The Elekta Fraxion™ system is not suitable for maxillary fixation in canine conformal radiation therapy techniques

In this prospective, exploratory study, we evaluated the positioning accuracy in a group of 15 dogs undergoing fractionated stereotactic radiotherapy for tumors affecting the head, using a modified human maxillary fixation device (Elekta Fraxion? system). Positioning was assessed using on‐board volumetric imaging, with a six‐degrees‐of‐freedom image registration technique. Prior to treatment delivery, CBCT images were obtained and patient alignment was corrected, in both translational and rotational planes, using a six‐degrees‐of‐freedom robotic patient positioning system (HexaPOD Evo RT System). The maximum angular inter‐fraction motions observed were 6.1° (yaw), 10.9° (pitch), and 4.5° (roll). The mean systematic translational errors were 4.7, 2.6, and 2.3 mm, mean random translational errors were 3.0, 2.2, and 2.5 mm, and mean overall translational errors were 2.4, 0.7, and 2.3 mm in the cranial‐caudal, lateral, and dorsal‐ventral directions, respectively. The mean systematic rotational errors were 1.17°, 0.77°, and 1.43°, the mean rotational random errors were 1.65°, 1.46°, and 1.34° and the mean overall rotational errors were 0.56°, 0.22°, and 0.29° in the yaw, pitch, and roll directions, respectively. The mean error of the three‐dimensional vector was 6.9 mm with a standard deviation of 3.8 mm. Ninety‐five percent of the three‐dimensional vectors were <14.8 mm. This study demonstrates that this maxillary fixation device relies on six‐degrees‐of‐freedom registration and an ability to apply corrections using a six‐degrees‐of‐freedom couch for accurate patient positioning and tumor targeting. Its use in conformal radiation therapy in dogs is not recommended.     

PRIMARY IRRADIATION OF CANINE INTRACRANIAL MASSES

Twenty-nine dogs received primary radiation therapy for intracranial lesions and clinical signs suggestive of neoplasia. Presumptive diagnosis and tumor categorization was based on computed tomographic or magnetic resonance images. Meningioma was the most likely tumor type in 22 dogs and glioma or choroid plexus tumors were tentatively identified in 4 and 3 dogs, respectively. Cobalt-60 radiation was delivered in 3 Gy fractions on a daily, Monday-through-Friday basis for a total dose of 48 Gy (16 fractions) in 28 dogs; one dog received 54 Gy. Two of 29 dogs died during treatment of signs suggestive of progressive tumor growth but were included in the overall evaluation of response to treatment. Median overall survival was 250 days (range 21-804). Mild acute radiation effects on normal tissue developed and did not influence outcome in any dog. Late radiation effects could not be evaluated in this study. No significant predictive indicators were identified from the clinical or imaging data. Radiation therapy is superior to medical treatment of brain tumors in dogs with steroids, is useful for tumors that are not currently operable and may be preferable to surgical resection in dogs if the mass appears infiltrative. However, 22/29 (76%) dogs died of recurrent progressive neuropathy suggestive of tumor regrowth or progression. Thus, alternative methods for delivery of radiation to dogs with brain tumors or novel combinations of therapy should continue to undergo evaluation.     

Successful use of prednisolone and radiation therapy in a dog with intracranial histiocytic sarcoma

The ideal treatment for intracranial histiocytic sarcoma (HS) remains unclear. Herein, we report a case of intracranial HS that was successfully treated using prednisolone and radiation therapy. The patient was a 9-year-old spayed female Pembroke Welsh Corgi that presented with epileptic seizures. Magnetic resonance imaging revealed a contrast-enhancing mass adjacent to the right piriform lobe. Prednisolone administration (1 mg/kg/day) decreased the lesion size. Additional palliative radiation therapy (total dose, 37 Gy) resulted in complete disappearance of the lesion. However, on day 164, the dog’s neurological signs deteriorated, and she was euthanized. Necropsy revealed an intracranial metastasis of HS via the cerebrospinal fluid without any extracranial metastasis. Nonetheless, combined prednisolone and radiation therapy might be effective in treating intracranial HS.     

INVITED REVIEW—NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

The evaluation of therapeutic response using cross‐sectional imaging techniques, particularly gadolinium‐enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging‐based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro‐oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment‐induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy‐induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.     

RETROSPECTIVE ANALYSIS OF BRAIN SCINTIGRAPHY IN 116 DOGS AND CATS

We performed a retrospective study of 100 dogs and 16 cats with planar brain scintigraphy and histopathologically established diagnoses from a total of 485 studies performed from 1976 to 1992. Necropsy (112) or surgical biopsies (4) diagnoses were categorized in two ways: first as focal brain disease, diffuse brain disease or normal; second as either neoplastic, non-neoplastic or normal. A radiologist reviewed brain scintigrams and categorized the studies as focal areas of increased accumulation, diffuse or poorly localized areas of increased accumulation, or normal. We calculated for this population of 116 animals that focal brain scintigrams had 75% sensitivity and 90% specificity for any focal brain disease. The sensitivity and specificity of a focal scintigraphic lesion for a brain tumor was 72% and 82% respectively. The sensitivity and specificity of a diffuse or poorly localized scintigraphic lesion as a test for diffuse brain disease was 40% and 88% respectively.     

Cerebrospinal fluid from a dog with neurologic collapse

A 3-year-old Staffordshire Terrier was presented to the Texas Veterinary Medical Center with a short progressive history of anorexia, weight loss, and weakness that had progressed to ataxia and collapse with empirical treatment. The dog was tetraparetic and obtunded. Results of a complete neurologic evaluation were consistent with severe, multifocal to diffuse disease involving the forebrain, spinal cord, and brainstem. Cerebrospinal fluid, obtained via cerebellomedullary cisternal puncture, was highly cellular and contained large atypical round cells with small numbers of nondegenerate neutrophils and large mononuclear cells. Rare eosinophils and small lymphocytes were noted. The atypical round cells were approximately 15–25 μm in diameter with a single nucleus set in a small amount of cytoplasm. The nuclei were typically round to slightly ovoid; however, occasional notched, lobulated, and reniform nuclei were observed. These cells were interpreted as malignant lymphocytes. Owing to a grave prognosis, the animal was euthanized and a necropsy was performed. No gross lesions were found in the central nervous system. Multiple sections of cerebellum, medulla, and spinal cord contained a diffuse neoplastic infiltrate that was predominantly meningeal with rare superficial neuropil invasion. The neoplastic cells were arranged in sheets, cords, and rosettes. Immunohistochemical staining for vimentin, pancytokeratin, CD3, CD79a, synaptophysin, S-100, and neuronspecific enolase was negative; glial fibrillary acidic protein (GFAP) staining was equivocal. Based on histologic findings, a diagnosis of medulloblastoma was made. This case documents the rare occurrence of a canine medulloblastoma and illustrates the difficulty in distinguishing between some embryonal brain tumors and lymphoma.     

MRI features of gliomatosis cerebri in a dog

The features of gliomatosis cerebri involving the brainstem and cerebellum in a 3-year-old dog are described. In magnetic resonance (MR) images, there was diffuse loss of the cerebellar folia and cerebellar gray and white matter contrast. Multiple illdefined T2-hyperintensities were present in the cerebellar parenchyma. A poorly defined, T2-hyperintense mass effect was present ventral to the pons and rostral medulla. No contrast enhancement was noted. Cerebrospinal fluid (CSF) was normal. Postmortem examination was consistent with gliomatosis cerebri, based on compatible histopathology and immunohistochemical findings. Although rare, gliomatosis cerebri should be included as a differential for diffuse infiltrative central nervous system (CNS) lesions.     

Pro- and anti-inflammatory cytokine expression and histopathological characteristics in canine brain with traumatic brain injury

We analyzed the expression level and cellular localization of pro- and anti-inflammatory cytokines and histopathologically characterized canine traumatic brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and vasogenic edema. Immunohistochemical evaluations suggested that both pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta (TGF-β)] were highly expressed in neurons and neutrophils. In particular, the highest magnitude of expression was identified for IL-1β and TGF-β. This data helps describe the pathologic characteristics of canine TBI, and may help in the design of potential therapeutic approaches to control secondary damage by inflammatory cytokines.     

IMAGING DIAGNOSIS—MALIGNANT PERIPHERAL NERVE SHEATH TUMOR PRESENTING AS AN INTRA‐AXIAL BRAIN MASS IN A YOUNG DOG

A 3‐year‐old Labrador retriever was presented with acute onset seizures. Magnetic resonance imaging demonstrated an intra‐axial mass affecting the right temporal lobe of the brain. Surgical resection and histopathological findings were most consistent with a malignant peripheral nerve sheath tumor. After initial recovery, deterioration 3 months post surgery prompted euthanasia. Post‐mortem revealed a mass protruding from the ventral surface of the temporal lobe, encroaching upon the optic chiasm and invading the brain. Histopathology findings were again consistent with malignant peripheral nerve sheath tumor. Although rare, this tumor should be included as a possible differential diagnosis for intra‐axial brain masses in dogs.     

Single fraction stereotactic radiation therapy (stereotactic radiosurgery) is a feasible method for treating intracranial meningiomas in dogs

The aim of this retrospective, pilot study was to evaluate stereotactic radiosurgery as a method for treating intracranial meningiomas in dogs. Included dogs had an imaging diagnosis of presumed intracranial meningioma, were treated using a standardized stereotactic radiosurgery protocol, and had a follow‐up time of >6 months after stereotactic radiosurgery. A single fraction of 16 Gy stereotactic radiosurgery was delivered to the tumor, with an internal simultaneously integrated boost to a total dose of 20–24 Gy to the central portion of the tumor. Thirty‐two dogs were sampled. One dog was euthanized in the periprocedural period, and 10 of the remaining 31 dogs (31%) experienced an acute adverse event (defined as declining neurologic function due to tumor progression or treatment‐associated complication within the first 6 months after stereotactic radiosurgery), three of which were fatal. Too few subjects (n = 6) had cross‐sectional imaging after stereotactic radiosurgery to determine an objective response rate; however, 17/30 (57%) dogs assessed for response had a perceived clinical benefit from treatment. The overall median survival time was 519 days (95% confidence interval: 330–708 days); 64% and 24% of dogs were alive at 1 and 2 years after stereotactic radiosurgery, respectively. Dogs with infratentorial tumor location and high gradient indices had shorter survival. There were no factors identified which were predictive of acute adverse event. Survival times reported herein are similar to what has previously been reported for other stereotactic and traditional fractionated radiotherapy protocols. Findings therefore supported the use of stereotactic radiosurgery as an alternative method for treating dogs with presumed intracranial meningiomas.     

The utility of intraoperative impression smear cytology of intracranial granular cell tumors: Three cases

Two adult male dogs (a 7‐year‐old shorthaired Chihuahua and 14‐year‐old Shih Tzu) and one adult female dog (a 9‐year‐old Maltese) presented for evaluation of new‐onset seizure activity. Magnetic resonance imaging of the brain demonstrated a large, poorly marginated T2‐weighted hyperintense, and strong contrast enhancing extra‐axial mass in each case. A surgical biopsy for histopathologic evaluation was elected in all cases, and intraoperative impression smears were successfully obtained. Intraoperative cytology identified a homogenous population of round to polygonal cells with central to eccentric nuclei, coarse chromatin, and variably amphophilic to eosinophilic granular cytoplasm. Cytologic findings led to a suspected diagnosis of granular cell tumor (GCT) in all cases. Histopathologic review identified a densely cellular, unencapsulated neoplastic mass comprised of sheets of large round to polygonal cells with abundant eosinophilic cytoplasm containing numerous eosinophilic intracytoplasmic granules, confirming the diagnosis of GCT in all cases. The cases reported here are unique in that they reveal an accurate intraoperative cytologic diagnosis of a rare canine central nervous system neoplasm. Intraoperative cytology of the intracranial masses could provide clinicians with important and quick diagnostic and prognostic information; therefore, expediting decisions made intraoperatively. Further research is warranted to determine the diagnostic accuracy of intraoperative cytology for neoplasia in veterinary patients.     

IMAGING DIAGNOSIS—MAGNETIC RESONANCE IMAGING FEATURES OF METASTATIC CEREBRAL LYMPHOMA IN A DOG

We describe histopathologically confirmed intracranial metastasis of cutaneous lymphoma. In magnetic resonance (MR) images there was a heterogeneous, contrast‐enhancing, extraaxial mass in the right parietal and piriform lobes at the level of the optic chiasm. Our MR imaging findings are consistent with reports in humans in that lymphoma masses have indistinct borders that are iso‐ to hyperintense relative to adjacent gray matter on T2‐weighted images. Our report varies from findings in humans in that the mass was extraaxial, whereas masses reported in humans are intraaxial. Contrast enhancement can be heterogeneous, as in our report, or homogeneous.     

Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation

A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC.     

Histiocytic Sarcoma with Central Nervous System Involvement in Dogs: 19 Cases (2006–2012)

Background

Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1–3 animals.

Objective

The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement.

Animals

Nineteen dogs with HS examined at veterinary referral hospitals.

Methods

Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis.

Results

Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days.

Conclusions and Clinical Importance

Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.     

A mixed apocrine gland tumor with metastases to the bone and bone marrow in a miniature poodle

A 10-year-old female miniature poodle had a mass in its carpal joint of the left forelimb. The tumor was divided into small multiple lobules by delicate connective tissues, and necroses were found in some of the central lobules. In some connective stromal areas, chondroid and osteoid tissues were formed. The tumor cells were similar to the structure of apocrine gland epithelial cells with apical blebs resembling apocrine secretion and eosinophilic secretary materials within the luminal space, and spindle cells were sometimes found in the basal area of the glandular structure. In some areas, tumor cells invaded in the blood vessels, bone and bone marrow. Immunohistochemically, the tumor cells forming tubulo-acinar to solid structures were intensely positive for cytokeratin and keratin K8/K18, and the spindle cells were positive for vimentin and alpha-smooth muscle actin. This case was diagnosed as a malignant mixed apocrine gland tumor with metastases to the bone and bone marrow.     

DYNAMIC CONTRAST‐ENHANCED MAGNETIC RESONANCE IMAGING OF CANINE BRAIN TUMORS

We evaluated dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) in canine brain tumors. Magnetic resonance data sets were collected on seven canine intracranial tumors with a 3 T magnet using a T1‐weighted fast spin echo fluid attenuated inversion recovery sequence after an IV bolus injection (0.2 mmol/kg) of Gd‐DTPA. The tumors were confirmed histopathologically as adenocarcinoma (n=1), ependymoma (n=1), meningioma (n=3), oligodendroglioma (n=1), and pituitary macroadenoma (n=1) The data were analyzed using a two‐compartment pharmacokinetic model for estimation of three enhancement parameters, E_R (rate of enhancement), K_el (rate of elimination), and K_ep (rate constant), and a model‐free phenomenologic parameter initial area under the Gd concentration curve (IAUGC) defined over the first 90 s postenhancement. Pearson's correlations were calculated between parameters of the two methods. The IAUGC has a relatively strong association with the rate of enhancement E_R, with r ranges from 0.4 to 0.9, but it was weakly associated with K_ep and K_el. To determine whether any two tumors differed significantly, the Kolmogorov–Smirnov test was used. The results showed that there were statistical differences (P<0.05) between distributions of the enhancement pattern of each tumor. These kinetic parameters may characterize the perfusion and vascular permeability of the tumors and the IAUGC may reflect blood flow, vascular permeability, and the fraction of interstitial space. The kinetic parameters and the IAUGC derived from DCE‐MRI present complementary information and they may be appropriate to noninvasively differentiate canine brain tumors although a larger prospective study is necessary.