14 Role of Guided – Fine Needle Biopsy of the Pancreatic Lesion

A variety of uncommon types of pancreatic carcinoma have been described, including acinar, adenosquamous, anaplastic, papillary, mucinous and microadenocarcinomas, each of which composes less than 5% of the total. All of these have similarly poor prognoses and are treated in a similar fashion. Also uncommon are mucinous cystic neoplasms (cystadenoma/cystadenocarcinoma) of the pancreas, which occur most frequently in the middle-aged women, and these are tipically located in the tail of the pancreas.

In clinical practice differential diagnosis of pancreatic masses is frequently a clinical challenge; often therapeutic decision in this context is mainly based on the ability to perform a diagnosis of malignancy or to exclude malignancy (Tamm & Charnsangavej, 2001).
It is well known that ductal adenocarcinoma is the most frequent cause of pancreatic mass, however other neoplasms such as lymphoma, metastasis, cystic tumors or benign conditions as chronic pancreatitis with different prognosis and treatment options can arise within the pancreas (Iglesias et al., 2010).
A pathologic diagnosis becomes therefore relevant for an adequate therapeutic strategy (Cohen et al., 2000).
At least 80% of the patients with suspected pancreatic cancer, have unresectable disease at diagnosis because of locoregional involvement or distant metastases , and it as been reported that only 7% of the patients have a tumour that is confined within the pancreas (National Cancer Institute, 2007).
Patients with suspected pancreatic cancer and imaging studies suggesting resectable tumour should undergo directly to surgery since no histologic diagnosis confirmation is required prior to surgical exploration unless neoadjuvant therapy is indicated (Zamboni et al., 2010).
As a matter of fact preoperative cytohistological diagnosis may risk dissemination of cancer cells, or developing complications (bleeding, pancreatitis, pancreatic leak) that can delay surgery and increase costs.
On the other hand a negative biopsy results in a patient with a high suspicion of cancer neoplasm that is not of help, due to a high possibility of a false negative result (Tillou et al., 1996).
Patients with metastatic or locally advanced but unresectable disease at imaging studies should undergo biopsy prior chemotherapy or radiation since a cytohistological diagnosis is recommended before initiating a cytostatic therapy coherently with the National Comprehensive Cancer Network (NCCN) guidelines for suspected pancreatic cancer.(Hartwig et al, 2009;Itani et al., 1997) Biopsies allow a cytohistological diagnosis and can differentiate pancreatic cancer between primary pancreatic lymphoma (Arcari et al., 2005), metastasis or benign focal lesion such as focal pancreatitis.

Primary pancreatic lymphoma and pancreatic metastasis
Primary pancreatic lymphoma (PPL) is a very rare disease, representing fewer than 2% of extra-nodal malignant lymphoma and 0,5% of all pancreatic masses (Arcari et al., 2005).
Fewer than 150 cases of PPL have been reported in the literature in English.Imaging techniques such as Us and CT scan can suggest a diagnosis of PPL but a cyto-hystological examination is mandatory for diagnosis and treatment planning of patients with suspicious PPL.Our group reported five cases of PPL and reviewing the literature it was concluded

Staging of pancreatic cancer (table 1)
Staging procedures include US, CT scanning, MRI, and EUS.A diagnostic laparoscopy may also be performed to detect peritoneal disease that is not visible radiologically.Regardless of these studies, an accurate histologic diagnosis is necessary to distinguish benign disease from carcinoma, islet cell tumors, and retroperitoneal lymphomas, because of the major therapeutic and prognostic differences among these disease entities.Criteria for surgical resection include absence of metastatic disease and absence of invasion of prominent local blood vessels.

Guide for pancreatic biopsy
Intraoperative needle biopsy of the pancreas has been performed with the fine-needle aspiration biopsy (FNAB) technique since the 1960's (Moossa & Altorki, 1983) and with the core tissue biopsy technique since 1970's (Ingram et al., 1978) subsequently ultrasound , computed tomography and endoscopic ultrasound became available to evaluate and characterize pancreatic masses and above all to guide a needle for the biopsy, avoiding the costs, morbidity and mortality of a major surgical procedure performed only to obtain a tissue sample for a cytohistological diagnosis (Civardi et al.,1986;Turner et a.l, 2010).
For many years percutaneous US and /or CT guided biopsy was routinely performed in situations in which a pancreatic biopsy was necessary, in 2002 the American Joint Committee on cancer has selected endoscopic ultrasound guided FNAB as "the procedure of choice" if available (Greene et al., 2002).
However, as recently reported, local expertise in and the availability of EUS and interventional radiology may determine the first procedure selected for a cytohistological diagnosis for a pancreatic mass (Zamboni et al., 2010 ).

TX
Primary tumor cannot be assessed

T0
No evidence of primary tumor

Tis
In situ carcinoma

T1
Tumor limited to the pancreas 2 cm or less in greatest dimension

T2
Tumor limited to the pancreas more than 2 cm in greatest dimension

T3
Tumor extends beyond the pancreas but without involvement of celiac axis or the superior mesenteric artery T4 Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor) Regional Lymph Nodes (N)

NX
Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis Table 1.Staging of pancreatic carcinoma

Methods of percutaneous guided biopsy
Patient preparation before any type of invasive procedure includes ruling out coagulation disorders with laboratory tests and obtaining written informed consent for the biopsy.Local anesthesia (lidocaine) is not routinely performed.(Zamboni et al., 2010;Civardi et al., 1986).

Percutaneous ultrasound
In the past for performing abdominal US-guided FNAB the "free-hand" technique was utilized (Civardi et al., 1986;Bret et al., 1982;Livraghi, 1984) subsequently puncturing probe became available and two types of probes are commonly used for interventional procedures: probes with lateral support and probes with noncontinuous crystals and central support; the former allow only oblique needle tracks, whereas the latter allow both vertical and oblique tracks.
Prior to perform the biopsy, a pancreatic lesion can be studied with conventional US, Doppler US, and CT, to evaluate the content of the lesion and to select the best route for biopsy, avoiding vessels and pleura.
In clinical practice when liver metastases are present in patients with suspected pancreatic cancer, the biopsy can be done in the liver metastasis, if safer for the patient and easier for the psysician.

Computed tomography
Computed tomography allows optimal visualization of the lesion and is superior to US in large fat patients , however radiation dose and the procedure length are the major limits of CT -guided pancreatic biopsy.
CT fluoroscopy can reduce procedure length because it allows a fast reconstruction of images, with a continuous update and the possibility of controlling acquisition and visualizing images in the room while performing the examination.
In addiction CT fluoroscopy allows visualizing the needle track from the entry point to the target, allowing faster and more efficient procedure (Zamboni et al., 2010).

Endoscopic ultrasound
Over the past decade, EUS has proven to be one of the most significant advantages in gastrointestinal endoscopy (Turner et al., 2010;Erickson, 2004) Since its introduction, EUS has offered improved accessibility to small pancreatic lesions, and its usefulness as a diagnostic tool has greately changed the therapeutic approach to pancreatic masses.
Since it was first reported in (Chang et al, 1994), EUS-guided FNAB of the pancreas has become a popular technique for the diagnosis and staging of cystic and solid lesions of the pancreas because it is relatively safe and accurate (Carrara et al., 2010;).
Thus, this diagnostic modality has become important in the management of patients with symptomatic or incidentally discovered pancreatic masses.

US, CT, or EUS for guide pancreatic FNAB
The relative diagnostic accuracy, safety and cost of US and CT-guided FNAB favor their use over EUS-FNAB for the diagnosis of unresectable pancreatic tumors.(Zamboni et al., 2010 ;Levy, 2006).
A randomized controlled trial EUS-FNAB and US/CT-FNAB failed to observe any statistically significant difference between the endoscopic and percutaneous approach in the diagnosis of pancreatic malignancy (Horwhat et al.,2006).
Several authors support the use of EUS-FNAB over percutaneuos approach because of the lower risk of seeding (Gilbert et al, 2001;Turner et al, 2010).In a review of 1406 cases with advanced pancreatic cancer who underwent nonsurgical biopsy (percutaneous-guided or EUS-guided sampling) were compared with cases who did not undergo biopsy, without observing any difference in overall median survival, so it was concluded that the risk of www.intechopen.comseeding is remote.(Hernandez et al., 2009).It was reported that the risk of seeding can be related to the number of needle passes: more number of needle passes more risk of seeding (Civardi et al., 1986;Fornari et al., 1989).
It must be emphasized that one-site cytopathological evaluation can improve the diagnostic yield of guided FNAB and can reduce the number of needle passes (Garcia et al., 2011).
A review of 182 patients undergoing EUS-guided FNAB of solid pancreatic lesions over a 2 years study period was reported (Garcia et al., 2011).Sample were either evaluated on site by a cytopathologist or processed by the endoscopist and sent to the pathology department for evaluation.
Diagnostic accuracy for malignancy, number of needle passes, adequate -specimen collection rate, cytological diagnosis , and final diagnosis and complications rate according to the presence or absence of on-site cytopathologist were evaluated.
Already, in 1988 our group reported the value of rapid staining and assessment of percutaneous ultrasound-guided fine needle aspiration biopsy in a series of 160 patients.(Civardi et al., 1988) The total series of FNAB had a sensitivity of 95.6%, a specificity of 100% and an overall accuracy of 97.3%.
The cumulative accuracy after each pass was calculated: a significant increase in diagnostic accuracy was found only after the second pass, the third and the fourth passes gave little further improvement.These results indicate that a rapid evaluation of the aspirated material during US-guided FNAB can reduce the number of punctures needed per case resulting in less disconfort and, probably a reduced likelihood of complications for the patient.
It must be emphasized that in this study the same physicians that performed the US-FNAB performed also the rapid staining evaluation for the adequacy avoiding the cytopathologist, minimizing the costs and improving the educational benefit of physicians.(Civardi et al., 1988).

Type of needle and results of guided biopsy
Biopsies of the pancreas can be performed with needle ranging in size from 18 to 25 gauge (G).Aspiration biopsies for cytological evaluation are performed with fine-needle (< 1mm in external diameter : from 20 to 25 G), cutting needle are used to obtain tissue cores, which allow hystopathological evaluation , these needle ranging in size from 18 to 23 G.
In table 2 are reported the results of sensitivity, specificity, overall accuracy, method of guidance, needle size of percutaneous pancreatic fine-needle aspiration biopsy.
The largest series reporting in the literature percutaneous FNAB of pancreatic masses show sensitivities ranging between 62% and 93%, accuracies between 72% and 94%.The majority of percutaneous FNAB are ultrasound guided, and the needle size range from 21 to 22 G (Tab 2).
FNAB cytology of pancreatic cancer are reported in figure 1 a , b, 2 a, b, 3 a, b; www.intechopen.com Table 3. Sensitivity, specificity, accuracy method of guidance and needle size (gauge) of percutaneous tissue core biopsy of pancreatic masses 372 CT-guided pancreatic biopsies with a 18 G cutting needle showed 90% sensitivity and accuracy (Karlson et al., 1996); similar results were reported in a series of 212 US guided percutaneous tissue core pancreatic biopsies, with 86% sensitivity and accuracy (Paulsen et al., 2006).
The largest series in the literature on percutaneous tissue core biopsy of pancreatic lesions report sensitivities and accuracies between 86% and 100% (Tab 3).Tissue core biopsy of primary pancreatic lymphoma and metastatic adenocarcinoma are reported in fig 5 a b and 6 a b c.Percutaneous core biopsy of pancreatic lesions is considered sensitive, safe and accurate (Zanaboni et al., 2010) however this procedure may have a higher complication rate than percutaneous FNAB (Fornari et al., 1989).
At our institution we routinely use FNAB with 22G needles when a pathologic diagnosis of pancreatic mass is required while tissue core biopsy with 20G or 21G needles is reserved when cytological diagnosis is inadequate or when lymphoma is suspected on cytological evaluation (Arcari et al., 2005)    * The presence of an on site-cytopathologist was associated with a significantly higher diagnostic sensitivity and overall accuracy for malignancy.Interventions with needle with a larger diameter seem cause more complications.

N of patients
The major complication of pancreatic biopsy can be hemorrhage, needle track seeding and pancreatitis.
Our group (29) reported the complications following 10.766 US-guided fine-needle abdominal biopsies.The mortality was 0.018%: the two reported deaths were due to hemoperitoneum and occurred in patients with hepatocellular carcinoma arizing in cirrotic liver.
The biopsy of pancreatic carcinoma was more dangerous for needle -track seeding (five of eight reported cases), however, it has been reported that peritoneal carcinomatosis may occur more frequently in patients who undergo percutaneous FNAB compared with those who have FUS-FNAB for the diagnosis of pancreatic cancer (Micames et al, 2003).

Conclusions
There is consensus in the literature of the appropriateness of obtaining a cytohystological diagnosis in patients with unresectable pancreatic neoplastic lesion, prior to initiate chemotherapy and/or radiation.
Although the American Joint Committeee on Cancer has selected EUS-guided FNAB as the procedure of choice, if available, we recall that there is wide variability in the world on the modalities for guide biopsy (US ; CT ; EUS) and for needle biopsy choice (FNAB or tissue core biopsy).
There is a consensus that local expertise, the availability of EUS and interventional percutaneous procedures may determine the choice for pancreatic biopsy.
In agreement with other authors (Zamboni et al., 2010) at our institution , in the appropriate setting, percutaneous US-guided FNAB is considered the first invasive approach of obtaining tissue diagnosis confirmation in patients with unresectable lesions.
However, guided FNAB or guided tissue core biopses remain invasive procedures and must be performed when informations so obtained benefits the patient.

Acknowledgments
Authors thanks Michela Monfredo, Gabriele Cremona and MariaRosa Cordani for the important support.

Table 2 .
in a multicenter study reviewed 510 patients who had a final diagnosis available and who had undergone ultrasound-guided fine needle biopsy of the Sensitivity, specificity, accuracy method of guidance and needle size (gauge) of percutaneous fine needle aspiration biopsy of pancreatic masses

Table 4 .
Sensitivity, specificity, accuracy needle size of endoscopic-guide pancreatic biopsy