Lymphoproliferative Disorders Flashcards
What is the difference between lymphoproliferative and myeloproliferative disorders?
LYMPHOPROLIFERATIVE = neoplasms of lymphocytes and plasma cells
MYELOPROLIFERATIVE = neoplasms of bone marrow stem cells, neutrophils, monocytes, erythrocytes, eosinophils, and basophils
What is the difference between lymphoma and lymphocytic leukemia?
LYMPHOMA = neoplasm affecting B or T cells confined to solid tissues
LL = neoplastic process of B or T cells involving bone marrow and/or blood
What is multiple myeloma?
specific B cell neoplastic process affecting plasma cell differentiation
How does the cytological presentation of acute lymphocytic leukemia compare to chronic lymphocytic leukemia?
ACUTE = undifferentiated/immature lymphocytes present, most common in cats infected by FeLV or FIV
CHRONIC = normal appearing and mature lymphocytes present
What lab findings is most important for diagnosing lymphoma ane leukemia? What are 3 differential diagnoses?
lymphocytosis
- excitement response
- neoplastic lymphoproliferative disease (lymphocytic leukemia)
- antigen stimulation in canine ehrlichiosis
What is also expected to see on lab results with lymphocytosis from canine ehrlichiosis?
- large granular lymphocytes
- polyclonal gammopathy
What 2 counts point toward leukemia in dogs?
- > 35000/µL**
- > 15000/µL and tick-borne disease negative
What must acute lymphocytic leukemia be differentiated from? How?
stage V lymphoma (leukemia phase)
ALL has rapid progression in dogs of any age, primarily found in the bone marrow (location tends to be more important than morphology)
Acute lymphocytic leukemia:
- nearly all lymphoid cells are large with prominent nucleoli
- platelets are not seen
- normal leukocytes are rare
- ALL primarily involves bone marrow, which is hypercellular and replaced by lymphoblasts
involvement of bone marrow differentiates it from stage V lymphoma
What are 5 clinical presentations of ALL?
- pale MM
- splenomegaly
- hepatomegaly
- lethargy
- weight loss
What is the most important lab finding with ALL? What 4 other findings are common?
lymphocytosis
- anemia
- thrombocytopenia
- neutropenia
- lymphoblasts in blood
How are lymphoblasts differentiated from lymphocyes?
- morphology: more cytoplasm, nucleoli
- immunophenotyping
- cytochemistry will be negative for most stains, but stain positive for non-specific esterase
What is the prognosis of ALL? How do the types of cells affect this?
poor - rapid, progressive clinical course with poor response to therapy
- CD34+ = extremely poor prognosis with a median survival of 16 days
- CD8+ = slightly better, 131-1068 days
- B cells = slightly better, 129-100 days
What are the 2 major differences between chronic lymphocytic leukemia and ALL?
- lymphocytes are small and appear well differentiated
- more common in dogs
What lab finding is most important for diagnosing chronic lymphocytic leukemia? What 3 differential diagnoses must be considered in cats?
lymphocytosis
- excitement response
- neoplastic lymphoproliferative disease (lymphocytic leukemia)
- antigen stimulation (Bartonella henselae)
What is a common cause of antigen stimulation causing lymphocytosis in dogs? How does it look on cytology?
Ehrlichia canis
large, granular lymphocytes, with a count rarely >10000/µL
What 6 clinical signs are seen in CLL?
- lethargy
- anorexia
- pale MM
- lymphadenopathy
- splenomegaly
- hepatomegaly
- similar to ALL
- tend to be asymptomatic
What lab finding is most commonly seen with CLL? What 4 other findings may be seen? What is commonly seen in cats?
lymphocytosis
- anemia
- thrombocytopenia
- increased small lymphocytes in bone marrow
- monoclonal gammopathy
FeLV negative
CLL:
- arrowheads = small neoplastic lymphocytes
- arrow = large lymphocytes
How are lymphocytes immunophenotyped by flow cytometry?
based on the proteins expressed on their surface
- T-cells = CD3, CD4, CD5, CD8
- B-cells = CD21, CD45, CD11
How is immunophenotyping used for prognosis of lymphoma/leukemia?
- CD34 expression predicts POOR outcome
- CD8 with high lymphocytosis has shorter survival time than with normal/decreased lymphocytes
- CD21 B-cells with large lymphocytes survive LESS time than patients with small cells
What 2 trends are seen with canine prognosis of lymphoma/leukemia?
- old dogs with B-cell leukemia survive longer than young dogs
- dogs with T-cell CLL and no anemia survive longer
What is lymphoma?
systemic, diverse, heterogeneous disease that results from the uncontrolled clonal expansion of malignant lymphocytes in solid tissue
What are some ways to classify lymphoma?
- anatomic distribution in body
- histologic distribution in organ
- cytomorphology
- immunophenotyping by flow cytometry, IHC, and PARR to detect B-cells, T-cells, and aberrant cells
- cell size
- grade by mitotic index
- MHC II expression
- stage at presentation
- molecular characteristics
- biological behavior (indolent, aggressive, response to treatment
What are the most common type of lymphoma?
60% B lymphomas
40% T lymphomas
How is cytology and histopathology used for classifying lymphoma?
CYTOLOGY = diagnosis
HISTOPATH = diagnosis and classification
- most lymphomas are diagnosed by cytology and histopathology is NOT performed
Aspirate from lymph nodes with high-grade B cell lymphoma:
- RED = atypical medium to large lymphoid cells with dispersed chromatin and multiple prominent nucleoli
- BLACK = large lymphoid cells relative to small lymphocytes
- GREEN = mitotic figure
(Diff Quik)
Aspirate from lymph nodes with high-grade B cell lymphoma:
> 85% of cells are morphologically distinct small-sized lymphocytes with round nuclei, loosely clumped chromatin and increased amounts of pale blue cytoplasm extending from one pole of the cell in a hand mirror configuration
What is multiple myeloma? When is survival time decreased?
proliferation of plasma cells at various sites in the bone marrow and eventually other tissues, with a small amount released into peripheral blood
if leukemia is present
What causes the clinical presentations of multiple myeloma? What 4 clinical signs present?
related to the presence of neoplastic plasma cells in the marrow and other tissues
- lethargy
- anorexia
- lameness
- polyuria and polydipsia
(nonspecific)
How does multiple myeloma affect the kidneys?
renal insufficiency caused by proteins interfering with tubular and glomerular function
- commonly secondary to excessive light chain production, hypercalcemia, and mineralization
How does multiple myeloma affect the blood?
blood hyperviscosity related to the immunoglobulins that the tumor cells produce
- leads to fundoscopic changes, retinal hemorrhages, and venous dilatation with tortuous retinal blood vessels —> CNS
How does multiple myeloma affect platelets?
thrombocytopenia caused by platelet defects due to immunoglobulins —> bleeding diathesis with epistaxis, gingival bleeding, intraocular hemorrhage, melena, hematuria
- prolonged prothrombin and partial thromboplastin times
What 3 lab findings are seen in multiple myeloma?
- > 20% plasma cells in bone marrow, usually in aggregates that must be differentiated from chronic antigenic stimulation
- monoclonal or biclonal gammopathy, usually with IgG, IgA,or IgM
- Bence-Jones proteins in urine - monoclonal immunoglobulin light chains
What is this?
Bence-Jones proteins in urine caused by monoclonal immunoglobulin light chain accumulation stained with IHC antiserum to the light chains
- characteristic yarn wound into a bundle formation
What 3 samples are preferred for electrophoresis to diagnose multiple myeloma? What does this test do?
- serum*
- urine
- body fluids
separates proteins (albumin and globulins) to determine if hyperglobinemia or multiple myeloma is suspected
Electrophoretogram patterns in serum:
A = normal
B = increased α-2 globulins and polyclonal gammopathy
- typical, but not specific for FIP and other inflammatory diseases
C = increased gamma region indicating monoclonal gammopathy
What is common to see on radiographs in cases of multiple myeloma?
foci of lytic bone
Multiple myeloma, lytic lesion:
- lateral stifle
- lytic punched out bone lesion in proximal tibia
What are 3 common signs of multiple myeloma in cats? What is extremely commonly seen in cats?
- atypical plasma cell morphology
- anemia
- bone lesions
organ involvement
What 4 findings are used to diagnose multiple myeloma?
- bone marrow plasmacytosis
- osteolytic bone lesions
- monoclonal hyperglobinemia
- Bence-Jones proteinuria
at least 2 must be seen
When is the prognosis of multiple myeloma worse? What 4 things are associated with shorter survival time?
azotemia or severe anemia, neutropenia, or thrombocytopenia
- hypercalcemia
- Bence-Jones proteinuria
- plasma cell leukemia
- extensive bone lesions
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
What does Sydney’s CBC show?
unremarkable - mild non-regenerative anemia, thought to be nonspecific finding secondary to underlying problems
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
What does Syndey’s chemistry profile show?
marked hyperglobulinemia
- if monoclonal, it may be caused by multiple myeloma, lymphoma, lymphatic leukemia, or infectious disease (leishmaniasis, ehrlichiosis)
- if polyclonal, it may be caused by chronic inflammation, infectious disease, neoplasia, or immune-mediated disease
hypercalcemia
- may be malignancy-associated (lymphoma, multiple myeloma, anal sac apocrine gland carcinoma, or bone neoplasia) due to hypoadrenocorticism, hyperparathyroidism, granulomatous disease, hypervitaminosis D, or renal failure
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
What does Sydney’s urinalysis show?
low urine specific gravity with inactive sediment, likely due to hypercalcemia
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
Sydney’s X-rays of the caudal vertebrae were unremarkable. What are possible differential diagoses?
- multiple myeloma (hyperglobinemia, hypercalcemia)
- lymphoma
- disc protrusion or other spinal involvement (proprioceptive ataxia unrelated to clinicopathologic findings)
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
Based on Sydney’s hyperglobulinemia, what should be ordered?
- serum protein electrophoresis
- urine protein electrophoresis
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
What does Sydney’s serum protein electrophoresis results show?
narrow spike-like peak in gamma region indicating monoclonal hyperglobulinmemia
- supports the assumption of neoplastic disease
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
If multiple myeloma is suspected, how can we find the tumor?
obtain bone marrow and X-rays of hind limbs
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
What does Sydney’s radiograph show?
right humerus - extensive bone lysis
CASE: Sydney, 14 y/o FS Lab mix
- PRESENTING: Hind limb ataxia and paralysis of the tail.
- HX: Hind limb ataxia and inability to raise tail for one week. Weight loss and reduced appetite noticed during the last month.
- PE: BAR. 2/9 BCS. Mild ataxia of both hind limbs. Complete loss of tail tonus with normal anal tone. Palpation of caudal lumbar vertebrae was painful. Proprioception was mildly delayed in both hind limbs and normal in the forelimbs. Spinal reflexes we normal in all 4 legs.
What does the ultrasound of Sydney’s spleen show?
hypoechoic nodules
- likely some type of infiltration and solid abnormal cell growth
What aspect of Sydney’s case supports multiple myeloma diagnosis?
- hypergolbulinemia
- osteolytic lesions in multiple bones
- plasma cell infiltration into spleen and bone marrow
