Banks

Dernell

Diamond

Fukui

Karin

Liptak

Loukopoulos

Morrison

Straw

Thompson

Vancil

Webb

Clinical Case Reports

English

Simon Cook

Alexander Civello

Richard Lam

Joe Fenn

David Neilson

Simon Priestnall

Steven De Decker

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Rapid postoperative recurrence of a cranial multilobular tumor of bone in a young dog

Cook, S

Civello, A

Lam, R

Fenn, J

Neilson, D M

Priestnall, S L

De Decker, S

RVC Research Online

CASE REPORTRapid postoperative recurrence of a cranial multilobulartumor of bone in a young dogSimon Cook1 , Alexander Civello2, Richard Lam1, Joe Fenn1, David Neilson1, Simon Priestnall2 &Steven De Decker11Queen Mother Hospital for Animals, Clinical Science and Services, Royal Veterinary College, London, UK2Department of Pathology and Pathogen Biology, Royal Veterinary College, London, UKCorrespondenceSimon Cook, Queen Mother Hospital forAnimals, Royal Veterinary College,Hawkshead Lane, AL9 7TA London, UK.Tel: +44 (0)1707 666366;Fax: +44 (0)1707 649384;E-mail: sdcook@rvc.ac.ukFunding InformationNo sources of funding were declared for thisstudy.Received: 20 April 2017; Revised: 15 August2017; Accepted: 12 September 2017Clinical Case Reports 2017; 5(12): 1995–1999doi: 10.1002/ccr3.1243Key Clinical MessageAlthough resection of multilobular tumors of bone can be associated with agood prognosis and long disease-free intervals in dogs, osteosarcomatous trans-formation should be considered a cause for rapid recurrence of clinical signs.KeywordsCraniotomy, neurology, osteosarcom, veterinaryCase ReportA 2-year and 11-month-old male neutered Jack RussellTerrier presented to the Queen Mother Hospital for Ani-mals, the Royal Veterinary College, University of Londonfor further evaluation of focal seizures and cervical hyper-esthesia of 7-day duration. General physical examinationwas within normal limits. Neurological examinationrevealed obtundation, bilaterally absent menace responses,and cervical hyperesthesia. No other abnormalities werenoted during the neurological examination. A multifocalneuroanatomical localization with forebrain and cervicalspinal cord involvement was considered most likely.Results of a complete blood count and a biochemistryprofile were within normal limits. The dog was premedi-cated with methadone 0.1 mg/kg IV. Diazepam (0.3 mg/kg IV) was administered prior to induction of anesthesiawith propofol (4-6 mg/kg IV dosed to effect). Anesthesiawas maintained with sevoflurane vaporized in oxygen.Magnetic resonance imaging (MRI; 1.5T Intera, PhilipsMedical Systems, Eindhoven, the Netherlands) of thehead included sagittal and transverse plane T2-weightedfast spin echo (repetition time [ms] [TR], echo time [ms][TE], 2882/110 in sagittal, and 5099/110 in transversalplane), transverse plane T2-weighted fluid-attenuatedinversion recovery (FLAIR) (TR/TE, 6000/120), and trans-verse T2*-weighted gradient echo sequences (TR/TE, 753/23, 18° flip-angle). Sagittal and transverse plane T1-weighted turbo-spin echo (T1W TSE) (TR/TE, 450/15)images were acquired before and after IV injection withgadolinium contrast (0.1 mmol/kg gadobutrol, Bayer plc,Strawberry Hill, UK). MRI examination demonstrated alarge (20 mm 9 21 mm 9 18 mm), well-demarcated,irregularly margined, left-sided, extra-axial mass, arisingwith a broad base from the left occipital bone, compress-ing the left occipital lobe and left cerebellar hemisphere(Fig. 1A and B). The mass was hypointense on T2-weighted, T1-weighted, FLAIR, and T2*-weightedgradient echo sequences compared to surrounding brainparenchyma. Peripheral contrast enhancement was pre-sent, and raised intracranial pressure was suggested by thepresence of a midline shift and foramen magnum hernia-tion. MRI of the cervical spinal cord demonstrated syrin-gomyelia. A subsequent computed tomography (CT;ª 2017 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use anddistribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.1995MX8000 IDT, Philips Medical Systems) study of the tho-rax and abdomen was within normal limits, while CT ofthe head demonstrated the mass to have a similar attenu-ation to bone (Fig. 1C). Although the largest portion ofthe mass was within the cranial vault, an extracranial por-tion was evident, with distortion of the lateral aspect ofthe occipital and parietal bones. Multilobular tumor ofbone, osteosarcoma, and chondroma was considered themost likely differential diagnoses at this time. The dogwas anesthetized the next day with the aforementionedprotocol and positioned in sternal recumbency. A com-bined left-sided rostrotentorial and caudal fossa cran-iotomy were performed, which allowed removal of thewell-defined bony mass en bloc (Fig. 2). The wound wasclosed routinely without performing a cranioplasty. Thedog recovered uneventfully from anesthesia. Intraopera-tive analgesia consisted of an IV constant rate infusion ofremifentanil (0.15–0.4 lg/kg/min), while early postopera-tive analgesia consisted of a combination of paracetamol(10 mg/kg IV q12 h), methadone (0.1–0.2 mg/kg IVq4 h), and dexamethasone (0.2 mg/kg IV q24 h). Thedog demonstrated ambulatory cerebellar ataxia andbilaterally absent menace responses the day after surgery.He gradually improved, was discharged from hospitaliza-tion 5 days after surgery and was, according to the own-ers, neurologically normal 7 days after surgery.Histopathological examination of cruciate sections repre-sentative of the mass and surgical margins revealed a neo-plasm composed of multiple islands and anastomosingtrabeculae of well-differentiated woven bone and occa-sional cartilage surrounded by few polygonal to spindloidcells, separated by thin, irregular fibrovascular septa.There was mild anisocytosis and anisokaryosis, and fivemitoses were observed in 10 high-power fields (Fig. 3).Neoplastic cells extended to the surgical margins. Thesefindings were consistent with a multilobular tumor ofbone (grade II) [1]. Eight days after surgery, the dogdeveloped hypermetria of the left thoracic limb, whichrapidly progressed to nonambulatory ataxia and a right-sided head tilt. Neurological examination revealed non-ambulatory vestibular ataxia, with a right-sided head tiltand a tendency for rolling and falling to the right side, amiotic right pupil, and disconjugate nystagmus, whichchanged directions with changes in position of the head.(A) (B)(C) (D)Figure 1. T2-weighted sagittal (A) and T2-weighted transverse (B) MR images and a CT image (C) of a 2-year and 11-month-old male JackRussell Terrier presented for further evaluation of focal seizures and cervical hyperesthesia. Transverse T2-weighted MR image at the time ofrecurrence of clinical signs (D). (A and B) A large, extra-axial, left-sided, hypointense mass associated with the skull (arrow) causes compression ofthe occipital lobe and left cerebellar hemisphere. (C) The mass is isodense to bone and contains stippled mineralized densities (arrow). (D) Apoorly demarcated hypointense mass lesion is visible at the same site of previous tumor resection (arrow). The mass is surrounded by a largeamount of perilesional edema, which is possibly caused by the previous surgery.1996 ª 2017 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.Rapid recurrence of an MLO postcraniotomy S. Cook et al.These findings were suggestive for a central vestibularsyndrome. General anesthesia was induced and main-tained with the aforementioned protocol. Repeat MRIexamination of the head revealed a large, poorly demar-cated, extra-axial mass lesion at the site of the previoussurgery. The lesion had a heterogeneous, predominantlyhypointense intensity on all sequences compared to sur-rounding brain parenchyma (Fig. 1D). No IV contrastmedium was administered during this study. Hematomaformation at the site of surgery and/or tumor regrowthwas considered the most likely causes for this postopera-tive neurological deterioration. The next day, the dog wasanesthetized again as described above and underwent sur-gical exploration of the previous surgery site. Surgeryrevealed a large firm mass lesion at the same site of previ-ous tumor resection (Fig. 2C), suggesting tumorregrowth. At this time, the owners of the dog electedeuthanasia during surgery. Postmortem examinationrevealed a roughly spherical, 20 9 15 9 15 mm bonymass that compressed the left occipital lobe and left cere-bellar hemisphere (Fig. 2D). Gross postmortem examina-tion of the thoracic cavity, abdominal cavity,appendicular, and axial skeleton did not reveal any evi-dence of tumor metastasis. Histopathological examinationof the mass revealed disorganized sheets of polygonal tospindloid cells, with occasional fibrous septa and bloodvessels. There were disorganized islands and trabeculae ofosteoid, woven bone, chondroid matrix and cartilage, andextensive necrosis. Anisocytosis and anisokaryosis weremarked, and 12 mitoses were counted per 10 high-powerfields (Fig. 3). The underlying compressed cerebellum waspartially malacic (necrotic). These findings were consis-tent with a multilobular tumor of bone with osteosarco-matous differentiation (grade III) [1].DiscussionMultilobular tumors of bone (MTBs) (synonyms; multi-lobular osteochondrosarcoma, chondroma rodens, carti-lage analogue of fibromatosis, calcifying aponeuroticfibroma, juvenile aponeurotic fibroma and multilobularchondroma or osteoma) are uncommon, but not rare,neoplasms in dogs, which most often affect the flat bonesof the skull [2]. Multiple additional sites including theaxilla, hard palate, os penis, ribs and pelvis have also beenreported [2–8]. Although the most common clinical pre-sentation is that of a solid and firm mass of the skull,neurological signs can result if compression of the brainoccurs. The nature of neurological signs is then reflectedby the specific location of the neoplasm. MTB is typically(A) (B)(C) (D)Figure 2. Intraoperative pictures of initial tumor removal (A and B), second surgery after recurrence of clinical sigs (C) and post mortemevaluation (D). (A) A mass associated with the skull is clearly visible (arrow). Rostral to the left and occipital protuberance indicated by OP. (B)Tumor removed en bloc after craniotomy. Rostral to the left. Forebrain (FB), tentorium cerebelli (TC), and cerebellum (C) indicated. (C) Secondsurgery 11 days after the first surgery indicates tumor regrowth (arrow) at the same site as the previous surgery. Rostral is to the left. (D) Largeextra-axial mass visible at the same site as previous tumor removal.ª 2017 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd. 1997S. Cook et al. Rapid recurrence of an MLO postcraniotomya slow-growing and locally invasive neoplasm with mod-erate potential for metastasis [2]. The relatively slowgrowth rate of this tumor allows it to grow to a relativelylarge size prior to causing clinical signs [2].Multilobular tumors of bone are locally invasive, andrecurrence after surgical resection is therefore common.Recurrence occurs typically only after a prolonged periodof time and affected dogs therefore have a long disease-free interval and long survival times after surgery [1, 2].In dogs undergoing surgical excision, with or withoutadjunctive radio- and/or chemotherapy, median time torecurrence was 14 months, while the median survivaltime was 22 months [1]. Even longer survival times werereported in another study, indicating median survivaltimes and times to recurrence of 797 days after surgery[2]. In dogs receiving chemotherapy alone a median sur-vival of 144 days is reported [9]. Surgery thereforeremains the treatment of choice and predictably, time tolocal recurrence has been reported to be shorter in dogswith a higher tumor grade (grade I to III, in which gradeIII represents the most malignant grade) and incompletesurgical margins (disease-free interval 330 days vs.1332 days with complete surgical margins) [2]. Despitethe presence of incomplete surgical margins in the dogdescribed in this report, local recurrence in 8 days wasstill considered an unusually short disease-free interval.Histopathological examination of both the originallyexcised tumor and the recurrent tumor revealed substan-tial morphological differences. The tissue obtained duringthe first surgery demonstrated relatively benign character-istics including a well-organized lobular or trabecularstructure, low cellularity and mild cellular pleomorphism,typical of MTB. The tumor regrowth, on the other hand,displayed a markedly disorganized structure, high cellular-ity, extensive necrosis, marked cellular pleomorphism,and a higher mitotic count. These histopathological find-ings were considered consistent with osteosarcomatoustransformation [10].Although MTB with more malignant characteristics hasoccasionally been reported, the authors of this report areunaware of previous cases that experienced such rapidtumor regrowth [1, 2, 7]. Little information is thereforeavailable on the frequency and risk factors for malignanttransformation of MTB in dogs. It is possible that the com-bination of pre-existing hypoxia within malignant tissue,tumor-derived immunosuppression, a local inflammatoryenvironment, and borderline immunosuppressive doses ofdexamethasone postprocedurally, all created an environmentconducive for malignant transformation [11–13]. Althoughthe tumor was resected en bloc, microscopic examinationindicated that tumor-free surgical margins had not beenachieved. It can therefore also not be excluded that the most(A) (B)(C) (D)Figure 3. H&E stained sections of a multilobular tumor of bone removed during the first surgery (A and B) and during postmortem examinationafter tumor regrowth was observed (C and D). (A) Anastomosing trabeculae of mature bone (B) and occasional cartilage (block arrow) separatedby fine fibrovascular septa (920, bar = 1 mm). (B) Fibrovascular septa (asterisk) and low numbers of neoplastic cells (NC) surrounding the bonytrabeculae (B) (9100, bar = 250 lm). (C) There is loss of trabecular architecture with neoplastic cells arranged in sheets with occasional bloodvessels (arrowhead). Inset – marked cellular and nuclear pleomorphism, prominent nucleoli, and a mitotic figure (line arrow) (9100,bar = 250 lm, inset bar = 10 lm). (D) Neoplastic cells undergo multifocal chondroid (C) and osseous (O) differentiation (9200, bar = 100 lm).1998 ª 2017 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.Rapid recurrence of an MLO postcraniotomy S. Cook et al.peripheral parts of the tumor already demonstrated moremalignant characteristics and that examination of theincompletely resected tumor therefore underestimated itsmalignant potential. It should also be noted that other clini-cal indications of malignancy, including presence of metas-tases, were not observed during the initial diagnosticinvestigations or postmortem examination.p53 index, as assessed by immunohistochemical label-ing, has been reported to show a strong correlation withtypical features of malignancy including histologic gradeand mitotic index [14]. Given the high grade and mitoticindex of the second sample, a high p53 index would beexpected. Although MTBs typically occur in middle toold-aged (median 8 years), medium to large-breed dogs,the dog in this report was less than 3 years old and con-sidered a small-breed dog as is rarely reported [2, 7, 10].The dog in this report also experienced a short durationof observed clinical signs before he was admitted for ini-tial diagnostic investigations. It is, however, unclear if theatypical breed, the young age of the dog, and the shortduration of clinical signs presented here could indeed beassociated with a more malignant character of the diag-nosed MTB. Further studies are therefore necessary toevaluate if signalment and clinical presentation can beused as prognostic indicators for dogs with MTB.This case report indicates that although resection ofMTBs is typically associated with a good prognosis, longdisease-free intervals, and prolonged survival, malignanttransformation of residual tumor should be considered apotential cause for rapid recurrence of clinical signs. Fur-ther studies are necessary to evaluate risk factors fortransformation for this type of neoplasia.AcknowledgmentsNone.Conflicts of InterestNone declared.AuthorshipSC: involved in case management, manuscript construc-tion, submission, and response to reviewers. AC: carriedout histopathology, manuscript drafting, figure prepara-tion, and response to reviewers. RL: performed imaginginterpretation, figure preparation, manuscript drafting,and revision. JF: involved in case management, revisionsurgery, manuscript drafting and revision. DN: involvedin case anesthesia, manuscript drafting, and revision. SP:carried out histopathology, manuscript drafting, figurepreparation, and response to reviewers. SDD: involved inconcept, case management, surgical intervention, manu-script construction and revisions, figure preparation, andresponse to reviewers.References1. Straw, R. C., R. A. LeCouteur, B. E. Powers, andS. J. Withrow. 1989. Multilobular osteochondrosarcoma ofthe canine skull: 16 cases (1978–1988). J. Am. Vet. Med.Assoc. 195:1764–1769.2. Dernell, W. S., R. C. Straw, M. F. Cooper, B. E. Powers,S. M. LaRue, and S. J. Withrow. 1998. Multilobularosteochondrosarcoma in 39 dogs: 1979–1993. J. Am.Anim. Hosp. Assoc. 34:11–18.3. Hay, C. W., R. Roberts, and K. Latimer. 1994.Multilobular tumour of bone at an unusual location in theaxilla of a dog. J. Small Anim. Pract. 35:636.4. Banks, T. A., and R. C. Straw. 2004. Multilobularosteochondrosarcoma of the hard palate in a dog. Aust.Vet. J. 82:409–412.5. Liptak, J. M., and N. Ehrhart. 2005. Bone and jointtumours. Pp. 761–773 in S. J. Ettinger and E. C. Feldman,eds. Textbook of veterinary internal medicine, 6th ed.W.B. Saunders, St. Louis.6. Webb, J. A., J. M. Liptak, S. A. Hewitt, and A. R. Vince.2009. Multilobular osteochondrosarcoma of the os penis ina dog. Can. Vet. J. 50:81–84.7. Diamond, S. S., C. P. Raflo, and M. P. 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Robinson.2003. Clinical and pathological relevance of p53 index incanine osseous tumors. Vet. Pathol. 40:237–248.ª 2017 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd. 1999S. Cook et al. Rapid recurrence of an MLO postcraniotomy

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Rapid postoperative recurrence of a cranial multilobular tumor of bone in a young dog

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