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Histopathologic Evaluation ofTissue Extracted on theRadiofrequency Probe AfterAblation of Liver Tumors:Preliminary Findings

OBJECTIVE. Our aim was to evaluate the histologic characteristics of tissue extracted onthe probe immediately after radiofrequency ablation of malignant tumors in the liver.

MATERIALS AND METHODS. From April to December 2001, 20 radiofrequency ab-lations were performed in 19 patients with primary (

n

= 17) and metastatic (

n

= 2) liver

masses. Track ablation according to device protocol was performed after each ablation. Tissue

was adherent to the probe after all radiofrequency probe passes. All pieces of tissue found on

the probe were collected and preserved in formalin.

RESULTS.

Tissue was examined by the study pathologist. In eight (40%) of 20 speci-

mens, coagulation necrosis was present. In five (25%) of 20 specimens, possibly nonviable

tissue was extracted, although some cell characteristics were identified. In seven (35%) of 20

specimens with hepatocellular carcinoma, possibly viable tissue was found. Five specimens

were identified as hepatocellular carcinoma, and two, as cirrhotic nodules.

CONCLUSION.

Histopathologic evaluation of the tissue extracted on the radiofrequency

probe after ablation is feasible. This study showed that coagulation necrosis was clearly present in

at least 40% of the patients, which proves that nonviable tissue can be seen immediately after ab-

lation. Whether this pathologic finding has prognostic value is not known.

umor ablation with thermal energy

sources, such as radiofrequency,

laser, or microwave, is receivingincreasing attention as treatment for focal ma-

lignant liver tumors [15]. These methods per-

mit local tumor destruction with minimal

damage to surrounding tissue and are being

used to treat focal hepatic malignancy.

Percutaneous, imaging-guided, radiofre-

quency ablation of tumors is used in patients

who are not considered candidates for anatomic

surgical hepatic resection because of age, co-

morbidity, or extent of disease. Radiofrequency

ablation has also been reported to reduce the

size of, or stabilize, hepatic tumors in patients

awaiting liver transplantation [6, 7].

Although complications of radiofre-quency ablation are rare [2], limitations of

thermal energy therapy include tumor seed-

ing along the ablation track [8], incomplete

tumor ablation [6,] and posttreatment recur-

rence [7, 9].

While performing a series of percutaneous

radiofrequency ablations of liver tumors, we

noticed that tissue always adhered to the

probe and its electrodes after each use, and

we postulated that histologic assessment of

the viability of this tissue might be feasible

and could conceivably be used in the futureas a predictor of treatment outcome. This

preliminary report describes the histopatho-

logic characteristics of tissue extracted from

the radiofrequency probe after 20 ablations

in 19 patients and shows that when the Ra-

diofrequency Interstitial Tumor Ablation

(RITA) system (RITA Medical Systems) is

used, there is always adequate amount of tis-

sue on the probe and its nine electrodes to al-

low histologic examination and provide

information regarding tissue damage.

Materials and Methods

The study was designed to examine the histo-

pathologic characteristics of tissue extracted from

the probe after radiofrequency ablation of liver tu-

mors. Institutional review board approval was ob-

tained, and all patients signed informed consent

forms before the procedure. This series included

patients who underwent percutaneous radiofre-

quency ablation with the RITA system, using CT

guidance. The procedures were performed with the

patients under general anesthesia or IV sedation at

Constantinos T. Sofocleous

1,2

Kenneth M. Klein

3

Basil Hubbi

4

Karen T. Brown

2

Stanley H. Weiss

5

George Kannarkat

4

Clay R. Hinrichs

1

Daniel Contractor

1

Philip Bahramipour

1

Allison Barone

1

Stephen R. Baker

1

Received August 28, 2003; accepted after revisionJ anuary 21, 2004.

1

Department of Radiology, University of Medicine andDentistry of New J erseyNewark, Newark, NJ .

2

Present address: Department of Interventional Radiology,Memorial Sloan-Kettering Cancer Center, Weil MedicalCollege, Cornell University, 1275 York Ave., New York, NY10021. Address correspondence to C. T. Sofocleous([email protected]).

3

Department of Pathology, University of Medicine andDentistry of New J erseyNewark, Newark, NJ .

4

New J ersey Medical School, University of Medicine andDentistry of New J erseyNewark, Newark, NJ .

5

Department of Epidemiology and Preventive Medicine,New J ersey Medical School, University of Medicine andDentistry of New J erseyNewark, Newark, NJ .

AJR

2004;183:209213

0361803X/04/1831209

American Roentgen Ray Society

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the discretion of the consulting attending anesthesi-

ologist while the patient was under continuous elec-

trophysiologic monitoring. Each ablation was

performed by one of four fellowship-trained attend-

ing interventional radiologists with similar experi-

ence in the performance of imaging-guided

percutaneous radiofrequency ablation. From April

to December 2001, tissue was collected from 20 ra-diofrequency ablation sessions performed in 19 pa-

tients with primary (

n

= 17) and metastatic (

n

= 2)

liver masses. Population demographics, preablation

tumor size and location, and pathologic findings are

presented in Table 1.

A detailed description of the radiofrequency

ablation system that we used has been made in a

prior publication that reported application of lap-

aroscopic radiofrequency ablation [10]. In short,

the radiofrequency generator (model 1500, RITA

Medical Systems) was activated to the power

needed (maximum, 150 W) to achieve a probe

temperature (average thermocouple temperature,

105C) resulting in cell death. The target tempera-

ture monitored by the thermocouple is maintained

for 514 min depending on the desired radius of

necrosis (35 cm). In two lesions larger than 5 cm

in diameter, two overlapping areas of 5-cm abla-

tions were performed at the same session. After

each ablation, a cooldown cycle was performed by

the automatic turnoff of the generator power.

Mean temperature of 70C at 60 sec after ablation

indicates that a technically successful ablation has

been performed [10]. Track ablation according to

device protocol (preservation of mean temperature

at

70C) is performed after the termination of

the ablation and cooldown cycles [10, 11], while

the probe is gradually withdrawn from the liver.We observed that macroscopically identifiable

tissue was always adherent to the probe and its

nine electrodes (tines or prongs) after each use

(Fig. 1). The entire amount of tissue was col-

lected from the needle of the thermal ablation

probe and all its reexpanded nine electrodes after

the completion of percutaneous radiofrequency

ablation. All the fragments of tissue found on the

probe and the electrodes after each radiofre-

quency ablation session were collected. The

specimens, measuring 511 mm in length (Fig.

1B), were collected by the interventional radiol-

ogist, placed in formalin, and sent to the labora-

tory for examination by the study pathologist.

The specimens were handled like any surgical

specimen: They were fixed in 10% formalin, de-

hydrated and embedded in paraffin, and then cut

into 5-

m-thick sections. They were subse-

quently stained with H and E and Masson

trichrome to define fibrosis.

The pathologic findings were classified as one

of the following: coagulation necrosis (nonviable

tissue), findings of coagulation necrosis without

identifiable cell characteristics (Fig. 2A); possibly

nonviable tissues, tumor cells that are smudged

and somewhat distorted, with poorly identified cy-

toplasm and nuclei identified between areas of co-

agulation necrosis (Fig. 2B); and possibly viabletissues, cell characteristics of malignant cells

(hepatocellular carcinoma) or cirrhotic nodules or

both (Fig. 2C).

Results

All tissue fragments were collected and

examined by the study pathologist. In eight

(40%) of 20 specimens, coagulation necrosis

(nonviable tissue) was present (Table 1 and

Fig. 2A) without any preservation of cellular

characteristics. In five (25%) of 20 speci-

mens, possibly nonviable tissue was classi-

fied, although some cell characteristics wereidentified (Table 1 and Fig. 2B). In these

specimens, areas of coagulation necrosis

were interrupted by the presence of cells that

preserved their cell membrane, protoplasm,

aHepatic segment of tumor location.

bPreablation size of lesion as shown on contrast-enhanced CT.cSignifies same patient and same lesion treated.

TABLE 1 Population Demographics, Preablation Tumor Size and Location, and Pathologic Findings

Patient No. Diagnosis SegmentaSizeb

(cm)Ascites Age (yr) Sex

Coagulation

Necrosis

Possibly

Nonviable

Possibly

Viable

1 Hepatocellular carcinoma VI, VII 5.5 Present 66 Male Present

2 Hepatocellular carcinoma V, VIII 6.5 45 Male Present3 Hepatocellular carcinoma IVA 4 58 Male Present

4 Hepatocellular carcinoma VII 2 52 Male Present

5 Hepatocellular carcinoma VIII, VII 4 Present 68 Male Present

6 Hepatocellular carcinoma VII 3.5 75 Female Present

7 Hepatocellular carcinoma V 3 Present 74 Female Present

7c Hepatocellular carcinomac V 2 Present 74 Female Present

8 Hepatocellular carcinoma IV 2 58 Male Present

9 Hepatocellular carcinoma VI 1.2 Present 44 Male Present

10 Breast metastasis VIII dome 4 56 Female Present

11 Breast metastasis V 2 35 Female Present

12 Hepatocellular carcinoma V, VI 3 Present 69 Male Present

13 Hepatocellular carcinoma IV 1.4 Present 63 Female Present

14 Hepatocellular carcinoma III 3.3 Present 62 Female Present

15 Hepatocellular carcinoma VI 4.3 53 Male Present

16 Hepatocellular carcinoma V 4.2 66 Female Present

17 Hepatocellular carcinoma V 2.7 48 Male Present

18 Hepatocellular carcinoma II 2 53 Male Present

19 Hepatocellular carcinoma V, VI 3.5 43 Male Present


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Histopathologic Evaluation After Ablation of Liver Tumors

AJ R:183, J uly 2004

211

and nuclei and were therefore identifiable. In

seven (35%) of 20 specimens, possibly via-

ble tissue was found: five cases with hepato-

cellular carcinoma and two with cirrhotic

nodules (Table 1). In five of these specimens,

several nests of cells with characteristics of

malignancy consistent with hepatocellular

carcinoma were present (Fig. 2C). In the

other two,

no evidence of malignancy was

found, but cellular characteristics diagnostic

of cirrhosis were present. Changes of coagu-lation necrosis, although present, were in-

consistent and much less evident in

specimens classified as possibly viable.

Discussion

Imaging-guided radiofrequency ablation

is a promising technique for the treatment of

unresectable hepatic tumors [4, 5], with a

relatively low incidence of complications [2,

12] and shortcomings such as incomplete tu-

mor ablation [6], tumor developing in a new

location [7], local tumor recurrence or pro-

gression [9], and tumor seeding of the percu-taneous ablation track [8].

In a prior study, radiofrequency ablation

of liver tumors using internally cooled elec-

trodes (Radionics) was followed by surgical

excision and subsequent pathologic exami-

nation that showed no coagulation necrosis

immediately after treatment. In specimens

removed and examined 3 days or later, defi-

nite contiguous coagulation necrosis with-

out intervening areas of viable tumor was

seen [13]. Our specimens extracted by the

RITA probe and evaluated immediately after

treatment showed coagulation necrosis in a

significant number (40%) of specimens. This

finding alone is interesting and worth report-

ing because it may prove to be a predictor of

outcome. In our patients in whom evidence

of viable hepatic tissue or malignancy or

both was present (60%), progression to irre-

versible coagulation and cellular death mightbe found later after treatment if one assumes

that radiofrequency ablation causes hepatic

injury and subsequent cell necrosis in a

pathophysiologic manner similar to that in

ischemic necrosis [13]. This question was

not addressed in our study, which did not in-

clude any late tissue evaluation from the area

of the ablated tumor. Several mechanisms

may cause cellular injury by radiofrequency

ablation [14]; the most likely one would be

due to radiofrequency-induced heating,

which presumably drives extracellular and

intracellular water out of the tissue and

causes coagulation necrosis [15]. Althoughreported for the first time, finding coagula-

tion necrosis immediately after ablation is

not surprising. Histopathologic findings 24

hr after radiofrequency ablation in a rabbit

liver model showed coagulation necrosis that

could be detected on MRI [16]. Coagulative

necrosis after radiofrequency ablation was

described in a pig liver model [17], and co-

arcted cytoplasm (coagulation), in a guinea

pig liver study [18] within the first day after

ablation. When the researchers evaluated the

effect of vascular occlusion on radiofre-

quency ablation in a porcine model [19], the

animals were immediately sacrificed after

ablation, and specimen examination and H

and E staining showed that the liver area

around the radiofrequency probe (four-elec-

trode probe, model 30, RITA Medical Sys-

tems) consisted of vacuolated hepatocytes

with frayed borders. In the inner zone of ab-lation around the probe, no intact hepatic tis-

sue was seen. Coagulated tissue with no

viable cells was found in the central pale

zone of ablation in a porcine model after us-

ing the LeVeen electrode (Radiotherapeu-

tics) [20]. When the researchers used a

similar technique with the hook electrodes

probe (RITA Medical Systems), the ablated

liver tumor was resected and evaluated

pathologically at a later time. The results

showed that in all cases, the ablated tissue

could be recognized on H and Estained sec-

tions as areas of disrupted cell outlines, pre-

served nuclear staining, and increasedcytoplasmic eosinophilia [21]. Tissue viabil-

ity immediately after radiofrequency abla-

tion with the LeVeen probe in the normal pig

liver has been evaluated with histochemical

(lactate dehydrogenase and nicotinamide ad-

enine dinucleotide-diaphorase-NADPH-dia-

phorase) and H and E stains, showing a core

of heat-coagulation tissue on the H and E not

stained by the histochemical stain, suggest-

Fig. 1.Tissue fragments extracted by radiofrequency ablation probe.A,Photograph showsneedle probe after radiofrequency ablation and removal from patients body, with fragments of extracted tissue on reexpanded electrodes.

B,Photograph shows fragment collected from probe, measured with ruler in centimeters.

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AJ R:183, J uly 2004

Sofocleous et al.

ing 100% cellular destruction [22]. H and E

staining showed thermal coagulation in spec-

imens collected 8 hr after radiofrequency ab-

lation of lung tumors in a large-animal model

[23]. Using this simple technique, we

showed that coagulation necrosis achieved

by radiofrequency ablation can be recog-

nized immediately on pathologic examina-

tion of the extracted tissue in almost half of

the cases.

This preliminary report shows that tissue

adherent to the radiofrequency probe after

ablation can be examined pathologically and

may show coagulation necrosis [22, 23]. Im-

mediate postablation pathologic examination

of tissue adherent to the radiofrequency

probe is technically feasible and may insti-

gate further investigation to determine its

value as a possible predictor of radiofre-

quency ablation outcomes.

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Fig. 2.Histopathologic findings after radiofrequency ablation.A,Photomicrograph shows coagulation necrosis immediatelyafter radiofrequency ablation of hepatocellular carcinoma(Table 1, patient 3).B,Photomicrograph shows possibly nonviable tissue. Coagu-lation necrosis is interrupted by nest of tumor (hepatocellularcarcinoma) cells, which are smudged and somewhat dis-torted. Cytoplasm and nuclei of tumor cells are not as clearlyseen (Table 1, patient 14).C,Photomicrograph shows possibly viable tissue. Note nest ofmalignant cells (hepatocellular carcinoma) (Table 1, patient 6).

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