Suspected olfactory meningioma and synchronous pituitary microadenoma in a canine patient treated with radiation therapy

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A 12.5-year-old spayed mixed-breed female Labrador was referred to Purdue Veterinary Hospital to treat hyperadrenocorticism of suspected pituitary origin. During MRI imaging, the presence of two possible brain neoplasms was detected: a possible right olfactory bulb meningioma and a microadenoma of the pituitary gland. The patient was treated with a fractionated course of radiation in both tumors, 15 treatments of 3Gy, which limited the tumor growth. Lysodren therapy corrected the hormonal dysregulation. The dog had a normal life for nearly three years and recently passed. Cancer cells were not found at necropsy. No MEN1 germline mutations were identified in constitutional DNA (from blood) via high-coverage whole genome sequencing. Dual brain tumor pituitary microadenoma meningioma radiation therapy MEN1 Figures Figure 1 Figure 2 Figure 3 Background Multiple distinct malignant tumors are rare in dogs. In a retrospective study, Rebhun and Thamm (2010)[ 1 ] reported a ~ 3% prevalence of multiple distinct primary tumors out of 1,722 dogs presented to the Oncology service at Colorado State University; none of the cases had a primary brain tumor. The description of synchronous primary neoplasms in canine brains is even more unusual: in 2007, MacKillop et al.[ 2 ] described a basset hound with a coexistent cerebellar tumor and a thalamic neoplasm [ 2 ]. Necropsy and pathology exam of this dog identified a medulloblastoma for the cerebellar tumor and an astrocytoma for the thalamic mass. Recently, Pons-Sorolla Casanova, Mariné, Pumarola, and Feliu-Pascual (2023)[ 3 ] published a brain collision tumor between a left frontal oligoastrocytoma and a fibrous meningioma [ 3 ]. Case Presentation A 12.5-year-old 23 kg spayed female Labrador mix dog was referred to the neurology service at Purdue University, College of Veterinary Medicine, for potential hypophysectomy. Three months prior, the dog was diagnosed with hyperadrenocorticism by the referring veterinarian after a wellness visit revealed elevated liver enzymes and the owner reported an increased appetite. The patient's veterinarian performed an ACTH test (5ug/dl [1.0–5.0] for basal value and 25.1ug/dl [8.0–17.0] post-stimulation). An ultrasound performed by a board-certified radiologist revealed a diffuse increase in liver echogenicity and a bilateral adrenomegaly (0.75cm thickness for the right gland, 1.09 cm for the left gland, normal < 0.7cm). The dog was started on S-Adenosyl methionine (SAMe) 425 mg once daily and Lysodren (mitotane) 1mg/kg twice daily. The patient's cortisol values stabilized by three months after starting therapy (basal value 5.1ug/dl [1.0–5.0], post-stimulation value 10.8/dl [8.0–17.0]). Neurology consultation. Upon the first evaluation by Purdue's neurology service, the owner reported intermittent tremors of the pelvic limb (upper part, side non-specified) without any conscious abnormality. The owner also described stumbling or intermittent scuffling of the same leg. The patient had a persistent increased appetite and was regularly panting. Neurological examination was normal except for inconsistent positional ventral strabismus of the right eye. Upon physical examination, a small subcutaneous mass was present on the right flank, and a left caudal rear mass was previously diagnosed as papilloma. Biochemical analysis revealed elevated liver enzymes, hypercholesterolemia, hyperamylasemia, and hyperkalemia (Table 1 ). Hematology was unremarkable except for clumped platelets. Three survey thoracic radiographs were unremarkable except for the liver size extending beyond the coastal arch with rounded margins. Table 1 Biochemical analysis. First biochemistry analysis. The letter “H” under the flag column represents a high value. The results, reference range, and unit measurements are provided for each test. (mg = miligrams, dl = deciliters, mmol = micromols, L = liters, g = grams, IU = international units, U = units, ALTv = alanine aminotransferase, GGT = gamma-glutamyl transferase ). Test Result Flag Reference Range Units Glucose 102 67–132 mg/dL Blood Urea Nitrogen 16 7–32 mg/d Creatinine 0.80 0.50–1.50 mg/dL Phosphorus 4.7 2.2–7.9 mg/dL Calcium 11.0 9.7–12.3 mg/dL Sodium 145 138–148 mmol/L Potassium 5.3 H 3.5-5.0 mmol/L Chloride 114 105–117 mmol/L Carbon Dioxide 23 13–24 mmol/L Anion Gap 13.3 9.0–18.0 mmol/L Total Protein 6.9 4.8–6.9 g/dL Albumin 4.0 H 2.3–3.9 g/dL Globulin 2.9 0.7–3.8 g/dL ALTv 187 H 3–69 U/L Alkaline Phosphatase 522 H 20–157 IU/L GGT 46 H 5–16 IU/L Total Bilirubin 0.50 0.10–0.80 mg/dL Cholesterol 309 H 125–301 mg/dL Amylase 685 378–1033 IU/L Lipase 1925 H 104–1753 IU/L An MRI (GE 1.5T 8 channel-23x, Milwaukee, WI) exam was performed under general anesthesia. A board-certified veterinary radiologist identified a T2W hyperintense, T1W hyperintense mass (size length 16.2 mm x height 14.2mm, width 8mm) in the right cerebral hemisphere, within the right olfactory bulb area. The mass was characterized by strong homogeneous contrast enhancement, a broad-based contact with the falx cerebri, and a dural tail. Mild lysis of or pressure on the cribriform plate was suspected. The radiologist concluded the diagnosis of a possible meningioma of the right olfactory bulb (Fig. 1 ). In addition, the neurohypophysis was prominent and displaced to the right and caudally, creating suspicion for a microadenoma ( size length 6 mm x height 5mm, width 5mm) (Fig. 1 ). Conclusion of the first referral consultation. The patient presented two synchronous brain tumors: a suspected right olfactory bulb meningioma without any obvious associated neurologic signs and a hypophyseal microadenoma associated with clinical signs of hyperadrenocorticism. Following a discussion with the owner and the concertation between internal medicine, neurology, and radiation oncology, radiation therapy was the elected treatment for both tumors. Before the radiation enrollment and with the imminent prospect of multiple anesthetic episodes, the dog underwent a cardiac examination with cardiac ultrasound; no cardiac abnormality was reported. Radiation therapy. Images acquisitions To realize the treatment plan, the patient was positioned in a vacuum bag with her head immobilized by a bite block and thermoplastic mask (Civco Medical Solutions, Uniframe base plate, Orange City, IA) (Fig. 2 ). The mask position was indexed to the radiation table couch. Thin slices of 0.625 mm were acquired from our CT scan machine ( VCT 64-slices, GE Healthcare, Milwaukee, WI) without and with IV contrast injection (Ultrafast Bayer Healthcare, Wayne, NJ). The acquired images were transferred to our treatment plan, Eclipse (Varian Eclipse v11.0, Varian Medical Systems, Palo Alto). The precontrast series images were registered and fused with the MRI (GE 1.5T 8 channel-23x, Milwaukee, WI) T1 + contrast series images. Radiation Plan Prescription A definitive treatment with ablative intent (15 fractions of 3 Gy) was prescribed for both suspected tumors. The intracranial meningioma was treated with an intensity-modulated radiation therapy technique (IMRT), and a three-dimensional, four-field treatment was elected for the pituitary microadenoma. Both plans were delivered during the same anesthetic events. Delivery The patient was treated every other day with a 6MV linear accelerator (Varian 6EX, MLC Millenium 120 Dose Rate 400MU/mn (Varian Medical Systems, Palo Alto, CA)). The machine is equipped with record verification software (Aria, Varian Medical systems Palo Alto), and patient position accuracy was checked before delivery with port films (Kodak ACR-2000i -Oncocepts Rochester, NY). This patient setup has been previously reported by our institution [ 4 ]. For growth disease volume, the olfactory meningioma (m) and the pituitary microadenoma (p) were considered as separated growth target volumes (GTVm and GTVp) and contoured on the T1W + contrast series. For the meningioma, 3 mm margins were added to the GTVm: 2mm for microscopic disease and 1 mm for positioning uncertainty to get the planned target volume (PTVm). For the microadenoma, 2mm margins were added to obtain the pituitary planned target volume (PTVp). Critical structures were contoured separately (i.e., eyes, lens, optical nerves, optical chiasma, brain, cerebellum, brainstem, spinal cord, and ear bulla). Two separate radiation plans were designed: 1) an IMRT for the meningioma and 2) a 3D conformal for the pituitary (Fig. 3 ). Each PTV dose was selected with the intent to receive more than 95% of the dose and less than 107%. A plan summation was realized to verify the cumulative dose and the separation between the two plans [ 5 – 7 ]. Before delivery, the IMRT treatment plan was reviewed by a physicist for quality insurance after comparing the planned fluence and the actual delivery fluence in a diode cylinder Arckcheck ™( Sun Nuclear, Melbourne, Florida). The plan was accepted as the difference in dose registered between the theoretical plan and the real plan delivered on the diodes cylinder matched. In other words, less than a 3% difference was observed for over 95% of the diode points selected (3mm distance). The patient received a total of 15 radiation sessions for both sites and recovered uneventfully from these treatments. She was discharged under prednisone 0.5mg/kg once a day to prevent brain radiation secondary effects, as well as S-Adenosylmethionine 425mg per day. The Lysodren 1mg/kg BID was continued. Patient Follow-up. The patient was rechecked at two weeks and one month after completion of the radiation treatment. The owner did not report any concern for appetite or water intake. Physical exams were unremarkable, and no radiation side effects were observed upon VRTOG (1.0) classification [ 8 ]. The steroid prescription was tapered off over six weeks. Six months after finishing radiation, the dog had a complete recheck with the neurology service. The owner reported the dog was doing well, with a stabilized appetite. Mild tremors of the legs were persistent. The neurological exam was unremarkable. The referring veterinarian performed repeat blood work before the recheck with neurology, and hematology results were within normal limits. The cholesterol and amylase values were normal, and the liver enzymes improved in comparison to the first visit but were still mildly elevated GGT 20u/l (RI 0-11u/l); ALKP 343 u/l (RI 23–212 u/l), ALT 125u/l RI(10-125U/l). Following the neurology consultation, the patient had an MRI under general anesthesia. The radiologist concluded that the size of the pituitary microadenoma remained stable, and the size of the intracranial meningioma was reduced ( size: length 10.5 mm x height 12 mm, width 6 mm . The owner declined further rechecks, but regular phone calls ensured the patient's health for over two years. Three years after the initial neurology consultation, the patient was brought to the emergency service for general fatigue, locomotion incapacity, and progressive decline in quality of life. The owner elected compassionate euthanasia and allowed necropsy. Necropsy. On gross exam, a frontal mass was present in the right cerebral hemisphere measuring ( size: length 17mm x height 12 mm, width 10 mm). T he pituitary mass (length 7 mm x height 6. mm, width 5mm) was also observed grossly. Multiple adhesions were present at the level of the frontal mass. On histopathology, moderate adrenal cortical nodular hyperplasia and multifocal hemosiderosis were visualized. The liver had mild chronic centro- lobular and periportal fibrosis. The frontal mass consisted only of fibrosis and multifocal microgliosis; no neoplastic cell population was observed. Similarly, no changes were found within the pituitary gland; no microadenoma could be found. Genetic Analysis. Germline mutations in the menin 1 ( MEN1) gene are known to lead to "multiple endocrine neoplasia type 1" (MEN1) syndrome in people [ 9 – 13 ], which is characterized by the development of multifocal neoplastic endocrine lesions together with other non-endocrine tumors, such as central nervous system meningiomas [ 9 , 14 – 16 ]. Genetic analysis was carried out to explore this patient's MEN1 gene for germline (constitutional) mutations. After obtaining informed, written consent for participation from the owner, an EDTA whole blood sample was obtained from the patient for genetic analysis (Purdue University IACUC #1901001840). DNA was extracted via a standard phenol-chloroform extraction method and then subjected to whole-genome sequencing (WGS) using Illumina HiSeq 150bp paired-end reads, with an average of 21X coverage. Raw data quality control and variant calling were performed utilizing a previously described standardized bioinformatics pipeline [ 17 ]. The sequence reads were trimmed using Trimmomatic [ 18 ] and aligned to the canine reference genome assembly CanFam4[ 19 ] using the Burrows-Wheeler Aligner[ 20 ]. Variant calling was performed using GATK's HaplotypeCaller[ 21 ], identifying single nucleotide polymorphisms (SNPs) and indels. BCFTools 1.17[ 22 ] was used to identify private variants in the patient dog compared to WGS from seven hundred thirty -control dog genomes from genetically diverse breeds, assuming no other dog in the WGS population carried the same disease allele. Private variants were analyzed assuming both an autosomal recessive and autosomal dominant mode of inheritance, and functional effects of variants were predicted with Ensembl Variant Effect Predictor [ 23 ]. Variants predicted to have a high or medium impact on the resulting amino acid sequence were prioritized for further investigation. Each medium or high-impact variant-containing gene was filtered through VarElect[ 24 ], which prioritized genes based on how often the provided phenotypic terms "meningioma" and "pituitary tumor" appeared in conjunction with that specific gene in other gene-centric databases. Two hundred sixty-five heterozygous variants of high or moderate effect were identified under the assumption of dominant inheritance, but no apparent candidate genes previously associated with MEN1 were identified. Only three variants of high or moderate impact were identified under an assumption of recessive inheritance, and again, no evident candidate genes previously associated with MEN1 were identified. Finally, the integrative genomics viewer software[ 25 ] was used for manual visual inspection of the entire candidate gene MEN1 ; this failed to identify any more significant, structural private variants in the affected dog. Discussion and conclusions Meningioma is described as the most prevalent tumor in canids [ 26 – 28 ]. The standard of treatment consists of surgery, radiation therapy, or both, depending on tumor location, surgical expertise, and access to a radiation facility. Prognosis with symptomatic medical management only (anticonvulsive drugs, steroids) is guarded; median survival is less than two months[ 26 ]. Dogs receiving radiation therapy have a median life expectancy of 1.5 to 2.5 years [ 26 – 30 ]. The radiation therapy options are a fractionated course or using stereotactic techniques [ 31 – 37 ]. Recently, veterinary radiation oncologists have opted for stereotactic radiation techniques, which require less anesthesia and patient hospitalization, with treatment realized in less than a week (usually three fractions, although a unique fraction is possible). Two recent publications [ 29 , 30 ] reported survival expectancy with stereotactic techniques as similar to or less favorable than fractionated protocols [ 26 – 28 ]. Pituitary tumors are often treated with radiation therapy, as the number of veterinary hospitals with surgeons trained for hypophysectomy is still limited. Prognosis is size dependent [ 31 – 33 ]: A diagnosis of macroadenoma is less favorable than a diagnosis of microadenoma, and even if radiation therapy controls the tumor growth, the hormonal stabilization of secreting tumors is inconsistent [ 31 , 32 ]. A hormonal control rate of around 40 % has een reported [ 31 , 32 ]. In recent years, pituitary tumors have also been treated with less radiation fractions (hypofractionation) and stereotactic techniques. The results have been disappointing regarding survival: six to ten months for the median [ 36 , 37 ] versus one to two years with fractionated treatments [ 31 , 32 ]. The presently described patient had a good quality of life, and the hyperadrenocorticism was stabilized with adequate cortisol values for over three years; this is above the median survival reported in the literature for both diseases. A limitation of our study is the absence of pathology results before the radiation treatment for the suspected meningioma. This would have been useful for diagnostic confirmation and the genetic investigations that could have been performed on DNA or RNA from the tumor sample. At necropsy, no tumor cells were observed, only fibrosis, suggesting either the radiation had cured the neoplasia or some remaining tumor cells were still present but at very low quantities, requiring more histological sections. In people, reports of intracranial meningioma with coexisting pituitary tumors are rare. Case reports mention 1) the occurrence of meningioma in the sella turcica after the treatment of a pituitary tumor either by surgery or radiation, with eventual recurrence of the pituitary tumor, and 2) the occurrence of pituitary tumor after the treatment of meningioma in the same area [ 38 , 39 ]. A larger cohort retrospective study described seven pituitary adenomas and distant intracranial meningiomas. 20% were associated with growth hormone production, and 30% were classified as prolactinomas [ 40 ]. The frequency of meningiomas in patients with MEN1 syndrome is being reported more frequently [ 41 , 42 ]. Patients with MEN1 syndrome usually have several endocrine tumor disorders, such as tumors of the adrenal glands, pituitary, parathyroids, endocrine pancreas, and carcinoids, often together with non-endocrine tumors of smooth muscles, skin, and the central nervous system, among others. This case study describes a patient with only one endocrine neoplasia, a pituitary tumor. Furthermore, the whole genome sequencing of constitutional (blood) DNA failed to identify any MEN1 variants. It should be noted that the WGS methodology used (150bp paired-end reads) is not ideal for discovering large structural rearrangements, so it is still possible for a MEN1 variant to have been missed. As mentioned above, without pre-treatment tumor samples, we could not sequence tumor DNA or RNA; it was also impossible to carry out any proteomic evaluations for MEN1 or other proteins in its pathway. In conclusion, this case study described a rare dual synchronous brain tumor presentation. A 12.5-year-old spayed female Labrador mix was treated with radiation therapy for a suspected olfactory meningioma and an ACTH-secreting pituitary microadenoma. The dog responded well to simultaneous treatment of both tumors for almost three years. Whole genome sequencing of constitutional DNA did not reveal any possible MEN1 mutations. At necropsy, residual tumor could not be identified. List Of Abbreviations Gy (Gray), DNA (Deoxyribonucleic Acid), ACTH (Adrenocorticotropic Hormone), SAMe (S-Adenosyl Methionine), MRI (Magnetic Resonance Imaging), IMRT (Intensity-Modulated Radiation Therapy), GTV (Gross Tumor Volume), GTVp (Gross Tumor Volume of the pituitary), GTVm (Gross Tumor Volume of meningioma), VRTOG (Veterinary Radiation Therapy Oncology Group), GGT (Gamma-Glutamyl Transferase), ALKP (Alkaline Phosphatase), ALT (Alanine Aminotransferase), MEN1 (Multiple Endocrine Neoplasia Type 1), WGS (Whole Genome Sequencing), SNP (Single Nucleotide Polymorphism). Declarations Ethics approval and consent to participate : Ethical review and approval were waived for this case report as it exclusively involved the analysis of clinical data from a patient treated with standard-of-care procedures. Genetic research analysis WGS was approved by Purdue University IACUC committee( IACUC #1901001840) with owner consent. Consent for publication : Owner has agreed to use patient data for a research publication. Availability of data and materials : data are not publicly available to ensure compliance with privacy and confidentiality policies governing veterinary patient information at Purdue University's veterinary teaching hospital. Competing interests : The authors declare that they have no competing interests. Funding : Purdue University IACUC #1901001840 funded genetic material analysis. The clinical case management was client-owned and paid. Authors' contributions : "Conception, IV. Design of the work IV, TB, KE. Acquisition, TB, IV, CMV, JB. Analysis, IV, CMV, JB. Interpretation of data IV, MS, KE, MS . Drafted work and substantively revised it, IV, CMV, TB, MS, KE . Authors have approved the submitted version (and any substantially modified version that involves the author's contribution to the study); Authors have agreed both to be personally accountable for the author's contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature." IV, CMV, TB, MS, JB, KE Acknowledgments : The authors thank Dr. Scott-Moncrieff, College of Veterinary, Purdue University, for supporting the study. References Rebhun RB, Thamm DH. Multiple Distinct Malignancies in Dogs: 53 Cases. J Am Anim Hosp Assoc 2010;46:20–30. https://doi.org/10.5326/0460020 . MacKILLOP E, THRALL DE, RANCK RS, LINDER KE, MUNANA KR. 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Front Neurol 2022;13. https://doi.org/10.3389/fneur.2022.1042106 . Spallone A. Meningioma as a Sequel of Radiotherapy for Pituitary Adenoma. Min - Minimally Invasive Neurosurgery 1982;25:68–72. https://doi.org/10.1055/s-2008-1053960 . Abs R, Parizel PM, Willems PJ, Van de Kelft E, Verlooy J, Mahler C, et al. The Association of Meningioma and Pituitary Adenoma: Report of Seven Cases and Review of the Literature. Eur Neurol 1993;33:416–22. https://doi.org/10.1159/000116986 . Falchetti A, Marini F, Luzi E, Giusti F, Cavalli L, Cavalli T, et al. Multiple endocrine neoplasia type 1 (MEN1): Not only inherited endocrine tumors. Genetics in Medicine 2009;11:825–35. https://doi.org/10.1097/GIM.0b013e3181be5c97 . Asgharian B, Chen Y-J, Patronas NJ, Peghini PL, Reynolds JC, Vortmeyer A, et al. Meningiomas May Be a Component Tumor of Multiple Endocrine Neoplasia Type 1. Clinical Cancer Research 2004;10:869–80. https://doi.org/10.1158/1078-0432.CCR-0938-3 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 15 Jul, 2024 Read the published version in Veterinary Oncology → Version 1 posted Editorial decision: Revision requested 10 Mar, 2024 Reviews received at journal 03 Mar, 2024 Reviewers agreed at journal 28 Feb, 2024 Reviewers invited by journal 01 Feb, 2024 Submission checks completed at journal 31 Jan, 2024 Editor assigned by journal 31 Jan, 2024 First submitted to journal 31 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3915487","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":270506835,"identity":"86fa09f3-6867-4b53-9638-c9790e5157d8","order_by":0,"name":"Isabelle Francoise Vanhaezebrouck","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYBACNuYDQLICxEwAEcxEaGEDqTxDihYGkBbGNlK08LHxGH4unHcncXt7juEDhgrrxAbCDuMxlp657VninDNvjA0YzqQToUW+LUGad9vhxBkSOWYSjG2HibGFLfk37xywFvMfjP+I0sJ8TJq3AWILA2MDkVqseY49M57B86xYIuFYujFBLfJtjM23eWruyM5gT9744UONtSxBLVBwAEIlEKkcScsoGAWjYBSMAmwAAPTYOreejSJOAAAAAElFTkSuQmCC","orcid":"","institution":"Purdue University West Lafayette","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Isabelle","middleName":"Francoise","lastName":"Vanhaezebrouck","suffix":""},{"id":270506836,"identity":"d69a9357-7e7d-4cd9-a022-19ac059ff650","order_by":1,"name":"Carlos Roberto Mendez-Valenzuela","email":"","orcid":"","institution":"Purdue University West Lafayette","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Carlos","middleName":"Roberto","lastName":"Mendez-Valenzuela","suffix":""},{"id":270506837,"identity":"882d2313-d53a-49c4-bf71-98d7bc4dac6b","order_by":2,"name":"R.Timothy Bentley","email":"","orcid":"","institution":"University of Liverpool","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"R.Timothy","middleName":"","lastName":"Bentley","suffix":""},{"id":270506838,"identity":"4dc350e2-5934-4d3f-88b4-8c2847028d25","order_by":3,"name":"Matthew Louis Scarpelli","email":"","orcid":"","institution":"Purdue University West Lafayette","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"Louis","lastName":"Scarpelli","suffix":""},{"id":270506839,"identity":"2cf65b97-313d-486d-a6c3-96606f8e6b31","order_by":4,"name":"Jeanna Blake","email":"","orcid":"","institution":"Purdue University West Lafayette","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jeanna","middleName":"","lastName":"Blake","suffix":""},{"id":270506840,"identity":"105877a8-c729-4308-a8b7-199cd1122a65","order_by":5,"name":"Kari J Ekenstedt","email":"","orcid":"","institution":"Purdue University West Lafayette","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kari","middleName":"J","lastName":"Ekenstedt","suffix":""}],"badges":[],"createdAt":"2024-02-01 00:37:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3915487/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3915487/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s44356-024-00001-4","type":"published","date":"2024-07-16T00:33:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50568155,"identity":"740c9e22-82cc-42cf-b700-83baaf1495a1","added_by":"auto","created_at":"2024-02-02 15:24:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":850559,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSagittal T1 post contrast MRI (GE 1.5T 8 channel-23x, Milwaukee, WI) view\u003c/strong\u003e: The left red arrow indicates the possible right olfactory bulb meningioma (\u003cem\u003esize length 6 mm, height 5 mm, width 5 mm)\u003c/em\u003e. The right red arrow indicates the likely neurohypophyseal microadenoma, which is prominent and displaced to the right and caudally.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3915487/v1/2c063cdb62fe051c6bcc1db9.png"},{"id":50568157,"identity":"ab49f0d1-f85d-40de-86cd-1a2a93333ec2","added_by":"auto","created_at":"2024-02-02 15:24:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2610489,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient positioned for treatment plan image acquisition. \u003c/strong\u003eThe patient was positioned and immobilized with various equipment (vacuum bag, thermoplastic mask (Civco Medical Solutions), Uniframe base plate, (Orange City, IA, Uniframe base plate, Orange City, IA)) to aquire the treatment planning images.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3915487/v1/564d19b1c254c82acd5b1857.jpg"},{"id":50568156,"identity":"6aebdc18-1a73-45cd-ba36-2d0df166136f","added_by":"auto","created_at":"2024-02-02 15:24:19","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":151096,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDose color distribution from treatment plans. \u003c/strong\u003eTwo axial views, (far left) one corresponding to the pituitary with a 3-D plan, and (middle) the olfactory meningioma with an IMRT plan.The sagital view (far right) visualizes both tumors with their corresponding plans. Scale at left is the color palate matching different doses expresssed in centy gray (cGy) to define the dose intensity associated color for each plan.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3915487/v1/4174077df0b75f7d0570a1fd.jpg"},{"id":60356387,"identity":"e20cc0ae-8b90-47cb-a2cd-75e2ffa8f185","added_by":"auto","created_at":"2024-07-16 00:34:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":18066243,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3915487/v1/d3d0439d-fb3a-4109-aef7-415821ef8f9a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Suspected olfactory meningioma and synchronous pituitary microadenoma in a canine patient treated with radiation therapy","fulltext":[{"header":"Background","content":"\u003cp\u003eMultiple distinct malignant tumors are rare in dogs. In a retrospective study, Rebhun and Thamm (2010)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] reported a\u0026thinsp;~\u0026thinsp;3% prevalence of multiple distinct primary tumors out of 1,722 dogs presented to the Oncology service at Colorado State University; none of the cases had a primary brain tumor. The description of synchronous primary neoplasms in canine brains is even more unusual: in 2007, MacKillop et al.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] described a basset hound with a coexistent cerebellar tumor and a thalamic neoplasm [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Necropsy and pathology exam of this dog identified a medulloblastoma for the cerebellar tumor and an astrocytoma for the thalamic mass. Recently, Pons-Sorolla Casanova, Marin\u0026eacute;, Pumarola, and Feliu-Pascual (2023)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] published a brain collision tumor between a left frontal oligoastrocytoma and a fibrous meningioma [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 12.5-year-old 23 kg spayed female Labrador mix dog was referred to the neurology service at Purdue University, College of Veterinary Medicine, for potential hypophysectomy. Three months prior, the dog was diagnosed with hyperadrenocorticism by the referring veterinarian after a wellness visit revealed elevated liver enzymes and the owner reported an increased appetite. The patient's veterinarian performed an ACTH test (5ug/dl [1.0\u0026ndash;5.0] for basal value and 25.1ug/dl [8.0\u0026ndash;17.0] post-stimulation). An ultrasound performed by a board-certified radiologist revealed a diffuse increase in liver echogenicity and a bilateral adrenomegaly (0.75cm thickness for the right gland, 1.09 cm for the left gland, normal\u0026thinsp;\u0026lt;\u0026thinsp;0.7cm). The dog was started on S-Adenosyl methionine (SAMe) 425 mg once daily and Lysodren (mitotane) 1mg/kg twice daily. The patient's cortisol values stabilized by three months after starting therapy (basal value 5.1ug/dl [1.0\u0026ndash;5.0], post-stimulation value 10.8/dl [8.0\u0026ndash;17.0]).\u003c/p\u003e \u003cp\u003e \u003cem\u003eNeurology consultation.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eUpon the first evaluation by Purdue's neurology service, the owner reported intermittent tremors of the pelvic limb (upper part, side non-specified) without any conscious abnormality. The owner also described stumbling or intermittent scuffling of the same leg. The patient had a persistent increased appetite and was regularly panting. Neurological examination was normal except for inconsistent positional ventral strabismus of the right eye. Upon physical examination, a small subcutaneous mass was present on the right flank, and a left caudal rear mass was previously diagnosed as papilloma. Biochemical analysis revealed elevated liver enzymes, hypercholesterolemia, hyperamylasemia, and hyperkalemia (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Hematology was unremarkable except for clumped platelets. Three survey thoracic radiographs were unremarkable except for the liver size extending beyond the coastal arch with rounded margins.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eBiochemical analysis.\u003c/b\u003e First biochemistry analysis. The letter \u0026ldquo;H\u0026rdquo; under the flag column represents a high value. The results, reference range, and unit measurements are provided for each test. (mg\u0026thinsp;=\u0026thinsp;miligrams, dl\u0026thinsp;=\u0026thinsp;deciliters, mmol\u0026thinsp;=\u0026thinsp;micromols, L\u0026thinsp;=\u0026thinsp;liters, g\u0026thinsp;=\u0026thinsp;grams, IU\u0026thinsp;=\u0026thinsp;international units, U\u0026thinsp;=\u0026thinsp;units, ALTv\u0026thinsp;=\u0026thinsp;alanine aminotransferase, GGT\u0026thinsp;=\u0026thinsp;gamma-glutamyl transferase\u003cem\u003e).\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eResult\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFlag\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference Range\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUnits\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67\u0026ndash;132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood Urea Nitrogen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u0026ndash;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emg/d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.50\u0026ndash;1.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhosphorus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2\u0026ndash;7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.7\u0026ndash;12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSodium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e138\u0026ndash;148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emmol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePotassium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5-5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emmol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChloride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e105\u0026ndash;117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emmol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarbon Dioxide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emmol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnion Gap\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.0\u0026ndash;18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emmol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.8\u0026ndash;6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.3\u0026ndash;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlobulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u0026ndash;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALTv\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u0026ndash;69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eU/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlkaline Phosphatase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u0026ndash;157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIU/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGGT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u0026ndash;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIU/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Bilirubin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.10\u0026ndash;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125\u0026ndash;301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmylase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e685\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e378\u0026ndash;1033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIU/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLipase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e104\u0026ndash;1753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIU/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAn MRI (GE 1.5T 8 channel-23x, Milwaukee, WI) exam was performed under general anesthesia. A board-certified veterinary radiologist identified a T2W hyperintense, T1W hyperintense mass \u003cem\u003e(size length 16.2 mm x height 14.2mm, width 8mm)\u003c/em\u003e in the right cerebral hemisphere, within the right olfactory bulb area. The mass was characterized by strong homogeneous contrast enhancement, a broad-based contact with the falx cerebri, and a dural tail. Mild lysis of or pressure on the cribriform plate was suspected. The radiologist concluded the diagnosis of a possible meningioma of the right olfactory bulb (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In addition, the neurohypophysis was prominent and displaced to the right and caudally, creating suspicion for a microadenoma (\u003cem\u003esize length 6 mm x height 5mm, width 5mm)\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eConclusion of the first referral consultation.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe patient presented two synchronous brain tumors: a suspected right olfactory bulb meningioma without any obvious associated neurologic signs and a hypophyseal microadenoma associated with clinical signs of hyperadrenocorticism. Following a discussion with the owner and the concertation between internal medicine, neurology, and radiation oncology, radiation therapy was the elected treatment for both tumors. Before the radiation enrollment and with the imminent prospect of multiple anesthetic episodes, the dog underwent a cardiac examination with cardiac ultrasound; no cardiac abnormality was reported.\u003c/p\u003e \u003cp\u003e \u003cem\u003eRadiation therapy.\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eImages acquisitions\u003c/strong\u003e \u003cp\u003eTo realize the treatment plan, the patient was positioned in a vacuum bag with her head immobilized by a bite block and thermoplastic mask (Civco Medical Solutions, Uniframe base plate, Orange City, IA) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mask position was indexed to the radiation table couch. Thin slices of 0.625 mm were acquired from our CT scan machine ( VCT 64-slices, GE Healthcare, Milwaukee, WI) without and with IV contrast injection (Ultrafast Bayer Healthcare, Wayne, NJ). The acquired images were transferred to our treatment plan, Eclipse (Varian Eclipse v11.0, Varian Medical Systems, Palo Alto). The precontrast series images were registered and fused with the MRI (GE 1.5T 8 channel-23x, Milwaukee, WI) T1\u0026thinsp;+\u0026thinsp;contrast series images.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eRadiation Plan Prescription\u003c/strong\u003e \u003cp\u003eA definitive treatment with ablative intent (15 fractions of 3 Gy) was prescribed for both suspected tumors. The intracranial meningioma was treated with an intensity-modulated radiation therapy technique (IMRT), and a three-dimensional, four-field treatment was elected for the pituitary microadenoma. Both plans were delivered during the same anesthetic events.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDelivery\u003c/strong\u003e \u003cp\u003eThe patient was treated every other day with a 6MV linear accelerator (Varian 6EX, MLC Millenium 120 Dose Rate 400MU/mn (Varian Medical Systems, Palo Alto, CA)). The machine is equipped with record verification software (Aria, Varian Medical systems Palo Alto), and patient position accuracy was checked before delivery with port films (Kodak ACR-2000i -Oncocepts Rochester, NY). This patient setup has been previously reported by our institution [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003cp\u003eFor growth disease volume, the olfactory meningioma (m) and the pituitary microadenoma (p) were considered as separated growth target volumes (GTVm and GTVp) and contoured on the T1W\u0026thinsp;+\u0026thinsp;contrast series. For the meningioma, 3 mm margins were added to the GTVm: 2mm for microscopic disease and 1 mm for positioning uncertainty to get the planned target volume (PTVm). For the microadenoma, 2mm margins were added to obtain the pituitary planned target volume (PTVp). Critical structures were contoured separately (i.e., eyes, lens, optical nerves, optical chiasma, brain, cerebellum, brainstem, spinal cord, and ear bulla).\u003c/p\u003e \u003cp\u003eTwo separate radiation plans were designed: 1) an IMRT for the meningioma and 2) a 3D conformal for the pituitary (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Each PTV dose was selected with the intent to receive more than 95% of the dose and less than 107%. A plan summation was realized to verify the cumulative dose and the separation between the two plans [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Before delivery, the IMRT treatment plan was reviewed by a physicist for quality insurance after comparing the planned fluence and the actual delivery fluence in a diode cylinder Arckcheck \u0026trade;( Sun Nuclear, Melbourne, Florida). The plan was accepted as the difference in dose registered between the theoretical plan and the real plan delivered on the diodes cylinder matched. In other words, less than a 3% difference was observed for over 95% of the diode points selected (3mm distance). The patient received a total of 15 radiation sessions for both sites and recovered uneventfully from these treatments. She was discharged under prednisone 0.5mg/kg once a day to prevent brain radiation secondary effects, as well as S-Adenosylmethionine 425mg per day. The Lysodren 1mg/kg BID was continued.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003ePatient Follow-up.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe patient was rechecked at two weeks and one month after completion of the radiation treatment. The owner did not report any concern for appetite or water intake. Physical exams were unremarkable, and no radiation side effects were observed upon VRTOG (1.0) classification [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The steroid prescription was tapered off over six weeks. Six months after finishing radiation, the dog had a complete recheck with the neurology service. The owner reported the dog was doing well, with a stabilized appetite. Mild tremors of the legs were persistent. The neurological exam was unremarkable. The referring veterinarian performed repeat blood work before the recheck with neurology, and hematology results were within normal limits. The cholesterol and amylase values were normal, and the liver enzymes improved in comparison to the first visit but were still mildly elevated GGT 20u/l (RI 0-11u/l); ALKP 343 u/l (RI 23\u0026ndash;212 u/l), ALT 125u/l RI(10-125U/l). Following the neurology consultation, the patient had an MRI under general anesthesia. The radiologist concluded that the size of the pituitary microadenoma remained stable, and the size of the intracranial meningioma was reduced (\u003cem\u003esize: length 10.5 mm x height 12 mm, width 6 mm\u003c/em\u003e. The owner declined further rechecks, but regular phone calls ensured the patient's health for over two years. Three years after the initial neurology consultation, the patient was brought to the emergency service for general fatigue, locomotion incapacity, and progressive decline in quality of life. The owner elected compassionate euthanasia and allowed necropsy.\u003c/p\u003e \u003cp\u003e \u003cem\u003eNecropsy.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eOn gross exam, a frontal mass was present in the right cerebral hemisphere measuring (\u003cem\u003esize: length 17mm x height 12 mm, width 10 mm). T\u003c/em\u003ehe pituitary mass \u003cem\u003e(length 7 mm x height 6. mm, width 5mm)\u003c/em\u003e was also observed grossly. Multiple adhesions were present at the level of the frontal mass. On histopathology, moderate adrenal cortical nodular hyperplasia and multifocal hemosiderosis were visualized. The liver had mild chronic centro- lobular and periportal fibrosis. The frontal mass consisted only of fibrosis and multifocal microgliosis; no neoplastic cell population was observed. Similarly, no changes were found within the pituitary gland; no microadenoma could be found.\u003c/p\u003e \u003cp\u003e \u003cem\u003eGenetic Analysis.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eGermline mutations in the \u003cem\u003emenin 1 ( MEN1)\u003c/em\u003e gene are known to lead to \"multiple endocrine neoplasia type 1\" (MEN1) syndrome in people [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], which is characterized by the development of multifocal neoplastic endocrine lesions together with other non-endocrine tumors, such as central nervous system meningiomas [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Genetic analysis was carried out to explore this patient's \u003cem\u003eMEN1\u003c/em\u003e gene for germline (constitutional) mutations.\u003c/p\u003e \u003cp\u003e After obtaining informed, written consent for participation from the owner, an EDTA whole blood sample was obtained from the patient for genetic analysis (Purdue University IACUC #1901001840). DNA was extracted via a standard phenol-chloroform extraction method and then subjected to whole-genome sequencing (WGS) using Illumina HiSeq 150bp paired-end reads, with an average of 21X coverage. Raw data quality control and variant calling were performed utilizing a previously described standardized bioinformatics pipeline [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The sequence reads were trimmed using Trimmomatic [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and aligned to the canine reference genome assembly CanFam4[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] using the Burrows-Wheeler Aligner[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Variant calling was performed using GATK's HaplotypeCaller[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], identifying single nucleotide polymorphisms (SNPs) and indels. BCFTools 1.17[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] was used to identify private variants in the patient dog compared to WGS from seven hundred thirty -control dog genomes from genetically diverse breeds, assuming no other dog in the WGS population carried the same disease allele. Private variants were analyzed assuming both an autosomal recessive and autosomal dominant mode of inheritance, and functional effects of variants were predicted with Ensembl Variant Effect Predictor [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Variants predicted to have a high or medium impact on the resulting amino acid sequence were prioritized for further investigation. Each medium or high-impact variant-containing gene was filtered through VarElect[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], which prioritized genes based on how often the provided phenotypic terms \"meningioma\" and \"pituitary tumor\" appeared in conjunction with that specific gene in other gene-centric databases. Two hundred sixty-five heterozygous variants of high or moderate effect were identified under the assumption of dominant inheritance, but no apparent candidate genes previously associated with MEN1 were identified. Only three variants of high or moderate impact were identified under an assumption of recessive inheritance, and again, no evident candidate genes previously associated with MEN1 were identified. Finally, the integrative genomics viewer software[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] was used for manual visual inspection of the entire candidate gene \u003cem\u003eMEN1\u003c/em\u003e; this failed to identify any more significant, structural private variants in the affected dog.\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eMeningioma is described as the most prevalent tumor in canids [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The standard of treatment consists of surgery, radiation therapy, or both, depending on tumor location, surgical expertise, and access to a radiation facility. Prognosis with symptomatic medical management only (anticonvulsive drugs, steroids) is guarded; median survival is less than two months[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Dogs receiving radiation therapy have a median life expectancy of 1.5 to 2.5 years [\u003cspan additionalcitationids=\"CR27 CR28 CR29\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The radiation therapy options are a fractionated course or using stereotactic techniques [\u003cspan additionalcitationids=\"CR32 CR33 CR34 CR35 CR36\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Recently, veterinary radiation oncologists have opted for stereotactic radiation techniques, which require less anesthesia and patient hospitalization, with treatment realized in less than a week (usually three fractions, although a unique fraction is possible). Two recent publications [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] reported survival expectancy with stereotactic techniques as similar to or less favorable than fractionated protocols [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Pituitary tumors are often treated with radiation therapy, as the number of veterinary hospitals with surgeons trained for hypophysectomy is still limited. Prognosis is size dependent [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]:\u003c/p\u003e \u003cp\u003eA diagnosis of macroadenoma is less favorable than a diagnosis of microadenoma, and even if radiation therapy controls the tumor growth, the hormonal stabilization of secreting tumors is inconsistent [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. A hormonal control rate of around 40 % has een reported [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In recent years, pituitary tumors have also been treated with less radiation fractions (hypofractionation) and stereotactic techniques. The results have been disappointing regarding survival: six to ten months for the median [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] versus one to two years with fractionated treatments [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The presently described patient had a good quality of life, and the hyperadrenocorticism was stabilized with adequate cortisol values for over three years; this is above the median survival reported in the literature for both diseases. A limitation of our study is the absence of pathology results before the radiation treatment for the suspected meningioma. This would have been useful for diagnostic confirmation and the genetic investigations that could have been performed on DNA or RNA from the tumor sample. At necropsy, no tumor cells were observed, only fibrosis, suggesting either the radiation had cured the neoplasia or some remaining tumor cells were still present but at very low quantities, requiring more histological sections.\u003c/p\u003e \u003cp\u003eIn people, reports of intracranial meningioma with coexisting pituitary tumors are rare. Case reports mention 1) the occurrence of meningioma in the sella turcica after the treatment of a pituitary tumor either by surgery or radiation, with eventual recurrence of the pituitary tumor, and 2) the occurrence of pituitary tumor after the treatment of meningioma in the same area [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. A larger cohort retrospective study described seven pituitary adenomas and distant intracranial meningiomas. 20% were associated with growth hormone production, and 30% were classified as prolactinomas [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe frequency of meningiomas in patients with MEN1 syndrome is being reported more frequently [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Patients with MEN1 syndrome usually have several endocrine tumor disorders, such as tumors of the adrenal glands, pituitary, parathyroids, endocrine pancreas, and carcinoids, often together with non-endocrine tumors of smooth muscles, skin, and the central nervous system, among others. This case study describes a patient with only one endocrine neoplasia, a pituitary tumor. Furthermore, the whole genome sequencing of constitutional (blood) DNA failed to identify any \u003cem\u003eMEN1\u003c/em\u003e variants. It should be noted that the WGS methodology used (150bp paired-end reads) is not ideal for discovering large structural rearrangements, so it is still possible for a \u003cem\u003eMEN1\u003c/em\u003e variant to have been missed. As mentioned above, without pre-treatment tumor samples, we could not sequence tumor DNA or RNA; it was also impossible to carry out any proteomic evaluations for MEN1 or other proteins in its pathway.\u003c/p\u003e \u003cp\u003eIn conclusion, this case study described a rare dual synchronous brain tumor presentation. A 12.5-year-old spayed female Labrador mix was treated with radiation therapy for a suspected olfactory meningioma and an ACTH-secreting pituitary microadenoma. The dog responded well to simultaneous treatment of both tumors for almost three years. Whole genome sequencing of constitutional DNA did not reveal any possible \u003cem\u003eMEN1\u003c/em\u003e mutations. At necropsy, residual tumor could not be identified.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eGy (Gray), DNA (Deoxyribonucleic Acid), ACTH (Adrenocorticotropic Hormone), SAMe (S-Adenosyl Methionine), MRI (Magnetic Resonance Imaging), IMRT (Intensity-Modulated Radiation Therapy), GTV (Gross Tumor Volume), GTVp (Gross Tumor Volume of the pituitary), GTVm (Gross Tumor Volume of meningioma), VRTOG (Veterinary Radiation Therapy Oncology Group), GGT (Gamma-Glutamyl Transferase), ALKP (Alkaline Phosphatase), ALT (Alanine Aminotransferase), MEN1 (Multiple Endocrine Neoplasia Type 1), WGS (Whole Genome Sequencing), SNP (Single Nucleotide Polymorphism).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/em\u003e: Ethical review and approval were waived for this case report as it exclusively involved the analysis of clinical data from a patient treated with standard-of-care procedures. \u0026nbsp;Genetic \u0026nbsp;research analysis WGS was \u0026nbsp;approved by Purdue University IACUC committee( IACUC #1901001840) with owner consent.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/em\u003e: Owner has agreed to use patient data for \u0026nbsp;a research publication.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e:\u003c/em\u003e data are not publicly available to ensure compliance with privacy and confidentiality policies governing veterinary patient information at Purdue University\u0026apos;s veterinary teaching hospital.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/em\u003e:\u0026nbsp;The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/em\u003e: Purdue University IACUC #1901001840 funded genetic material analysis. The clinical case management was client-owned and paid.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/em\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026quot;Conception,\u0026nbsp;IV.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eDesign of the work IV, TB, KE. Acquisition, TB, IV, CMV, JB. Analysis, IV, CMV, JB.\u0026nbsp;Interpretation of data\u0026nbsp;IV, MS, KE, MS\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eDrafted work and substantively revised it,\u0026nbsp;IV, CMV, TB, MS, KE\u003cstrong\u003e. \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e have approved the submitted version (and any substantially modified version that involves the author\u0026apos;s contribution to the study);\u003c/p\u003e\n\u003cp\u003eAuthors\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ehave agreed both to be personally accountable for the author\u0026apos;s contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u0026quot;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIV, CMV, TB, MS, JB, KE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/em\u003e: The authors thank Dr. Scott-Moncrieff, College of Veterinary, Purdue University, for supporting the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRebhun RB, Thamm DH. 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Meningiomas May Be a Component Tumor of Multiple Endocrine Neoplasia Type 1. Clinical Cancer Research 2004;10:869\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1158/1078-0432.CCR-0938-3\u003c/span\u003e\u003cspan address=\"10.1158/1078-0432.CCR-0938-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"veterinary-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Veterinary Oncology](https://veterinaryoncology.biomedcentral.com/)","snPcode":"44356","submissionUrl":"https://submission.springernature.com/new-submission/44356/3","title":"Veterinary Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Dual brain tumor, pituitary microadenoma, meningioma, radiation therapy, MEN1","lastPublishedDoi":"10.21203/rs.3.rs-3915487/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3915487/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe authors report on the rare occurrence of dual synchronous primary brain tumors in a canine patient, successful treatment with radiation therapy, and medical therapy with patient stabilization for almost three years. A 12.5-year-old spayed mixed-breed female Labrador was referred to Purdue Veterinary Hospital to treat hyperadrenocorticism of suspected pituitary origin. During MRI imaging, the presence of two possible brain neoplasms was detected: a possible right olfactory bulb meningioma and a microadenoma of the pituitary gland. The patient was treated with a fractionated course of radiation in both tumors, 15 treatments of 3Gy, which limited the tumor growth. Lysodren therapy corrected the hormonal dysregulation. The dog had a normal life for nearly three years and recently passed. Cancer cells were not found at necropsy. No \u003cem\u003eMEN1\u003c/em\u003e germline mutations were identified in constitutional DNA (from blood) via high-coverage whole genome sequencing.\u003c/p\u003e","manuscriptTitle":"Suspected olfactory meningioma and synchronous pituitary microadenoma in a canine patient treated with radiation therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-02 15:24:14","doi":"10.21203/rs.3.rs-3915487/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-03-10T11:37:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-03T13:17:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d1af1bd0-0828-41df-b24a-75b6ef20d22c","date":"2024-02-28T11:45:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-01T17:21:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-01T01:54:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-01T01:54:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Veterinary Oncology","date":"2024-02-01T00:19:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"veterinary-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Veterinary Oncology](https://veterinaryoncology.biomedcentral.com/)","snPcode":"44356","submissionUrl":"https://submission.springernature.com/new-submission/44356/3","title":"Veterinary Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"11f515e4-ce28-4950-9171-4b9d197c0a55","owner":[],"postedDate":"February 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-07-16T00:33:51+00:00","versionOfRecord":{"articleIdentity":"rs-3915487","link":"https://doi.org/10.1186/s44356-024-00001-4","journal":{"identity":"veterinary-oncology","isVorOnly":false,"title":"Veterinary Oncology"},"publishedOn":"2024-07-16 00:33:51","publishedOnDateReadable":"July 16th, 2024"},"versionCreatedAt":"2024-02-02 15:24:14","video":"","vorDoi":"10.1186/s44356-024-00001-4","vorDoiUrl":"https://doi.org/10.1186/s44356-024-00001-4","workflowStages":[]},"version":"v1","identity":"rs-3915487","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3915487","identity":"rs-3915487","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}