IMAGING DIAGNOSIS—COMPUTED TOMOGRAPHIC, SURGICAL, AND HISTOPATHOLOGIC CHARACTERISTICS OF AN INFILTRATIVE ANGIOLIPOMA IN A DOG MICHAEL B. KRAUN, NATHAN C. NELSON , CHARLOTTE HOLLINGER
A 6-year-old female spayed Shetland Sheepdog presented for evaluation of a subcutaneous mass over the right prescapular region. The mass had been cytologically diagnosed as a lipoma by the referring veterinarian 20 months prior, but had grown significantly and was very firm. CT scan of the mass was suggestive of neoplasia; however, the tissue of origin could not be determined. Histopathologic evaluation diagnosed infiltrative angiolipoma, and marginal resection of the tumor was performed. Infiltrative angiolipomas are benign but locally aggressive neoplasms uncommonly reported in veterinary medicine. This report correlates the clinical, C 2014 American College of Veterinary CT, and histopathologic characteristics of an infiltrative angiolipoma. Radiology. Key words: angiolipoma, computed tomography, dog, histopathology.
mately 10 × 12 cm, firm, multilobular, subcutaneous mass extending from the cranial border of the right scapula to the jugular groove on the right side of the caudal neck. The mass was well circumscribed but firmly fixed to the underlying tissues and was nonpainful on palpation. Based on the history and clinical findings, primary differentials included intermuscular or infiltrative lipoma and various types of sarcoma. A complete blood count, serum biochemistry, and urinalysis were performed and were unremarkable. A CT scan of the patient’s neck and thorax were recommended to further evaluate the extent and character of the mass for surgical planning. Tissue biopsy of the mass (incisional or excisional) was planned pending CT scan findings.
Signalment, History, and Clinical Findings
A
6-YEAR-OLD female spayed Shetland Sheepdog presented for evaluation of a large subcutaneous mass over the right prescapular region. The dog’s owner had first noticed a much smaller mass at the site approximately 20 months earlier. Fine needle biopsy and cytology performed at that time by the referring veterinarian led to a diagnosis of lipoma. No treatment was performed, and the owner was instructed to monitor for changes in the size or character of the mass. At a recheck appointment shortly before referral, the owner reported that the mass had increased gradually in size since initial diagnosis, with much more rapid growth in recent weeks. However, the dog was otherwise asymptomatic. Because of the proximity of the mass to a number of vital structures in the caudal cervical region, the patient was referred for further evaluation. On presentation to the teaching hospital, the dog was bright, alert, and responsive with normal vital parameters. Physical examination was unremarkable with the exception of mild mandibular prognathism and the previously reported mass. Because of the patient’s long hair coat, the mass was not appreciable on visual examination alone. Palpation of the right prescapular region revealed an approxi-
Imaging, Diagnosis, and Outcome The patient was routinely anesthetized and CT performed of the cervical and cranial thoracic region using a 16-slice CT machine (BrightspeedTM , General Electric Medical Systems, Milwaukee, WI). The patient was placed in sternal recumbency, and temporary apnea induced by hyperventilating the patient prior to image acquisition. Contiguous, transverse, 1.25 mm thick images were helically acquired (mA: 350, kVp: 120, matrix: 512 × 512, collimator pitch: 1.375, 0.8 s tube rotation time, 28 cm field of view) and reconstructed using a soft tissue reconstruction algorithm. Images were acquired from the midaspect of the head through the midthorax. Following initial acquiR sition, 37 ml of iopamidol (Isovue 300 mgI/ml, Bracco
From the Department of Small Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, Veterinary Medical Center, 736 Wilson Road, East Lansing, MI 48824 (Kraun, Nelson), and the Diagnostic Center for Population and Animal Health, 4125 Beaumont Road, Lansing, MI 48910 (Hollinger). Address correspondence and reprint requests to Nathan C. Nelson, at the above address. E-mail: [email protected]. Received February 8, 2014; accepted for publication March 26, 2014. doi: 10.1111/vru.12178
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FIG. 1. Precontrast (A) and postcontrast (B) images of the right cervical mass. Note the general poor contrast enhancement of the mass, its well-defined margins, as well as internal fat attenuating regions. Window = 400, Level = 50.
Diagnostics, Princeton, NJ) were administered as a hand injected bolus, and CT imaging was repeated after a 60 s delay. There was a large mass along the right caudal cervical region measuring approximately 12 cm in the dorsoventral direction, 7 cm in the mediolateral direction, and 10 cm in the craniocaudal direction (Fig. 1A). The mass was soft tissue attenuating and only minimally contrast enhancing (average attenuation values increased only 3–5 Hounsfield Units after administration of contrast medium, Fig. 1B). The mass had a heterogeneous appearance with a welldefined periphery. Within the mass were rounded, confluent, soft tissue attenuating regions with adjacent, thin, fat attenuating septa. The mass extended from the level of the second cervical vertebra to the lateral aspect of the midscapula. It wrapped around the cranial and ventral aspects of the right scapulohumeral joint and displaced the right external jugular vein ventrally. A mild, patchy unstructured interstitial pattern was present in the right lung adjacent to the heart, interpreted as anesthesia- and recumbencyassociated atelectasis. The tissue of origin of the mass could not be clearly defined from the CT scan, though the mass was thought to be arising from muscle, subcutaneous connective tissue, or vasculature. The well-defined appearance of the mass, minimal contrast enhancement, and lack of evidence of metastasis within the included portion of the thorax were thought to make benign neoplasia (e.g., lipomatous tumors, hemangioma) most likely; however, malignant neoplasia (e.g., liposarcoma, hemangiosarcoma, soft tissue sarcoma), massive granulation tissue response, or tissue hyperplasia were also considered as differential diagnoses. Incisional biopsy was performed to further characterize the mass prior to definitive surgical treatment. An approximately 4 cm, dorsoventrally oriented skin incision was made cranial to the scapula over the center of the mass; the underlying tissue was noted to be pseudoencapsulated and
FIG. 2. Histologic section showing blood-filled vascular spaces supported by collagenous trabeculae, lined by flattened endothelial cells, and interspersed with well-differentiated adipocytes. Asterisks indicate luminal thrombi. Hematoxylin and eosin stain, 400×.
dark purple in color. A wedge of tissue was removed and submitted for histopathologic analysis, and two-layer closure of the biopsy incision was performed. Histologic sections examined consisted of fragments of a nonencapsulated, poorly circumscribed, expansile, vasoformative neoplasm composed of blood-filled vascular spaces supported by thin, collagenous trabeculae, and interspersed with moderate adipose tissue (Fig. 2). Vascular channels were lined by well-differentiated, attenuated endothelial cells characterized by small to moderate quantities of eosinophilic cytoplasm, ovoid to fusiform nuclei, dense chromatin, and inapparent nucleoli. No mitoses or cells with morphologic atypia were found. Few vascular spaces contained variably mature fibrin thrombi. Adipocytes were well differentiated with single, large, nonstaining, discrete cytoplasmic vacuoles and small, peripheralized, condensed nuclei. Low to moderate numbers of scattered and aggregated lymphocytes, plasma cells, and macrophages were
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FIG. 4. Histologic section showing infiltrative neoplastic blood-filled vascular spaces and adipocytes causing regional myodegeneration. Hematoxylin and eosin stain, 125×; inset 400×.
FIG. 3. Image of the tumor described here following surgical removal. For orientation, dorsal is at the top of the image and cranial is to the right. The scar from the prior incisional biopsy is visible in the center of the excised skin.
also present within the supporting collagenous stroma. Based on the combination of intermixed proliferative vascular channels and adipose tissue without cellular features of malignancy, the initial diagnosis was angiolipoma. Eleven days following definitive diagnosis, marginal resection of the tumor was performed (Fig. 3). A dorsoventrally oriented, elliptical skin incision was made, extending from just to the right of the dorsal midline to the right jugular groove. A 2 cm margin of skin was removed on either side of the scar from the previous biopsy site. The platysma and cleidocervicalis muscle were incised along the caudal aspect of the incision site. The mass was dissected off of the omotransversarius muscle and the serratus ventralis cervicis muscle. The fascia of the splenius muscle and a portion of the rhomboideus cervicis muscle were excised where the tumor was adherent to these structures. Finally, transection of the platysma and cleidocervicalis muscle cranial to the tumor allowed for removal of the mass. Because of the significant dead space created by removal of the mass, a R R closed suction drain (Jackson-Pratt Hemaduct , Cardinal Health, McGaw Park, IL) was placed; closure of the surgical site was routine. The entire mass was submitted for histopathologic evaluation and two representative sections were histologically examined. As in the initial incisional biopsy, sections consisted of nonencapsulated, proliferative vascular spaces
lined by well-differentiated endothelium and admixed with well-differentiated, proliferative adipocytes. These excisional sections further revealed a multilobular and infiltrative growth pattern with severe multifocal to locally extensive skeletal muscle invasion (Fig. 4). Affected muscle bundles had regional myocyte degeneration characterized by variable myocyte size and staining intensity, sarcoplasmic fragmentation, and rare karyolysis. A final diagnosis of infiltrative angiolipoma was made. The mass was too large to confirm complete excision without extensive margin evaluation, which was deemed unnecessary, as no attempt was made to obtain wide surgical margins. No follow-up treatment with radiation or chemotherapy was pursued. The primary author has maintained telephone contact with the dog’s owner, a human physician; diligent at-home monitoring by the owner has revealed no evidence of regrowth of the tumor to the time of submission of this manuscript 16 months postoperatively.
Discussion The infiltrative neoplasm described in this report had both adipose and vascular components, resulting in an unusual CT appearance that complicated prioritization of differential diagnoses. Ultimately, histopathologic evaluation led to a diagnosis of infiltrative angiolipoma. Angiolipomas (hemangiolipomas) were first described as a distinct entity in human medicine in 1960.1 and are considered common, benign neoplasms in humans.2 In contrast, these tumors, especially the infiltrative form, continue to be rarely reported in domestic animals. To the authors’ knowledge, only four previous cases of infiltrative angiolipoma have been reported in dogs.3–6
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Clinically, angiolipomas occur as slow-growing subcutaneous masses that, in humans, show a predilection for the subcutis of the trunk and extremities, especially the forearm.2 Similar anatomic distribution around the trunk appears to occur in dogs; however, these tumors can occur in any site containing mesodermal tissue.4 Using classifications borrowed from human medicine, angiolipomas can be subdivided by growth pattern into noninfiltrative and infiltrative.7,8 or alternatively, into solitary, multiple, and infiltrative types.4 Noninfiltrative angiolipomas, which are more common in adolescent and young adult humans, are generally encapsulated and lack invasion into surrounding tissues. Infiltrative angiolipomas occur more often in older patients.9,10 The infiltrative angiolipoma reported here, as well as two previously published canine cases.4,5 occurred on the neck. Interestingly, angiolipomas of the human neck also tend to be infiltrative.11 The pathogenesis behind the formation of angiolipomas is unknown, though trauma has been suggested as a possible cause in humans.11 Angiolipomas in humans are reported to be painful;4,9,10 this does not appear to be the case in the patient described here, nor has tumor-associated pain been described in previous veterinary patients.4,5 Due to the apparent scarcity of angiolipomas, and especially infiltrative angiolipomas, in veterinary medicine, descriptions of the imaging, gross, and histopathologic characteristics of these tumors are limited. While diagnosis of neoplasms has been enhanced by the availability of CT11 only two previous reports of the CT appearance of canine infiltrative angiolipomas have been published.3,5 The first report3 described a 12-year-old Labrador Retriever with a lipomatous mass occupying the spinal canal and several lumbar vertebral bodies. In addition to severe bone remodeling, the tumor caused an extradural compression of the spinal cord, leading to progressive paresis of the pelvic limbs. Unfortunately, while a spine CT was performed on this patient, a detailed description of the mass itself was not published. Furthermore, while the lipomatous tumor was undeniably infiltrative, histopathologic evaluation revealed only a sparse vascular component. In contrast, the infiltrative angiolipoma described in the second case report5 involved the right parotid salivary gland of a 6-year-old South African Boerbel and had much more in common with the tumor in the Shetland Sheepdog reported here. The Boerbel’s mass was described as firm, well circumscribed, and firmly fixed to the underlying tissues. It had been slowly growing over approximately 18 months prior to diagnosis, and the patient was clinically normal aside from the presence of the mass. Notably, when a CT scan was performed, this tumor also had a “slightly hypoattenuating mottled to lobulated appearance with a few hyperattenuating mineralized specks throughout,” but lacked the marked hypoattenuating appearance expected of adipose
2015
tissue.5 Additionally, the mass was poorly contrast enhancing despite its vascular component. Histologically, angiolipomas are characterized by mature adipose tissue interspersed with thin-walled blood vessels without cellular atypia.4,11 The ratio of vascular and adipose components varies.2,11 Histologic differentials include lipoma, hemangioma, and their malignant counterparts.4,11 However, the distinctive combination of well-differentiated vascular and adipose proliferations excludes each of these differentials. Furthermore, the presence of fibrin thrombi is not expected in lipomas.4,5,9 Microscopically, angiolipomas can be described as having capillary, cavernous, mixed, or cellular patterns based on features of the vascular proliferation.4 The angiolipoma reported here was infiltrative with a cavernous histologic pattern; the subcutaneous mass composed of mixed adipose tissue and blood vessels behaved similar to an infiltrative lipoma. Based on the degree of muscular involvement, intramuscular hemangioma was considered as a differential diagnosis in this case. Intramuscular hemangiomas are also vasoformative neoplasms that have a variable adipose component. Differentiation of these two types of neoplasms is subjective, but because intramuscular hemangiomas develop within muscle, the presence of a subcutaneous mass external to the skeletal muscle, as in this case, supports an invasive growth pattern and a diagnosis of infiltrative angiolipoma.4 In human medicine, the distinction between these neoplasms is changing, and some authors suggest a continuum may exist between intramuscular hemangioma, infiltrating angiolipoma, and infiltrative lipoma.12 In the current case, both lipomatous and angiomatous neoplasms were considered as differential diagnoses, though the CT appearance of the tumor did not fit perfectly with either. Lipomas, the most frequently encountered fat containing tumors in dogs, have well defined CT characteristics. Namely, these masses are homogenously fat attenuating (−80 to −100 HU)5 and are indistinguishable from normal subcutaneous fat on CT scans.13 Liposarcomas, though more rare, have also been described on CT. They may appear very similar to benign lipomas, but tend to be more nodular in appearance and often have thicker septa and a larger component of nonadipose tissue.14 There are few reports describing the CT appearance of hemangioma15 and hemangiosarcoma16 in dogs; however, they may display heterogeneous contrast enhancement, which in hemangiosarcoma has been attributed to pooling of contrast material within vascular regions of the mass.16 The unusual CT appearance and lack of contrast enhancement of the infiltrative angiolipomas reported here and in the South African Boerbel5 were likely a consequence of their complex mixture of adipose and vascular tissues. The relative hyperattenuation of the Shetland
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Sheepdog’s tumor on CT probably resulted from the significant vascular component identified histologically. Regarding the lack of contrast enhancement seen, lipomatous tumors typically are not enhanced by the administration of intravenous contrast agent.13 Similar to hemangiosarcomas, it has been suggested that contrast enhancement of angiolipomas could theoretically vary depending on the amount of blood vessels present in the mass17 however, the discrepancy between the vascularity of the tumor reported here and its minimal contrast enhancement is notable. In this patient, postcontrast imaging was initiated after a short delay following injection of contrast. A longer delay (of minutes or more) may have resulted in greater enhancement of the mass, but this is unlikely given the similar findings of a previous report.5 Alternatively, the lack of contrast enhancement in some angiolipomas could be related to decreased vascular supply due to occlusion of the blood vessels by microthrombi.5 As in this case, histologic sampling is often required for definitive diagnosis of angiolipomatous neoplasms.5,11 Cytologic evaluation, as with other nonmalignant vascular proliferations, is hampered by the difficulty of detecting the vascular component and differentiating it from nonneoplastic endothelial cells.11,18 Similarly, distinction between nonneoplastic and benign, or even very well-differentiated malignant, adipocytes is a cytologic challenge.18,19 Finally, the relative absence of tissue architecture cytologically necessitates that histopathology be performed for confirmation of infiltrative behavior.
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Complete surgical excision is the treatment of choice for angiolipomas (both solitary and infiltrative) in humans and dogs.3,4,11 Although infiltrative angiolipomas do not undergo malignant transformation, they tend to recur following incomplete excision4,9 and a recurrence rate of 50% is reported in humans.11 In cases where involvement of vital structures makes complete resection of the tumor impossible, surgical debulking may be of benefit in order to maintain quality of life.5 Incomplete excision was considered acceptable in this case because of the tumor’s large size, benign nature, and intimate association with several vital structures in the neck (common carotid artery, external jugular vein, vagosympathetic trunk, trachea, etc.). While radiation therapy was not performed in this case and has not been reported in treatment of infiltrative angiolipomas specifically, external beam radiation has shown promise in limiting growth and recurrence of infiltrative lipomas and can be employed postoperatively or as a sole method of palliative treatment.20 This case report provides an additional differential diagnosis (infiltrative angiolipoma) to consider when faced with CT images of an atypical fat-containing tumor. In the case described here, marginal resection of the infiltrative angiolipoma has provided long-term remission without the need for additional treatment. ACKNOWLEDGMENT
The authors wish to thank Dr. Rebecca Smedley for assistance with histopathology.
REFERENCES 1. Howard WR, Helwig EB. Angiolipoma. Arch Dermatol 1960;82: 924–931. 2. Fletcher CDM. Soft tissue tumors. In: Fletcher CDM (ed): Diagnostic histopathology of tumors. 3rd ed. London: Churchill Livingstone Elsevier, 2007; 1527–1592. 3. Reif U, Lowrie CT, Fitzgerald SD. Extradural spinal angiolipoma associated with bone lysis in a dog. J Am Anim Hosp Assoc 1998;34: 373–376. 4. Liggett AD, Frazier KS, Styer EL. Angiolipomatous tumors in dogs and a cat. Vet Pathol 2002;39:286–289. 5. Kitshoff AM, Millward IR, Williams JH, Clift SJ, Kirberger RM. Infiltrative angiolipoma of the parotid salivary gland in a dog. J S Afr Vet Assoc 2010;81:258–261. ˜ Horv´ath A, ˜ Horv´ath L. Kutya an6. Jakab C, N´emeth T, Jerzsele A, ´ ´ giolipom´aj´anak diagnozisa klaudin-5 marker seg´ıts´eg´evel. Onkologiai eset ˜ ismertet´ese. Magyar Allatorvosok Lapja 2010;132:145–150. 7. Dionne GP, Seemayer TA. Infiltrating lipomas and angiolipomas revisited. Cancer 1974;33:732–738. 8. Lin JJ, Lin F. Two entities in angiolipoma. A study of 459 cases of lipoma with review of literature on infiltrating angiolipoma. Cancer 1974;34:720–727. 9. Saydam L, Bozkurt MK, Ugur MB, Ozcelik T, Kutluay L. Angiolipoma of the neck: a case report. Ear Nose Throat J 2005;84:375–377. 10. Nicholson B, Prendergast T, Myers EM. Angiolipoma of the neck. Am Surg 2012;78:325–326. ´ J, Lu´aces R, Lorenzo Franco F, Garc´ıa-Rozado A, Cre11. Arenaz Bua spo Escudero JL, Fonseca Capdevila E, et al. Angiolipoma in head and neck:
report of two cases and review of the literature. Int J Oral Maxillofac Surg 2010;39:610–615. 12. Agamanolis DP, Dasu S, Krill CE. Tumors of skeletal muscle. Hum Pathol 1986;17:778–795. 13. McEntee MC, Thrall DE. Computed tomographic imaging of infiltrative lipoma in 22 dogs. Vet Radiol Ultrasound 2001;42:221–225. 14. Kransdorf MJ, Bancroft LW, Peterson JJ, Murphey MD, Foster WC, Temple HT. Imaging of fatty tumors: Distinction of lipoma and welldifferentiated liposarcoma. Radiology 2002;224:99–104. 15. Lee H, Jung D, Moon J, Kim N, Lee J. Clinical characteristics and outcomes of primary adrenal hemangioma in a dog. Res Vet Sci 2013;95: 572–575. 16. Fukuda S, Kobayashi T, Robertson ID, Oshima F, Fukazawa E, Nakano Y, et al. Computed tomographic features of canine nonparenchymal hemangiosarcoma. Vet Radiol Ultrasound 2014;doi: 10.1111/vru.12136. 17. Sibala JL, Chang CH, Lin F, Thomas JH. CT of angiolipoma of the breast. AJR Am J Roentgenol 1980;134:840–841. 18. Tyler RD, Cowell RL, Meinkoth JH. Cutaneous and subcutaneous lesions. In: Cowell RL, Tyler RD, Meinkoth JH, DeNicola DB (eds): Cowell and Tyler’s diagnostic cytology and hematology of the dog and cat. 3rd ed. St. Louis: Mosby Elsevier, 2008. 19. Raskin RE. Skin and subcutaneous tissues. In: Raskin RE, Meyer D (eds): Canine and feline cytology: a color atlas and interpretation guide. 2nd ed. St. Louis: Saunders Elsevier, 2010. 20. McEntee MC, Page RL, Mauldin GN, Thrall DE. Results of irradiation of infiltrative lipoma in 13 dogs. Vet Radiol Ultrasound 2000;41: 554–556.
A 6-year-old female spayed Shetland Sheepdog presented for evaluation of a subcutaneous mass over the right prescapular region. The mass had been cytologically diagnosed as a lipoma by the referring veterinarian 20 months prior, but had grown significantly and was very firm. CT scan of the mass was suggestive of neoplasia; however, the tissue of origin could not be determined. Histopathologic evaluation diagnosed infiltrative angiolipoma, and marginal resection of the tumor was performed. Infiltrative angiolipomas are benign but locally aggressive neoplasms uncommonly reported in veterinary medicine. This report correlates the clinical, C 2014 American College of Veterinary CT, and histopathologic characteristics of an infiltrative angiolipoma. Radiology. Key words: angiolipoma, computed tomography, dog, histopathology.
mately 10 × 12 cm, firm, multilobular, subcutaneous mass extending from the cranial border of the right scapula to the jugular groove on the right side of the caudal neck. The mass was well circumscribed but firmly fixed to the underlying tissues and was nonpainful on palpation. Based on the history and clinical findings, primary differentials included intermuscular or infiltrative lipoma and various types of sarcoma. A complete blood count, serum biochemistry, and urinalysis were performed and were unremarkable. A CT scan of the patient’s neck and thorax were recommended to further evaluate the extent and character of the mass for surgical planning. Tissue biopsy of the mass (incisional or excisional) was planned pending CT scan findings.
Signalment, History, and Clinical Findings
A
6-YEAR-OLD female spayed Shetland Sheepdog presented for evaluation of a large subcutaneous mass over the right prescapular region. The dog’s owner had first noticed a much smaller mass at the site approximately 20 months earlier. Fine needle biopsy and cytology performed at that time by the referring veterinarian led to a diagnosis of lipoma. No treatment was performed, and the owner was instructed to monitor for changes in the size or character of the mass. At a recheck appointment shortly before referral, the owner reported that the mass had increased gradually in size since initial diagnosis, with much more rapid growth in recent weeks. However, the dog was otherwise asymptomatic. Because of the proximity of the mass to a number of vital structures in the caudal cervical region, the patient was referred for further evaluation. On presentation to the teaching hospital, the dog was bright, alert, and responsive with normal vital parameters. Physical examination was unremarkable with the exception of mild mandibular prognathism and the previously reported mass. Because of the patient’s long hair coat, the mass was not appreciable on visual examination alone. Palpation of the right prescapular region revealed an approxi-
Imaging, Diagnosis, and Outcome The patient was routinely anesthetized and CT performed of the cervical and cranial thoracic region using a 16-slice CT machine (BrightspeedTM , General Electric Medical Systems, Milwaukee, WI). The patient was placed in sternal recumbency, and temporary apnea induced by hyperventilating the patient prior to image acquisition. Contiguous, transverse, 1.25 mm thick images were helically acquired (mA: 350, kVp: 120, matrix: 512 × 512, collimator pitch: 1.375, 0.8 s tube rotation time, 28 cm field of view) and reconstructed using a soft tissue reconstruction algorithm. Images were acquired from the midaspect of the head through the midthorax. Following initial acquiR sition, 37 ml of iopamidol (Isovue 300 mgI/ml, Bracco
From the Department of Small Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, Veterinary Medical Center, 736 Wilson Road, East Lansing, MI 48824 (Kraun, Nelson), and the Diagnostic Center for Population and Animal Health, 4125 Beaumont Road, Lansing, MI 48910 (Hollinger). Address correspondence and reprint requests to Nathan C. Nelson, at the above address. E-mail: [email protected]. Received February 8, 2014; accepted for publication March 26, 2014. doi: 10.1111/vru.12178
Vet Radiol Ultrasound, Vol. 56, No. 3, 2015, pp E31–E35.
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FIG. 1. Precontrast (A) and postcontrast (B) images of the right cervical mass. Note the general poor contrast enhancement of the mass, its well-defined margins, as well as internal fat attenuating regions. Window = 400, Level = 50.
Diagnostics, Princeton, NJ) were administered as a hand injected bolus, and CT imaging was repeated after a 60 s delay. There was a large mass along the right caudal cervical region measuring approximately 12 cm in the dorsoventral direction, 7 cm in the mediolateral direction, and 10 cm in the craniocaudal direction (Fig. 1A). The mass was soft tissue attenuating and only minimally contrast enhancing (average attenuation values increased only 3–5 Hounsfield Units after administration of contrast medium, Fig. 1B). The mass had a heterogeneous appearance with a welldefined periphery. Within the mass were rounded, confluent, soft tissue attenuating regions with adjacent, thin, fat attenuating septa. The mass extended from the level of the second cervical vertebra to the lateral aspect of the midscapula. It wrapped around the cranial and ventral aspects of the right scapulohumeral joint and displaced the right external jugular vein ventrally. A mild, patchy unstructured interstitial pattern was present in the right lung adjacent to the heart, interpreted as anesthesia- and recumbencyassociated atelectasis. The tissue of origin of the mass could not be clearly defined from the CT scan, though the mass was thought to be arising from muscle, subcutaneous connective tissue, or vasculature. The well-defined appearance of the mass, minimal contrast enhancement, and lack of evidence of metastasis within the included portion of the thorax were thought to make benign neoplasia (e.g., lipomatous tumors, hemangioma) most likely; however, malignant neoplasia (e.g., liposarcoma, hemangiosarcoma, soft tissue sarcoma), massive granulation tissue response, or tissue hyperplasia were also considered as differential diagnoses. Incisional biopsy was performed to further characterize the mass prior to definitive surgical treatment. An approximately 4 cm, dorsoventrally oriented skin incision was made cranial to the scapula over the center of the mass; the underlying tissue was noted to be pseudoencapsulated and
FIG. 2. Histologic section showing blood-filled vascular spaces supported by collagenous trabeculae, lined by flattened endothelial cells, and interspersed with well-differentiated adipocytes. Asterisks indicate luminal thrombi. Hematoxylin and eosin stain, 400×.
dark purple in color. A wedge of tissue was removed and submitted for histopathologic analysis, and two-layer closure of the biopsy incision was performed. Histologic sections examined consisted of fragments of a nonencapsulated, poorly circumscribed, expansile, vasoformative neoplasm composed of blood-filled vascular spaces supported by thin, collagenous trabeculae, and interspersed with moderate adipose tissue (Fig. 2). Vascular channels were lined by well-differentiated, attenuated endothelial cells characterized by small to moderate quantities of eosinophilic cytoplasm, ovoid to fusiform nuclei, dense chromatin, and inapparent nucleoli. No mitoses or cells with morphologic atypia were found. Few vascular spaces contained variably mature fibrin thrombi. Adipocytes were well differentiated with single, large, nonstaining, discrete cytoplasmic vacuoles and small, peripheralized, condensed nuclei. Low to moderate numbers of scattered and aggregated lymphocytes, plasma cells, and macrophages were
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FIG. 4. Histologic section showing infiltrative neoplastic blood-filled vascular spaces and adipocytes causing regional myodegeneration. Hematoxylin and eosin stain, 125×; inset 400×.
FIG. 3. Image of the tumor described here following surgical removal. For orientation, dorsal is at the top of the image and cranial is to the right. The scar from the prior incisional biopsy is visible in the center of the excised skin.
also present within the supporting collagenous stroma. Based on the combination of intermixed proliferative vascular channels and adipose tissue without cellular features of malignancy, the initial diagnosis was angiolipoma. Eleven days following definitive diagnosis, marginal resection of the tumor was performed (Fig. 3). A dorsoventrally oriented, elliptical skin incision was made, extending from just to the right of the dorsal midline to the right jugular groove. A 2 cm margin of skin was removed on either side of the scar from the previous biopsy site. The platysma and cleidocervicalis muscle were incised along the caudal aspect of the incision site. The mass was dissected off of the omotransversarius muscle and the serratus ventralis cervicis muscle. The fascia of the splenius muscle and a portion of the rhomboideus cervicis muscle were excised where the tumor was adherent to these structures. Finally, transection of the platysma and cleidocervicalis muscle cranial to the tumor allowed for removal of the mass. Because of the significant dead space created by removal of the mass, a R R closed suction drain (Jackson-Pratt Hemaduct , Cardinal Health, McGaw Park, IL) was placed; closure of the surgical site was routine. The entire mass was submitted for histopathologic evaluation and two representative sections were histologically examined. As in the initial incisional biopsy, sections consisted of nonencapsulated, proliferative vascular spaces
lined by well-differentiated endothelium and admixed with well-differentiated, proliferative adipocytes. These excisional sections further revealed a multilobular and infiltrative growth pattern with severe multifocal to locally extensive skeletal muscle invasion (Fig. 4). Affected muscle bundles had regional myocyte degeneration characterized by variable myocyte size and staining intensity, sarcoplasmic fragmentation, and rare karyolysis. A final diagnosis of infiltrative angiolipoma was made. The mass was too large to confirm complete excision without extensive margin evaluation, which was deemed unnecessary, as no attempt was made to obtain wide surgical margins. No follow-up treatment with radiation or chemotherapy was pursued. The primary author has maintained telephone contact with the dog’s owner, a human physician; diligent at-home monitoring by the owner has revealed no evidence of regrowth of the tumor to the time of submission of this manuscript 16 months postoperatively.
Discussion The infiltrative neoplasm described in this report had both adipose and vascular components, resulting in an unusual CT appearance that complicated prioritization of differential diagnoses. Ultimately, histopathologic evaluation led to a diagnosis of infiltrative angiolipoma. Angiolipomas (hemangiolipomas) were first described as a distinct entity in human medicine in 1960.1 and are considered common, benign neoplasms in humans.2 In contrast, these tumors, especially the infiltrative form, continue to be rarely reported in domestic animals. To the authors’ knowledge, only four previous cases of infiltrative angiolipoma have been reported in dogs.3–6
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Clinically, angiolipomas occur as slow-growing subcutaneous masses that, in humans, show a predilection for the subcutis of the trunk and extremities, especially the forearm.2 Similar anatomic distribution around the trunk appears to occur in dogs; however, these tumors can occur in any site containing mesodermal tissue.4 Using classifications borrowed from human medicine, angiolipomas can be subdivided by growth pattern into noninfiltrative and infiltrative.7,8 or alternatively, into solitary, multiple, and infiltrative types.4 Noninfiltrative angiolipomas, which are more common in adolescent and young adult humans, are generally encapsulated and lack invasion into surrounding tissues. Infiltrative angiolipomas occur more often in older patients.9,10 The infiltrative angiolipoma reported here, as well as two previously published canine cases.4,5 occurred on the neck. Interestingly, angiolipomas of the human neck also tend to be infiltrative.11 The pathogenesis behind the formation of angiolipomas is unknown, though trauma has been suggested as a possible cause in humans.11 Angiolipomas in humans are reported to be painful;4,9,10 this does not appear to be the case in the patient described here, nor has tumor-associated pain been described in previous veterinary patients.4,5 Due to the apparent scarcity of angiolipomas, and especially infiltrative angiolipomas, in veterinary medicine, descriptions of the imaging, gross, and histopathologic characteristics of these tumors are limited. While diagnosis of neoplasms has been enhanced by the availability of CT11 only two previous reports of the CT appearance of canine infiltrative angiolipomas have been published.3,5 The first report3 described a 12-year-old Labrador Retriever with a lipomatous mass occupying the spinal canal and several lumbar vertebral bodies. In addition to severe bone remodeling, the tumor caused an extradural compression of the spinal cord, leading to progressive paresis of the pelvic limbs. Unfortunately, while a spine CT was performed on this patient, a detailed description of the mass itself was not published. Furthermore, while the lipomatous tumor was undeniably infiltrative, histopathologic evaluation revealed only a sparse vascular component. In contrast, the infiltrative angiolipoma described in the second case report5 involved the right parotid salivary gland of a 6-year-old South African Boerbel and had much more in common with the tumor in the Shetland Sheepdog reported here. The Boerbel’s mass was described as firm, well circumscribed, and firmly fixed to the underlying tissues. It had been slowly growing over approximately 18 months prior to diagnosis, and the patient was clinically normal aside from the presence of the mass. Notably, when a CT scan was performed, this tumor also had a “slightly hypoattenuating mottled to lobulated appearance with a few hyperattenuating mineralized specks throughout,” but lacked the marked hypoattenuating appearance expected of adipose
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tissue.5 Additionally, the mass was poorly contrast enhancing despite its vascular component. Histologically, angiolipomas are characterized by mature adipose tissue interspersed with thin-walled blood vessels without cellular atypia.4,11 The ratio of vascular and adipose components varies.2,11 Histologic differentials include lipoma, hemangioma, and their malignant counterparts.4,11 However, the distinctive combination of well-differentiated vascular and adipose proliferations excludes each of these differentials. Furthermore, the presence of fibrin thrombi is not expected in lipomas.4,5,9 Microscopically, angiolipomas can be described as having capillary, cavernous, mixed, or cellular patterns based on features of the vascular proliferation.4 The angiolipoma reported here was infiltrative with a cavernous histologic pattern; the subcutaneous mass composed of mixed adipose tissue and blood vessels behaved similar to an infiltrative lipoma. Based on the degree of muscular involvement, intramuscular hemangioma was considered as a differential diagnosis in this case. Intramuscular hemangiomas are also vasoformative neoplasms that have a variable adipose component. Differentiation of these two types of neoplasms is subjective, but because intramuscular hemangiomas develop within muscle, the presence of a subcutaneous mass external to the skeletal muscle, as in this case, supports an invasive growth pattern and a diagnosis of infiltrative angiolipoma.4 In human medicine, the distinction between these neoplasms is changing, and some authors suggest a continuum may exist between intramuscular hemangioma, infiltrating angiolipoma, and infiltrative lipoma.12 In the current case, both lipomatous and angiomatous neoplasms were considered as differential diagnoses, though the CT appearance of the tumor did not fit perfectly with either. Lipomas, the most frequently encountered fat containing tumors in dogs, have well defined CT characteristics. Namely, these masses are homogenously fat attenuating (−80 to −100 HU)5 and are indistinguishable from normal subcutaneous fat on CT scans.13 Liposarcomas, though more rare, have also been described on CT. They may appear very similar to benign lipomas, but tend to be more nodular in appearance and often have thicker septa and a larger component of nonadipose tissue.14 There are few reports describing the CT appearance of hemangioma15 and hemangiosarcoma16 in dogs; however, they may display heterogeneous contrast enhancement, which in hemangiosarcoma has been attributed to pooling of contrast material within vascular regions of the mass.16 The unusual CT appearance and lack of contrast enhancement of the infiltrative angiolipomas reported here and in the South African Boerbel5 were likely a consequence of their complex mixture of adipose and vascular tissues. The relative hyperattenuation of the Shetland
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Sheepdog’s tumor on CT probably resulted from the significant vascular component identified histologically. Regarding the lack of contrast enhancement seen, lipomatous tumors typically are not enhanced by the administration of intravenous contrast agent.13 Similar to hemangiosarcomas, it has been suggested that contrast enhancement of angiolipomas could theoretically vary depending on the amount of blood vessels present in the mass17 however, the discrepancy between the vascularity of the tumor reported here and its minimal contrast enhancement is notable. In this patient, postcontrast imaging was initiated after a short delay following injection of contrast. A longer delay (of minutes or more) may have resulted in greater enhancement of the mass, but this is unlikely given the similar findings of a previous report.5 Alternatively, the lack of contrast enhancement in some angiolipomas could be related to decreased vascular supply due to occlusion of the blood vessels by microthrombi.5 As in this case, histologic sampling is often required for definitive diagnosis of angiolipomatous neoplasms.5,11 Cytologic evaluation, as with other nonmalignant vascular proliferations, is hampered by the difficulty of detecting the vascular component and differentiating it from nonneoplastic endothelial cells.11,18 Similarly, distinction between nonneoplastic and benign, or even very well-differentiated malignant, adipocytes is a cytologic challenge.18,19 Finally, the relative absence of tissue architecture cytologically necessitates that histopathology be performed for confirmation of infiltrative behavior.
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Complete surgical excision is the treatment of choice for angiolipomas (both solitary and infiltrative) in humans and dogs.3,4,11 Although infiltrative angiolipomas do not undergo malignant transformation, they tend to recur following incomplete excision4,9 and a recurrence rate of 50% is reported in humans.11 In cases where involvement of vital structures makes complete resection of the tumor impossible, surgical debulking may be of benefit in order to maintain quality of life.5 Incomplete excision was considered acceptable in this case because of the tumor’s large size, benign nature, and intimate association with several vital structures in the neck (common carotid artery, external jugular vein, vagosympathetic trunk, trachea, etc.). While radiation therapy was not performed in this case and has not been reported in treatment of infiltrative angiolipomas specifically, external beam radiation has shown promise in limiting growth and recurrence of infiltrative lipomas and can be employed postoperatively or as a sole method of palliative treatment.20 This case report provides an additional differential diagnosis (infiltrative angiolipoma) to consider when faced with CT images of an atypical fat-containing tumor. In the case described here, marginal resection of the infiltrative angiolipoma has provided long-term remission without the need for additional treatment. ACKNOWLEDGMENT
The authors wish to thank Dr. Rebecca Smedley for assistance with histopathology.
REFERENCES 1. Howard WR, Helwig EB. Angiolipoma. Arch Dermatol 1960;82: 924–931. 2. Fletcher CDM. Soft tissue tumors. In: Fletcher CDM (ed): Diagnostic histopathology of tumors. 3rd ed. London: Churchill Livingstone Elsevier, 2007; 1527–1592. 3. Reif U, Lowrie CT, Fitzgerald SD. Extradural spinal angiolipoma associated with bone lysis in a dog. J Am Anim Hosp Assoc 1998;34: 373–376. 4. Liggett AD, Frazier KS, Styer EL. Angiolipomatous tumors in dogs and a cat. Vet Pathol 2002;39:286–289. 5. Kitshoff AM, Millward IR, Williams JH, Clift SJ, Kirberger RM. Infiltrative angiolipoma of the parotid salivary gland in a dog. J S Afr Vet Assoc 2010;81:258–261. ˜ Horv´ath A, ˜ Horv´ath L. Kutya an6. Jakab C, N´emeth T, Jerzsele A, ´ ´ giolipom´aj´anak diagnozisa klaudin-5 marker seg´ıts´eg´evel. Onkologiai eset ˜ ismertet´ese. Magyar Allatorvosok Lapja 2010;132:145–150. 7. Dionne GP, Seemayer TA. Infiltrating lipomas and angiolipomas revisited. Cancer 1974;33:732–738. 8. Lin JJ, Lin F. Two entities in angiolipoma. A study of 459 cases of lipoma with review of literature on infiltrating angiolipoma. Cancer 1974;34:720–727. 9. Saydam L, Bozkurt MK, Ugur MB, Ozcelik T, Kutluay L. Angiolipoma of the neck: a case report. Ear Nose Throat J 2005;84:375–377. 10. Nicholson B, Prendergast T, Myers EM. Angiolipoma of the neck. Am Surg 2012;78:325–326. ´ J, Lu´aces R, Lorenzo Franco F, Garc´ıa-Rozado A, Cre11. Arenaz Bua spo Escudero JL, Fonseca Capdevila E, et al. Angiolipoma in head and neck:
report of two cases and review of the literature. Int J Oral Maxillofac Surg 2010;39:610–615. 12. Agamanolis DP, Dasu S, Krill CE. Tumors of skeletal muscle. Hum Pathol 1986;17:778–795. 13. McEntee MC, Thrall DE. Computed tomographic imaging of infiltrative lipoma in 22 dogs. Vet Radiol Ultrasound 2001;42:221–225. 14. Kransdorf MJ, Bancroft LW, Peterson JJ, Murphey MD, Foster WC, Temple HT. Imaging of fatty tumors: Distinction of lipoma and welldifferentiated liposarcoma. Radiology 2002;224:99–104. 15. Lee H, Jung D, Moon J, Kim N, Lee J. Clinical characteristics and outcomes of primary adrenal hemangioma in a dog. Res Vet Sci 2013;95: 572–575. 16. Fukuda S, Kobayashi T, Robertson ID, Oshima F, Fukazawa E, Nakano Y, et al. Computed tomographic features of canine nonparenchymal hemangiosarcoma. Vet Radiol Ultrasound 2014;doi: 10.1111/vru.12136. 17. Sibala JL, Chang CH, Lin F, Thomas JH. CT of angiolipoma of the breast. AJR Am J Roentgenol 1980;134:840–841. 18. Tyler RD, Cowell RL, Meinkoth JH. Cutaneous and subcutaneous lesions. In: Cowell RL, Tyler RD, Meinkoth JH, DeNicola DB (eds): Cowell and Tyler’s diagnostic cytology and hematology of the dog and cat. 3rd ed. St. Louis: Mosby Elsevier, 2008. 19. Raskin RE. Skin and subcutaneous tissues. In: Raskin RE, Meyer D (eds): Canine and feline cytology: a color atlas and interpretation guide. 2nd ed. St. Louis: Saunders Elsevier, 2010. 20. McEntee MC, Page RL, Mauldin GN, Thrall DE. Results of irradiation of infiltrative lipoma in 13 dogs. Vet Radiol Ultrasound 2000;41: 554–556.
