Incidental left paraaortic mass in a patient with gall bladder adenocarcinoma: A diagnostic challenge.

A 72-year-old male with intermittent abdominal pain for the past year presented to the gastroenterology outpatient department (OPD). He described the pain as episodic, localized to the right hypochondrium, and mild in intensity, not interfering with his daily activities. On examination, his abdomen was soft and nontender, with normal bowel sounds audible. He had been on medication for hypertension for the past 6 years, and his medical history was otherwise unremarkable. An ultrasound (USG) of the abdomen and pelvis was recommended, given the possibility of biliary pathology. The ultrasound revealed an echogenic, nonmobile lesion with vascular flow on color Doppler, measuring 10 × 5 mm near the fundus of the gallbladder, suggestive of a gallbladder polyp. Additionally, the common bile duct (CBD) showed fusiform dilatation, measuring up to 3 cm in maximum diameter, without any evidence of obstructive pathology. His blood counts and liver function tests were within normal limits. Due to the polyp's size, raising suspicion for malignancy, and the risk of malignancy associated with a choledochal cyst, cross-sectional imaging of the abdomen and pelvis via computed tomography (CT) and magnetic resonance imaging (MRI) was performed.

Informed written consent was obtained from the patient to construct a case report based on his condition and the use of anonymized radiological and pathological images to represent it.

Contrast-enhanced CT scan of the abdomen showed an enhancing intraluminal polypoidal lesion measuring 13.0 × 8.0 mm in the fundus of the gallbladder, without any evidence of extraluminal extension ( Fig. 1 A). Fusiform dilatation of the extrahepatic biliary tree, having a maximum diameter of 38 mm, spanning a length of 4.8 cm from its distal end was observed without involvement of the intrahepatic biliary radicals. No obstructive lesion was identified in the distal course of the CBD contributing to this dilatation. The MRI confirmed the biliary tract findings observed on the CT scan ( Figs. 3 A and B). Additionally, it revealed short-segment, symmetrical circumferential thickening of the distal CBD, with a maximum thickness of 3.2 mm. These findings were likely due to repeated inflammation associated with the choledochal cyst; however, the possibility of malignancy could not be completely ruled out. Fig. 1 CECT abdomen and pelvis showing (A) enhancing polypoidal lesion in the gall bladder fundus (yellow arrow), along with fusiform dilatation of most of the extrahepatic biliary tree consistent with choledochal cyst (yellow star); (B) Hyperdense heterogeneously enhancing left paraaortic mass lesion with central necrotic area being supplied by direct branch from celiac artery (orange arrow); (C) The left para-aortic mass (yellow star) is closely related to the left adrenal gland inferiorly (green arrow). Fig 1: CECT abdomen and pelvis showing (A) enhancing polypoidal lesion in the gall bladder fundus (yellow arrow), along with fusiform dilatation of most of the extrahepatic biliary tree consistent with choledochal cyst (yellow star); (B) Hyperdense heterogeneously enhancing left paraaortic mass lesion with central necrotic area being supplied by direct branch from celiac artery (orange arrow); (C) The left para-aortic mass (yellow star) is closely related to the left adrenal gland inferiorly (green arrow). What caught our attention, however, was a large left infradiaphragmatic paraaortic mass. The mass was well-defined, longitudinally oriented, relatively hyperdense, and demonstrated heterogeneous enhancement with a central nonenhancing area ( Figs. 1 B and 1 C). The lesion was supplied by a direct branch arising from the celiac axis ( Fig. 1 B). It abutted the fundus of the stomach anteriorly, the left adrenal gland inferiorly ( Fig. 1 C), and the left crus of the diaphragm posteriorly. The mean attenuation value of the lesion, excluding the nonenhancing region, was +40 HU in the precontract phase and the maximum attained attenuation value was +90HU. The absolute and relative washout was calculated to be 56.8% and 29.8% respectively ( Fig. 2 ). These parameters are important in categorizing tumors arising from the adrenal gland which is one of the differentials diagnosis in our case. Fig. 2 CECT abdomen and pelvis showing attenuation value to the mass lesion in its inferior aspect in the noncontrast (A), arterial phase (B), portal phase, (C), and 15-minute delayed phase (D). The maximum mean attenuation value exhibited by the lesion was +90HU. Fig 2: CECT abdomen and pelvis showing attenuation value to the mass lesion in its inferior aspect in the noncontrast (A), arterial phase (B), portal phase, (C), and 15-minute delayed phase (D). The maximum mean attenuation value exhibited by the lesion was +90HU. The left paraaortic lesion exhibited a heterogeneous iso- to low-signal intensity on T1-weighted images and low to intermediate signal intensity on T2-weighted and fat-suppressed images, along with a cystic area within ( Figs. 3 C and D). The solid component of the lesion demonstrated diffusion restriction ( Figs. 3 E and F) . No evidence of flow voids or intralesional fat was observed. Fig. 3 MRI abdomen and pelvis in various sequences and planes; (A) Heavily weighted T2 3D MRCP image showing the fusiform dilatation of the extrahepatic biliary system. (B) T2 fat-saturated axial image showing hypointense polypoidal gall bladder lesion(blue arrow). (C) T2 weighted coronal image showing well-defined lesion having heterogeneously intermediate to low T2 signal with a central necrotic area (orange star) inferiorly related to left adrenal gland (green arrow) and superiorly to the fundus of stomach(blue arrow). (D) T1 weighted axial image showing low T1 signal of the left paraaortic lesion. (E) DWI and (F) ADC image showing evidence of diffusion restriction in the inferior aspect (yellow arrows). Fig 3: MRI abdomen and pelvis in various sequences and planes; (A) Heavily weighted T2 3D MRCP image showing the fusiform dilatation of the extrahepatic biliary system. (B) T2 fat-saturated axial image showing hypointense polypoidal gall bladder lesion(blue arrow). (C) T2 weighted coronal image showing well-defined lesion having heterogeneously intermediate to low T2 signal with a central necrotic area (orange star) inferiorly related to left adrenal gland (green arrow) and superiorly to the fundus of stomach(blue arrow). (D) T1 weighted axial image showing low T1 signal of the left paraaortic lesion. (E) DWI and (F) ADC image showing evidence of diffusion restriction in the inferior aspect (yellow arrows). With the incidentaloma being hyperdense, showing heterogeneous enhancement, delayed washout, and its close relation to the left adrenal gland, the most likely diagnosis was a tumor arising from the paraganglionic system, with no clear distinction between paraganglioma and pheochromocytoma. The relatively low to intermediate T2 signal and the lack of postcontrast attenuation reaching the typical cutoff value of +120 HU were features that differed from the typical definition of pheochromocytoma. Based on these findings, under precautionary measures for the hypertensive crisis due to a sudden storm of catecholamine, the patient underwent a Whipple procedure for the removal of the choledochal cyst and the suspicious polypoidal gallbladder lesion. The presence of thickening in the distal CBD prompted the surgeons to go for a more extensive surgery in this particular case. During the exploration of the left retroperitoneum, a highly vascular mass, separate from the left adrenal gland and stomach, was discovered and excised. The specimens were sent for histopathological examination. His intraoperative and postoperative periods were uneventful. Histopathological study of the gallbladder polyp revealed well-differentiated adenocarcinoma extending up to the muscle layer without perineural and lymphovascular invasion. The remaining portion of the gall bladder demonstrated severe active cholecystitis with intestinal metaplasia and additional adenomyosis. The choledochal cyst and the rest of the biliary tree was free of tumor. The final diagnosis according to the AJCC (pTNM) was T1bN0. Grossly, the left para aortic mass appeared as nodular brown tissue with solid, dark brown areas. On sectioning, the tumor was well-circumscribed, composed of solid nests of tumor cells separated by scant vascular stroma, displaying the typical Zellballen pattern. The tumor cells were polygonal to oval, with moderate to abundant granular cytoplasm and round nuclei ( Figs. 4 A and B). Intranuclear inclusions were observed, and some cells showed small nucleoli. Mitotic figures were infrequent, and necrosis was absent. Further immunohistochemical (IHC) analysis demonstrated strong positivity for synaptophysin, chromogranin, and INSM1 ( Fig. 4 C). Approximately 2-3% of the cells showed positivity for Ki-67. These findings supported the diagnosis of paraganglioma. Fig. 4 Oncopathological study including Hematoxylin and Eosin staining (A) at low power view of the sections of the lesion and figure (B) is high power view of the section of the lesion. The individual cells are round to polygonal in shape with moderate to abundant amount of granular cytoplasm. Nuclei are round to oval with prominent nucleoli in some of them. Necrosis and mitotic figures are not seen. (C) Immunohistochemistry staining positive for chromogranin (CGA) and Synaptophysin. Fig 4: Oncopathological study including Hematoxylin and Eosin staining (A) at low power view of the sections of the lesion and figure (B) is high power view of the section of the lesion. The individual cells are round to polygonal in shape with moderate to abundant amount of granular cytoplasm. Nuclei are round to oval with prominent nucleoli in some of them. Necrosis and mitotic figures are not seen. (C) Immunohistochemistry staining positive for chromogranin (CGA) and Synaptophysin. Upon retrospective questionnaire, it was discovered that the patient occasionally experienced palpitations and had started taking anti-hypertensive medications for the past 4 years.

This case highlights the diagnostic complexity of incidental findings in imaging, particularly in the evaluation of biliary pathologies and para-aortic masses. The discovery of a large left paraaortic mass in an elderly with concurrent gall bladder malignancy initially raised concerns about malignancy due to its vascularity and atypical imaging characteristics. However the absence of regional lymphadenopathy and discrepancy between the size of gallbladder lesion and paraaortic mass favored the diagnosis towards PPGL in contrary to metastasis. Despite the challenge in distinguishing between paraganglioma and pheochromocytoma based solely on imaging, histopathological examination and immunohistochemistry confirmed the diagnosis of extra-adrenal paraganglioma. The patient's history of palpitations, although retrospectively identified, is consistent with catecholamine-secreting tumors like paragangliomas. This case underscores the importance of a multidisciplinary approach involving imaging, pathology, and biochemical testing in diagnosing and managing rare, complex tumors. As demonstrated here, early surgical intervention can lead to favorable outcomes, with careful follow-up required given the potential for metastasis, especially in extra-adrenal retroperitoneal paragangliomas.

Pooling of carcinogens in conditions causing biliary stasis or malignant degeneration of the metaplastic changes after chronic inflammation are considered to be the underlying pathogenesis of gallbladder carcinoma [ 15 ]. The importance of closely scrutinizing the gallbladder for subtle morphologic abnormalities that may indicate cancer, particularly in those with high risk of developing gallbladder carcinoma cannot be emphasized enough. Despite most cases being diagnosed in childhood, some portion of the choledochal cyst cases are diagnosed later in adulthood resulting in increased risk of malignant transformation [ 16 ]. The Todani type I and IV choledochal cysts types are the ones most often associated with malignant transformation [ 6 ]. Associated biliary malignancy should always be in mind when the patient with choledochal cyst have associated factors like age more than 40 years, absence of gallstones, elevated tumor marker and presence of AUPBD. In a study carried out in Korea on adult patient with choledochal cyst and associated malignant tumors, it was seen that 9.9% cases had associated biliary tract malignancy out of which 50% had cholangiocarcinoma and 43.8% had gall bladder carcinoma [ 17 ]. Different studies have also shown that gallbladder carcinoma was much more common in patient with AUPBD and without CBD dilatation than in cases with choledochal cyst [ 17 , 18 ]. The presence of an enhancing gall bladder polypoidal lesion in the background of associated choledochal cyst is highly suggestive of the polyp harbouring malignancy. Owing to the rich lymphatic drainage of the gall bladder, lymphatics are the main modality of spread of harboured tumor cells. Pericholecystic lymphatics firstly enter the hepatoduodenal ligament and then travel further down via 3 routes, cholecystoretropancreatic, cholecystoceliac and cholecystomesenteric pathway to finally reach the retroperitoneal node near the left renal vein [ 19 ]. The absence of enlarged regional nodes i.e. nodes along the common bile duct, hepatic artery, portal vein and cystic duct in our case was one of the main points not in favor of the incidental left paraaortic mass being a nodal mass. Additionally the discrepancy in the size of primary lesion and the left paraaortic mass points towards possibility of 2 different pathology in play and further makes the paraaortic mass representing nodal metastasis incongruous. Identification of the location, shape and internal architecture of a lesion by imaging modalities are the key steps in diagnosing retroperitoneal lesion. Primary retroperitoneal lesion are relatively uncommon as compared to lesions arising secondarily from retroperitoneal regions [ 7 ]. Keeping this in mind adrenals are the most common organ from which the lesion could arise. Adrenal incidentaloma with nonspecific features including heterogeneity, density of 10HU or more in unenhanced CT, slow contrast washout on adrenal protocol CT, no signal dropout on chemical selective MRI, and signal hyperintensity on T2 weighted MR images are mostly attributed to metastasis, pheochromocytoma, and adrenal cortical carcinomas [ 20 , 21 ]. Owing to the rich capillary network, typically PPGL presents as a lesion having a density of 10HU or more on unenhanced CT with avid enhancement of the solid component, reduced washout rates, and “light bulb” bright lesion on T2 weighted imaging comparable to the intensity of CSF [ 13 , 22 ]. However PPGL shows a varied enigmatic imaging spectrum ranging from resembling an adenoma to metastases, for which they are truly labeled as the “chameleon”. The pathological basis of inconsistent enhancement and contrast material washout are varied pathological degeneration producing abnormal capillary network [ 13 , 20 ]. Approximately 35% of cases of pheochromocytoma are misclassified as adenomas or metastases owing to the atypical appearance of lack of high signal intensity at T2-weighted MR imaging in comparison to CSF and liver. There is a considerable overlap between the MRI appearance of pheochromocytoma and other adrenal lesions and the lack of high signal intensity on T2-weighted MR Imaging therefore cannot exclude pheochromocytoma [ 23 ]. A large study aimed at describing the various appearances of adrenal pheochromocytomas on T2-weighted MRI, a broad range of patterns was observed. The most common was 1) heterogeneous with multiple high-signal intensity areas (39%), followed by 2) homogenous, either isointense or slightly hyperintense to the spleen and hypointense to CSF (34%), 3) heterogeneous marbled appearance (16%), and lastly, 4) the classic homogenous high-signal intensity, isointense to CSF (11%), in descending order of frequency. No MRI features were found to be predictive of malignancy [ 24 ]. The characteristic “salt and pepper” appearance of paragangliomas is caused by punctate areas of low signal intensity, which correspond to flow voids from the tumor's vascularity, and hyperintense areas, which indicate hemorrhage. This feature is more commonly observed in head and neck paragangliomas, as well as in other hypervascular tumors [ 9 ]. Functional imaging can also be utilized, using radioactive isotopes that mimic catecholamine and identifying its site of production. The sensitivity of ¹²³I-MIBG ranges from 85% to 88% for pheochromocytomas and from 56% to 75% for paragangliomas, while its specificity varies between 70% and 100% for pheochromocytomas and 84% to 100% for paragangliomas. Functional imaging is useful in the context when the whole body is evaluated to detect extra-adrenal pheochromocytoma and metastatic disease and while assessing for tumor recurrence [ 25 , 26 ]. Despite having similar clinical and radiological features, PPGLs differ in the prognosis and likelihood of metastasis [ 14 ]. Malignancy is defined by metastasis and not local invasion so there is a distinction between exhibiting malignant potential and actual clinical features of malignancy. The traditional rule of 10 was a helpful approximation, however, the current research stresses on a more complex scenario with the rate of metastases to be rather dependent on the site of tumor origin [ 27 ]. Extra-adrenal paragangliomas tend to be more aggressive than their adrenal counterparts, with metastases occurring in 20-70% of cases, compared to 2-10% in adrenal paragangliomas. The identification of tumor foci at sites not native to chromaffin tissue often diagnoses metastasis. Bones, lymph nodes, and lungs are common metastasis sites involved [ 14 ]. The size and location of the primary tumor are significant clinical risk factors for metastasis and decreased overall survival with the latter being a stronger predictor. Metastasis was commonly associated with primary tumors mostly located in the mediastinum followed by infradiaphragmatic paraaortic area including the organ of Zuckerkandl [ 28 ]. While the histological diagnosis is generally straightforward due to the distinct morphological features, the current role of pathology is limited to diagnosing primary or metastatic tumors and identifying features suggestive of malignant potential or hereditary disease [ 14 , 29 ]. Histologically the typical Zellballen appearance is built up by chief cells which are usually surrounded by a network of thin blood vessels and supporting cells. The chief cells are strongly positive for neuroendocrine markers of both first (Chromogranin A(Cg A), Synaptophysin) and second generation(ISL1, INSM 1). Cg A is the major constituent of the catecholamine-containing secretory granules and is the single most specific and reliable generic neuroendocrine marker currently used in pathological practice. Except for rare subtypes gangliocytic paragangliomas and cauda equine paraganglioma keratin expression is almost always absent. Ki-67 is a proliferation marker whose higher levels are considered to be associated with increased mitotic activity and risk of metastatic spread. PPGL often have unpredictable behavior and metastasizes late, highlighting the importance of long-term follow-up [ 29 , 30 ]. Recurrent and multicentric PPGL are seen to occur in association with multitumor syndromes including VHL, NF1, and multiple endocrine neoplasia type 2 (MEN2) which are identified by detection of the von Hippel Lindau (VHL), Neurofibromatosis type (NF1) and Rearranged during transfection ( RET ) genes [ 29 , 30 ].

Gall bladder carcinoma, the fifth most common gastrointestinal malignancy is also the most common and most aggressive biliary malignancy. Majority (98%) of the primary malignancy of gallbladder arises from the epithelium with adenocarcinoma accounting for 90% of cases [ 1 , 2 ]. Morphologically gallbladder carcinoma can present in any 3 forms, as a mass completely occupying the gallbladder lumen, focal or diffuse asymmetric gallbladder wall thickening or an intraluminal polypoidal lesion [ 1 ]. About 15%-25% of the gall bladder carcinomas are detected as polypoidal lesions, for which the differentials include adenomatous or hyperplastic cholesterol polyp, uncommon tumors like carcinoid or even rarely metastases from melanoma [ 3 ]. Primary sclerosing cholangitis, congenital anomalies like choledochal cyst, anomalous pancreaticobiliary junction (AUPBD) and low insertion of cystic duct are described to have association with gallbladder malignancy [ 4 ]. Choledochal cyst are congenital abnormal disproportionate dilatation of any portion of the bile ducts after excluding a possible obstructive pathology. The etiology for these congenital anomaly appears to be multifactorial, however there has been a close association between choledochal cyst and AUPBD. These cyst are prone in developing complications like cholecystitis, recurrent cholangitis, biliary stricture, choledocholithiasis, recurrent acute pancreatitis, and malignant transformation. Although most cysts are diagnosed in childhood, almost 25% are diagnosed in adulthood [ 5 ]. Diagnosis of adult choledochal cyst is often delayed due to nonspecific clinical symptoms or symptoms obscured by secondary hepatobiliary disease. Delay in diagnosis and treatment can extend for years, resulting in increased risk of malignant transformation which is most often seen in Todani type I and IV cysts [ 6 ]. Primary retroperitoneal neoplasm constitutes a diverse group of benign and malignant tumors that arise within the retroperitoneal space but outside the major organs. These rare tumors pose a significant diagnostic challenge to radiologists in defining the precise location, determining its extent, and characterization of specific pathologic subtypes. Identifying their specific tumor components, tumor vascularity and specific pattern of spread can take us a step closer to correctly recognizing them [ 7 ]. The occurrence of a lesion in the paraspinal location strongly indicates the tumor to have neurogenic origin. However, they can deviate from their usual occurrence and arise in atypical locations including the urinary bladder, bowel wall, abdominal wall, and gallbladder [ 8 , 9 ]. Pheochromocytomas and paragangliomas (PPGL) are rare catecholamine-secreting neurogenic tumors that arise from the paraganglia, which consist of specialized neural crest cells closely associated with the autonomic nervous system. These tumors extend symmetrically from the base of the skull to the pelvic floor, adjacent to the sympathetic ganglia and plexus [ 9 ]. According to the 2022 WHO classification of paragangliomas and pheochromocytomas, paragangliomas can be either sympathetic or parasympathetic. Sympathetic paraganglioma secrete norepinephrine; pheochromocytoma secrete epinephrine whereas parasympathetic paragangliomas are nonsecretory and typically occur in the head and neck [ 10 ]. The term “pheochromocytoma” is used specifically for intra-adrenal paragangliomas, which represent the classic sympathetic form [ 11 ]. PPGL are seen in 2-8 individuals per million population per year and accounts for approximately 0.1% of individuals with hypertension [ 12 ]. Excess catecholamine production leads to the classic presentation of hypertension, which may be episodic and associated with the triad of palpitations, headaches, and diaphoresis. Up to 10% of cases remain clinically silent, and tumors in these cases tend to be larger, often accompanied by hemorrhage and cystic changes, compared to their hyperfunctioning functioning counterparts. Atypical pathological features may include necrosis, calcification, fibrosis, and lipid degeneration [ 13 ]. Despite similar clinical and radiologic features, pheochromocytoma and paragangliomas differ in prognosis and likelihood of metastatic spread [ 14 ]. We present a case of an elderly man who was being worked up for biliary pathology to have an incidental hypervascular infradiaphragmatic left paraaortic lesion.