Musculoskeletal    tumors  origins, diagnosis and behaviorBrian G Caserto DVM DACVP     bgc7@cornell.edu  S2-116 Schurman ...
Origin of Neoplasia•   Multistep process    •   Accumulation of multiple        mutations leading to        unregulated ce...
Cell Cycle ComponentsG0--> G1G1-->S
Cell Cycle Regulation•   Normal Cell Cycle controls    •   Checkpoints        •   G1/S- Rb and p53        •   Growth facto...
Classic Theory of      Carcinogenesis• Classic initiation promotion sequence of  carcinogenesis
  • Initiation- Permanent ...
Carcinogenesis• Initiator  followed by  promotor  causes  neoplasia
Tumor antigens• Tumor Antigen • Novel protein or other antigens • overexpression of endogenous self antigens • antigens ex...
Bone Cells• Osteoblasts             • Chondrocytes      • Osteoclasts• Osteocytes              • Blood vessels       • mon...
Bone Formation          (modeling)• Endochondral – Cartilage precursor – Cartilage is removed and replaced by osteoid    •...
Embryology•   Speckled =    Endochondral•   White =    Intramembranous•   Blue = Neural crest
Endochondral Ossification               •   Long bones               •    Vertebrae               •   Base of the          ...
Intramembranous         ossification• Direct differentiation of mesechymal cells into  osteoblasts (no cartilage model)    ...
Bone Remodeling•   Bone Metabolic Unit    •   Activation of Osteoblasts-        Osteoclasts    •   Osteoclast resorption o...
Patterns of Radiographic        Bone Pathology•   Geographic    •   Least aggressive    •   Well defined margins    •   Cle...
Bone Response to                   Neoplasia•   Periosteal woven bone    •   Any damage- clinical or subclinical with     ...
Bone and Cartilage producing tumorsOssifying fibroma, Osteochondromatosis,Osteoma, Chondroma, Multilobular tumor of bone,O...
Osteosarcoma
Osteosarcoma
Osteosarcoma
248      Equine OSA              Brief Communications and C                                 Overal                        ...
Genetics of Osteosarcoma•   Rb- Retinoblastomas (hypermethylation), Osteosarcoma•   p53- Osteosarcoma- 30-85%•   CDKN2A/P1...
Diagnosis•   Signalment and history•   Radiographs/CT/MRI can help•   Cytology    •   Osteoid can be detected    •   Alk p...
potential OSA specific               markers•   Tropomyosin Related Kinase A    receptor- Nerve and bone    •   Binds Nerve...
Teleangiectatic Osteosarcoma
TelangiectaticOsteosarcoma
Variants of             Osteosarcoma• Osteoblastic• Chondroblastic                  Poor Prognosis• Telangiectatic• Fibrob...
Grading and Prognosis              •         Tumor Grading                    •      Young dogs had higher grade tumors   ...
Non-medullary OSA• Periosteal- Low grade malignancy, slow growth, may not  be invasive  • can be chondroblastic or fibrobla...
Multilobular Tumor of        Bone•   Slow growing, potentially malignant•   Skulls, dogs, horse, cat (intramembranous bone...
ogical interpretation was the frontal neoplasm, probably an osteosarcoma or                          a mesenchymal sinuses...
Chondrosarcoma
Ferret Chordoma
Multiple Cartilaginous      Exostoses
Osteochondroma•   Osteochondroma/ Multiple Cartilaginous    Exostoses    •   scapula, ribs, vertebrae, pelvis        •   c...
Feline    Osteochondromatosis•   Progressive enlargement (neoplastic)    •   16 months- 8 years old    •   Disfigurement, p...
Vitamin A toxicosis• Cervical  Vertebal  Exostosis
Ossifying fibroma• Intramembranous bones only • Horse, slow progressive,   may cause disfigurement,   may recur • mandible, ...
Dog Ossifying Fibroma204                                    Brief Communications and Case Reports                         ...
Nasal Osteoma Cow
Other Mesenchymal  Tumors of Bonemyxoma, hemangioma/sarcoma, fibrosarcoma,  liposarcoma, giant cell tumor of bone
Hemangiosarcoma
Hemangiosarcoma
Hemangiosarcoma• Breeds • Boxer, German Shepherd, Great   Danes • Medullary and expansive, eventually   lytic
Hemangiosarcoma
Hemangiosarcoma
Liposarcoma
Metastatic Liposarcoma
Giant Cell Tumor of            Bone• Rare in animals• expansile osteolytic• ends of long bones• Resemble osteoclasts  but ...
Benign Tumor-like                      lesions•   Exhuberant fracture callus•   Cysts    •   Solitary bone cysts        • ...
Benign Tumor-Like                 Lesions•   Aneuysmal bone cysts    •   Expansile, lytic, contained by a        thin peri...
Invasive andMetastatic Neoplasms Squamous cell carcinoma, malignant melanoma,    prostatic carcinoma, histiocytic sarcoma,...
Tumors of the Jaw• Squamous cell carcinoma • 77 percent have osteoclastic resorption   (dogs)• Maxillary fibrosarcoma • 68%...
Mandibular SCC
Mandibular SCC
Maxillary Fibrosarcoma
Maxillary Fibrosarcoma
Metastatic Carcinoma• Metastasis of  carcinomas can  cause bone lysis,  sclerosis or  periosteal  proliferation
Prostatic Carcinoma                        No. 5                  OSTEOMALACIA IN SCLEROTIC     BONE METASTASES       *   ...
Neoplasia of the Digits•      Dogs                                           • Cats     •       Squamous cell             ...
Acrometastasis• Mets to distal limbs • Cats- Bronchial carcinoma, mammary   carcinoma • Humans- Mammary, prostate,   pulmo...
Tumors of the    JointSynovial carcoma, histiocytic sarcoma,            myxosarcoma
Synovial Sarcoma• Origin  • Joint capsule  • Tendon Sheaths• Behavior  • Invasive, ostelytic  • Metastatic• Differentiatio...
Hematopoietic   tumorsPlasma cell myeloma, lymphoma
Lymphoma-Subperiosteal
Lymphoma• Occurs most often with Multicentric  lymhoma • Dogs, cats, cattle• Multiple discrete punched out lesions  in mul...
LGL Leukemia• Dog, Rats • Large   Granular   Lymphocytic   Leukemia • Ostelytic
Plasma cell myeloma•   Multicentric, lytic lesions•   Active hematopoietic areas•   Produce Ig or fragments•   Monoclonal ...
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Musculoskeletal tumors

  1. 1. Musculoskeletal tumors origins, diagnosis and behaviorBrian G Caserto DVM DACVP bgc7@cornell.edu S2-116 Schurman Hall
  2. 2. Origin of Neoplasia• Multistep process • Accumulation of multiple mutations leading to unregulated cell proliferation • Tumor progression- Average of 90 mutant genes – in general no single oncogene can fully transform non- immortalized cells in vitro.
  3. 3. Cell Cycle ComponentsG0--> G1G1-->S
  4. 4. Cell Cycle Regulation• Normal Cell Cycle controls • Checkpoints • G1/S- Rb and p53 • Growth factors- upregulate fos, jun, myc - increased levels of cyclin/CDK complexes- Phosphorylate Rb- dissociates from E2F - upregulation of more cyclins/CDK • Cyclins/CDK complexes • DNA damage sensor, repair- DNA damage leads to increased p53 - increased p21 and Cell cycle arrest- GADD45 repairs DNA- p53 degraded by MDM2- if not degraded leads to Apoptosis • Apoptosis • Epigenetics • Histone deacetylation, DNA methylation and microRNA • Hypermethylated in Cancer1 (HIC1)- loss of function by methylation leads to inactivation of p53 in 50-85% of mouse OSA and 17% of pediatric OSA
  5. 5. Classic Theory of Carcinogenesis• Classic initiation promotion sequence of carcinogenesis
 • Initiation- Permanent cell mutation (carcinogen) • Promotors- Non-tumorogenic by themselves, but can induce tumors in initiated cells- non-permanent, multiple acts of proliferation
  6. 6. Carcinogenesis• Initiator followed by promotor causes neoplasia
  7. 7. Tumor antigens• Tumor Antigen • Novel protein or other antigens • overexpression of endogenous self antigens • antigens expressed during development- Oncofetal antigens• Mouse model of OSA • MAGE, SSX, and SART-3 • Possible therapeutic targets • T cell mediated tumor therapy
  8. 8. Bone Cells• Osteoblasts • Chondrocytes • Osteoclasts• Osteocytes • Blood vessels • monocyte/macrophage• Hematopoietic cells • Osteoprogenitor lineage • Stromal fibrous and cells adipose tissue
  9. 9. Bone Formation (modeling)• Endochondral – Cartilage precursor – Cartilage is removed and replaced by osteoid • Long bones • Base of the skull, occipital bone • Ribs, vertebrae, hips
  10. 10. Embryology• Speckled = Endochondral• White = Intramembranous• Blue = Neural crest
  11. 11. Endochondral Ossification • Long bones • Vertebrae • Base of the skull • Pelvis
  12. 12. Intramembranous ossification• Direct differentiation of mesechymal cells into osteoblasts (no cartilage model) • Calvaria • Horizontal ramus of the mandible
  13. 13. Bone Remodeling• Bone Metabolic Unit • Activation of Osteoblasts- Osteoclasts • Osteoclast resorption of bone • Formation of bone Woven Bone to Lamellar in normal remodeling
  14. 14. Patterns of Radiographic Bone Pathology• Geographic • Least aggressive • Well defined margins • Clearly demarcated • Possible sclerotic margins• Motheaten • gradual transition from normal to abnormal bone • more aggressive • malignant tumors and osteomyelitis• Permeative • Aggressive lesions with rapid growth and invasion • Poorly demarcated • Osteosarcoma and osteomyelitis
  15. 15. Bone Response to Neoplasia• Periosteal woven bone • Any damage- clinical or subclinical with produce periosteal reactive bone • Response to instability • Fracture repair• Bone Lysis • Increased osteoclastic activity is common• Sclerosis • Increased osteoblastic activity is common- Sclerosis • from tumor related chemicals • repair of lost bone • Generally no inflammation involved
  16. 16. Bone and Cartilage producing tumorsOssifying fibroma, Osteochondromatosis,Osteoma, Chondroma, Multilobular tumor of bone,Osteosarcoma, Chondrosarcoma
  17. 17. Osteosarcoma
  18. 18. Osteosarcoma
  19. 19. Osteosarcoma
  20. 20. 248 Equine OSA Brief Communications and C Overal expans distort nounce areas o the cas The ce border matrix entiatio with in cytopla osteoid Clin 20 year predile neutere
  21. 21. Genetics of Osteosarcoma• Rb- Retinoblastomas (hypermethylation), Osteosarcoma• p53- Osteosarcoma- 30-85%• CDKN2A/P16 Loss/ and impairment of p14(ARF)• TP 53- adrenocortical tumors, Choroid plexus carcinoma and to a lesser extent OSA• Wnt10b- overexpression leads to increased bone formation and stimulates NFkB and Notch signaling in human OSA• Epigenetics • RASSF1A (ras association domain family 1A) - Tumor suppressor gene involved in Apoptosis- Silenced in human cancer of ovary, kidney, stomach, urinary bladder, thyroid gand, and neuroblastoma • Hypermethylated in Cancer1 (HIC1)- loss of function by methylation leads to inactivation of p53 in 50-85% of mouse OSA and 17% of pediatric OSA• Canine OSA • Beta Catenin- Increased cytoplasmic concentrations in canine OSA- primary or metastatic. No relation to survival time. Different mutation than in Human OSA • P53- Higher cytoplasmic levels in osteosarcoma compared to other sarcomas, and highest in chondroblastic OSA, lowest in telangiectatic • PDGF-beta overexpressed as a result of inflammation- astrocytoma and osteosarcoma
  22. 22. Diagnosis• Signalment and history• Radiographs/CT/MRI can help• Cytology • Osteoid can be detected • Alk phos positive • 100% sensitive • 89% specific• Histopath • biopsies must include periosteum and endosteum • osteosarcoma may resemble granulation tissue, fracture callus, reactive bone • Osteochondroma require proper orientation to differentiate from chondroma/osteoma
  23. 23. potential OSA specific markers• Tropomyosin Related Kinase A receptor- Nerve and bone • Binds Nerve Growth Factor- normal cell differentiation, mitogenesis, and survival (anti-apoptosis)• CXCR4- Metastasis • pediatric and canine OSA participates in metastasis • Metastasis to lungs, bone, lymph nodes • receptor for SDF-1 (CXCL12)- hematopoietic stem cells
  24. 24. Teleangiectatic Osteosarcoma
  25. 25. TelangiectaticOsteosarcoma
  26. 26. Variants of Osteosarcoma• Osteoblastic• Chondroblastic Poor Prognosis• Telangiectatic• Fibroblastic• Etiology • Inherited, Inflammation, ionizing radiation, viruses
  27. 27. Grading and Prognosis • Tumor Grading • Young dogs had higher grade tumors • Osteoblastic more aggressive than fibroblastic • Distal tumors higher grade • Cranial tumors lower grade • Canine survival- Axial > Appendicular >Vet Pathol 39:2, 2002 Grading System for Canine Osteosarcoma 241 Mandibular J Comp Pathol (2007) vol. 136 (1) pp. 65-73 Table 1. Classification for tumor grade determination using a predetermined histologic scores for canine osteosarcoma. Tumor Grade Pleomorphism Mitoses Tumor Matrix Tumor Cells Necrosis I 0–1 ( 25%) 10 1 ( 50%) 1 ( 25%) 0–1 ( 25%) II 2 (25–50%) 10–20 2 (25–50%) 2 (25–50%) 2 (25–50%) III 3–4 ( 50%) 21 3 ( 25%) 3–4 ( 50%) 3–4 ( 50%) Veterinary Pathology Online (2002) vol. 39 (2) pp. 240middle), procurement of a fine-needle aspiration biopsy MNGC; 3 large number of MNGC). The whirl formation – Cats- Appendicular tumors and axial corrected longer survival and scale of 0 to 3 (0(FNAB), plasma alkaline phosphatase (AP) level tumors have was estimated on a slower metastasis than dogs formation; no whirlfor the steroid-induced fraction (normal range, 40–120 U/ 1 minimal whirl formation; 2 moderate whirl formation;liter),38 presence of metastases at time of diagnosis, and type 3 maximal whirl formation). Number of mitoses was cal-
  28. 28. Non-medullary OSA• Periosteal- Low grade malignancy, slow growth, may not be invasive • can be chondroblastic or fibroblastic• Parosteal- rare in animals • Well differentiated but malignant • fibrous, osseous, cartilage • long bones, skull • rare in dogs • better clinical course and long term survival than medullary OSA in humans
  29. 29. Multilobular Tumor of Bone• Slow growing, potentially malignant• Skulls, dogs, horse, cat (intramembranous bones)• Histo • Islands of crude bone or cartilage surrounded by thin rim of poorly differentiated spindle cells • Can compress brain, spinal nerves • Malignant transformation distorts normal architecture- infiltrative growth into adjacent tissues or metastasis to the lungs• Recurrence after removal• Radiographs- nodular to stippled pattern
  30. 30. ogical interpretation was the frontal neoplasm, probably an osteosarcoma or a mesenchymal sinuses and extended caudally to the external occipital protuberance. A stippled mi identified dorsal to and including the calvaria, frontal, parietal, and occipital bones. The mass a MUltilobular Tumor of and left frontal sinuses. Proliferation of new bone was observed involving the frontal, parietal, bones. The mass extended into the cranial vault, compressing the cerebral hemispheres and th Case History There was a slight deviation of the falx cerebri to the left. The mass measured approximately 1 Bone An 11-year-old, spayedin depth, and 9 terrierin length. Enhancement was not appreciated with intravenous administratio female, Staffordshire cm was presented to the University of Georgia Veterinary Teaching Hospital for examination of a mass on the cranium (Fig. 1 A and B). The owners first noticed atrophy of the musculature of this dog!s head in October,(Conray 400). lothalamate 2003 and a noticeable incline of the head had developed by April, 2004. The owners also related that the dog had experienced several episodes of disorientation over the past few months.pearance of a Wright-stained biopsy imprint of a multilobular tumor of bone. A. Two a stellate to spindle appearance. B. Neoplastic cells with a plasmacytoid (upper left) andpearance. C. A multinucleated cell resembling an osteoclast.composed of multilobulated neoplastic tissues consisting of irregular islands of well defined4). The neoplastic islands consisted of osteoblasts and osteoclasts surrounded by spindle cells. nt within irregular lacunae and were occasionally binucleated. Mitotic figures were rare (< 1 ew). The histologic diagnosis was a low-grade multilobular tumor of bone. Figure 1. Frontal and lateral views of a multilobular tumor of bone on the cranium of a dog (the haircoat has been shaved prior to surgery). Physical examination revealed a large mass on the head. On palpation, the cranial mass was very firm, immobile, and non-painful. It measured 25 cm across the dorsum of the head from ear to ear, 15 cm from the base of the ear forward to the frontal bone, and 8.5 cm from the base of the ears to the dorsum of the head. The remainder of the physical examination was within normal limits. 3 Clinical laboratory abnormalities included mild leukocytosis (WBC = 15,600 x 10 /"l; reference interval = 5.1 to 13 x 3 10 /"l), increased alkaline phosphatase activity (ALP = 240 U/L; reference interval = 13 to 122 U/L), and a urine specific gravity of 1.005. Thoracic radiographs were unremarkable. There was no evidence of pulmonary metastases. Computed tomography (CT) of the head was performed to evaluate the extent of the mass (Fig. 2). Transverse images were made from the level of the third maxillary premolar caudally to the second cervical vertebra. The mass was visualized at the level of the frontal sinuses and extended caudally to the external occipital protuberance. A stippled mineral opacity mass was identified dorsal to and including the calvaria, frontal, parietal, and occipital bones. The mass also involved the right and left frontal sinuses. Proliferation of new bone was observed involving the frontal, parietal, and dorsal occipital bones. The mass extended into the cranial vault, compressing the cerebral hemispheres and thalamus bilaterally. There was a slight deviation of the falx cerebri to the left. The mass measured approximately 12.4 cm in width, 7.5 cm in depth, and Histologic section of a multilobular tumor of bone with intravenous administration of 60 ml of sodium Figure 4. 9 cm in length. Enhancement was not appreciated Figure 2. Multilobular tumor of bone involving the skull and
  31. 31. Chondrosarcoma
  32. 32. Ferret Chordoma
  33. 33. Multiple Cartilaginous Exostoses
  34. 34. Osteochondroma• Osteochondroma/ Multiple Cartilaginous Exostoses • scapula, ribs, vertebrae, pelvis • cartilage capped protrusions near regions of endochrondral ossification (metaphysis) • marrow cavities continuous with underlying bone • Dogs, horse • Growth ceases at skeletal maturity • malignant transformation is rare • Polyostotic form (MCE) has poor prognosis- rapid progression and euthanasia
  35. 35. Feline Osteochondromatosis• Progressive enlargement (neoplastic) • 16 months- 8 years old • Disfigurement, pain, encroachment of joints or tendons • Random distribution including intramembranous bones • Rib > Scapula > Vert > Skull > Pelvis > Limbs • Not limited to metaphysis • Underlying cortex remains intact • Presence of viral particles- importance in not understood
  36. 36. Vitamin A toxicosis• Cervical Vertebal Exostosis
  37. 37. Ossifying fibroma• Intramembranous bones only • Horse, slow progressive, may cause disfigurement, may recur • mandible, maxilla, nasal sinuses, face, skull, monostotic, well demarcated, not capped with cartilage • DDX: Fibrous dysplasia (non-neoplastic)
  38. 38. Dog Ossifying Fibroma204 Brief Communications and Case Reports Vet Pathol 45:2, 2008 Fig. 1. Computed tomographic scan; skull; dog. An expansile mass destroys alveolar and cortical bone in thedorsal aspect of the left hemimandible and extends into gingival tissue along the buccal and lingual aspects of thefirst molar tooth. Inset: Cross-section of the left hemimandibulectomy specimen through first molar tooth.
  39. 39. Nasal Osteoma Cow
  40. 40. Other Mesenchymal Tumors of Bonemyxoma, hemangioma/sarcoma, fibrosarcoma, liposarcoma, giant cell tumor of bone
  41. 41. Hemangiosarcoma
  42. 42. Hemangiosarcoma
  43. 43. Hemangiosarcoma• Breeds • Boxer, German Shepherd, Great Danes • Medullary and expansive, eventually lytic
  44. 44. Hemangiosarcoma
  45. 45. Hemangiosarcoma
  46. 46. Liposarcoma
  47. 47. Metastatic Liposarcoma
  48. 48. Giant Cell Tumor of Bone• Rare in animals• expansile osteolytic• ends of long bones• Resemble osteoclasts but IHC suggests histiocytic origin• Mostly benign in humans but locally recur
  49. 49. Benign Tumor-like lesions• Exhuberant fracture callus• Cysts • Solitary bone cysts • Metaphyses of long bones • young dogs and children • Mono/Polyostotic, lytic, expansile • Narrowing of cortex, little bone reaction • Surrounded by shelves of bone • Pathologic fracture is common • cysts filled with clear or sanguinous fluid
  50. 50. Benign Tumor-Like Lesions• Aneuysmal bone cysts • Expansile, lytic, contained by a thin periosteum, internal soap bubble appearance on rads • Tubular bones, spine in humans • May contain solid areas, loose connective tissues• Intra-osseous epidermoid cysts • contain pale cream colored crumbly keratin • Digits skull in humans • rare in dogs, and horse
  51. 51. Invasive andMetastatic Neoplasms Squamous cell carcinoma, malignant melanoma, prostatic carcinoma, histiocytic sarcoma,acanthomatous epulis, subungual melanoma, nailbed keratoacanthoma, bronchial adenocarcinoma
  52. 52. Tumors of the Jaw• Squamous cell carcinoma • 77 percent have osteoclastic resorption (dogs)• Maxillary fibrosarcoma • 68% invasive, may be periosteal in origin• Melanoma • Invasive in 50% of cases
  53. 53. Mandibular SCC
  54. 54. Mandibular SCC
  55. 55. Maxillary Fibrosarcoma
  56. 56. Maxillary Fibrosarcoma
  57. 57. Metastatic Carcinoma• Metastasis of carcinomas can cause bone lysis, sclerosis or periosteal proliferation
  58. 58. Prostatic Carcinoma No. 5 OSTEOMALACIA IN SCLEROTIC BONE METASTASES * Chlarhon CJi a/.• Common in humans and dogs • Sclerotic bone metastasis (humans) • hypocalcemia,wide band of osteoid FIG.2. The tissue (black)embedded in calcified hypophosphatemia, with- bone corresponds to a period out vitamin D therapy. Notice the elevatedmarrow (Goldner stained in bone nests of malignant cells Alk Phos section, undecalcified bone). • Increased production of poorly mineralized osteoid (50% of cases) • Prostatic osteoblastic ing two to six months of treatment with vitamin D and and/or his calcium absorption which is dependen factor produced by 1 patients does provide indirect calcium in four Group a relative vitamin D deficiency. evidence, however, that a relative vitamin D deficiency Other factors may contribute to the bone chan cancer cellsincrease the histologic indications of osteomalacia, may observed in sclerotic bone metastasis from prostatic which is also dependent on the increased bone formation cer such as estrogen therapy. The role of estrogens ei level. The marked reduction in the prostatic cell pop- on vitamin D or bone metabolism cannot be determ ulation noted on biopsies following estrogen therapy in this study since all of the patients except one w could thus also encourage the regression of osteomalacia estrogen treated. Estrogens are known to inhibit the by decreasing the bone formation rate. In this regard, sorption process in vitrd and in vivo" and to decr
  59. 59. Neoplasia of the Digits• Dogs • Cats • Squamous cell carcinoma – Squamous cell carcinoma • more metastatic • median survival 73 days potential – Fibrosarcoma • Melanoma (subungual) – Metastatic adenocarcinoma • poor prognosis and – Osteosarcoma median survival of – Mast cell tumor 365 days – Hemangiosarcoma • Soft tissue sarcoma – Malignant fibrous histiocytoma • Mast cell tumor Vet Pathol (2007) vol. 44 (3) pp. 362-5Vet Pathol (2007) vol. 44 (3) pp. 355-61
  60. 60. Acrometastasis• Mets to distal limbs • Cats- Bronchial carcinoma, mammary carcinoma • Humans- Mammary, prostate, pulmonary carcinoma
  61. 61. Tumors of the JointSynovial carcoma, histiocytic sarcoma, myxosarcoma
  62. 62. Synovial Sarcoma• Origin • Joint capsule • Tendon Sheaths• Behavior • Invasive, ostelytic • Metastatic• Differentiation • Spindyloid to stellate cells • Fibroblastic • Myxomatous
  63. 63. Hematopoietic tumorsPlasma cell myeloma, lymphoma
  64. 64. Lymphoma-Subperiosteal
  65. 65. Lymphoma• Occurs most often with Multicentric lymhoma • Dogs, cats, cattle• Multiple discrete punched out lesions in multiple bones in appendicular and axial skeleton• Rare hypercalcemia
  66. 66. LGL Leukemia• Dog, Rats • Large Granular Lymphocytic Leukemia • Ostelytic
  67. 67. Plasma cell myeloma• Multicentric, lytic lesions• Active hematopoietic areas• Produce Ig or fragments• Monoclonal spikes on serum electrophoresis• Bence jones proteinuria less often• Hyperviscosity syndrome and hypercalcemia occasional and have poor response to therapy• Radiographic lesions in 2/3 dogs and 30% horses
  68. 68. Questions?

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