A comparative study of sonographic and histopathologic findings of tumorous lesions in the parotid gland

Vol. 88 No. 6 December 1999

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL AND MAXILLOFACIAL RADIOLOGY

Editor: Sharon L. Brooks

A comparative study of sonographic and histopathologic findings of tumorous lesions in the parotid gland Mayumi Shimizu, DDS, PhD,a Jürgen Ußmüller, Priv Doz, Dr Med,b Joerg Hartwein, Prof Dr Med,c Karl Donath, Prof Dr Med, Dr HC,d Fukuoka, Japan, and Pforzheim and Hamburg, Germany KYUSHU UNIVERSITY, SILOAH HOSPITAL, AND HAMBURG UNIVERSITY

Objective. The purpose of this study was to clarify which histopathologic features are visualized on sonograms by comparing sonomorphologic and histopathologic analyses of parotid tumorous lesions on the same plane.

Study design. Boundaries, shapes, echo intensity level, distribution of internal echoes, and acoustic enhancement on sonograms of 86 parotid tumorous lesions were retrospectively compared with the histopathologic findings. Results. Unclear boundaries on sonograms corresponded to abundant connective tissue with scattered tumor cell nests. Polygonal shapes on sonograms were revealed to represent tumor cell infiltration on histopathologic sections. The “very hypoechoic” lesions showed significantly high ratio of cystic areas (P < .05) in Warthin tumor. The weakly hyperechoic structures on sonograms were connective tissue, hyaline, and necrotic and keratinized materials. Attenuated posterior echoes were observed in malignant tumors with abundant connective tissue and metaplastic bone formation. Conclusions. To facilitate correct sonographic diagnosis, it is important to ascertain the correlation between sonomorphology and histopathology.

(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:723-37)

In recent years, ultrasonography has become the modality of choice for diagnosing salivary gland diseases because of its ease of use and absence of ionizing radiation. Compared with other imaging techniques, such as plain radiography, sialography and computed tomography, ultrasonography is reported to be superior, not only in detecting tumorous lesions1-5 but also in describing the structure and even the vascularity of the lesions.6 In contrast with fine-needle aspiration biopsy, ultrasonography is not associated with damage to facial nerve branches. This work was supported in part by Deutscher Akademischer Austausch-dienst and carried out at University Hospital Eppendorf, Hamburg University. aInstructor, Department of Oral & Maxillofacial Radiology, Faculty of Dentistry, Kyushu University. bPrivatdozent and Oberarzt, Ear-Nose-Throat Clinic, University Hospital Eppendorf, Hamburg University. cProfessor and Chairman, Ear-Nose-Throat Clinic, Siloah Hospital. dProfessor and Chairman, Department of Oral Pathology, Institute for Pathology, Hamburg University. Received for publication Jan 19, 1999; returned for revision Apr 4, 1999; accepted for publication Jun 21, 1999. Copyright © 1999 by Mosby, Inc. 1079-2104/99/$8.00 + 0 7/16/101806

There have been many reports on the differential diagnosis of parotid tumors by means of B-mode ultrasonography.1-14 However, most of these reports have been restricted to the sonomorphology of individual histopathologic entities, such as pleomorphic adenoma, Warthin tumor, lipoma, cyst, and lymphadenitis.1,3,7-11 The histopathologic nature of lesions was not always analyzed in detail, and it remains unclear how the ratio and distribution of histopathologic components correlate with sonographic findings. Other approaches to differentiating among parotid tumors have included measurement of their attenuation coefficients and velocity15-19 and use of A-mode sonography.20,21 In these investigations, however, a variety of histopathologic components have been ignored. In addition, it is difficult to use the results for clinical diagnosis, as combined acoustic factors constitute a complex sonogram. The interpretation of wave forms is also very difficult. There are many kinds of tumorous lesions in the parotid region, and the operation and therapy planning depends on the diagnosis. For example, because pleomorphic adenomas have a tendency to recur if the 723

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Table I. Features on sonograms

Table II. Histopathologic diagnoses and numbers of cases

Feature

Class

Boundary

Very clear Relatively clear Partially unclear Shape Oval Lobular Polygonal Echo intensity level Glandular parenchymal; slightly hypoechoic Very hypoechoic Distribution of Homogeneous internal echoes Multiple anechoic areas Heterogeneous with characteristic structures Heterogeneous without characteristic structures Acoustic enhancement Enhanced (posterior echoes) Unchanged Attenuated

capsule is damaged during surgery, a partial parotidectomy is recommended for this tumor. On the other hand, enucleation is sufficient for Warthin tumors. Lipomas can be observed, as long as they are not too large. Therefore, we have to make more precise differential diagnoses, not simply differentiate malignant lesions from benign ones. For making exact diagnoses, it is important to clarify the sonomorphologic variation of individual histopathologic entities. For this reason, we analyzed the sonomorphology of parotid tumorous lesions preoperatively. The histopathologic findings of the extirpated lesions were then analyzed. The purpose of this retrospective study was to clarify which histopathologic features are reflected on sonograms by comparing sonomorphologic with histopathologic analysis on the same planes. The results should be useful in the effort to make more precise sonographic diagnosis of parotid tumorous lesions.

MATERIAL AND METHODS Patients Eighty-six tumorous parotid gland lesions in 84 patients (Ear-Nose-Throat Clinic of Hamburg University, November 1993 to August 1995) were analyzed. Two lesions were found in each of 2 patients. The patients were 50 males and 34 females from 13 to 83 years of age (mean age, 50.6 years). Sonographic features Before surgical intervention, ultrasonography was performed by means of a linear small parts scanner electronic sonography unit (7.5 MHz center frequency; Quantum 2000, Siemens; Erlangen, Germany). All images were obtained by a single operator (M.S.) under

Benign lesions Pleomorphic adenoma Warthin tumor Other benign lesions Lipoma Basal cell adenoma Cyst Lymphadenitis Miscellaneous Myoepithelial parotitis Epithelioid cellular parotitis Angiolymphoid hyperplasia Cystic lymphoid hyperplasia in AIDS Malignant tumors Acinic cell carcinoma Cystadenocarcinoma Mucoepidermoid carcinoma Salivary duct carcinoma Fibrosarcoma Malignant lymphoma Metastatic tumor

72 22 30 20 4 2 4 5 5 1 1 1 2 14 2 2 2 1 1 2 4

the condition set for “small parts” (gain, 55 dB; dynamic range, 55 dB; 4 points focus; depth, 53 mm) with a wedge-form standoff device. Gain, focus, and depth were kept constant as much as possible; however, if a lesion was large, they were changed as needed. Several images of both transverse and longitudinal scan sections were obtained at the greatest dimensions of the lesions. The contralateral (normal) parotid glands were also examined. After surgery, the extirpated lesions were examined again to confirm that the scanning planes were the same as those at the preoperative examination so that histopathologic sections would be prepared on these planes for comparison. Sonographic features of the lesions are listed in Table I. With regard to boundaries, if a lesion had either a thin hyperechoic line on the anterior side or a capsulelike structure, we categorized it as “very clear.” If a lesion showed no distinct thin hyperechoic line on the anterior side or showed no capsulelike structure but no interruption of the contour, we categorized it as “relatively clear.” If a contour showed any interruption, it was classified as “partially unclear.” For echo intensity level, if a lesion showed approximately the same echo intensity level as glandular parenchyma, it was termed “glandular parenchymal level.” If anechoic areas in a lesion accounted for less than 50% of the lesion, it was categorized as “slightly hypoechoic”; if more than 50%, as “very hypoechoic.” For the distribution of internal echoes, we categorized “multiple anechoic areas” as a specific class. We categorized other characteristic findings of internal echoes, such as a hilus and regularly

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Table III. Boundaries and shapes on sonograms Histopathologic diagnosis (no. of cases)

Very clear

Boundaries Relatively clear

Pleomorphic adenoma (22) Warthin tumor (30) Other benign lesions (20) Lipoma (4) Basal cell adenoma (2) Cyst (4) Lymphadenitis (5) Miscellaneous (5) Malignant tumors (14) Totals (86)

5 21 (1*)

17 8 (6*)

3 1 3 4 3 (1*) 2 (2*) 42

1 1 1 1 2 5 (3*) 36

Partially unclear

Lesion shapes Oval

Lobular

Polygonal

– 1

2 19 (3*)

20 8 (3*)

– 2 (1*)

Unclassifiable – 1

– – – – – 7 (5*) 8

1 1 3 5 1 2 (2*) 34

3 1 1 – 3 (1*) 7 (5*) 43

– – – – – 4 (2*) 6

– – – – 1 1 (1*) 3

*No. of cases with tumor cell infiltration into capsules.

distributed hyperechoic lines, as “heterogeneous with characteristic structures.” Acoustic enhancement was estimated by comparison with the echo intensity level in the anterior part of the normal parotid gland. If there was internal shadow that caused partial attenuation of the posterior echoes, we classified the image as “attenuated (posterior echoes).” Analysis of sonograms was performed by two observers (M.S. and J.U.) preoperatively. Interpretations of images were done with several adjacent images, either transversal or longitudinal scans, whichever were more characteristic. Consensus was reached in cases of initial disagreement.

Histopathologic analysis Histopathologic sections were prepared on the same planes as described in the preceding section. Hematoxylin and eosin (H-E) staining, periodic acidSchiff (PAS) staining, and Astra blue staining were performed in each case. These sections were analyzed under a light microscope. For the morphometric study, we first digitized histopathologic images through a microscopic analyzing system (Vidas 21; Kontron, Munich, Germany), then analyzed the data with applications—Adobe Photoshop (Adobe Systems Inc, San Jose, Calif) and NIH Image (National Institutes of Health, Washington DC)—on a personal computer (Apple Macintosh Quadra 840AV; Apple Computer, Inc, Cupertino, Calif). Analytic points on histopathologic sections were (1) the average thickness of the connective tissue on the anterior side and all around each lesion and (2) the quality of connective tissue (dense or loose). In cases of malignant tumors without history of fine-needle aspiration biopsy, the portion containing infiltrative tumor cells was analyzed. For Warthin tumors, the cystic area ratio, the greatest diameter, and the ratio of PAS-positive or Astra blue-positive areas to the area of the whole

lesion were analyzed. Ratios of each histopathologic component to the whole lesion were analyzed in 77 of 86 cases. Nine cases (1 cyst, 2 parotitis, 1 cystadenocarcinoma, 1 fibrosarcoma, and 4 metastatic tumors) were excluded because in each of these we could not observe the whole lesion on histopathologic sections.

Comparison of sonographic and histopathologic findings Sonographic features were compared with histopathologic findings in each case to clarify the following issues: 1. relationship between the clarity of boundaries on sonograms and findings of connective tissue around lesions on histopathologic sections 2. relationship between shapes on sonograms and malignancy on histopathologic sections 3. relationship between echo intensity level and the ratio of histopathologic components 4. relationship between distribution of internal echoes and the ratio of histopathologic components 5. relationship between acoustic enhancement and the ratio of histopathologic components. RESULTS Histopathologic diagnoses Table II shows the histopathologic diagnoses of 86 lesions. There were 72 benign lesions (58 benign tumors) and 14 malignant tumors. The acinic cell carcinomas, the cystadenocarcinomas, and one of the mucoepidermoid carcinomas (well-differentiated type) were tumors with low-grade malignancy. Sonographic features and their correlation with histopathology Boundaries. Table III shows boundaries of lesions on sonograms. Seven cases of Warthin tumor showed

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B Fig 1. A, Longitudinal sonogram of an acinic cell carcinoma. Preoperative assessments of this lesion were “very clear” boundary, “lobular” shape, “slightly hypoechoic,” and “homogeneous” internal echoes with “enhanced” posterior echoes. (Note: All sonographic images accompanying this article have been magnified to same level as histologic images; boundaries therefore seem more indistinct than in original images.) B, Histopathologic image (H-E–stained section) of lesion seen in Fig 1, A. Tumor cell infiltration of normal gland is only partially visualized (arrow).

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B Fig 2. A, Transverse sonogram of a salivary duct carcinoma. Preoperative assessments of this lesion were “relatively clear” boundary, “lobular” shape, “slightly hypoechoic,” and “heterogeneous internal echoes with characteristic structures” with “unchanged” posterior echoes. (Because Figs 2, A and 2, B are at same magnification, posterior echoes are not shown.) B, Histopathologic image (H-E–stained section) of lesion seen in Fig 2, A. Tumor is surrounded by thick connective tissue.

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B Fig 3. A, Longitudinal sonogram of a mucoepidermoid carcinoma (well-differentiated type). Preoperative assessments of this lesion were “partially unclear” boundary, “lobular” shape, “slightly hypoechoic,” and “heterogeneous internal echoes without characteristic structures” with “attenuated” posterior echoes. B, Histopathologic image (H-E–stained section) of lesion seen in Fig 3, A. Mucus-containing tumor cell nests (arrows) are scattered among thick connective tissue.

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B Fig 4. A, Transverse sonogram of a malignant lymphoma. Preoperative assessments of this lesion were “partially unclear” boundary, “polygonal” shape (arrows), “slightly hypoechoic,” and “heterogeneous internal echoes with characteristic structures” with “enhanced” posterior echoes. B, Histopathologic image (H-E–stained section) of lesion seen in Fig 4, A. Tumor cell infiltration into normal gland is indicated (arrow).

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Table IV. Relationship between echo intensity level and ratio of histopathologic components Ratio of histopathologic components (%): average (range) Echo intensity level (no. of cases)

Tumor cells

Glandular 29.8 (5-95) parenchymal; slightly 25.8 (5-50) hypoechoic (49) 93.75 (90-95) 92.5 (90-95) – 5.0 92.5 (92-93) 3.0 55.0 (20-90) 20.0 – Very hypoechoic (28) 20.0 (10-30) 12.4 (1-45) 0.7 (0-2) – – –

Lymphocytes

Cysts

Other mesenchymal tissue

Diagnosis (no. of cases)

– 35.0 (15-85) – – 88.3 (85-90) 15.0 4.0 (3-5) – – – 95.0 – 21.4 (2-70) – 95.0 17.5 (10-25) 95.0

– 39.2 (10-80) – – – – 2.5 (2-3) 89.0 – 30.0 – – 60.6 (0-95) 95.7 (93-97) – 75.0 (70-80) –

70.2 (5-95) – 6.75 (5-10) 7.5 (5-10) 11.7 (10-15) 80.0 1.0 (0-2) 8.0 45.0 (10-80) 50.0 5.0 80.0 (70-90) 5.6 (0-96) 3.6 (3-5) 5.0 7.5 (5-10) 5.0

Pleomorphic adenoma (20) Warthin tumor (12) Lipoma (4) Basal cell adenoma (2) Lymphadenitis (3) Angiolymphoid hyperplasia (1) Acinic cell carcinoma (2) Cystadenocarcinoma (1) Mucoepidermoid carcinoma (2) Salivary duct carcinoma (1) Malignant lymphoma (1) Pleomorphic adenoma (2) Warthin tumor (18) Cyst (3) Lymphadenitis (2) Cystic lymphoid hyperplasia in AIDS (2) Malignant lymphoma (1)

tumor cell infiltration into capsules because of fineneedle aspiration biopsy. Malignant tumors showed partially unclear boundaries only in 7 (50%) of 14 cases. Of the 2 cases with low-grade malignant tumors, boundaries on their sonograms were assessed as “very clear” (Fig 1, A). Infiltration of tumor cells into the normal gland (Fig 1, B) and into the capsule was only partially detectable even on the histopathologic sections. (There was no history of fine-needle aspiration biopsy in these cases.) Three of 5 cases with “relatively clear” boundaries in malignant tumors (Fig 2, A) had thick connective tissue around the tumors (Fig 2, B). One tumor had infiltrated the sternocleidomastoid muscle; because the infiltrated portion was on the lateral side of the tumor, it could not be assessed as infiltration. Two cases with “partially unclear” boundaries (Fig 3, A) had large amounts of connective tissue in which tumor cell nests were scattered (Fig 3, B). We analyzed the relationship between recognition of a capsulelike structure on sonograms and the average thickness of the connective tissue on the anterior side and all around the lesions. Our results showed that the average thickness of the connective tissue had no relationship to recognition of a capsulelike structure on sonograms. Capsules were observed on the histopathologic sections in all cases in which capsulelike structures were recognized on sonograms. In 4 cases, we recognized capsulelike structures on the sonograms even though the capsules were less than 0.2 mm in thickness on the histopathologic sections. However, there were also 5 false-negative cases (approximately 11%) in which the capsules were less than 0.2 mm thick.

The average thickness of connective tissue on the anterior sides and all around the lesions on the histopathologic sections had no correlation with the clarity of boundaries on sonograms. In addition, whether connective tissue was dense or loose had no relationship to clarity of boundaries on sonograms. Shapes. Table III shows lesion shapes on sonograms. Malignant tumors, with 2 exceptions, showed either lobular or polygonal (Fig 4, A) morphology. The pointed portion of the polygonal lesion on sonograms was revealed on the histopathologic sections to be tumor cell infiltration (Fig 4, B). Echo intensity level. Table IV shows the relationship between echo intensity level on sonograms and the ratio of histopathologic components. Warthin tumors (Fig 5) showed both levels of echo intensity; we therefore analyzed the relationship between echo intensity level and the ratio of cystic areas in Warthin tumors. As shown in Fig 6, there was a significant difference (P < .05 by the Student t test) in the ratio of cystic areas between the “slightly hypoechoic” group and the “very hypoechoic” group. There were 2 cases in which cystic areas accounted for less than 10% of the lesion, though they showed very hypoechoic internal echoes on sonography. One showed regressive change on the histopathologic sections, and the whole tumor had been replaced by connective tissue. The other tumor consisted of more than 80% lymphocytes. We also analyzed how the nature of fluid components in Warthin tumors determined the echo intensity level. There were no statistically significant differences between echo intensity level and PAS-positive and Astra blue-positive ratios.

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B Fig 5. A, Transverse sonogram of a Warthin tumor. Preoperative assessments of this lesion were “very clear” boundary, “oval” shape, “very hypoechoic,” internal echoes with “multiple anechoic areas” and “unchanged” posterior echoes. B, Histopathologic image (H-E–stained section) of lesion seen in Fig 5, A. Multiple cystic areas with large variation in size are seen.

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Fig 6. Relationship between echo intensity level and ratio of cystic areas in Warthin tumors. Values represent means ± SD. Significant difference is observed between “slightly hypoechoic” group and “very hypoechoic” group (P < .05).

One case of malignant lymphoma showed very hypoechoic internal echoes, though there were no cystic areas. This tumor had uniform cells densely arranged within the lesion. One pleomorphic adenoma case, in which the tumor contained mainly chondroid components, also showed a very hypoechoic sonogram. Two lipoma cases showed approximately the same echo intensity level as the glandular parenchyma. One had muscle fibers in the lesion. The other showed the same histopathologic features as the remaining lipomas, the sonograms of which revealed a slightly hypoechoic appearance. This tumor was approximately 8 cm in diameter and 500 g in weight, and it was tightly compressed under the skin. Distribution of internal echoes. Table V shows the relationship between distribution of internal echoes on sonograms and the ratio of histopathologic components. Most pleomorphic adenomas (91%) showed homogeneous internal echoes. Almost all of our cases (86%) had stroma-rich pleomorphic adenomas (Fig 7); tumor cell nests were scattered in myxomatous stroma. However, some cell-rich pleomorphic adenomas, 1 case of basal cell adenoma, and the acinic cell carcinomas (solid growth pattern) also showed homogeneous internal echoes, though the cell types were different from that of stroma-rich pleomorphic adenomas. Warthin tumors showed multiple anechoic areas in 28 (93%) of 30 cases. We analyzed the relationship between the recognition of anechoic areas on sonograms and the greatest cystic area diameter on histopathologic sections of Warthin tumors. The results show that cystic areas less than 2 mm diameter could not be sonographi-

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cally assessed as anechoic areas, whereas those with diameters exceeding 3 mm were readily detectable. Cysts showed homogeneous internal echoes, the exception being 1 dermoid cyst. Half of our malignant tumors showed heterogeneous internal echoes without characteristic structures; we could obtain the ratios of histopathologic components in only two of these cases. Tumors with abundant connective tissue tended to show heterogeneous internal echoes. However, hyperechoic structures in lesions seemed to influence distribution of internal echoes more strongly in malignant tumors. Comparison with histopathologic findings (Table VI) revealed necrotic portions, keratinization in a squamous cell carcinoma, abundant collagen, and hyaline to be observable as hyperechoic structures within heterogeneous internal echoes on sonograms. A strongly hyperechoic spot with an acoustic shadow on sonograms of a fibrosarcoma was found to represent metaplastic bone formation in this lesion. Table VI shows that benign lesions also presented hyperechoic structures on sonograms. Strongly hyperechoic spots with the comet sign on sonograms of myoepithelial parotitis were microliths 0.5 to 0.8 mm in diameter. Except for this case, benign lesions did not show strongly hyperechoic spots. Weakly hyperechoic spots on the sonograms of benign lesions appeared to correspond to connective tissue or hyaline material in the lesions. Septumlike structures on sonograms were revealed to be connective tissue septa on histopathologic sections. Hyperechoic lines on the sonograms of lipomas were revealed to be connective tissue and, in one case, muscle fibers. In a dermoid cyst, the hyperechoic lines on the sonogram corresponded to desquamated keratinized material. Hila on the sonograms of lymphadenitis were connective tissue histopathologically. Hyperechoic structures were observed in 9 pleomorphic adenomas (40.9%), 19 Warthin tumors (63.3%), 6 other benign tumors (100%), 1 cyst (25%), 4 cases of lymphadenitis (80%), 5 miscellaneous lesions (100%), and 10 malignant tumors (71.4%). Acoustic enhancement. Table VII shows the relationship between acoustic enhancement on sonograms and the ratio of histopathologic components. Pleomorphic adenoma showed acoustic enhancement in 16 (73%) of 22 cases. However, there was no difference in histopathologic components between the cases with enhanced posterior echoes and those with unchanged posterior echoes. Warthin tumors showed acoustic enhancement in 11 (37%) of 30 cases. We analyzed the relationship between acoustic enhancement on sonograms and the ratio of cystic areas in Warthin tumors; no significant difference was observed. We had only 2 cases with attenuated posterior echoes. Both were malignant lesions, one a well-differ-

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Table V. Relationship between distribution of internal echoes and ratio of histopathologic components Distribution of internal echoes (no. of cases) Homogeneous (30)

Multiple anechoic areas (30) Hetero 1 (15)

Hetero 2 (2)

Ratio of histopathologic components (%): average (range) Other Tumor cells Lymphocytes Cysts mesenchymal tissue 25.1 (2-95) 11.25 (2.5-20) 90.0 – – 92.5 (92-93) 3.0 – 18.6 (2-50) – 67.5 (40-95) 93.75 (90-95) 95.0 2.0 – 5.0 20.0 – 55.0 (20-90)

– 26.25 (2.5-50) – – 95.0 4.0 (3-5) – 95.0 26.7 (2-80) 17.5 (10-25) – – – – 90.0 (85-95) 15.0 – 95.0 –

– 62.5 (30-95) – 97.0 – 2.5 (2-3) 89.0 – 51.1 (0-93) 75.0 (70-80) – – – 93.0 – – 30.0 – –

74.9 (5-98) – 10.0 3.0 5.0 1.0 (0-2) 8.0 5.0 3.6 (0-96) 7.5 (5-10) 32.5 (5-60) 6.25 (5-10) 5.0 5.0 10.0 (5-15) 80.0 50.0 5.0 45.0 (10-80)

Diagnosis (no. of cases) Pleomorphic adenoma (20) Warthin tumor (2) Basal cell adenoma (1) Cyst (2) Lymphadenitis (1) Acinic cell carcinoma (2) Cystadenocarcinoma (1) Malignant lymphoma (1) Warthin tumor (28) Cystic lymphoid hyperplasia in AIDS (2) Pleomorphic adenoma (2) Lipoma (4) Basal cell adenoma (1) Cyst (1) Lymphadenitis (4) Angiolymphoid hyperplasia (1) Salivary duct carcinoma (1) Malignant lymphoma (1) Mucoepidermoid carcinoma (2)

Hetero 1, Heterogeneous with characteristic structures; Hetero 2, heterogeneous without characteristic structures.

entiated mucoepidermoid carcinoma (Fig 3) and the other a fibrosarcoma with metaplastic bone formation.

DISCUSSION We analyzed which histopathologic features were visualized on sonograms by comparing sonomorphology (regarding boundaries, lesion shapes, echo intensity levels, distribution of internal echoes, acoustic enhancement) with histopathology on the same planes. Boundaries We observed partially unclear boundaries in 8 of 86 lesions. One of these was a Warthin tumor that showed highly degenerated histopathology; all of the other 7 cases were malignant tumors. We could not detect the infiltrated portion in 50% of the malignant lesions because of the extreme smallness of these portions or because of the thickness of the connective tissue around the lesions. However, inasmuch as the lesions with partially unclear boundaries were all malignant (with the exception of a single Warthin tumor, as mentioned), this feature should be emphasized in differentiating malignant from benign lesions. If we observed capsulelike structures on the sonograms, capsules were later confirmed on the histopathologic sections, even when the thickness of the connective tissue was less than 0.2 mm. This observation suggests that it is not only the average thickness of the connective tissue that affects the recognition of

capsulelike structures on sonograms: variable thickness of the capsule might also affect this recognition. Our results showed that the average thickness of the connective tissue around the lesions had no relationship to the clarity of the boundaries on sonograms. The clearer boundaries of Warthin tumors in most cases might be explained by the larger difference in impedance between the inside and the outside of this tumor in comparison with pleomorphic adenomas. The shapes of the tumors might also influence the clarity of the boundaries on sonograms. Oval Warthin tumors had clearer boundaries than lobular pleomorphic adenomas.

Shapes Four of 6 polygonal lesions were malignant. If polygonal lesions are seen on sonograms, we should initially consider malignancy. Malignant tumors were also lobular in 50% of cases. However, pleomorphic adenomas (91%) and other benign lesions also showed lobular morphology. Therefore, other sonomorphologic features should be considered in differentiating malignant from benign lesions in cases in which the lesions are lobular. Echo intensity level In our cases with Warthin tumors, the ratio of cystic areas correlated with the echo intensity level on sonograms. It is well known that cystic areas show echo-

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B Fig 7. A, Transverse sonogram of a pleomorphic adenoma. Preoperative assessments of this lesion were “relatively clear” boundary, “lobular” shape, “slightly hypoechoic,” and “homogeneous” internal echoes with “enhanced” posterior echoes. B, Histopathologic image (H-E–stained section) of lesion seen in Fig 7, A. Tumor cells are scattered among myxomatous stroma.

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free zones.21 Our results thus correspond to those of an earlier report. When the cysts contained pus or debris, they appeared as solid lesions on the sonograms.22 Therefore, we hypothesized that the difference in the nature of fluid components in Warthin tumors might reflect the echo intensity level. There was, however, no relationship between these two factors. Besides cystic areas, dense cellular areas also showed echo-free zones.20 We had one Warthin tumor comprised of more than 80% lymphocytes, the sonograms of which showed very hypoechoic internal echoes. One malignant lymphoma with uniform small cells also showed very hypoechoic internal echoes. However, the other malignant lymphoma showed a higher echo intensity level, though the ratios of histopathologic components of the two cases were equal. This suggests that density and distribution of cells might also be important factors in echo intensity level. One pleomorphic adenoma with abundant chondroid components and 1 Warthin tumor with connective tissue replacement showed very hypoechoic internal echoes. These results suggest that chondroid and collagen, which have a large attenuation coefficient,18 might show very hypoechoic echoes if their conformation is dense and uniform. Two lipomas showed approximately the same echo intensity level as glandular parenchyma. These cases might be atypical among parotid tumorous lesions. Because only lipomas showed such echogenicity, however, this feature may merit emphasis as one of the sonomorphologic features of lipomas.

Distribution of internal echoes In the present study, stroma-rich pleomorphic adenomas, some cell-rich pleomorphic adenomas, one basal cell adenoma, and the acinic cell carcinomas showed similar distributions of internal echoes. Ohyachi19 also reported that myxomatous and cellular type pleomorphic adenomas, acinic cell carcinomas, and 2 of 3 basal cell adenomas showed similar attenuation coefficients. It might be difficult to differentiate these tumors from each other, as they also have similar shapes. Warthin tumors showed multiple anechoic areas sonographically in 93% of cases. This feature should be emphasized in diagnosing Warthin tumors. However, we recognized no anechoic areas on sonograms of Warthin tumors in which the greatest diameter of the cystic areas was less than 2 mm. This observation suggests that Warthin tumors with many small (<2 mm) cystic areas might be misdiagnosed as other solid benign tumors, such as pleomorphic adenomas. Heterogeneous internal echoes without specific features, such as anechoic areas or a hilus, should

Table VI. Histopathologic features corresponding to hyperechoic structures on sonograms Hyperechoic structures

Corresponding histopathology

Strongly hyperechoic Connective tissue spots Metaplastic bone Microliths Weakly hyperechoic Connective tissue spots Connective tissue Connective tissue Hyaline Necrosis Keratinazed material Unclear Unclear Unclear Unclear Septa

Lines

Hila

Connective tissue Connective tissue Connective tissue Connective tissue Connective tissue Hyaline Hyaline Unclear Unclear Connective tissue Connective tissue Connective tissue Connective tissue

Diagnosis (no. of cases) Mucoepidermoid carcinoma (1) Fibrosarcoma (1) Parotitis (1) Pleomorphic adenoma (2) Warthin tumor (9) Basal cell adenoma (1) Pleomorphic adenoma (2) Mucoepidermoid carcinoma (1) Metastatic tumor (1) Pleomorphic adenoma (3) Warthin tumor (1) Lipoma (1) Mucoepidermoid carcinoma (1) Pleomorphic adenoma (4) Warthin tumor (6) Lipoma (2) Parotitis (2) Cystic lymphoid hyperplasia in AIDS (2) Cystadenocarcinoma (1) Malignant lymphoma (1) Warthin tumor (1) Pleomorphic adenoma (1) Warthin tumor (5) Lipoma (3) Basal cell adenoma (1) Angiolymphoid hyperplasia (1) Acinic cell carcinoma (1) Warthin tumor (1) Lipoma (1) Cyst (1)

Connective tissue Hyaline Muscle fibers Keratinazed material Unclear Warthin tumor (2) Unclear Metastatic tumor (1) Connective tissue Lymphadenitis (4)

prompt consideration of malignant lesions. Hila were observed only in lymphadenitis; therefore, hila merit notice as one of the important sonomorphologic features of lymphadenitis. Other hyperechoic structures were observed in a variety of lesions. However, strongly hyperechoic spots were observed either in malignant tumors or in parotitis with microliths. If a strongly hyperechoic spot is observed on sonograms, malignancy should be taken into consideration. Hyperechoic structures that were observed on sonograms were attributed to differences in impedance between reflective substances and the other compo-

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Table VII. Relationship between acoustic enhancement and ratio of histopathologic components Acoustic enhancement (no. of cases) Enhanced (37)

Unchanged (36)

Attenuated (1)

Ratio of histopathologic components (%): average (range) Tumor Other cells Lymphocytes Cysts mesenchymal tissue 29.8 (5-95) 13.1 (2.5-30) 95.0 0.7 (0-2) – – 92.0 – 30.0 (5-80) 21.0 (2-50) 92.5 (90-95) 92.5 (90-95) – 5.0 93.0 3.0 90.0 20.0 – 20.0

– 26.6 (2.5-80) – – 95.0 17.5 (10-25) 5.0 95.0 – 26.7 (2-70) – – 88.3 (85-90) 15.0 3.0 – – – 95.0 –

– 59.8 (10-95) – 95.7 (93-97) – 75.0 (70-80) 3.0 – – 47.25 (0-88) – – – – 2.0 89.0 – 30.0 – –

nents of the lesions.23 According to our results, these substances were connective tissue (mainly collagen), metaplastic bone, and microliths, as well as hyaline, necrotic and keratinized materials, and muscle fibers. Among these substances, bone, muscle, and connective tissue (collagen) reportedly have high impedance.16,23 When the lesion shows necrosis or degeneration, the internal echoes increase because of the newly constructed reflective points.24 Adipose tissue has a lower impedance than other soft tissues,23 possibly explaining the high reflex in the one lipoma case involving muscle fibers, between adipose tissue and muscle fibers. These findings correspond to those of Gritzmann.25

Acoustic enhancement Acoustic enhancement occurs with weak attenuation in a lesion, and cysts show marked acoustic enhancement.26 Three of 4 cysts in our cases showed enhanced posterior echoes. Pleomorphic adenomas showed acoustic enhancement in most of our cases (73%), whereas only 37% of Warthin tumors showed such enhancement. These observations correspond to those of Mann and Wachter.11 In the study of Ohyachi,19 the attenuation coefficient of Warthin tumors was the lowest, but there was no significant difference in comparison with that of myxomatous pleomorphic adenomas. Our results suggest that not only the attenuation coefficient but also the uniformity of internal echoes reflects acoustic enhancement.

70.2 (5-98) 0.5 (0-5) 5.0 3.6 (3-5) 5.0 7.5 (5-10) – 5.0 70.0 (20-95) 5.05 (0-96) 7.5 (5-10) 7.5 (5-10) 11.7 (10-15) 80.0 2.0 8.0 10.0 50.0 5.0 80.0

Diagnosis (no. of cases) Pleomorphic adenoma (16) Warthin tumor (11) Lipoma (1) Cyst (3) Lymphadenitis (2) Cystic lymphoid hyperplasia in AIDS (2) Acinic cell carcinoma (1) Malignant lymphoma (1) Pleomorphic adenoma (4) Warthin tumor (19) Lipoma (2) Basal cell adenoma (2) Lymphadenitis (3) Angiolymphoid hyperplasia (1) Acinic cell carcinoma (1) Cystadenocarcinoma (1) Mucoepidermoid carcinoma (1) Salivary duct carcinoma (1) Malignant lymphoma (1) Mucoepidermoid carcinoma (1)

Attenuation of posterior echoes is due to substances with high acoustic impedance, and bone and stones show marked acoustic shadows.23 In our case of welldifferentiated mucoepidermoid carcinoma, a large amount of irregular connective tissue was thought to be the source of attenuation. In conclusion, although sonography cannot replace histopathologic examination, ultrasonography, in contrast with fine-needle aspiration biopsy, presents no risk of damage to facial nerve branches, and it is superior to other imaging modalities in describing the structure of tumorous lesions. Findings on sonograms can provide valuable information about histopathology, such as tumor cell infiltration or abundant connective tissue in malignant tumors. In addition, sonography may help distinguish benign from malignant tumors in the parotid region. We believe that sonomorphology facilitates accurate diagnosis of parotid lesions. We thank Mr A. Pommert (Institute of Mathematics and Computer Science in Medicine, University Hospital Eppendorf, Hamburg University, Hamburg, Germany) and Drs K. Yoshiura (Assistant Professor, Department of Oral & Maxillofacial Radiology, Faculty of Dentistry, Kyushu University, Fukuoka, Japan) and K. Araki (Associate Professor, Department of Dental Radiology, School of Dentistry, Showa University, Tokyo, Japan) for helpful discussion and pertinent comments on the manuscripts. We also thank Ms Tomrlin for photographs, and we thank our coworkers in the Department of Oral Pathology and the EarNose-Throat Clinic for their cooperation.

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Reprint reiquests: Mayumi Shimizu, DDS, PhD Department of Oral & Maxillofacial Radiology Faculty of Dentistry, Kyushu University Maidashi 3-1-1, Higashi-ku Fukuoka, 812-8582 Japan E-mail: [email protected]