Test 4: lab 2 bones and blood Flashcards
Hindlimb and section of ribs from a 1-year-old monkey.
Description:
The tibia and fibula are twisted and have a bowed contour. Several ribs have nodular swellings in the mid-shaft region (blue arrow) (i.e., rib fractures with fracture callus) as well as enlarged, bulbous physes (black arrow) resulting in prominent costochondral junctions.
Name the disease:
Possible causes:
Rickets
In mammals, rickets is most often caused by dietary deficiencies in vitamin D or phosphorus. Insufficient UV light exposure (i.e., during the winter months) can also lead to deficiency in active vitamin D. Other potential causes of rickets include heredita ry errors in vitamin D formation/metabolism, paraneoplastic syndromes affecting phosphorous levels, or malabsorption in the gut (e.g., not enough vitamin D is absorbed, presence of minerals that inhibit PO4 absorption).
What phase of bone remodeling is abnormal in rickets?
Mineral deposition (mineralization of osteoid and/or cartilagenous templates of the growth plates) is deficient in rickets (disease of young growing animals) and osteomalacia (disease of adults). In both juveniles and adults, large seams of unmineralized osteoid are deposited, but osteoclasts can’t resorb unmineralized osteoid and thus can’t remodel “old” bone. Bone eventually fails, resulting in pathologic fractures of trabecular bone (microfractures or infractions, “compression fractures”) and eventually of compact co rtical bone.
In rickets, failure of mineralization of growth plate cartilage leads to growth plate deformities (expanded zone of hypertrophy) and decreased primary bone trabeculae at the ossification front. Physes are enlarged and “flared” because OCLs can’t resorb newly formed trabeculae to taper the metaphyses to the diaphysis in these “cut back” zones. Eventually, bone cortices are affected to the point where they become bowed/deformed because the unmineralized bone is “soft” not brittle.
Tissue from an 18-year-old cat with severe azotemia, anemia, and hyperphosphatemia. The mandible is pliable.
Name the disease:
Pathogenesis:
Fibrous osteodystrophy (specifically, renal fibrous osteodystrophy due to secondary hyperparathyroidism)
Kidney disease with loss of functional nephrons → decreased GFR → decreased phosphorous excretion → hyperphosphatemia → CaPO4 crystallization, precipitation & deposition (uremic mineralization!) → decreased serum ionized calcium → increased PTH secretion → increased osteoclast activation, decreased osteoblast activation, increased fibroblast differentiation → excessive bone resorption with fibrous replacement (rubber jaw!)
Also, remember that:
Kidney failure → reduced Vitamin D activation → decreased calcium!
If this were a young cat, what other metabolic bone disease might occur concurrently with Fibrous osteodystrophy ?
Rickets (due to inadequate generation of active Vitamin D3)
Fibrous osteodystrophy= rubber jaw
renal fibrous osteodystrophy due to secondary hyperparathyroidism
What other lesions might you see in this cat with rickets and Fibrous osteodystrophy (see urinary lectures)?
Small, irregular/shrunken, firm kidneys (chronic kidney disease), bilaterally enlarged parathyroid glands (bilateral parathyroid gland hyperplasia), and uremic mineralization (predilection sites: sublingual tissue, parietal pleura, gastric mucosa, and the left atrium (in dogs).
Femoral head from a 6-year-old German shepherd dog with progressive lameness of both hindlimbs, reduced range of motion and pain on manipulation of both coxofemoral joints. The canine glenohumeral joint is from a different dog but shows similar lesions.
Describe the lesions
Morphologic diagnosis
Describe the lesions: The femoral head is flattened. The articular cartilages are diffusely thinned (eroded) to focally ulcerated with excavations into the subchondral bone. In some ulcerated areas, the subchondral bone has a “polished” appearance (eburnation from bone-on-bone contact). The synovial membrane is discolored tan-to-brown and is markedly thickened with villous projections. The joint capsule is thickened by firm white-tan tissue as well as several palpable 0.5-1.0 cm diameter bony nodules (osteophytes).
Morphologic diagnosis: Glenohumeral and femoral head: Severe chronic degenerative joint disease (or degenerative osteoarthritis) with cartilage ulcers and subchondral eburnation, villous synovial hypertrophy, joint capsule fibrosis, and periarticular osteophytosis.
N.B. from Dr. Engiles - “Don’t worry - I would never make you come up with a morph like this for the exam. Just be able to recognize and anticipate these changes in a severely degenerated joint”
Why is the synovial membrane brown?
Hemarthrosis. Intra-articular hemorrhage is broken down into hemosiderin (brown) pigment by macrophages. Joint fluid should be pale yellow but if there has been hemorrhage from the synovial membrane and/or exposed subchondral bone (ie deep cartilage ulcers) synovial fluid can be red-orange to brown-tinged. In chronic DJD, joint fluid has reduced viscosity due to reduced hyaluronic acid and other proteoglycans
Likely etiology for the femoral head lesions in this German shepherd dog
Congenital canine hip dysplasia → excessive joint laxity.
Tissue from a 14-year-old Standardbred mare that was euthanized for severe, progressive right hind lameness.
Describe the lesions in the stifle joint:
Morphologic diagnosis:
The caudomedial rim of the medial meniscus has a near-complete tear. The fibrocartilage along the margins of the tear is dull yellow and frayed. Two irregular oval ulcers (~3 cm x 2 cm) are centered on the medial femoral condyle and medial tibial plateau. Nodular osteophytes extend along the medial tibial plateau and intercondylar eminence. There is fibrous thickening of the joint capsule and synovial hypertrophy.
Medial meniscal tear with severe chronic degenerative joint disease (or degenerative osteoarthritis).
The medial meniscal tear resulted in severe instability that initiated the degenerative process in the other tissue components of the joint.
Bones from the elbow of a senior-aged goat that had difficulty ambulating and rising to stand. Note how these bones do not come apart, and the joint is effectively fused due to severe bridging osteophytosis (worse on the lateral side than medial side). Provide the term for “self fusion” of an end-stage degenerative joint:
Ankylosis
Provide the term for surgical fusion of a join
Arthrodesis
The MC3 (third metacarpal bone) of a 3-year-old Thoroughbred racehorse that sustained an incomplete, simple lateral condylar fracture that was repaired by surgical fixation using cortical bone screws placed in lag fashion, which resulted in good compression o f the fracture fragment.
Which stage of healing (early or late) is this fracture in? How did you make that judgement?
This fracture is in the early stages of healing. Although the fracture fragment is in close anatomic apposition to the parent bone, there still remains a narrow gap that was likely spanned by granulation tissue (or possibly unmineralized osteoid) without adequate time to form a mineralized bony callus before the horse was euthanized (in this case, for aspiration pneumonia - an unfortunate complication of general anesthesia during the fracture repair surgery).
The benefit of internal fixation is that by placing the fracture fragment in close apposition to the parent bone, it minimize s the size of the bony callus needed to stabilize and heal the fracture and thus markedly reduces healing time compared to conservative managem ent. If the fragments are immediately apposed, direct bone healing can occur (fracture healing without a bony callus) minimizing the time to heal.
Contrast the MC3 fracture to that of the beef cow that sustained a complete, severely displaced oblique diaphyseal humeral fr acture. Note the size of this fracture fragment, the size of the callus and the distortion of the diaphysis and distal metaphysis/epiphysis.
This bovine humerus represents the extreme version of a common complication of fracture healing - which one?
This is a wonderful example of a bony malunion. Although there is abundant bony callus stabilizing the fracture fragment, the severe distal and oblique displacement of the diaphysis has resulted in severe shortening and distortion of the bone. Given the oste ophytes surrounding the distal epiphysis of the humerus, this fracture likely created aberrant biomechanical forces on this joint tha t led to secondary DJD.
The amount and smooth quality of the bone that formed the callus is not compatible with osteomyelitis, which would be much mo re porous (like “Swiss cheese” quality of bone seen we saw with ‘bovine lumpy jaw’ from the alimentary lectures).
These are the antebrachia (radius and ulna) from the left and right forelimbs of a 4-month-old gilt (female juvenile pig) that was euthanized for severe bilateral fore- and hindlimb lameness of 2-weeks duration. Autopsy reveals these lesions as well as severe fibrinosuppurative arthritis of the left and right hind tarsocrural joints with an opaque, yellow-pink exudate (see associated image).
The farmer reports this gilt had Salmonella enterocolitis at 3 months of age but had recovered. At this point, the viscera are within normal limits.
Describe the lesions you see in the distal ulnar metaphyseal physes (hint: you can compare the ulnar growth plates to the growth plates of the distal radii):
Morphologic diagnoses:
Expanding and effacing both distal ulnar physes are friable pink-tan exudates. The exudates extend into the metaphyses and form an irregularly scalloped margin where they partially efface and abut medullary trabecular bone (bone lysis).
Severe bilateral chronic septic physitis
These are the antebrachia (radius and ulna) from the left and right forelimbs of a 4-month-old gilt (female juvenile pig) that was euthanized for severe bilateral fore- and hindlimb lameness of 2-weeks duration. Autopsy reveals these lesions as well as severe fibrinosuppurative arthritis of the left and right hind tarsocrural joints with an opaque, yellow-pink exudate (see associated image).
The farmer reports this gilt had Salmonella enterocolitis at 3 months of age but had recovered. At this point, the viscera are within normal limits.
Given the history and autopsy findings what is the likely etiopathogenesis of the lesions in the hock and these growth plates?
Salmonella enterocolitis → intestinal vascular invasion with bacteremia → hematogenous dissemination → bacterial seeding of the joints and capillaries at the ossification front of the growth plates → fibrinosuppurative polyarthritis and physitis
Given these lesions in the gilt, what other anatomic locations of the bones are commonly involved in this process?
What is a predisposing cause of neonatal sepsis?
Epiphyses. In addition to septic arthritis (polyarthritis) and metaphyseal physitis, septic epiphysitis is another common manifestation of hematogenous spread of bacteria in young, fast-growing animals.
Failure of passive transfer (inadequate amounts of colostrum or ingestion of poor-quality colostrum → inadequate transfer of material antibodies). Common routes of entry include the umbilicus and the gastrointestinal and respiratory tracts.
These gross specimens represent the same disease process in two different dogs. Both bones are examined in cross-section and are regionally effaced by an expansile, multilobulated, firm to hard mass that partially fills the medullary cavity and extends into the
surrounding tissue. The mass does not extend through the articular cartilage into the joint space.
Diagnosis:
Osteosarcoma
What are the critical diagnostic features of Osteosarcoma ?
What is the biologic behavior of these neoplasms?
The three main critical diagnostic features of this neoplasm are osteolysis (lytic foci), osteoproliferation, and production of tumor osteoid by neoplastic osteoblasts.
Malignant and highly aggressive with rapid metastasis to lungs and other organs or bones. Metastases are often present at the time of diagnosis, and surgical excision alone is seldom curative.
Bone marrow myeloid hyperplasia, high M:E, and left shift
Anemia with erythroid hyperplasia
Anemia with erythroid hypoplasia
Bone marrow plasma cells greater than 30%, Bence-Jones proteins in urine
Bone marrow myeloid hyperplasia, high M:E, and left shift - b
Anemia with erythroid hyperplasia - a
Anemia with erythroid hypoplasia - c
Bone marrow plasma cells greater than 30%, Bence-Jones proteins in urine - d multiple myeloma??
Explain your decisions:
Bone marrow myeloid hyperplasia, high M:E, and left shift
This is consistent with an increased demand for inflammatory cells, with high demand for neutrophils resulting in release of immature stages (left shift). This can be seen in an acute bacterial infection, matching the acute suppurative bronchopneumonia.
explain why
Anemia with erythroid hyperplasia
This is a regenerative response in response to blood loss, such as a hemoabdomen. With hemorrhage, you can also expect to see megakaryocyte hyperplasia and a decreased M:E ratio.
Anemia with erythroid hypoplasia
This is a non-regenerative response to blood loss, consistent with anemia of chronic disease. In addition to the chronic inflammation, chronic renal disease can also lead to decreased erythropoietin, further exacerbating the decrease in red blood cell production.
Bone marrow plasma cells greater than 30%, Bence-Jones proteins in urine
Multiple myeloma (a malignant neoplasm of plasma cells) can present with lytic lesions in multiple bones. Bence-Jones protein is comprised of parts of immunoglobulins (particularly, the light chain) that are produced by the neoplastic plasma cells.
Prescapular lymph nodes from a 9-year-old golden retriever dog.
Description of the affected lymph node:
The lymph node is severely enlarged and effaced by pale tan tissue that bulges on cut-section
Prescapular lymph nodes from a 9-year-old golden retriever dog.
What is the form of lymphoma that presents with generalized lymph node enlargement?
What are some diagnostic tests that help with subtyping a lymphoma and/or with differentiating lymphoma from lymphocytic inflammation?
Multicentric lymphoma
Histopathology, immunohistochemistry (IHC), and PCR for Antigen Receptor Rearrangements (PARR). Note that PARR is used for genotyping lymphoma, not immunophenotyping!
Kidney from a 12-year-old mixed breed dog. This dog had numerous greatly enlarged lymph nodes and splenomegaly. Also, the nodules seen here are present in multiple organs.
Description:
The renal cortex as well as the adjacent soft tissue contains multiple large and occasionally coalescing, soft, round, pale tan to white nodules.
Tissues from an 8-year-old dog that presented in severe respiratory distress.
Description of the cranial mediastinum:
The mass expanding the cranial mediastinum is multilobulated, pale tan to gray, and soft with several small cystic foci and areas of hemorrhage.
Tissues from an 8-year-old dog that presented in severe respiratory distress.
Top two potential diagnoses for a neoplasm at this location:
What could cause respiratory distress in this patient? Consider conditions associated with your differential diagnoses.
Lymphoma or thymoma
**Myasthenia gravis **(a paraneoplastic syndrome associated with thymoma) may cause megaesophagus with secondary aspiration pneumonia. The large mass could deviate/compress the trachea or compress the lungs and cause severe atelectasis as well.
Spleen from a dog. Description:
There is an approximately 3 cm diameter, smooth, soft, red-brown, raised nodule on the spleen. An approximately 4 cm X 3 cm area of the splenic capsule is regionally thickened and pale tan (capsular fibrosis; this is a non-specific and clinically insignificant finding).
Differential diagnosis for this type of nodule includes:
What is the clinical significance for each of your potential diagnoses?
Hemangiosarcoma, nodular lymphoid hyperplasia, hematoma
Hemangiosarcoma is a malignant and aggressively metastatic neoplasm. Lymphoid hyperplasia and hematoma are generally not associated with clinical signs and are benign findings. Hemorrhage into the lymphoid nodule to form a hematoma can make this benign lesion difficult to distinguish grossly from hemangiosarcoma, a malignant neoplasm. The vast majority of hyperplastic lymphoid nodules in the spleen have no clinical significance but hemorrhage can occur into the hyperplastic nodule and if severe can occasionally rupture and result in bleeding into the abdomen.
Based on gross appearance alone, can you confidently diagnose the nodule without further tests?
No! The only way to diagnose a particular nodule is through histopathological evaluation. Hemorrhage into the lymphoid nodule to form a hematoma can make this benign lesion difficult to distinguish grossly from hemangiosarcoma, a malignant neoplasm.
A single spleen may have several nodules of multiple etiologies (e.g., a single spleen may have nodules of hyperplasia, hematoma, and hemangiosarcoma simultaneously or in any combination).
Spleen from a dog.
Description:
What are general differentials for splenic nodules of a firm consistency?
The spleen is enlarged with dozens of firm, pale tan, 3-7 cm diameter, irregularly round nodules that expand and efface the parenchyma. The nodules do not bleed on cut section.
Nodular hyperplasia, granulomas, abscesses, or neoplasia (primary or metastatic).
This is a histiocytic sarcoma. What is the behavior of this neoplasm, and what are predisposed breeds?
Histiocytic sarcoma is a malignant neoplasm that may spread to multiple organs, including the liver and lungs. Predisposed breeds include Bernese mountain dogs, rottweilers, golden retrievers, and flat-coated retrievers.
There are many types of histiocytes, and histiocytic sarcoma typically arises from interstitial dendritic cells. In the splee n, histiocytic sarcoma may also arise from splenic macrophages. This particular subtype is prone to phagocytose and destroy red blood cells (“hemophagocytic histiocytic sarcoma”), leading to anemia.
Spleen from a dog. The spleen is severely enlarged, soft to firm, irregularly contoured, and did not bleed on cut-section.
Differential diagnoses for primary neoplasia in this spleen
Lymphoma and histiocytic sarcoma are the top differential diagnoses for this spleen. This is a case of lymphoma. Splenic stromal sarcomas can also produce non-bloody splenic lesions, but they present in a more nodular pattern. Hemangiosarcoma would be both nodular and bloody.
Spleen from a dog. The spleen is severely enlarged, soft to firm, irregularly contoured, and did not bleed on cut-section.
What are non-neoplastic differential diagnoses for a diffusely large, “meaty” spleen?
What are possible diagnoses for a diffusely enlarged spleen that bleeds on cut-section?
Chronic infectious disease, chronic hemolytic anemia, diffuse granulomatous diseases, disseminated follicular hyperplasia, storage material (e.g., amyloidosis, or lysosomal storage diseases like Gaucher’s disease), extramedullary hematopoiesis.
Congestion (e.g., torsion, euthanasia with barbiturates), septicemia.
Larynx and soft tissues from a 10-year-old dog.
Description:
The tonsils are bilaterally severely expanded by pale tan, soft to firm tissue. Along the surface of the tongue are numerous tan, 2-4 mm diameter, firm, exophytic, verrucous nodule
Is the lesion in the tonsils more likely to be a primary or metastatic neoplasm? Differential diagnosis if primary?
This is most likely a primary neoplasm since the tonsil lacks afferent lymphatic vessels. Primary neoplasms of the tonsil include lymphoma or squamous cell carcinoma; this case is a lymphoma.
The nodules on the tongue are oral papillomas. It is unusual for an older dog to have so many oral papillomas exist and persist for a long time unless the animal is immunocompromised in some way. What are some factors that lead to acquired immunodeficiency in dogs?
Acquired immunodeficiency can be caused by pregnancy, aging, malnutrition, toxins, or drugs, particularly corticosteroids (which have anti-inflammatory properties and can immunosuppress at high levels) or chemotherapeutic agents (which kill replicating cells, such as immune cell precursors in the bone marrow). A number of viruses can kill immune cells and/or immune cell precursors, leading to immunosuppression.
