Introduction

Liver is a common site of primary and secondary malignant tumors, secondary involvement / metastasis being more common. The most common site of primary malignancy metastasizing to the liver being carcinoma breast, lung and colon. (1)(2) In oncology, in diagnostic / staging as well as surveillance CT scan of patients, small liver lesions are frequently found. These lesions may not show typical morphology to characterize them into either benign or malignant categories and FNAC/biopsy is sometimes difficult in inexperienced hands. In patients with known malignancy, definite characterization of these lesions into benign vs malignant is crucial in determining the prognosis and treatment. Jones et al (3) reported in their study that liver lesions less than or equal to 15 mm were found in 17% of the cases and were benign in 51% of the 82% of patients with known malignancy. Schwartz et al(4) in their study reported that hepatic lesions less than or equal to 1 cm, deemed too small to characterize, are most often benign, but approximately 11.6% of these lesions were malignant. Schwartz et al also reported in their study that when these too small to characterize liver lesions were followed, the average reported time for increase in size of these TSTC liver lesions was 13 months if malignant in etiology.

Colin et al(5) reported that almost all of the malignant liver lesions were diagnosed within four weeks, but required long term follow up and un-necessary increased imaging for benign lesion. In patients with liver cirrhosis or focal fatty lesions, it was difficult to differentiate between regenerative nodules or focal fatty lesions from hepatocellular carcinoma (HCC) and such lesions required longer follow up (range of follow up was 2 – 42 weeks). More likely diagnosis in cirrhotic liver is HCC, followed by the high and low grade dysplastic nodules. In cirrhotic liver, liver nodules less than 1 cms require follow up with ultrasound every 3 months while nodules between 1 to 2 cms size require histopathological correlation if imaging findings are atypical. (6)

Stacey et al(7) in their study found that upto 30% of liver lesions, deemed too small to characterize on CT scan, remained indeterminate on MRI. However, follow up imaging and histopathology diagnosis (in few) showed no significant interval change/resolved and benign nature of these lesions respectively. However, when followed up, mean follow up was 60.6 weeks. Unnecessary follow for small lesions increases patient’s anxiety and more repeated imaging studies were performed for benign than malignant lesions. White paper of the ACR on management of incidental liver lesion describes that most of the liver lesions less than 1 cms are benign; however suggests follow up MRI after 3 – 6 months in high risk patients for further characterization of these lesions. They also suggest hepatic MRI for liver lesions between 1 – 1.5 cms with suspicious features on imaging. (8)

However, when patient has known extra-hepatic malignancy, it becomes important to characterize these small liver lesions into benign and malignancy, especially when imaging findings are atypical. Sometimes it becomes difficult to differentiate new onset small liver lesion into benign or malignant, if malignant then labeled as disease progression. Timely intervention of liver metastasis in selected patients has favorable prognosis and delay in diagnosis has poorer prognosis and reduced survival.(9)(10)(11)(12)(13) When solitary or few, as seen often in colorectal cancer where metastatectomy/RFA/intraarterial chemotherapy can be performed(14)(15), to characterize these TSTC liver lesions into benign and malignant, tissue diagnosis is important. Also resection of isolated liver metastasis in carcinoma breast which can be the site of isolated recurrence (16) tissue diagnosis prior to surgery is important.So if these lesions are intervened early with USG guided FNAC / biopsy which is cost effective, reliable and easily available, early diagnosis is possible with early treatment and this long follow up without appropriate treatment can be avoided.

Therefore, when the suspicion of liver metastasis is high, even when the lesion is small, it is essential to sample it and to get a final cytological / histopathological diagnosis that will aid in precise patient management and in turn improve the outcome.

Materials and Methods

This is a single institution retrospective study performed at National Cancer Institute, Nagpur, Maharashtra, India. Retrospective data was collected of patients who have undergone FNAC / biopsy of small liver lesions during 01.01.2019 to 31.10.2021. Data was collected from the radiology dataset of patients available at the institute. During this period, total 1455 USG guided FNAC and biopsies were performed, out of which 899 were FNACs and 556 were biopsies. Of these, total 53 procedures were performed on liver nodules including 34 FNAC and 19 biopsies, out of which 28 nodules in 26 patients met out study criteria, i.e., liver lesion size less than or equal to 20 mm. Out of these 28 nodules, FNAC was performed on 26 nodules and biopsy on 2 nodules.Ultrasound guided percutaneous aspirations were done in 26 nodules. For FNAC, 25 G spinal needles were used and for deep lesions in segment VII/VIII which were beyond the reach of the spinal needle that is9.8 cm long, 23G 15 cm chiba needle was used to obtain tissue. Slides prepared from the aspirate and transferred to the coplin jar containing 95% ethyl alcohol solution. Few dry smears were also prepared.

Biopsy was done using an 18 G BARD coaxial biopsy needle and 17 G BARD biopsy gun. Multiple cores, at least 4 cores in 4 different positions of the cutting edge, were obtained. Also more cores were obtained by changing the needle position if required.Samples were sent to the pathology department for further cytological / histopathological reporting.

Technique:

Prior to FNAC/biopsy, liver lesion is evaluated with ultrasound, approach decided and point of entry is marked on skin. FNAC / biopsy can be done using either intercostal, subcostal or transabdominal / sub- xiphoid approach depending upon the location of the liver lesion. (Fig. 1) Then entry site and surrounding area is cleaned with alcohol / betadine. Transducer and wire is covered with sterile probe cover with jelly inside over the transducer, which is important to avoid soiling of the probe and to maintain proper aseptic technique. Local anesthesia with 2% lignocaine is given at the site of entry involving skin and underlying soft tissue along the proposed needle trajectory. Then under ultrasound guidance, a FNAC / biopsy needle is inserted into the lesion avoiding the vessels. Keep the tract of the needle tangential to the ultrasound beam, with this entire tract of the needle can be visualized and, vessels can be avoided using color doppler technique. It is always preferred to put the needle parallel to the vessels and not perpendicular to it, to avoid transection of vessels while taking cores with a gun. (Fig. 2, 3 and 4) We prefer to do the procedures during normal breathing and the needle can be advanced in whichever phase of respiration the lesion is more conspicuous. However, for smaller lesions, those located beneath the rib and deeply seated lesion in segment VII/VIII, breathhold (either during inspiration / expiration) is required. (Fig. 5) While doing FNAC, move the needle to & fro and let the sample collect in the needle with the capillary action and check for the same by looking at the needle hub. If the sample does not collect in the needle, then gentle suction with a syringe is given. Care should be taken not to give excessive negative pressure in the syringe to prevent hemorrhagic aspirate. Generally it requires 2-3 passes for FNAC. Slides are prepared from the aspirate and transferred to the coplin jar containing 95% ethyl alcohol solution. It is better to perform the procedure under the presence of cytologists who can check for the adequacy of the sample obtained and avoiding inconclusive FNAC and repeat procedures. For biopsy, after confirming the position of the needle in the lesion (preferably at the periphery in larger lesion), semiautomatic biopsy gun is inserted and cores are taken. At least 4 cores in 4 different directions of the curing edge are taken and transferred to the container containing formalin.

Figure 04: 69 Y / Male, operated case of carcinoma colon, on observation. Surveillance CT scan shows an irregular hypodense lesion in right lobe of liver (black arrow in a) and associated focal IHBR dilatation (yellow arrow in a). Correlative ultrasound shows an irregular hyperechoic lesion in right lobe of liver (black arrow in b). USG guided FNAC was done (c) with needle close to the branch of portal vein (white arrow in c) and is avoided.

Primary & Secondary Outcome

Primary outcome is to describe the importance of ultrasound guided FNAC/biopsy of small liver lesions.

Secondary outcome is to address technical difficulties in the FNAC / biopsy of small liver lesions and methods to deal with them.

Inclusion & Exclusion Criteria Inclusion Criteria:

1.Patient with known malignancy with small liver lesions of size less than 20 mm

2.Biopsy / FNAC was performed at our institution and histopathology / cytology report available.

Exclusion Criteria:

1.Patient with known malignancy with liver lesions of size more than 20 mm

Statistical Analysis

In this research paper, the collected data has been methodically categorized into distinct groups, allowing for a comprehensive and systematic analysis of the research subject. The subsequent presentation includes a detailed breakdown of data distribution, expressed in terms of percentages. This quantitative approach not only elucidates the prevalence of each category but also uncovers significant trends and patterns within the dataset, thereby enhancing the overall depth and clarity of the findings.

Ethics

The study was approved by the Ethics Committee, National Cancer Institute, Nagpur, Maharashtra, India, on dated 13.08.2021 Approval number is NCI/EC/2018/017/08//2021. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Results

Patient demographic are given in table 1. There are a total 28 nodules in 26 patients, out of which biopsy was done on 2 nodules and FNAC was done on 26 nodules. Out of 26 patients, 11 were male patients and 15 female, with 8 cases of carcinoma breast (30.76%), 7 cases of colo-rectal cancer (26.92%) 3 cases of lung cancer (11.54%), 1 carcinoma buccal mucosa (3.84%), 1 carcinoma cricopharynx (3.84%), 1 case of carcinoma soft palate (3.84%), 1 carcinoma esophagus (3.84%), 1 carcinoma pancreas (3.84%), 1 case of carcinoma urinary bladder (3.84%) and 1 carcinoma cervix (3.84%). 1 patient (3.84%) was being evaluated for liver SOL. (Table 2) Liver lesion sizes range from 5 mm to 20 mm, with mean size of 12.68 mm and median size of 12.5 mm. 1 out of 28 lesions was located in segment II (3.57%), 11 in segment III (39.28%), 3 in segment IVA (10.71%), 2 in segment IVB (7.14%), 3 in segment V (10.71%), 1 in segment VI (3.57%),

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