermittent visual disturbances. Two days prior to admission, he experienced episodes of transient loss of consciousness. His medical history was significant for insulin-dependent Type diabetes mellitus. On presentation, the patient exhibited progressive neurological symptoms, including altered mentation and focal neurological deficits. He was afebrile and hemodynamically stable. Laboratory investigations showed normal serum amylase, CA 19-9, and CEA levels. Serum lipase levels was mildly elevated to approximately two times the upper limit of normal. No other significant laboratory abnormalities were noted. Contrast-enhanced magnetic resonance imaging (MRI) of the brain performed at the previous hospital demonstrated multiple ring-enhancing lesions, notably involving the left middle cerebellar peduncle and periventricular region of the left lateral ventricle. The lesion in the cerebellar peduncle measured up to 2.5 cm and was associated with significant perifocal edema, resulting in mass effect on the fourth ventricle and subsequent dilatation of the third and bilateral lateral ventricles, consistent with non-communicating hydrocephalus (Figure 1). The radiologic differential diagnoses included cerebral toxoplasmosis, pyogenic abscess, or metastatic disease.

Based on the MRI findings, a positron emission tomography (PET) scan was conducted in our hospital, revealing a hypermetabolic lesion in the pancreatic head with additional focal uptake in the pancreatic body. There were no evidence of pancreatic duct dilation, fat stranding, peripancreatic or lymphadenopathy, and no radiologic features strongly suggestive of primary pancreatic malignancy were identified. In contrast, several of the previously noted ring-enhancing brain lesions demonstrated relative hypometabolism on PET imaging.

Several differential diagnoses were considered at this stage, including pancreatic adenocarcinoma, primary pancreatic lymphoma, infectious etiologies, and metastatic disease. Pancreatic adenocarcinoma was initially suspected due to the presence of a focal hypermetabolic lesion in the pancreatic head lesion on PET imaging. However, this diagnosis became less likely given the absence of characteristic radiology features, including pancreatic duct dilatation or vascular invasion, as well as normal tumor marker levels and only mildly elevated lipase.

Primary pancreatic lymphoma was also considered, particularly in light of the systemic and neurological manifestations. Nevertheless, imaging did not demonstrate typical features such as bulky homogeneous enlargement or significant lymphadenopathy, making this diagnosis less probable. Metastatic disease was another consideration but PET scan results failed to reveal a clear primary malignancy.

Infectious etiologies were therefore increasingly favored. In particular, as toxoplasmosis was considered the most likely diagnosis given the presence of multiple ring-enhancing brain lesions on MRI.

A key diagnostic challenge was the discordance between hypermetabolic pancreatic lesions and hypometabolic brain lesions of PET imaging, which complicated differentiation between malignant and infectious etiologies. Additionally, the absence of fever and largely unremarkable laboratory findings contributed to diagnostic uncertainty.

To further clarify the nature of the pancreatic lesion, the patient underwent EUS, which revealed a hypoechoic, irregular mass in the pancreatic head (Figure 2). EUS-guided FN was performed with a 22-gauge acquired needle (Boston Scientific). Three passes were made into the pancreatic head lesion under Doppler guidance to avoid vascular structures. Histopathological analysis revealed pancreatic tissue infiltrated by chronic inflammatory cells. Some cyst-like structures containing bradyzoites were found, which are pathognomonic for Toxoplasma gondii (Figure 3). Histopathological and serological evidence of Toxoplasma confirmed the diagnosis of pancreatic toxoplasmosis. Figure 4 has summarized the timeline of the events for this case.

The patient was subsequently initiated on standard anti-toxoplasmosis therapy, including clindamycin 3x600 mg and cotrimoxazole 3x1920 mg, along with intravenous antibiotics (meropenem 3x1 gram and moxifloxacin 1x400 mg), antifungal therapy (fluconazole 1x200 mg IV drip), and supportive care. During hospitalization, the patient’s condition deteriorated due to sepsis in the setting of multiple concurrent infections, including cytomegalovirus infection, suspected tuberculosis, and pneumocystis pneumonia. The clinical course was further complicated by multiorgan failure and the development of acute respiratory distress syndrome.

3 Discussion

Toxoplasma gondii is an opportunistic protozoan capable of affecting nearly any organ system in immunocompromised individuals, with the central nervous system being the most commonly involved site. In contrast, extracerebral manifestations—particularly those involving the gastrointestinal tract—are uncommon (7).

Pancreatic involvement by T. gondii is exceedingly rare and typically presents as pancreatitis, mass-like lesions, or nodules that may mimic neoplastic processes. To date, no epidemiological studies have specifically reported the incidence of pancreatic toxoplasmosis; available knowledge is limited to isolated case reports. Ahuja et al. described a case of necrotizing pancreatitis associated with disseminated toxoplasmosis in a 34-year-old AIDS patient who developed multiorgan failure (8). Other reports have documented pancreatitis secondary to toxoplasmosis in patients undergoing immunosuppressive therapy or solid organ transplantation. In such cases, T. gondii may directly invade pancreatic tissue, triggering inflammation and necrosis. Notably, in many of these cases, the diagnosis was established only postmortem (9, 10). In HIV-infected individuals, reactivation of latent toxoplasmosis is the likely pathophysiological mechanism, while in transplant recipients, primary infection with T. gondii from donor tissue may occur. The pancreas, particularly its endocrine β-cells, may be targeted directly by the parasite or indirectly through immune-mediated mechanisms (10). In our case, we could not confirm the immunodeficiency status of the patient since the patient rejected tests for HIV; which became the major limitation of our case report and for further elaborated management.

Pancreatic toxoplasmosis can manifest as nodular lesions that are often radiologically indistinguishable from malignant neoplasms. Imaging modalities such as computed tomography (CT), and MRI are commonly used in the initial evaluation,with PET serving as an adjunct in selected cases. Among these modalities, MRI offers superior sensitivity (96.9%) and specificity (90.8%) compared to CT (sensitivity 80.6%, specificity 86.4%) for characterizing pancreatic lesions (11).

Contrast-enhanced CT remains widely accessible and is often the first-line imaging tool, with a reported sensitivity of 80.6% and specificity of 86.4% for the detection of pancreatic tumors. MRI offers superior soft tissue contrast and has demonstrated higher diagnostic accuracy, with a sensitivity of 96.9% and specificity of 90.8% for characterizing pancreatic lesions (11). PET using 18F-fluorodeoxyglucose (FDG) is valuable in identifying metabolically active lesions and assessing for systemic involvement. It is particularly useful when conventional imaging is inconclusive or when multiple lesions are present. However, PET has limited specificity, as inflammatory and infectious lesions—including toxoplasmosis—may also exhibit increased FDG uptake, thereby mimicking malignancy. The reported sensitivity and specificity of FDG-PET for detecting pancreatic cancer range from 85% to 94% and 65% to 97%, respectively, depending on the study population and lesion type. In the context of pancreatic toxoplasmosis, PET may yield false-positives due to the inflammatory response associated with parasitic infection (12).

EUS has emerged as a cornerstone modality in the evaluation of pancreatic lesions, especially when conventional imaging such as CT or MRI yields inconclusive results. By combining high-resolution imaging with real-time tissue sampling, EUS offers both diagnostic and therapeutic potential. EUS may detect small pancreatic lesions <2–3 cm in diameter (13). According to multiple studies, the diagnostic performance of EUS varies with lesion size. For pancreatic nodules measuring between 10 and 20 mm, sensitivity ranges from approximately 76% to 92%, with specificity reported as high as 93.8% to 100%. In contrast, for nodules 10 mm or smaller, sensitivity ranges from 40% to 100%, while specificity remains relatively high, between 80% and 100% (14). When EUS is combined with fine-needle aspiration (FNA) or fine-needle biopsy (FNB), its diagnostic accuracy is significantly enhanced. A recent meta-analysis reported that EUS-FNA achieves a sensitivity of 94.8% and specificity of 98.6% in diagnosing pancreatic cancer (15). EUS-FNB, which allows for the collection of core tissue samples, has shown comparable diagnostic accuracy, with pooled sensitivity and specificity rates of 90.8% and 96.5%, respectively. These techniques are particularly valuable in distinguishing malignant from benign lesions, guiding clinical management decisions. Despite its advantages, EUS also has limitations. Its diagnostic accuracy can be operator-dependent, and certain lesion characteristics, such as small size (<20 mm) or ill-defined margins, may reduce the effectiveness of EUS-guided tissue acquisition. In such cases, the use of contrast agents and the involvement of experienced operators can enhance diagnostic yield (16). In our case, the histopathological examination of the tissue was consistent with pancreatic toxoplasmosis. Polymerase chain reaction (PCR) testing for Toxoplasma was not performed, as the histopathological findings were considered sufficient for diagnosis. However, the absence of molecular confirmation represents a limitation in our case.

The treatment of pancreatic toxoplasmosis follows the principles of systemic toxoplasmosis management. The standard regimen consists of pyrimethamine (200 mg on day 1, followed by 75 mg/day if weight ≥60 kg or 50 mg/day if <60 kg) combined with sulfadiazine (3000 mg twice a day if weight ≥60 kg or 2000 mg twice a day of <60 kg) and folinic acid 10–15 mg/day for six weeks. Alternative regiments include pyrimethamine in combination with clindamycin (600–900 mg four times a day) and folinic acid or trimethoprim (5 mg/kg twice a day)/sulfamethoxazole (25 mg/kg twice a day). In cases of intolerance, atovaquone (1500 mg twice a day) in combination with pyrimethamine and folinic acid may be considered (17). In our case, the standard sulfadiazine–pyrimethamine regimen was not administered due to its unavailability in Indonesia. Additionally, atovaquone was also not accessible. Therefore, an alternative regimen consisting of clindamycin and cotrimoxazole was initiated.

4 Conclusion

Pancreatic toxoplasmosis is a rare manifestation of Toxoplasma gondii infection. Its clinical and radiologic presentation may closely mimic pancreatic neoplasia, posing a significant diagnostic challenge. This case highlights the critical role of EUS with FNB in the evaluation of pancreatic lesions, enabling definitive diagnosis through tissue sampling. Clinicians should maintain a high index of suspicion for infectious etiologies, including toxoplasmosis, in the differential diagnosis of pancreatic masses.

Patient perspective

The patient was initially conscious and able to participate in clinical decision-making. However, the patient declined HIV testing during the early stage of hospitalization. As his condition progressed, he developed worsening neurological symptoms and was no longer able to provide further input. The patient’s family described the initial symptoms, particularly progressive neurological deficits and episodes of loss of consciousness, as distressing and alarming. They also reported that the period of diagnostic uncertainty, including concerns about possible malignancy, contributed to significant anxiety. Despite medical management, the patient’s rapid clinical deterioration and the development of multiple complications were emotionally overwhelming for the family.

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Footnotes

Edited by: Ferga Gleeson, Mayo Clinic, United States

Reviewed by: Mustafa Zanyar Akkuzu, Diyarbakır Gazi Yaşargil Training and Research Hospital, Türkiye

Mathew Vadukoot Lazar, Lifecare Hospital, United Arab Emirates