Preoperative Differential Diagnosis of Canine Adrenal Tumors Using Triple-Phase Helical Computed Tomography
Orie Yoshida1, Kenji Kutara1, Mamiko Seki1, Kumiko Ishigaki1, Kenji Teshima1, Chieko Ishikawa1, Gentoku Iida1 , Kazuya Edamura1 , Yumiko Kagawa2 , and Kazushi Asano1
1Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan and 2North Lab, Sapporo, Hokkaido, Japan
Corresponding Author
Kazushi Asano Laboratory of Veterinary Surgery Department of Veterinary Medicine College of Bioresource Sciences Nihon University 1866 Kameino Fujisawa, Kanagawa 252-0880, Japan asano.kazushi@nihon-u.ac.jp
Submitted October 2014 Accepted June 2015
DOI:10.1111/vsu.12462
Objective: To characterize the computed tomography (CT) findings for canine adrenal tumors, including cortical adenoma, cortical adenocarcinoma, and pheochromocytoma, and to evaluate the feasibility and usefulness of preoperative triple-phase helical CT for differentiation of tumor types and surgical planning.
Study Design: Retrospective study.
Animals: Dogs with adrenal tumors (n=36).
Methods: All dogs underwent triple-phase helical CT, followed by adrenalectomy and histopathological diagnosis of the resected mass. Precontrast images, arterial, venous, and delayed phase images were obtained. In all cases, morphological characteristics and CT values and calculations, including the percentage enhancement washout ratio, relative percentage washout, enhancement washin, and enhancement washout, were analyzed and compared among the tumor types.
Results: Of the 36 dogs with adrenal masses, cortical adenocarcinoma was most commonly diagnosed (16 dogs), followed by pheochromocytoma (13 dogs), and cortical adenoma (7 dogs). The precontrast minimum CT value and enhancement washout between venous and delayed phases in the cortical adenoma were significantly higher than those in the cortical adenocarcinoma. The maximum CT values of the precontrast image and arterial and venous phases, the enhancement washin and washouts, percentage enhancement washout ratio, and relative percentage washout in the pheochromocytomas were significantly higher than those in cortical adenocarcinoma.
Conclusion: The differential diagnosis of canine adrenal tumors was feasible based on triple-phase CT findings, including morphological features, CT values, and intratu- moral contrast attenuation. Preoperative diagnosis using triple-phase helical CT may be useful for surgical planning in dogs with adrenal tumors.
Primary adrenal gland neoplasias reportedly represent about 0.17-0.76% of all tumors in dogs. Cortical adenoma and cortical adenocarcinoma are the most common canine adrenal tumors, followed by medullary pheochromocytoma.1-4 Regardless of the tumor origin, adrenalectomy is the treat- ment of choice in dogs with primary adrenal tumors. How- ever, perioperative mortality rates have been reported to be relatively high (20-60%) as a result of various complica- tions.2,5-9 Previous studies have reported tumor type as a prognostic factor because the intraoperative complications, including hypotension, hypertension, heavy hemorrhage, arrhythmias, and hypoxia, have the tendency to occur in corti- cal adenocarcinoma and pheochromocytoma.4,9 In addition, preoperative administration of phenoxybenzamine was reported to be useful for reducing the perioperative mortality rate in canine pheochromocytoma.1º Therefore, preoperative diagnosis is clinically important for the treatment of canine adrenal tumors.
Diagnostic imaging techniques have a great impact on the preoperative evaluation and surgical planning of canine adrenal tumors. Abdominal radiography is one of the primary examinations required and is reported to enable localization of adrenocortical tumors of sufficient size (≥20 mm in diame- ter) or mineralization.11 However, this technique cannot detect canine adrenal tumors that are small in size or evaluate infiltration to surrounding tissues and large vessels. Abdomi- nal ultrasound allows more sensitive detection of adrenal masses and can evaluate the size, shape, and caudal vena cava invasiveness of canine adrenal tumors.7,12-14 However, abdominal ultrasound is unable to differentiate between adre- nocortical and adrenomedullary tumors in dogs.15
In people, computed tomography (CT) can aid in the dif- ferential diagnosis of cortical adenoma, which accounts for the majority of adrenocortical tumors. This technique has been reported to show unenhanced CT values of <10 Houns- field units (HU) in adrenal masses because cortical adenoma
generally contains an abundance of intracytoplasmic lipid.16,17 However, ~30% of all cortical adenomas have been shown to have relatively small amounts of intracytoplas- mic lipid.18 Therefore, the evaluation of unenhanced CT val- ues alone is insufficient for the differential diagnosis of cortical adenoma. Furthermore, some pheochromocytomas have shown similar unenhanced CT values and contrast- enhanced patterns as cortical adenomas. 18,19
Development of multidetector helical CT ensured that dynamic CT could be used to evaluate the hemodynamics of abdominal organs. Triple-phase helical CT can be used to rap- idly scan the whole abdomen in 3 phases including arterial, venous, and delayed phases. In previous human studies, mul- tiphase helical CT has demonstrated that the contrast medium is excreted rapidly in cases of cortical adenoma and gradually in cases of cortical adenocarcinoma.20-22 Thus, use of triple- phase helical CT has attempted to differentiate cortical ade- noma from other types of adrenal tumors based not only on comparison of CT attenuation values in each phase but also on calculation of the percentage enhancement washout (PEW) ratio and relative percentage washout (RPW), which represent the fraction of contrast medium eliminated from the tumor.20-26 Additional evaluation of PEW and RPW may enhance the accuracy of differential diagnosis in people with adrenal tumors.
On the other hand, a limited number of reports have described CT findings of adrenal tumors in dogs27-29 or measured CT values of the adrenal gland in healthy dogs.30 One previous study did compare CT and histopathologic find- ings in dogs with primary adrenal tumors, but the intratu- moral localization and transition of contrast enhancement was not evaluated.31 In addition, CT revealed overlapping charac- teristics between adrenal tumor types. There are no reports evaluating the clinical potential of CT for differential diagno- sis of adrenal tumors using PEW and RPW in dogs. The objectives of this study were to characterize the CT findings of canine adrenal tumors, including cortical adenoma, cortical adenocarcinoma, and pheochromocytoma, and to evaluate the feasibility and usefulness of preoperative triple-phase helical CT for differentiation of tumor types and for surgical plan- ning. We hypothesized that triple-phase helical CT, including the calculation of PEW and RPW, could be useful for preoper- ative differential diagnosis of canine adrenal tumors.
MATERIALS AND METHODS
Animals
Thirty-six client-owned dogs were included in this study. All dogs were referred to the Animal Medical Center of Nihon University with suspicion of primary adrenal masses between April 2007 and November 2013. During the first consultation, abdominal radiology and ultrasound revealed adrenal masses in all dogs and all animals subsequently underwent triple- phase helical CT followed by adrenalectomy.
Triple-Phase Helical CT
A 22-24 gauge over-the-needle catheter was placed into the cephalic vein and dogs were premedicated with midazolam hydrochloride (0.2 mg/kg) and butorphanol tartrate (0.2 mg/ kg IV). Intratracheal intubation was performed after induction with propofol (3-7 mg/kg IV, to effect). General anesthesia was maintained by mechanical ventilation with isoflurane (1.5-2%) and oxygen (2 L/min).
All dogs were positioned in ventral recumbency and scans were obtained on a 16-slice multidetector helical CT scanner (Aquilion 16; Toshiba Medical Systems Co, Otawara, Japan). The scanning parameters were as follows: gantry rota- tion time, 0.5 seconds; slice thickness, 1-2 mm; reconstruc- tion interval, 0.5-1 mm; table speed, 16-32 mm/rotation; helical pitch, 16; X-ray tube potential, 120 kV; and X-ray tube current, 150 mA. All helical scans were started at the tip of the wing of the ilium in a cranial direction and covered the entire liver.
Iohexol (Ioverin 300; Teva Pharma Japan, Inc, Nagoya, Japan) contrast medium was administered at a dose of 2.5 mL/kg (750 mgI/kg) by the cephalic vein with a power injector (Auto Enhance A-60; Nemoto-Kyorindo Co, Tokyo, Japan). The injection time was 15-20 seconds (injection speed, 0.3-3 mL/s). In cases where the injection speed was calculated to exceed 3 mL/s, the injection time of the contrast medium would have been within 20 seconds, and so the injec- tion speed was fixed at 3 mL/s (injection time, 21-31 sec- onds). Precontrast (before the injection of contrast medium), arterial phase (~20 seconds after the start of injection of con- trast medium), venous phase (~40 seconds after the start of injection), and delayed phase (~120 seconds after the start of injection) scans were obtained by using a protocol previously reported for the liver.32 Scanning time for each phase was approximately 8 seconds. In all dogs, obtained images were transferred to an image processing workstation after scanning (AZE Virtual Place Plus, AZE Co, Tokyo, Japan).
Image Analysis
All CT images were reviewed retrospectively on a dedicated computer workstation and blindly analyzed by 1 veterinarian (OY). The location of the lesion (left or right), shape of the mass margin (smooth or lobulated), presence of intratumoral calcification, and presence of caval tumor thrombi were recorded. In the arterial phase, the largest transverse dimen- sion of each adrenal mass was measured in the plane cor- rected to be parallel to the vertebral line and intervertebral space. The minimum diameter of the aorta was also measured in the same manner at the cranial level of the celiac arterial bifurcation (T13-L1). In addition, the ratio of the largest transverse adrenal mass dimension to the minimum diameter of the aorta (Ad/Ao ratio) was calculated.
CT attenuation values were recorded in HU. Circular or ovoid regions of interest (ROI) of 30 mm2 in size were placed on the axial plane of the largest adrenal dimension for all measurements of CT values in each adrenal mass. Each ROI was placed in the same area of the precontrast and phased CT
| AP-PEW = | Maximum CT value in arterial phase - Maximum CT value in delayed phase × 100 |
| Maximum CT value in arterial phase - Maximum CT value in pre-contrast image | |
| Maximum CT value in venous phase - Maximum CT value in delayed phase × 100 | |
| VP-PEW = | Maximum CT value in venous phase - Maximum CT value in pre-contrast image |
| RPW = | Maximum CT value in arterial phase - Maximum CT value in delayed phase × 100 |
| Maximum CT value in arterial phase |
images. Calcification and blood vessels were excluded from ROI.
In each dog, enhancement and minimal enhancement patterns were assessed in the same ROI for each phase and compared with the precontrast image. An enhancement pat- tern was defined when the enhanced CT values increased by ≥50 HU, whereas a minimal enhancement pattern was defined as an increase of <50 HU. In addition, heterogeneous and homogeneous patterns were evaluated in the axial plane of the largest adrenal mass dimension for each phase. A heterogeneous pattern was defined when the difference between the maximum and minimum CT values was ≥20 HU, whereas a homogenous pattern was defined as a differ- ence of <20 HU.
In each dog, PEW in the arterial phase (AP) and venous phase (VP) as well as RPW were calculated (Fig 1). Enhance- ment washin (increase in CT value due to contrast medium inflow) and enhancement washout (decrease in CT value due to contrast medium outflow) between the arterial and venous phases (enhancement washout AP-VP), between the arterial phase and the delayed phase (DP; enhancement washout AP- DP), and between the venous and DPs (enhancement washout VP-DP) were calculated (Fig 2).
Surgical Procedure and Histopathological Diagnosis
Adrenalectomy was performed by 1 veterinary surgeon (KA). All dogs were positioned in dorsal recumbency. An abdomi- nal ventral midline approach with or without bilateral/unilat- eral paracostal incisions was performed as needed. Complete en bloc resection of tumors was accomplished in all cases. Resected tumor tissues were fixed in 10% neutral buffered
formalin and embedded in paraffin. Sections were stained with hematoxylin and eosin. Histopathological diagnoses were reviewed by 1 veterinary pathologist (YK). In only 1 case, adjunctive immunohistochemical examinations were performed for the diagnosis of cortical adenocarcinoma.
Data Analysis
Statistical tests were performed using commercially available statistical analysis software (Stat Mate III, ATMs Co, Tokyo, Japan, and GraphPad Prism version 6.0 for Macintosh, Graph Pad Software Inc, San Diego, CA). Data on age, body weight, maximum adrenal mass diameter, minimum aortic diameter, Ad/Ao ratio, CT values, AP-PEW, VP-PEW, RPW, enhance- ment washin, enhancement washout AP-VP, enhancement washout AP-DP, and enhancement washout VP-DP were rep- resented as median [range] and were statistically compared between cortical adenoma, cortical adenocarcinoma, and phe- ochromocytoma using the Kruskal-Wallis H-test, followed by Dunn’s post hoc correction test. Sex, tumor location, contrast enhancement level and pattern, tumor margin shape, intratu- moral calcification, and tumor thrombosis into the caudal vena cava were analyzed by a x2 test, followed by Yates’ post hoc correction test. P <. 05 was considered statistically significant.
RESULTS
Thirty-six dogs (10 males and 26 females; median age, 11 years [6.4-15 years]) were included in the study. Diagnoses were cortical adenoma (7 dogs), cortical adenocarcinoma (16
Enhancement washin = Maximum CT value in arterial phase - Maximum CT value in pre-contrast image
Enhancement washout AP-VP = Maximum CT value in arterial phase - Maximum CT value in venous phase
Enhancement washout AP-DP = Maximum CT value in arterial phase - Maximum CT value in delayed phase
Enhancement washout VP-DP = Maximum CT value in venous phase - Maximum CT value in delayed phase
Figure 2 Formulas used to calculate computed tomography (CT) enhancement washin and enhancement washout between phases. AP, arterial phase; VP, venous phase; DP, delayed phase.
| All Tumors | Tumor Type | P-Value | |||||
|---|---|---|---|---|---|---|---|
| Cortical Adenoma | Cortical Adenocarcinoma | Pheochromocytoma | CA vs. CAC | CA vs. PHEO | CAC vs. PHEO | ||
| Number of dogs (Right-sided; left-sided) | 36 (R 16; L 20) | 7 (R 2; L 5) | 16 (R 9; L 7) | 13 (R 5; L 8) | .442 | .960 | .562 |
| Intratumoral calcification Number of dogs (%) | 13 (36.1%) | 1 (14.3%) | 10 (62.5%) | 2 (15.4%) | .094 | .555 | .029 |
| Tumor shape Smooth or Lobulated | Smooth 26 Lobulated 10 | Smooth 7 Lobulated 0 | Smooth 13 Lobulated 3 | Smooth 6 Lobulated 7 | .578 | .055 | .113 |
| Caval tumor thrombus Number of dogs (%) | 15 (41.7%) | 0 (0%) | 5 (31.3%) | 10 (76.9%) | .171 | .005 | .081 |
| Tumor size (cm) Mean [range] | 2.83 [1.27-12.64] | 1.90 [1.27-2.99] | 2.70 [1.57-7.68] | 4.38 [1.49-12.64] | .454 | .024 | .331 |
| Aorta size (cm) Mean [range] | 0.75 [0.42-1.32] | 0.77 [0.55-1.29] | 0.73 [0.42-1.27] | 0.73 [0.53-1.32] | 1.000 | 1.000 | 1.000 |
| Ad/Ao ratio Mean [range] | 3.46 [1.24-11.60] | 2.50 [1.40-3.71] | 3.45 [1.24-10.97] | 4.76 [2.02-11.60] | .408 | .023 | .366 |
CA, corical ademona; CAC, cortical adenocarcinoma; PHEO, pheochromocytoma; Ad/Ao ratio, largest transverse adrenal mass dimension to the min- imum diameter of the aorta.
dogs), and pheochromocytoma (13 dogs). One of the cases of pheochromocytoma involved a tumor that had recurred in the same area. Breeds were as follows Shih Tzu and Miniature Dachshund (4 dogs each), Beagle, Chihuahua, Golden Retriever, and Shetland Sheepdog (3 dogs each), Maltese, Miniature Schnauzer, Toy Poodle, and Wire-haired Fox Terrier (2 dogs each), and American Cocker Spaniel, Bulldog, Pomeranian, Shiba, Pembroke Welsh Corgi, Yorkshire Terrier, West Highland White Terrier, and Mixed breed (1 dog each). The median body weight of the dogs was 8.2 kg [3.1-27.7 kg]. Tumor location was on the right side in 16/36 dogs (44.4%) and on the left side in 20/36 dogs (55.6%). Age, sex, breed, body weight, and tumor location were not significantly different between the tumor types.
CT Characteristics (Table 1) Intratumoral calcification was observed in 10/16 dogs (62.5%) with cortical adenocarcinoma. Intratumoral calcifica-
tion was significantly higher in cortical adenocarcinoma com- pared with pheochromocytoma. Caval tumor thrombus was observed in 10/13 dogs (76.9%) with pheochromocytoma. Caval tumor thrombus was significantly higher in pheochro- mocytoma compared with cortical adenoma. The minimum diameter of the aorta showed no significant difference among tumor types. Maximum diameter of the mass and the Ad/Ao ratio of pheochromocytoma were significantly higher than the corresponding values for cortical adenoma. Lobulated mar- gins were not detected in any of the cortical adenomas. In contrast, mass margins were lobulated in 7/13 dogs (53.8%) with pheochromocytoma. The presence of lobulated margins was significantly increased in pheochromocytoma when com- pared with cortical adenoma.
CT Values and Enhancement Patterns (Tables 2-5; Fig 3)
Maximum CT values of cortical adenocarcinoma were signif- icantly lower than those of pheochromocytoma in the
| Phase | Cortical Adenoma | Cortical Adenocarcinoma | Pheochromocytoma | P-Value | |||
|---|---|---|---|---|---|---|---|
| CA vs. CAC | CA vs. PHEO | CAC vs. PHEO | |||||
| Precontrast | Maximum | 49.0 [27.5-55.1] | 38.7 [10.4-55.8] | 50.0 [43.2-55.4] | .725 | .963 | .023 |
| Minimum | 43.8 [30.7-62.8] | 31.8 [0.20-50.5] | 47.6 [24.1-55.2] | .034 | 1.000 | .011 | |
| Arterial phase | Maximum | 113.3 [49.5-204.0] | 70.8 [23.1-119.2] | 204.1 [84.5-323.1] | .381 | .159 | <. 001 |
| Minimum | 59.9 [38.3-156.2] | 39.2 [12.5-114.3] | 104.3 [25.3-227.3] | .078 | 1.000 | .005 | |
| Venous phase | Maximum | 122.3 [69.7-162.4] | 90.1 [41.2-242.1] | 152.3 [95.3-207.9] | 1.000 | .328 | .020 |
| Minimum | 72.2 [34.1-126.9] | 43.6 [10.1-155.6] | 98.2 [24.9-174.9] | .391 | 1.000 | .098 | |
| Delayed phase | Maximum | 106.3 [79.2-167.4] | 93.8 [48.8-199.2] | 114.3 [98.9-157.6] | 1.000 | 1.000 | .200 |
| Minimum | 86.7 [57.0-142.7] | 61.6 [22.4-159.5] | 91.2 [25.2-142.5] | .696 | 1.000 | .508 | |
CA, cortical ademona; CAC, cortical adenocarcinoma; PHEO, pheochromocytoma.
| Enhanced CT Values Increased By | Tumor Type | P-value | ||||
|---|---|---|---|---|---|---|
| Cortical Adenoma | Cortical Adenocarcinoma | Pheochromocytoma | CA vs. CAC | CA vs. PHEO | CAC vs. PHEO | |
| ≥50 HU | 7 | 10 | 13 | .171 | – | .044 |
| <50 HU | 0 | 6 | 0 | |||
precontrast image as well as the arterial and venous phases. Minimum CT values of cortical adenocarcinoma were signifi- cantly lower than those of cortical adenoma and pheochromo- cytoma in the precontrast image. A minimal enhancement pattern was observed in 6/36 (16.7%) of all the masses in all phases. These 6 masses were all cortical adenocarcinomas and 5 (83.3%) had intratumoral calcification. In the venous phase, a heterogeneous pattern was observed in most cases of pheochromocytoma and cortical adenocarcinoma but only half of the cases of cortical adenoma. Contrast homogeneity number of cortical adenoma was significantly different between cortical adenocarcinoma and pheochromocytoma. In the precontrast image and arterial and delayed phases, con- trast homogeneity was not significantly different among tumor types.
The AP-PEW, VP-PEW, RPW, enhancement washin, enhancement washout AP-VP, enhancement washout AP-DP, and enhancement washout VP-DP values were significantly different between cortical adenocarcinoma and pheochromo- cytoma. In contrast, enhancement washout VP-DP showed a significant difference between cortical adenoma and cortical adenocarcinoma, and there were no significant differences in any of the calculated parameters between cortical adenoma and pheochromocytoma.
DISCUSSION
In our study, characteristic CT findings of pheochromocy- toma included a larger size, lobulated tumor margins, the presence of caval thrombi, and a heterogeneous pattern in the venous phase. Previous studies have demonstrated that pheo-
chromocytoma is generally large in size and nonencapsulated, and the occurrence of caval invasion ranged from 25 to 60%.12,33 In our study, caval tumor thrombus was observed in 10/13 (76.9%) of dogs with pheochromocytoma, and none of the cortical adenomas. Therefore, the results suggest that triple-phase helical CT could be useful for differentiating phe- ochromocytoma from cortical adenoma.
In people, unenhanced CT values of <10 HU are sug- gested to enable the differentiation of cortical adenoma from other adrenal tumors because cortical adenoma generally con- tains an abundance of intracytoplasmic lipid.16,17 However, of all the adrenal tumors in our study, only 2 cortical adeno- carcinomas had precontrast minimum CT values of <10 HU. In canine cortical adenocarcinoma, areas of hemorrhage within the tumors are common because of rupture of thin- walled vessels.34 Precontrast minimum CT values are thought to be decreased in cortical adenocarcinoma because of intratu- moral necrosis or hemorrhage. However, the size of the 2 cortical adenocarcinomas with precontrast minimum CT val- ues of <10 HU in our study was small, and histopathology did not reveal necrosis and hemorrhage within the tumors. Therefore, the assessment of precontrast CT values for the differential diagnosis of cortical adenoma and cortical adeno- carcinoma is thought to differ between dogs and people.
When differentiating adrenocortical tumors in dogs, a tumor size of ≥2.0 cm was reported to indicate cortical ade- nocarcinoma.35 However, there were both cortical adenocar- cinomas of <2.0 cm and cortical adenomas of ≥2.0 cm in our study. In addition, tumor size was not significantly differ- ent between cortical adenoma and cortical adenocarcinoma. Thus, the differential diagnosis of canine adrenocortical tumors based on size may be misleading. In our study,
| Phase | Enhancement Pattern | Tumor Type | P-Value | ||||
|---|---|---|---|---|---|---|---|
| Cortical Adenoma | Cortical Adenocarcinoma | Pheochromocytoma | CA vs. CAC | CA vs. PHEO | CAC vs. PHEO | ||
| Precontrast | Homogeneous | 7 | 14 | 13 | .328 | – | 186 |
| Heterogeneous | 0 | 2 | 0 | ||||
| Arterial phase | Homogeneous | 1 | 5 | 1 | .736 | .755 | .273 |
| Heterogeneous | 6 | 11 | 12 | ||||
| Venous phase | Homogeneous | 4 | 2 | 1 | .025 | .015 | .672 |
| Heterogeneous | 3 | 14 | 12 | ||||
| Delayed phase | Homogeneous | 3 | 4 | 3 | .392 | .357 | .904 |
| Heterogeneous | 4 | 12 | 10 | ||||
CA, cortical adenoma; CAC, cortical adenocarcinoma; PHEO, pheochromocytoma.
| Parameter | Cortical Adenoma | Cortical Adenocarcinoma | Pheochromocytoma | P-Value | ||
|---|---|---|---|---|---|---|
| CA vs. CAC | CA vs. PHEO | CAC vs. PHEO | ||||
| Arterial Phase-PEW | 12.4 [-9300 - 64.2] | -103.9 [-981.8-9.8] | 50.3 [-748.6 -68.9] | .354 | .433 | .001 |
| Venous Phase-PEW | 18.2 [-127.0-35.1] | -1.6 [-110.8-32.7] | 31.8 [-34.9 -45.4] | .778 | .188 | .001 |
| Relative percentage washout | 7.0 [-93.9-54.2] | -42.6 [-221.6 -5.6] | 37.9 [-94.2-56.6] | .263 | .531 | .001 |
| Enhancement washin | 58.2 [0.5-166.7] | 28.9 [1.1 -79.5] | 151.0 [7.2-246.2] | .463 | .248 | <. 001 |
| Enhancement washout AP-VP | -5.5 [-41.3-71.9] | -19.7 [-153.8-12.6] | 50.2 [-55.8 - 111.5] | .395 | .699 | .003 |
| Enhancement washout AP-DP | 6.0 [-54.1-105.2] | -25.4 [-87.7-6.7] | 89.8 [-53.9- 167.7] | .258 | .448 | <. 001 |
| Enhancement washout VP-DP | 9.4 [-26.3 - 33.3] | -1.2 [-42.2-66.1] | 39.1 [-15.8 - 58.0] | .039 | 1.000 | .002 |
PEW, percentage enhancement washout ratio; DP, delayed phase; CA, cortical adenoma; CAC, cortical adenocarcinoma; PHEO, pheochromocy- toma; enhancement washin, increase in CT value due to contrast medium inflow; enhancement washout AP-VP, decrease in CT value due to con- trast medium outflow between the arterial and venous phases; enhancement washout AP-DP, decrease in CT value due to contrast medium outflow between the arterial and delayed phases; enhancement washout VP-DP, decrease in CT value due to contrast medium outflow between the venous and delayed phases.
enhancement washout VP-DP was significantly different between cortical adenoma and cortical adenocarcinoma. Therefore, precontrast minimum CT values, enhancement washout VP-DP, and contrast homogeneity in the venous phase may represent CT indicators for the differentiation of cortical adenoma and cortical adenocarcinoma.
Our study suggests that minimum and maximum CT val- ues in the precontrast image and arterial phase, maximum CT value in the venous phase, AP-PEW, VP-PEW, RPW, enhancement washin, enhancement washout AP-VP, enhancement washout AP-DP, enhancement washout VP-DP, and intratumoral calcification are useful for differentiating pheochromocytoma from cortical adenocarcinoma in dogs. The histopathological structure of pheochromocytoma is thought to induce rapid inflow and outflow of contrast medium. On the other hand, the CT findings of human pheo- chromocytoma are nonspecific because of various histopatho- logical features, including hypervascularity36 and myxoid degeneration in the cytoplasm.19 Triple-phase helical CT is therefore suggested to have more powerful diagnostic capa- bilities in dogs with pheochromocytoma when compared with people.
In the characteristic CT findings of canine pheochromocy- toma, a high rate of caval invasiveness and high CT values in precontrast images in our study were similar to the results of the previous study.31 However, no parameters other than the aforementioned findings showed significant differences among the adrenal tumor types in the previous study. The discrepan- cies of the results between the two studies may be derived from the numbers of cases, the manner of ROI setting, and the condition and procedure of CT scans. Unlike the previous study, the intratumoral hemodynamics of each adrenal tumor could be clarified in detail by the evaluations of enhancement washin and washouts, PEW, and RPW in our study.
In our study, the calculation of enhancement washin, enhancement washout AP-VP, enhancement washout AP-DP, and enhancement washout VP-DP demonstrated the intratu- moral hemodynamics of different adrenal tumors in dogs. In
adrenocortical tumors, contrast medium flowed slowly into the tumors and the maximum contrast enhancement was in the venous phase. In contrast, contrast medium flowed quickly into adrenomedullary tumors. In adrenocortical tumors, cortical adenoma showed more rapid excretion of contrast medium than cortical adenocarcinoma. On the other hand, contrast medium was excreted quickly in cases of pheochromocytoma, and CT values were rapidly attenuated. The assessment of tumor hemodynamics based on AP-PEW, VP-PEW, RPW, and enhancement washin and washouts has the potential to reflect the extent of tumor angiogenesis; however, further investiga- tions on the comparison of tumor hemodynamics and histopa- thology are required in canine adrenal tumors.
In our study, the morphological features of adrenal tumors, precontrast CT values, and calculation of AP-PEW, VP-PEW, RPW, enhancement washin, enhancement washout AP-VP, enhancement washout AP-DP, and enhancement wash- out VP-DP were suggested to allow differential diagnosis of canine adrenal tumors. However, taking only one of the afore- mentioned parameters into consideration may cause misdiag- nosis. In 1 case with cortical adenoma, the precontrast CT values, AP-PEW, VP-PEW, RPW, enhancement washin, enhancement washout AP-VP, enhancement washout AP-DP, and enhancement washout VP-DP were similar to those in cortical adenocarcinoma cases. In contrast, these parameters in 1 case with cortical adenocarcinoma were similar to those in cortical adenoma cases. Furthermore, AP-PEW, VP-PEW, enhancement washout AP-VP, enhancement washout AP-DP, and enhancement washout VP-DP in 1 case with pheochromo- cytoma were similar to the values found for cortical adenocar- cinoma. Therefore, the combination of several parameters obtained and calculated from triple-phase helical CT is required for the differential diagnosis of canine adrenal tumors.
Perioperative management of adrenocortical and adreno- medullary canine tumors usually varies because of the secre- tion of different hormones from these tumor types. In cases of functional adrenal tumors, preoperative differential diagnosis is feasible and is based not only on diagnostic imaging
Cortical Adenoma
Cortical Adenocarcinoma
Pheochromo- cytoma
Precontrast
Arterial Phase
Venous Phase
Delayed Phase
techniques but also on clinical signs, physical examination, blood and urine tests, systemic blood pressure measurement, electrocardiogramadrenocorticotropic hormone stimulation tests, and measurement of catecholamines and their metabo- lites. However, preoperative differential diagnosis is difficult in cases of nonfunctional adrenal tumors. In particular, nor- mal plasma catecholamine levels can lead to a missed preop-
erative diagnosis of pheochromocytoma. Despite normal preoperative catecholamine levels in cases of pheochromocy- toma, tachycardia, arrhythmia, hypertension, and cardiac arrest may occur suddenly during intraoperative manipulation of these tumors.37,38 In human medicine, triple-phase helical CT has been demonstrated to enable the preoperative differ- ential diagnosis of adrenal tumors.25 Based on the results of
our study, triple-phase helical CT is suggested to be useful for the preoperative differential diagnosis of canine adrenal tumors. The preoperative differential diagnosis has a great impact on the informed consent and preparation for anesthe- sia and surgery.
In conclusion, our study demonstrates the morphological features, precontrast CT values, and intratumoral contrast attenuation of canine adrenal tumors, including cortical ade- noma, cortical adenocarcinoma, and pheochromocytoma by using triple-phase helical CT. Intratumoral contrast attenua- tion could be evaluated with PEW, RPW, and enhancement washin and washouts. Triple-phase helical CT has the poten- tial for preoperative differential diagnosis and, therefore, may provide essential information for surgical planning in the treatment of adrenal tumors in dogs.
DISCLOSURE
The authors declare no conflicts of interest related to this report.
REFERENCES
1. Withrow SJ, Vail DM, Page RL: Tumors of the endocrine system, in Lunn KF, Page RL (eds): Withrow and McEwen’s small animal clinical oncology (ed 5). St. Louis, MO, Elsevier Saunders, 2012, pp 504-531
2. Anderson CR, Birchard SJ, Powers BE, et al: Surgical treatment of adrenocortical tumors: 21 cases (1990-1996). J Am Anim Hosp Assoc 2001;37:93-97
3. Lang JM, Schertel E, Kennedy S, et al: Elective and emergency surgical management of adrenal gland tumors: 60 cases (1999-2006). J Am Anim Hosp Assoc 2011;47:428-435
4. Massari F, Nicoli S, Romanelli G, et al: Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc 2011;239:216-221
5. Scavelli TD, Peterson ME, Matthiesen DT: Results of surgical treatment for hyperadrenocorticism caused by adrenocortical neoplasia in the dog: 25 cases (1980-1984). J Am Vet Med Assoc 1986;189:1360-1364
6. van Sluijs FJ, Sjollema BE, Voorhout G, et al: Results of adrenalectomy in 36 dogs with hyperadrenocorticism caused by adreno-cortical tumour, Vet Q 1995;17:113-116
7. Kyles AE, Feldman EC, De Cock HEV, et al: Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994-2001). J Am Vet Med Assoc 2003;223:654-662
8. Barthez PY, Marks SL, Woo J, et al: Pheochromocytoma in dogs: 61 cases (1984-1995). J Vet Intern Med 1997;11: 272-278
9. Barrera JS, Bernard F, Ehrhart EJ, et al: Evaluation of risk factors for outcome associated with adrenal gland tumors with or without invasion of the caudal vena cava and treated via adrenalectomy in dogs: 86 cases (1993-2009). J Am Vet Med Assoc 2013;242:1715-1721
10. Herrera MA, Mehl ML, Kass PH, et al: Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing
adrenalectomy for pheochromocytoma. J Vet Intern Med 2008;22: 1333-1339
11. Voorhout G, Stolp R, Rijnberk AD, et al: Assessment of survey radiography and comparison with x-ray computed tomography for detection of hyperfunctioning adrenocortical tumors in dogs. J Am Vet Med Assoc 1990;196:1799-1803
12. Besso JG, Penninck DG, Gliatto NM: Retrospective ultrasonographic evaluation of adrenal lesions in 26 dogs. Vet Radiol Ultrasound 1997;38:448-455
13. Hoerauf A, Reusch C: Ultrasonographic characteristics of both adrenal glands in 15 dogs with functional adrenocortical tumors. J Am Anim Hosp Assoc 1999;35:193-199
14. Davis MK, Schochet RA, Wrigley R: Ultrasonographic identification of vascular invasion by adrenal tumors in dogs. Vet Radiol Ultrasound 2012;53:442-445
15. Fossum TW: Surgery of the adrenal and pituitary glands, in Fossum TW, Caplan ER (eds): Small animal surgery (ed 4). St. Louis, MO, Elsevier Saunders, 2013, pp 633-649
16. Korobkin M, Giordano TJ, Brodeur FJ, et al: Adrenal adenomas: relationship between histologic lipid and CT and MR findings. Radiology 1996;200:743-747
17. Korobkin M, Brodeur FJ, Yutzy GG, et al: Differentiation of adrenal adenomas from nonadenomas using CT attenuation values. Am J Roentgenol 1996;166:531-536
18. Boland GW, Lee MJ, Gazelle GS, et al: Characterization of adrenal masses using unenhanced CT: an analysis of the CT literature. Am J Roentgenol 1998;171:201-204
19. Blake MA, Krisnamoorthy SK, Boland GW, et al: Low density pheochromocytoma on CT: a mimicker of adrenal adenoma. Am J Roentgenol 2003;181:1663-1668
20. Johnson PT, Horton KM, Fishman EK: Adrenal mass imaging with multidetector CT: pathologic conditions, pearls, and pitfalls. Radiographics 2009;29:1333-1351
21. Slattery JM, Blake MA, Kalra MK, et al: Adrenocortical carcinoma: contrast washout characteristics on CT. Am J Roentgenol 2006;187:W21-W24
22. Blake MA, Kalra MK, Sweeney AT, et al: Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-Minute delay. Radiology 2006;238:578-585
23. Pena CS, Boland GWL, Hahn PF, et al: Characterization of indeterminate (lipid-poor) adrenal masses: use of washout characteristics at contrast-enhanced CT. Radiology 2000;217:798- 802
24. Kamiyama T, Fukukura Y, Yoneyama T, et al: Distinguishing adrenal adenomas from nonadenomas: combined use of diagnostic parameters of unenhanced and short 5-minute dynamic enhanced CT protocol. Radiology 2009;250:474- 481
25. Foti G, Faccioli N, Mantovani W, et al: Incidental adrenal lesions: accuracy of quadriphasic contrast enhanced computed tomography in distinguishing adenomas from nonadenomas. Eur J Radiol 2012;81:1742-1750
26. Park BK, Kim CK, Kwon GY, et al: Re-evaluation of pheochromocytomas on delayed contrast-enhanced CT: washout enhancement and other imaging features. Eur J Radiol 2007;17: 2804-2809
27. Rosenstein DS: Diagnostic imaging in canine pheochromocytoma. Vet Radiol Ultrasound 2000;41:499-506
28. Schultz RM, Wisner ER, Johnson EG, et al: Contrast-enhanced computed tomography as a pre-operative indicator of vascular invasion from adrenal masses in dogs. Vet Radiol Ultrasound 2009;50:625-629
29. Morandi F, Mays JL, Newman SJ, et al: Imaging diagnosis- bilateral adrenal adenomas and myelolipomas in a dog. Vet Radiol Ultrasound 2007;48:246-249
30. Bertolini G, Furlanello T, De Lorenzi D, et al: Computed tomographic quantification of canine adrenal gland volume and attenuation. Vet Radiol Ultrasound 2006;47:444-448
31. Gregori T, Mantis P, Benigni L, et al: Comparison of computed tomographic and pathologic findings in 17 dogs with primary adrenal neoplasia. Vet Radiol Ultrasound 2015; 56:153-159
32. Kutara K, Seki M, Ishikawa C, et al: Triple-phase helical computed tomography in dogs with hepatic masses. Vet Radiol Ultrasound 2014;55:7-15
33. Gilson SD, Withrow SJ, Wheeler SL, et al: Pheochromocytoma in 50 dogs. J Vet Intern Med 1994;8:228-232
34. Meuten DJ: Tumors of the adrenal gland, in Capen CC (ed): Tumors in domestic animals (ed 4). Ames, IA, A Blackwell Publishing Co, 2002, pp 629-638
35. Labelle P, Kyles AE, Farver TB, et al: Indicators of malignancy of canine adrenocortical tumors: histopathology and proliferation index. Vet Pathol 2004;41:490-497
36. Blake MA, Kalra MK, Maher MM, et al: Pheochromocytoma: an imaging chameleon. Radiographics 2004;24:S87-S99
37. Tobias KM, Johnston SA: Adrenal glands, in Adin CA, Nelson RW (eds): Veterinary surgery small animal (vol 2). St. Louis, MO, Elsevier Saunders, 2012, pp 2033-2042
38. Von Dehn BJ, Nelson RW, Feldman EC, et al: Pheochromocytoma and hyperadrenocorticism in dogs: six cases (1982-1992). J Am Vet Med Assoc 1995;207:322-324