Chronic pancreatitis: Focal pancreatitis or cancer? Is there a role for FNA/biopsy? Autoimmune pancreatitis

EUS and tissue sampling to distinguish focal pancreatitis from pancreatic carcinoma

EUS imaging has become routine for evaluation of pancreatic masses because of the staging information provided and ability to obtain a tissue diagnosis. However, distinction of pancreatic carcinoma from other malignant and benign pancreatic disorders, in particular focal chronic pancreatitis is particularly difficult. Efforts to increase the accuracy of sonographic imaging have included ultrasound contrast administration [1] [2] and use of a self-learning computer program for image analysis. [3] Early results offer promise as to their utility as an adjunctive measure to improve diagnostic accuracy. However, further study is needed to clarify the role of these techniques before general use can be advocated. Until then these techniques should be regarded as investigational.

The addition of fine needle aspiration (FNA) and cytologic review improves evaluation of pancreatic masses providing a sensitivity of ∼80 - 90 %, specificity of ∼95 - 100 %, and accuracy of ∼90 - 95 % [4] [5] [6] [7] [8] [9] [10]. While FNA is a valuable tool in some, it may not be necessary in all. Although EUS FNA safely provides a high diagnostic accuracy in pancreatic cancer patients [8] [11] [12], measures should be taken to eliminate unnecessary pancreatic biopsy and to minimize the risk in those whom FNA is indicated. EUS findings most significantly impact clinical decision making in patients with equivocal computed tomography (CT) findings as defined by uncertain presence of a mass and/or potential resectability. EUS is used to verify the presence or absence of a mass and for locoregional staging. When EUS detects unresectable disease then FNA allows a tissue diagnosis. In patients with an apparent resectable mass on CT, EUS appears to maintain a useful role in searching for occult hepatic [13] and/or distant nodal metastases [14], either of which precludes surgery for curative intent. It is in patients with a presumed resectable tumor on PPCT and EUS that the need for a preoperative tissue diagnosis is most debated. There are several potential advantages and disadvantage of pursuing a tissue diagnosis in this setting.

Potential disadvantages in pursuing a tissue diagnosis include:

1.) The false negative rate of 15 - 20 % that results from pancreatitis and associated inflammation or fibrosis, sampling error, bloody aspirates and errors of cytological interpretation [7] [15] [16]. A negative biopsy leaves great uncertainty as to whether it represents a true negative or false negative finding, particularly in those with a high clinical suspicion. Therefore a negative result seldom influences the decision to proceed to surgery.

2.) The risk for complications including pancreatitis, bleeding, and tumor seeding of the peritoneum and/or needle tract [11] [15] [17] [18] [19]. Although relatively infrequent (∼1 - 2 %), their occurrence may delay, complicate, or even preclude surgical intervention. For this reason, many surgeons avoid biopsy of any pancreatic mass that appears potentially resectable.

Potential advantages for pursing a tissue diagnosis include:

1.) Confirmation of a ductal carcinoma so patients may receive neoadjuvant chemotherapy and/or radiation therapy prior to surgery.

2.) The ability to identify an islet cell tumor, lymphoma, small cell carcinoma, metastatic disease, as well as non-malignant processes such as autoimmune or non-specific chronic pancreatitis. Patients with these disorders typically benefit from alternate management strategies [20] [21]. Use of clinical, laboratory, non-invasive imaging, and EUS appearance may offer clues as to the presence of these alternate diagnoses and guide biopsy in this setting.

3.) Many prefer a preoperative tissue diagnosis due to the associated morbidity and mortality of pancreatic surgery and risk of resecting a benign mass. Some would argue that despite the poorer outcomes in some centers, clinical decision-making should be the same. This opinion, however, must be balanced by the affect on physicians and patients who experience poor operative outcomes following resection of what is later realized to be a benign lesion.

4.) Provision of additional information that may assist in preoperative patient and family counseling and selection of therapy. During patient counseling, the differential diagnosis and management options are explained to the patient as well as the ∼5 % chance of resecting a benign process [22]. Patients are informed as to the need for resection regardless of the underlying pathology. This approach spares unnecessary biopsy. However, patient concerns often do necessitate EUS FNA and allow focusing the preoperative discussion on the therapy of a known malignancy.

When the decision is made to pursue a tissue diagnosis, steps may be taken to optimize the technique to increase diagnostic accuracy and to minimize the need and risk of pancreatic biopsy including:

1.) Availability of an onsite cytotechnologist or cytopathologist [7] [15] [16], which improves the diagnostic sensitivity by ∼10 % compared to performing a predetermined number of biopsies [23].

2.) Prioritizing the sequence of EUS FNA by directing initial biopsies to sites most significantly impacting tumor stage and patient management [24] [25]. This may be achieved through sequential biopsy of: 1.) suspected liver metastases, 2.) malignant appearing mediastinal lymph nodes, 3.) ascitic fluid, 4.) malignant appearing ”distant” abdominal lymph nodes, 5.) a malignant appearing local lymph nodes, and then 6.) pancreatic FNA if malignancy is not present in the other sites. This approach avoids need for pancreatic FNA in 10 - 20 % of patients [7] [15] [19] [26] [27] [28].

3.) Needle caliber. Limited data support the contention that large caliber (19-gauge) standard needles as well as trucut biopsy needles enhance diagnostic sensitivity [29] [30] and potentially after fewer needle passes [31]. Also, EUS TCB enable diagnosis of pathologic states that are difficult to diagnose using FNA alone including AIP, lymphoma, and vascular tumors [30] [32]. However, these needles are more difficult to use and have an uncertain safety profile.

4.) Special stains and molecular markers. Diagnosis may be aided by use of special stains for neuroendocrine tumors, flow cytometry for lymphoma, and IgG4 staining for AIP. Initial data support the utility of molecular markers such as p53 gene mutation [33], K-ras mutation [34] [35] [36], telomerase activity [35], MUC1 and MUC 2 analysis [37], digital image analysis [38], and fluorescence in situ hybridization [38]. These markers may help distinguish benign from malignant tumors when applied to tissue samples or pancreatic fluid. Although results are encouraging and offer promise as an adjunctive measure to improve diagnostic accuracy, their use is still investigational. Further study is needed to clarify the role of these techniques before their use can be widely advocated.

Summary

EUS provides high resolution imaging and guides biopsy often allowing distinction of benign from malignant pancreatic masses when other studies are unable to make this distinction. Controversy centers mostly on appropriate patient selection for FNA. For many patients with a pancreatic mass lesion, there is a clear role for attempted tissue diagnosis and for many others, the role is uncertain and FNA is discouraged. No one approach suits all patients or physicians. FNA findings often do serve as a useful piece of the diagnostic puzzle and may tipp the scales in favor of resection or careful observation for those in whom the diagnosis, resectability, and/or operability are in question. In addition, much of the reluctance for pancreatic biopsy lingers from prior uncertainty regarding the safety of EUS FNA, which based on recent reports appears to be an overstated concern. However, the perceived need to obtain a tissue diagnosis in all patients is discouraged. Instead practice patterns should be guided by patient desires and operability, the wishes of the consulting physicians, local expertise, and one’s practice settings. It is also important that each endosonographer be aware of the performance characteristics of EUS, percutaneous, and surgical biopsy in their center. Diagnostic sensitivities and specificities lower than those reported in the literature further reduce the value of FNA and argue against pancreatic biopsy. The overriding consideration must be the potential impact of FNA results on clinical decision making, prognosis, and management. When biopsies are deemed necessary, we should employ methods for acquiring FNA samples shown to reduce the need for pancreatic biopsy, to enhance diagnostic accuracy, and improve safety.

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