Oral Biosciences & Medicine
Oral Biosci Med 1 (2004), No. 1     10. Mar. 2004

Oral Biosci Med 1/2004, S. 55-60

Liver Ultrasound in Oral Squamous Cell Carcinoma

Giuseppe Colella a / Salvatore Cappabianca b / Amerigo Giudice a / Crispian Scully c

Abstract

Purpose:
The presence of metastases plays a fundamental role in staging of patients with head and neck cancer before treatment. The aim of this study was to determine the role of ultrasonography (US) of the liver in the evaluation of patients with oral squamous cell carcinoma (OSCC).

Materials and Methods:
The records were reviewed of 131 patients with OSCC (age range 29-84 years, mean 55) who had undergone a routine plain chest X-ray, an ultrasound examination and CT scan of the head and neck and/or the thorax, an enzyme and ultrasound examination of the liver and sometimes a bone scintigraphy.

Results:
US exam showed no signs of liver metastases in 126/131 patients. In the other 5 patients focal alterations of liver eco-pattern were identified, raising the possibility of liver metastases. Only one case of true positive findings of liver metastases was identified in a patient with T2, N0 OSCC of the tongue.

Conclusion:
In this series we identified only one case of liver metastases from 131 patients retrospectively evaluated. Ultrasound screening in patients with OSCC seems unjustified.

Key words:
squamous cell carcinomas of head and neck, ultrasonography, liver metastases


In the evaluation of patients affected by malignant tumours in the head and neck, the identification of metastases plays a fundamental role in staging before treatment (Ferlito et al, 2001; Righini et al, 2001). The most common sites of distant metastases (DM) from squamous cell carcinomas (SCC) of head and neck are the lungs, bones and liver (Ferlito et al, 2001; Johnson, 2001; Nilssen et al, 1999).

The overall incidence of DM detected in patients with SCC in the head and neck ranges from 11% to 40% with significant differences in percentage of DM, between clinical and autopsy series (Ferlito et al, 2001; Johnson, 2001; Nilssen et al, 1999; Righini et al, 2001; Stirrett et al, 1953).

The presence of DM however, influences the management of the patient dramatically. Liver screening procedures for detection of occult metastases were introduced as a clinical tool as early as 1953 by Stirrett (Stuckensen, 2000). Recently ultrasound scanning has become the preferred method for performing this procedure. Belson et al (1980) reported the role of bone and liver scans in metastasis detection in 132 patients with head and neck cancer. Belson et al (1980) and Troell et al (1995) analysed 97 patients with SCC detecting chest, bone and hepatic metastasis.

Righini et al (2001) made a clinical retrospective study of 267 patients with cancer of the upper respiratory and digestive tract using ultrasound scanning as the screening test for the detection of liver metastasis. De Bree et al (2000) analysed screening test values in patients with head and neck cancer. A liver screening scan is routinely included in the initial pre-treatment evaluation of patients with oral squamous cell carcinoma in our institutions. Thus, the aim of this study was to determine the role of ultrasonography (US) of the liver in the evaluation of DM in patients with SCC of the oral cavity (OSCC).

MATERIAL AND METHODS

A retrospective review of 131 patients (age range 29-84 years, mean 55) with tongue, floor of the mouth, retromolar, cheek, soft and hard palate and gingival OSCC was performed. Primary tumour stage, T and N, and tumour differentiation G were considered and related to the presence of DM. A clinical evaluation was performed on all patients, and investigations included plain chest radiography, ultrasound examination and CT scan of the head and neck and/or the thorax, ultrasound examination of the liver, and bone scintigraphy in M1 cases.

Laboratory tests for detection of liver function included assays of: gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, and bilirubin levels.

Liver ultrasound was performed using the Sonolayer 350 (Toshiba medical, Tokyo, Japan) fitted with a 3.75 MHz probe. Sonographic evaluation included high resolution grey scan and a colour-coded duplex sonographic scan. In all cases ultrasound scans were performed by the same experienced radiologist. Evidence of nodular areas with poor defined margin characterised by mixed pattern, with prevalence of hypoechoic pattern were considered indicative for liver metastasis.

RESULTS

Clinical T-stage assessment prior to therapy was: T1=18, T2=32, T3=22, T4=59; and N stage was: N0=62, N1=23, N2=38, N3=3, NX=3. Of the 131 patients studied, only nine (7%) had DM: in lung (5), bone (3), and liver (1).

US exam showed no signs of liver metastases in 126/131 patients. In the other 5 patients focal alterations of liver eco-pattern were identified, raising the possibility of liver metastases. Consequently these 5 patients underwent CT scan of the upper abdomen using conventional equipment in 2 cases and multislice CT in 3.

On the basis of these CT findings, related with US features, a definitive diagnosis of metastasis was confirmed in only 1 case, while hepatic adenoma hypothesized in 1 case was confirmed with subsequent fine-needle aspiration biopsy (Fig. 1).


Fig. 1  Liver ultrasound (Sonolayer 350, Toshiba Medical, Tokyo, Japan) evidences a nodular area with poorly defined margin with prevalence of hypoechoic pattern suggestive for liver metastasis.


In 1 case a hepatic cavernous haemangioma was found and in the remaining 2 cases, multislice CT proved no signs of abnormal contrast enhancement of the liver and CT values of suspected areas showed reduced HU values in all phases of hepatic perfusion - indicative of multicentric steatosis. Thus only a single true case of liver metastasis was found and was histologically confirmed.

In this unique case, the patient had T2, N0 OSCC of the tongue while the grading of the cellular population was assessed as G2. The patient was further investigated for other primary tumours of the gastrointestinal tract, but no other neoplasia was found. Metastases were also found in the lung (n=5), bone (n=3), and liver (n=1) (Table 1).

Table 1 Metastases

Name

Age

Sex

Primary site

Histology

Grading

TNM

Stage

Liver enzyme elevation

AB

56

F

Cheek

Squamous

G1

T1 N0 M0

I

CE

67

F

Cheek

Squamous

G2

T4 N2 M0

IV

CO

60

M

Cheek

Squamous

G2

T2 N0 M0

II

GGT,BIL >

DB

74

F

Cheek

Squamous

G1

T1 N2 M0

IV

DI B

51

M

Cheek

Squamous

G2

T2 N0 M0

II

FE

77

M

Cheek

Squamous

G1

T1 N0 M0

I

FE

76

M

Cheek

Squamous

G1

T1 N0 M0

I

GA

69

F

Cheek

Squamous

G3

T3 N2 M0

IV

IO

68

M

Cheek

Squamous

G1

T2 N0 M0

II

LO

72

M

Cheek

Squamous

G2

T4 N0 M0

IV

MA

74

M

Cheek

Squamous

G2

T2 N0 M0

II

MA

23

M

Cheek

Squamous

G1

T2 NO MO

II

NA

55

M

Cheek

Squamous

G2

T1 N1 M0

III

AP >

NI

64

M

Cheek

Squamous

G1

T2 N0 M0

II

PA

83

F

Cheek

Squamous

G2

T3 N0 M0

III

PE

78

F

Cheek

Squamous

G2

T2 N0 M0

II

RA

61

M

Cheek

Squamous

G1

T1 N0 M0

I

SA

55

M

Cheek

Squamous

G1

T2 N1 M0

III

SA

64

F

Cheek

Squamous

G1

T1 N0 M0

I

GOT;GPT;GGT >

SI

66

F

Cheek

Squamous

G1

T4 N1 M0

IV

SO

46

F

Cheek

Squamous

G1

T1 N0 M0

I

GPT >

TA

57

F

Cheek

Squamous

G1

T1 N1 M0

III

VO

70

M

Cheek

Squamous

G1

T2 N0 M0

II

BIL >

ZI

50

M

Cheek

Squamous

G1

T1 N0 M0

I

AB

70

M

Cheek

Squamous

G1

T4 N1 M0

IV

AB

67

M

Cheek

Squamous

G1

T2 N1 M1

III

BI

73

M

Cheek

Squamous

G1

T3 NX M0

III

BR

69

F

Cheek

Squamous

G1

T2 N0 M0

II

MO

66

M

Cheek

Squamous

G1

T4 N0 M0

IV

GOT;GPT;GGT;AP >

AE

62

M

Floor of the mouth

Squamous

G2

T1 N1 M0

III

GGT >

BO

73

M

Floor of the mouth

Squamous

G1

T2 N0 M0

II

CI

68

M

Floor of the mouth

Squamous

G1

T1 N2 M1

IV

GGT;GOT;GPT;BIL >

CO

70

M

Floor of the mouth

Squamous

G1

T4 N2 M0

IV

GGT,GOT,AP >

CR

51

M

Floor of the mouth

Squamous

G1

T2 N2 M0

IV

GGT,GOT,GPT,AP,BIL>

D'AN

73

F

Floor of the mouth

Squamous

G1

T1 N0 M0

I

DE M

52

M

Floor of the mouth

Squamous

G1

T4 N2 M0

IV

GGT,BIL>

DI D

60

F

Floor of the mouth

Squamous

G1

T4 N2 M0

IV

GOTe GPT>

FO

71

F

Floor of the mouth

Squamous

G2

T4 N2 M0

IV

GA

59

M

Floor of the mouth

Squamous

G1

T4 N1 M0

IV

GGT >

GU

76

M

Floor of the mouth

Squamous

G1

T2 N0 M0

II

IU

60

M

Floor of the mouth

Squamous

G1

T4 N3 M0

IV

LA

65

M

Floor of the mouth

Squamous

G2

T2 NX M0

II

GGT >

LA

55

M

Floor of the mouth

Squamous

G1

T4 N2 M0

IV

GPT >

LO

72

M

Floor of the mouth

Squamous

G2

T2 N0 M0

II

GGT,BIL >

MA

65

M

Floor of the mouth

Squamous

G1

T4 N2 M0

IV

MA

40

M

Floor of the mouth

Squamous

G1

T2 N0 M0

II

GGT >

MA

70

M

Floor of the mouth

Squamous

G1

T2 N1 M0

III

OR

82

M

Floor of the mouth

Squamous

G3

T4 N2 M1

IV

PA

69

M

Floor of the mouth

Squamous

G1

T2 N2 M0

IV

RU

82

M

Floor of the mouth

Squamous

G2

T3 N1 M1

III

SA

81

M

Floor of the mouth

Squamous

G2

T2 N2 M0

IV

SI

71

M

Floor of the mouth

Squamous

G2

T4 N0 M0

IV

SI

72

M

Floor of the mouth

Squamous

G1

T2 N0 M0

II

SO

44

M

Floor of the mouth

Squamous

G3

T4 N2 M1

IV

TO

61

M

Floor of the mouth

Squamous

G1

T4 N1 M0

IV

BIL >

VF

61

M

Floor of the mouth

Squamous

G2

T2 N0 M0

II

BE

77

F

Gingival mucosa

Squamous

G1

T1 N0 M0

I

CA

61

F

Gingival mucosa

Squamous

G1

T1 N2 M0

IV

CM

53

F

Gingival mucosa

Squamous

G1

T2 NO Mo

II

DM

54

M

Gingival mucosa

Squamous

G2

T4 N2 M0

IV

GOT;GPT;GGT >

LA

66

F

Gingival mucosa

Squamous

G1

T3 N1 M0

III

GOT;GPT;GGT >

NA

52

M

Gingival mucosa

Squamous

G1

T4 N2 M0

IV

NA

60

F

Gingival mucosa

Squamous

G1

T2 N0 M0

II

SI

25

F

Gingival mucosa

Squamous

G1

T4 N1 M0

IV

CA

45

M

Hard palate

Squamous

G1

T4 N0 M0

IV

GGT >

CE

74

M

Hard palate

Squamous

G2

T4 N2 M0

IV

CS

73

F

Hard palate

Squamous

G1

T3 N0 M0

III

DI T

77

F

Hard palate

Squamous

G2

T2 N0 M0

II

GU

80

F

Hard palate

Squamous

G1

T4 N2 M0

IV

BIL >

GE

55

M

Retro-molar trig

Squamous

G3

T4 N2 M0

IV

AP >

TA

40

M

Retro-molar trig

Squamous

G1

T2 N0 M0

II

AA

60

M

Retro-molar trig.

Squamous

G1

T4 N0 M0

IV

FE

76

F

Retro-molar trig.

Squamous

G2

T4 N0 M0

IV

FO

66

M

Retro-molar trig.

Squamous

G2

T1 N0 M0

I

FR

48

M

Retro-molar trig.

Squamous

G1

T4 N2 M0

IV

IA

69

M

Retro-molar trig.

Squamous

G1

T4 N2 M0

IV

JA

70

M

Retro-molar trig.

Squamous

G2

T1 N0 M0

I

RA

45

F

Retro-molar trig.

Squamous

G1

T4 N2 M0

IV

SA

60

F

Retro-molar trig.

Squamous

G2

T2 NO MO

II

SO

43

M

Retro-molar trig.

Squamous

G1

T4 N1 M0

IV

GGT,GOT,GPT,BIL >

CI

72

M

Soft palate

Squamous

G1

T4 N0 M0

IV

LU

46

M

Soft palate

Squamous

G2

T3 N0 M0

III

AM

38

M

Tongue

Squamous

G2

T1 N3 M0

IV

BA

61

M

Tongue

Squamous

G2

T1 N1 M0

III

BE

68

M

Tongue

Squamous

G1

T4 N2 M0

IV

GOT >

BS

44

F

Tongue

Squamous

G3

T3 N1 M0

III

CA

83

F

Tongue

Squamous

G2

T2 N0 M0

II

CE

53

M

Tongue

Squamous

G2

T4 N2 M0

IV

CM

68

M

Tongue

Squamous

G1

T1 N2 M0

IV

CO

71

M

Tongue

Squamous

G2

T2 N0 MO

II

DA

45

F

Tongue

Squamous

G2

T4 N3 M0

IV

AP >

D'A

69

M

Tongue

Squamous

G1

T4 N0 M0

IV

D'AN

42

M

Tongue

Squamous

G2

T2 N0 M0

II

DE

68

F

Tongue

Squamous

G1

T2 N0 M0

II

DE R

68

M

Tongue

Squamous

G2

T2 N0 M1

IV

GGT;GPT >

DE S

62

F

Tongue

Squamous

G1

T3 N0 M0

III

DO

83

M

Tongue

Squamous

G2

T2 N2 M0

IV

ES

23

M

Tongue

Squamous

G2

T4 N1 M1

IV

ES

69

F

Tongue

Squamous

G1

T1 N1 M0

III

ES

75

F

Tongue

Squamous

G2

T2 N0 M0

II

FA

66

F

Tongue

Squamous

G1

T4 N2 M0

IV

GGT,GOT,AP >

FE

77

F

Tongue

Squamous

G2

T2 N0 M0

II

FR

58

M

Tongue

Squamous

G2

T1 N0 M0

I

GE

78

M

Tongue

Squamous

G2

T3 N1 M0

III

LE

44

F

Tongue

Squamous

G2

T2 N0 M0

II

LU

64

M

Tongue

Squamous

G1

T2 N2 M0

IV

MA

29

F

Tongue

Squamous

G1

T3 N0 M0

III

MA

80

F

Tongue

Squamous

G1

T2 N0 M0

II

MA

65

F

Tongue

Squamous

G1

T1 N0 M0

I

MA

61

F

Tongue

Squamous

G1

T1 N1 M0

III

MA

73

M

Tongue

Squamous

G2

T4 N2 M1

IV

MA

65

M

Tongue

Squamous

G1

T2 N0 M0

II

ME

74

F

Tongue

Squamous

G1

T4 N2 M0

IV

AP >

OR

48

F

Tongue

Squamous

G1

T3 N0 M0

III

PA

59

M

Tongue

Squamous

G1

T4 N2 M0

IV

PA

52

M

Tongue

Squamous

G1

T2 N1 M0

III

PI

55

M

Tongue

Squamous

G1

T1 N0 M0

I

BIL >

PO

73

F

Tongue

Squamous

G2

T1 N0 M0

I

RU

73

F

Tongue

Squamous

G2

T1 N0 M0

I

SA

57

F

Tongue

Squamous

G2

T1 N1 M0

III

GOT;GPT;AP;BBIL >

SA

61

M

Tongue

Squamous

G1

T4 NX M0

IV

SA

40

M

Tongue

Squamous

G1

T1 N0 M0

I

AP >

SI

69

M

Tongue

Squamous

G1

T4 N1 M0

IV

SO

73

M

Tongue

Squamous

G2

T4 N1 M0

IV

TA

68

M

Tongue

Squamous

G3

T4 N2 M0

IV

TE

66

M

Tongue

Squamous

G1

T3 N2 M0

IV

ZI

74

M

Tongue

Squamous

G1

T1 N0 M0

I

AA

56

M

Tongue

Squamous

G1

T4 N2 M1

IV

CV

68

M

Tongue

Squamous

G1

T1 N2 M0

IV

GGT >

DI M

53

M

Tongue

Squamous

G2

T2 N0 M0

II

GOT,GPT,BIL>

MO

62

M

Tongue

Squamous

G1

T2 N0 M0

II

BIL >


DISCUSSION

Liver metastases are rare in patients with OSCC in the absence of other DM; whereas lung metastases are more frequently associated with OSCC (Belson et al, 1995; Stuckensen et al, 2000; Taylor et al, 1976). In this series of 131 patients with OSCC, we found only one case of liver metastases, accounting for less than 1%.

Crile was the first author to notice the possibility of DM associated with head and neck carcinomas (Crile, 1906; Felix et al, 1976). Belson et al (1980) reported no liver metastases in 132 patients with head and neck cancer, while Troell et al (2000) in an analysis of 97 patients reported 2 cases of hepatic metastases, stating these to be rare in the absence of other DM. Righini et al (2001) in their clinical retrospective study, found liver metastasis in 4 of 267 patients with cancer of the upper respiratory and digestive tract, with a higher incidence of liver metastases in patients with SCC of larynx. Bertrand et al (1995) analysed 200 patients with upper aero-digestive tract SCC and found an incidence of liver metastasis of 0.6%, while De Bree et al (2000) reported an incidence of 1%.

Some authors found a relation between T stage and DM, others show a clear correlation with N stage, number of lymph node metastases and involvement of lower nodes (Ferlito et al, 2001; Johnson, 2001; Papac, 1984; Taylor, 1976). Furthermore the incidence of liver metastases is significantly associated with the site of the primary tumour and with differentiation degree of tumours (Belson et al, 1995; Ferlito et al, 2001; Papac, 1984).

Belson et al (1995) outlined discrete criteria for obtaining liver scans in HN cancer patients: hepatic enlargement or nodularity with abnormal liver function. They concluded that routine scanning is a non-worthwhile procedure.

Ferlito et al (2001) showed how extensive screening for DM detection is rarely justified in patients with SCC of the upper digestive tract, and we agree with the opinion that only some histological types of primary tumours and higher stages of SCC and tumour location could justify screening, such as liver ultrasound.

Adenoid cystic carcinoma, basalyoid squamous cell carcinoma, and neurcendocrine carcinomas have a greater propensity to DM as do primary tumours of the oropharynx and hypopharynx, particularly in advanced T stage (Ferlito et al, 2001). Considering OSCC, only advanced stage (III or IV) or poorly differentiated histological types are associated with a relatively high frequency of DM, and the lung is the preferential site, while liver metastases are quite rare (Ferlito et al, 2001).

Clinically, liver metastases are asymptomatic in early stage. Laboratory tests have been used as a screening method for liver metastases but are neither specific nor sensitive, while radio-immunochemical sampling of tumours antigens, such as carcinoembryonic antigen and alpha-fetoprotein, show high sensitivity but very low specificity; and consequently imaging techniques such as US and CT, represent an important potential screening tool for detecting liver metastases (Johnson, 1996; Stuckensen, 2000).

US is relatively inexpensive and easy to perform, and its accuracy is higher than 90% (Felix et al, 1976).

On the other hand, US is extremely operator-dependent. In cases of detected US alterations with unequivocal characteristics, more specific examinations such as abdominal CT scan or an MRI were indicated (Arunachalam et al, 2002; Nilssen et al, 1999; Stirrett et al, 1953; Stuckensen et al, 2000; Tan et al, 1999). In the present series, 4 cases of suspected metastases when studied with CT scans demonstrated non-metastatic lesions.

CONCLUSIONS

Liver metastases rarely occur in SCC of the oral cavity. Ultrasound scanning is a relatively inexpensive and accurate technique for the detection of liver metastases, and the procedure is not associated with any radiation exposure (De Bree, 2000; Tan et al, 1999; Troell, 1995). It serves as a sufficient confirmatory test in patients with elevated liver enzyme and positive tumour markers (Johnson, 2001).

However, our data confirm that because of the low frequency of liver metastases found by ultrasound scanning, this screening does not appear to be justified.

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Authors:

a Giuseppe Colella
Seconda Universita' Degli Studi Di Napoli, Facolta' di Medicina e Chirurgica, Department Of Head And Neck Pathology, Napoli, Italy.

b Salvatore Cappabianca
Seconda Universita' Degli Studi Di Napoli, Facolta' di Medicina e Chirurgica, Dipartimento di Internistica Clinica e Sperimentale, Napoli, Italy.

c Crispian Scully
Eastman Dental Institute for Oral Health Care Sciences, and International Centres for Excellence in Dentistry, University College London, London, UK.

Prof. Giuseppe Colella, Seconda Università degli Studi di Napoli, Istituto di Chiruriga Maxillo-Facciale, Piazza Miraglia, Napoli, Italy, E-mail giuseppe.colella@unina2.it