Ultrasonography of spleen and liver in staging Hodgkin's disease

European Jounial ofRadiology. 13 (1991) 181-186 0 1991 Else&r Science Publishers B.V. All rights reserved. 0720-048X/91/$03.50

EURRAD

181

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llTltrasonography of spleen and liver in staging Hodgkin’s disease T. Siniluoto, M. Ptiv&mlo

and M. Alavaikko

Departments of Diagnostic Radiology and Pathology, UniversityCentral Hospital, Universityof Oulu. Oulu, Finland (Received

Key wordk: Hodgkin’s disease, ultrasound

15 November

1990; accepted

after revision 5 June 1991)

study; Hodgkin’s disease, spleen; Hodgkin’s disease, liver; Ultrasound disease

study, Hodgkin’s

Abstract

Ultrasound (US) findings and accuracy in detecting splenic and hepatic involvement were analysed in 137 unselected, untreated patients with Hodgkin’s d&ease. Histology was available from the spleens of 61 patients and the livers of 59 patients. In 20 patients the spleen appeared abnormal at US; containing focal hypoechoic lesions in 14, being enlarged in 13 and inhomogeneous in 2 patients. Most focal lesions were < 10 mm. The sensitivity of US in detecting involvement of the spleen was 54% and the specificity 100% ; the ability of US to detect hypoechoic splenic lesiong improved during the study period. Focal hypoechoic hepatic lesions were found in three patients; histological examination of these showedlbenign changes in one and suspicious finding in the second. In the third the lesion disappeared during chemotherapy. In three cases with deiinitive histological evidence of liver involvement, US results were false-negative. The results indicate a higher diagnostic efficacy for US in the; detection of splenic than hepatic involvement by Hodgkin’s disease.

Introductioh Treatment of Hodgkin’s disease is based on an accurate definition of nodal and extranodal involvement [ 11. The spleen land liver, after the lymph nodes, are the most common sites of abdominal spread of Hodgkin’s disease; inbasion of the spleen occurring in 30-40x, and of the liver in 5- 10% of previously untreated patients WHOundergo staging laparotomy [l-3]. Clinical examination and noninvasive imaging techniques have shown disappointing results in assessment of the histological state of the spleen and liver [ l-81. Splenectomy is superior to imaging studies and is the only certain method of assessing whether or not the spleen is involved and, therefore, many patients still undergo staging lapurotomy and splenectomy for diagnostic purposes [9-lo]. Abdominal US has been part of the routine clinical staging of kodgkin’s disease at our institution since the early 1989s. The present report is a retrospective analysis ofl the results of US of the spleen and liver from Address for ireprints: Topi Siniluoto, Department of Diagnostic Radiology, University of Oulu, Kajaanintie 52, SF-90220 Oulu, Finland.

January 198 1 to December 1989 in previously untreated patients with Hodgkin’s disease. Special attention was paid to the ability of US to detect the early focal lesions of Hodgkin’s disease. Patients and Methods The study group comprised 78 males and 59 females ; mean age 43 years (range 11-87) with Hodgkin’s disease. They were admitted to Oulu University Central Hospital between January 1981 and December 1989 and underwent abdominal US examination prior to starting therapy or undergoing laparotomy. Clinically, without reference to the results of the imaging studies, 40 patients were assessed as having Stage I disease, 59 as having Stage II, 9 patients Stage III and 14 patients Stage IV disease. In 15 additional patients presenting with intra-abdominal disease, the diagnosis was unknown at the time of the US examination. In 6 patients splenomegaly was suspected on abdominal palpation. US studies were performed using a Toshiba SAL 20A scanner with a 2.25 MHz transducer during 1981-1984, supplemented with a Picker 80L compound scanner in selected patients to delineate the lesion more accurately. A GE 3000 RT with a 3.5 MHz

182

Fig. 2. Hodgkin’s disease, nodular sclerosing type with supraclavicular lymphadenopathy. US revealed one 10 mm solitary splenic lesion (arrows). LK = left kidney. Fig. 1. Hodgkin’s disease, nodular sclerosing type, presenting initially with cervicosupraclavicular and mediastinal lymphadenopathy. Of multiple small splenic nodules, two are seen in the figure. Systemic chemotherapy resulted in normalization of the splenic structure.

hypoechoic considered

lesions within the spleen and the liver were abnormal.

Results sector transducer was used in 1985 and Toshiba 77/90/100 scanners with 3.75/5 MHz convex transducers were used in 1986- 1989. The original US reports and sonograms were reviewed in order to define the prevalence and the US patterns of the splenic and liver abnormalities. Repeat US studies were also reviewed to assess whether abnormal findings on a previous examination had changed. The US findings were compared with both clinical findings and the histological diagnoses of the spleen (n = 61) and liver (n = 59). Histological specimens were obtained at splenectomy in 58 patients and wedge liver biopsy with or without supplementing line needle biopsies of the liver in 56 patients within (mean) 3 weeks (range 1 day - 9 weeks) after the US study, or at autopsy in 2 patients performed within three weeks. In two patients specimens were obtained by percutaneous fineneedle aspiration biopsy (FNAB) of the spleen or the liver. A splenic length 3 14 cm or the presence of

Spleen At ultrasonography the spleen appeared normal or showed insignificant abnormality in 117 patients (85.6%). In 20 patients (14.6%) US findings were abnormal (positive). In 15 of these there were focal solid lesions in the spleen or it was diffusely inhomogeneous, and splenomegaly (length 14-21 cm) was found in 12 patients. Structural abnormalities in the spleen were found in 4.3 % of patients during the years 1981-1984 and in 17.6% from 1985 to 1989 (Table 1). The spleen was normal in size (< 14 cm) in 8 and enlarged (range 14-2 1 cm) in 5 of the patients with focal splenic lesions. Both of the spleens with an inhomogeneous structure were enlarged (16 and 20 cm in length, respectively). In 10 of the 13 patients with focal splenic lesions the foci were multiple and in 9/13 they measured < 10 mm in diameter. They were rather well-defined in 6/13 of patients and poorly defined in 7/13 (Table 1). The

TABLE 1 Summary of the results of US examination Time period

No. of patients

of the spleen

Abnormal finding

Splenomegaly

Focal lesions

Irregular structure

all


>lcm

1981-1984 1985-1989

69 68

7 13

I 5

3 10

1 8

2 2

0 2

1981-1989

137

20

12

13

9

4

2

Fig. 3. Fever of unknown origin. Small, ill-defined splenic (a) and hepatic (b)Ilesions (arrows) sonographically evident. Histological examination of the splenectomy specimen revealed less than 5 mm infiltrates of Hodgkin’s disease (mixed cellular). Histological involvement suspected in the wedge Ilive r biopsy specimen.

lesions were hypoechoic and fairly homogeneous (Figs. 1, 2 and 3a), except for the largest lesion which contained both hypoechoic and anechoic areas (Fig. 4). There were 6 false-negative and no false-positive US studies of the spleen in the patients who had bioptic verification (Table 2). Thus the overall accuracy of US to detect splenic involvement was 90 %, with a sensitivity of 54% and a specificity of 100%. In the9 patients without histological confirmation of the focal splenic lesions, follow-up US examinations during chemotherapy showed complete disappearance of the lesions. In one additional patient who initially only had splenomegaly, follow-up studies showed normalization of splenic size supporting the clinical evidence of remission. In three patients who had abnormal US findings initially and subsequent clinical evidence of

disease-progression, no follow-up US examinations were performed. US confirmed the presence of splenomegaly in all 6 patients who had a palpably enlarged spleen and showed focal (in 1 patient) or diffuse structural change (in 1 patient) (Fig. 5). The prevalence of an abnormal US finding of the spleen was 5.0% in clinical stage I disease, 8.5% in Stage II, 11.1% in Stage III, 57.1% in Stage IV and in 26.7% of those who were examined with US prior to confirmation of the diagnosis of Hodgkin’s disease. Concurrent retroperitoneal or other abdominal lymphadenopathy was evident at US in 14 of the 20 patients who had abnormal US finding in the spleen. Concurrent splenic hilar lymphadenopathy was seen in 2 patients.

TABLE 2

TABLE 3

Comparison patients.

of US findings

and histology

of the spleen

in 61

Comparison US finding

US findings

Patients

of US findings and histology of the liver in 59 patients Patients

Histology

Histology positive

pos.

susp.

neg.

negative

Abnormal Norma1

1

I*

0

54

6

48

Total

61

13

48

* Focal lesions of three, splenomegaly alone in 2, a large focal splenic tumor with splenomegaly in one and an enlarged, inhomogeneous spleen in one patient.

Norma1 Hypoechoic lesion(s) Hyperechoic lesion

56 2

3 0

0

53

1

1

1

0

0

1

All

59

3

1

55

pos. = positive; susp. = suspicious;

neg. = negative.

184

Fig. 4. Large inhomogeneous tumor (arrow) within the upper pole of the spleen. Primary Hodgkin’s disease of the spleen, lymphocytic depletion type. A hypoechoic liver lesion was also present and disappeared during chemotherapy.

Liver Focal hypoechoic hepatic lesion(s) were observed in 3 patients (solitary in 2, multiple in one; diameter l-2 cm). In one of them, wedge liver biopsy findings were histologically suspect for involvement (Fig. 3b). In another patient, a hypoechoic hepatic lesion was not confirmed histologically but disappeared during chemotherapy (Table 3). In the third patient, a hypoechoic hepatic lesion proved histologically to be benign fibrosis. Three additional patients with histologically confirmed hepatic involvement had normal US. Solitary hyperechoic liver lesions were found in 4 patients. These lesions were probably benign, caused by local fatty infiltration or hemangioma. Concurrent splenic and nodal abnormalities in 5 patients who had histologically or clinically confirmed liver involvement, are presented in Table 4. Discussion Primary Hodgkin’s disease of the spleen is rare [ 111. In most cases invasion of the spleen is presumed to

Fig. 5. Mixed cellular Hodgkin’s disease with intra-abdominal presentation. Spleen enlarged with inhomogeneous echostructure without any discrete focal lesions. Splenectomy revealed Hodgkin’s disease of the spleen caused by numerous l-2 mm largely confluent/coalescing infiltrates. Similar lesions were found in the wedge liver biopsy specimen. occur through hematogenous dissemination [ 121. On gross examination, splenic involvement is usually visible as small nodules, and microscopic examination only exceptionally reveals invasion in the absence of macroscopic lesions [1,3,13]. . Lymphomatous splenic nodules of Hodgkin’s disease may be seen as focal hypoechoic parenchymal lesions at US, and such lesions are considered the most important signs of lymphomatous involvement of the spleen [ 14,151. Less rarely a target type of splenic lesion [ 161 or diffuse structural changes [ 171 due to Hodgkin’s disease may occur. In the present study focal solid lesions of the spleen were found in 10% of the patients and all were hypoechoic except the largest solitary lesion, which also contained anechoic areas. The results of the present study confirm the importance of focal hypoechoic lesions as a sign of lymphomatous involvement of the spleen. The nature of the

TABLE 4 Concurrent

splenic and lymph node abnormalities

Method of confirmation of liver involvement

in 5 patients with histologically

Spleen

or clinically confirmed liver involvement Lymph nodes

us+

Histology +

us+

LAG +

Histology +

212 l/l 212

212 O/l l/2

-

us follow-up* (2)

212 O/l 212

212

212 l/l l/2

Total (5)

415

515

315

212

415

Biopsy (2) Autopsy (1)

* Disappearance of solitary or multiple hypoechoic Note: LAG = lymphangiography.

lesions initially present.

185

hypoechoic lesions was usually confirmed by clinical follow-up during chemotherapy resulting in complete disappearance of the lesions in all cases. Histological verification seems to be necessary only in those rare cases in which the disease presents solely with involvement of the spleen or other intra-abdominal organs, or if the US pattern is atypical. At the initial diagnosis the lymphomatous lesions are usually 10 mm or less in diameter, and difficult to detect by noninvasive imaging techniques [2,15,18-201. Magnetic resonance imaging (MRI) and US may be superior to CT for disclosing small infiltrates of Hodgkin’s disease in the spleen [ 151. At CT the minimum detectable diameter is reported to be approximately 1 cm, but even larger lesions are often overlooked [ 201. While the majority (69%) of the focal splenic lesions detected were < 10 mm in diameter in the whole series the prevalence of focal lesions visible at US was higher during 1985-1989 than 1981-1984 (15% versus 4%). This difference is probably due to improved accuracy of US in detecting small lesions during the latter time period (Table 1). Thus at present, US can in a signilicant number of patients detect early involvement of the spleen. In 2 patients examined during the latter period, the splenic structure was diffusely inhomogeneous without any discrete nodules. In one of them the US finding was histologically verified as coalescence of lymphomatous nodules of a few mm in size . Our results indicate that modem US equipment with high resolution is a prerequisite for the detection of small lymphomatous infiltrates of the spleen. The use of sector or convex transducers further facilitates visualization of the entire spleen. The results of this study demonstrate an improvement in the detection rate of focal involvement compared with previous series [ 7,16,19]. Glees et al. [27] based their diagnosis of splenic involvement of Hodgkin’s disease solely on splenomegaly and diffuse hypoechogenicity of the spleen. Sekiya et al. [ 191 reported only 1 of 17 histologically positive spleens to have definite ultrasonic focal lesions and Wemecke et al. [ 161 reported that 6 of 89 patients, who were examined as a part of the initial staging or restaging, had focal splenic lesions on US. Gritzmann et al. [ 141 found a higher number (12 patients) of focal splenic lesions in 67 selected, histologically confirmed cases. A spleen length > 14 cm [ 2 1,221 was defined as splenomegaly and was seen in 12 cases. However, the small number of histologically confirmed cases and inadequate follow-up data of cases with splenomegaly does not permit definite conclusions to be made regarding the reliability of this parameter. Accurate estimation of the

splenic volume may improve the reliability of the estimation of splenic size [ 201. As our study was retrospective, splenic volume could not be estimated. Diffuse increase or decrease in the echogenicity of the spleen has been observed in Hodgkin’s disease, but is difficult to interpret reliably and is nonspecific, occurring in both benign and malignant conditions [ 7,171. An enlarged, slightly hyperechoic spleen was found in only one case in our series. Splenectomy revealed a few small lymphomatous infiltrates, the diffuse hyperechoic pattern, however, corresponded to benign reactive change in the splenic parenchyma. There were 6 false-negative, histologically confirmed US examinations, in all but one with macroscopically visible lesions Q 10 mm in 5 patients and < 2 cm in one. Probable reasons for the false-negative results were the small size of the lesions, minimal differences in acoustic properties between the lesions and the rest of the spleen, and the occasional incomplete visualization of the entire spleen. Thus staging laparotomy with splenectomy should still be considered when the US finding of the spleen (and the liver) is negative and treatment with external radiotherapy is planned. As has been reported before, estimation of the splenic size by palpation was found to be a poor indicator of splenic involvement [3,6,23-251. Clinical examination was inferior to US and particularly insensitive in detecting patients in whom moderate splenomegaly (14- 16 cm in length) or small hypoechoic splenic lesions were evident at US examination. Liver

Hepatic involvement by Hodgkin’s disease is almost invariably secondary to splenic involvement [ 11. While an earlier autopsy report [ 261 of patients with generally an advanced disease indicated that 86.5 y0 of the hepatic lesions of Hodgkin’s disease were diffuse and only a minority were nodular, more recent reports based upon laparoscopy and laparotomy findings [27,28] have shown that the early lesions of Hodgkin’s disease are usually focal. Hepatomegaly and abnormal liver function tests are unreliable indicators of hepatic involvement [28]. The detection of liver involvement by noninvasive imaging studies is difficult [ 8,19,29]. At US a liver involved in Hodgkin’s disease may exhibit texture abnormalities similar to those of the spleen [ 16,19,30]. The results of the present series were disappointing, because in all three patients in whom there was histological evidence of hepatic involvement US failed to show this, and in only two more patients did the follow-up data (disappearance of the ultrasonically evident hypoechoic lesions) indicate a true-positive US finding.

186

The results indicate that US is less reliable in defining the state of the liver than that of the spleen at initial diagnosis of Hodgkin’s disease. The small number of histologically confirmed positive cases, however, makes it difficult to draw definite conclusions. A hypoechoic hepatic lesion may also prove to be benign, as in one of our patients, in whom the liver lesion was the only ultrasonically detectable abdominal abnormality. Concomitant US evidence of splenic involvement, or US or lymphographic evidence of abdominal lymph node involvement are usually present in patients with liver involvement (Table 4). Prospective series are needed to find out whether careful scanning can improve the accuracy of US to detect early lymphomatous lesions of the liver. Benign hyperechoic focal hepatic lesions are not uncommon incidental findings in abdominal US examination and are usually caused by local fatty infiltrations or hemangiomas [ 16,301. Such lesions have not been reported to be caused by infiltrates of Hodgkin’s disease and should never be interpreted as a sign of hepatic involvement without biopsy confirmation. References 1 Kaplan HS. Hodgkin’s disease, 2nd edn. Cambridge, MA: Harvard University Press, 1980. 2 Castellino RA, Hoppe RT, Blank N, Young SW, Neumann C, Rosenberg SA, Kaplan HS. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin’s disease. AJR 1984; 143: 37-41. 3 Kadin ME, Glatstein E, Dorfman RF. Clinicopathologic studies of 117 untreated patients subjected to staging laparotomy for the staging of Hodgkin’s disease. Cancer 1971; 27: 1277-1294. 4 Carroll BA, Ta HN. The ultrasonic appearance of extranodal abdominal lymphoma. Radiology 1980; 136: 419-425. 5 Glees JP, Barr LC, McElwain TJ, Peckham MJ, Gazet J-C. The changing role of staging laparotomy in Hodgkin’s disease: a personal series of 310 patients. Br J Surg 1982; 69: 181-187. 6 Milder MS, Larson SM, Bagley CM Jr, DeVita VT Jr, Johnson RE, Johnston GS. Liver-spleen scan in Hodgkin’s disease. Cancer 1973; 31: 826-834. 7 Glees JP, Taylor KJW, Gazet J-C, Peckham MJ, McCready VR. Accuracy of gray-scale ultrasonography of liver and spleen in Hodgkin’s disease and the other lymphomas compared with isotope scans. Clin Radio1 1977; 28: 233-238. 8 Zornoza J, Ginaldi S. Computed tomography in hepatic lymphoma. Radiology 1981; 138: 405-410. 9 Sarna GP. Hodgkin’s disease, non-Hodgkin’s lymphomas. In: Stein JP, ed. Internal Medicine. Boston: Little and Brown, 1983; 1644-1652. 10 Scott JS, Dawson AA, Proctor SJ, Allan NC. The place of staging laparotomy in the management of Hodgkin’s disease. Clin Radio1 1984; 35: 261-263.

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