11/9 - Hematopoetic and Lymphoid System Flashcards
what are plasma cell tumors
- multiple myeloma
- plasmacytoma
what do B-cell proliferations in plasma cell neoplasma contain
neoplastic plasma cells that virtually always secrete monoclonal Ig or Ig fragments which serve as tumor markers and often have pathologic consequences
what is the most common and deadly of plasma cell neoplasms
multiple myeloma
difference between normal plasma and myeloma
normal (polyclonal) - lots of different types of whole antibodies
intact Ig myeloma (monoclonal) - whole Ab and excess light chains and too many of both
what makes up heavy chain of normal antibody
G, A, M, E, D
what makes up light chain of normal antibody
kappa, lambda
M proteins are also called what
Bence Jones
what is the monoconal Ig identified in the blood referred to as
M protieins (in reference to multiple myeloma)
where are M proteins restricted
plasma and extracellular fluid
when and where is bence jones/m proteins excreted
in urine in abscnce of glomerular damage
neoplastic cells synthesize excess what
light chains (kappa or lambda) along with complete Igs
light chains also excreted in urine also called what
bence jones proteins
what is plasma cell neoplasm commonly associated with lytic bone lesions, hypercalcemia,renal failure, and acquired immuneabnormalities
multiple myeloma
what is most dominated disease in multiple myeloma? where else seen
dominated: bone disease:
seen in lymph nodes and extranodal sites
who gets multiple myeloma
Incidence higher in men and people of African
descent
Peak age is 65-70 years
is multiple myeloma homo or heretrogenous
heterogenous
proliferation and survival of myseloma cells are dependent on what
dependent upon several cytokines, most notable IL-6, which is an important growth factor for plasma cells
what produces multiple myeloma
produced by tumor cells themselves and
by resident marrow stromal cells
[High OR low] serum levels of IL-6 in patients with active disease are associated with poor prognosis
HIGH
what cytokine is important in multiple myeloma
IL-6
- Usually present as destructive plasma cell
tumors involving the axial skeleton - Bones most affected are the vertebral
column, ribs, skull pelvis, femur, clavicle,
and scapula
multiple. myeloma
multiple myeloma bone lesions radiographically
Bone lesions appear radiographically as
punched-out defects, usually |-4 cm in
diameter
high levels of what in the blood of multiple myeloma patients
M protein
most characteristic symptom of multiple myeloma
Bone pain, particularly in the lumbar spine, is
the most characteristic presenting feature
symptoms of multiple myeloma
Hypercalcemia (C)
Renal dysfunction (R)
Anemia (A)
Bone pain with lytic lesions punched out lesions”(B)
common cause of death of multiple myeloma patients
Renal insufficiencies and failure are a common cause of death - kidneys become overburdened with the excess circulating light chain proteins of the tumor cells
what do multiple myeloma cells produce
produce abnormal clonal, complete or
incomplete, immunoglobulins which can be
detected in the blood and in the urine
in multiple myeloma, abnormal immunoglobulin, usually a light chain, was
previously referred to as ___
Bence-Jones protein
what suppress normal humoral immunity in multiple myeloma
neoplastic cells
oral manifestations of mulptiple myeloma
- Jaws involved in 30% of cases
- Jawbone pain and paresthesia
- Petechial hemorrhage of oral mucosa
- Bleeding tendency
- Infections
- Patients often on IV bisphosphonates- results in medication related osteonecrosis of bone (MRONJ)
- Prognosis depends on stage of disease
multiple myeloma treatment
what is unifocal, monoclonal, neoplastic proliferation of plasma cells that usually arise within bone?
plasmacytoma
are extramedullary lesions in plasmacytoma COMMON or UNCOMMON
uncommon
who gets plasmacytoma? where?
> . males; average age at diagnosis is 55 years
in spine
symptoms of plasmacytoma? what does it look like in xray
swelling or bone pain
well-defined, unilocular radiolucency
how is plasmacytoma treated
radiation therapy
virtually all patients with plasmacytoma develop ___ by 15 years following their diagnosis
MM (multiple myeloma)
what displays a mixture of properties, which they share with macrophages such as self-maintenance and ontogeny
langerhan cells
what is capable of presenting antigen and actively presenting antigen and actively migrate to the draning lymph nodes, which qualifies them as DCs
langerhans cells
what is an umbrella term designated for variety of prolierative disorders of dendritis cells or macrophages
Histiocytosis
what is a clonal (genetically identical) proliferation of a special type of immature dendritic cell
langerhans cell histiocytosis
LBH lies between when spectrum
malignant and benign spectrum
in LCH, majorit have driver mutations in what genes
cancer associated genes
neoplastic cells in LCH express what
chemokine receptors
normal LC expression vs LCH cells
Normal LCs express CCR6
neoplastic express CCR6 and CCR7
what do LCH neoplastic cells with CCR6 and CCR7 allow
allowing the neoplastic cells to migrate into tissues that express the relevant chemokines- CCL20 in skin and bones and CCL19 and CCL21 in lymphoid organs
what has abundant, often vacuolated cytoplasm and vesicular nuclei containing linear grooves or folds
proliferating LC
characteristic morphology of LCH
Birbeck granules in cytoplasm and kidney bean shaped cells
who gets LCH
- Rare; 1to 2 newborns per million per year
- May occur at any age but is more likely to occur in those <15 years of age
LCH clinical features
what are the LCH prognostic category classifications
- single organ involvement
- multiorgan involvement
what is part of LCH single organ involvement
- unifocal disease
- mutifocal disease
what is part of LCH multiorgan involvement
- no organ dysfunction
- organ dysfunction (low risk and high risk)
low risk - skin, LN, bone and or pit gland
high risk - lung, liver, spleen and or BM
traditional clinical classifications of LCH
- Monostotic or polyostotic eosinophilic granuloma
- Chronic disseminated histiocytosis
(Hand-Schuller-Christian disease) - Acute disseminated histiocytosis (letterer-Siwe disease)
what is LCH that involves solitary or multiple bone lesions without visceral involvement
Monostotic or polyostotic eosinophilic granuloma
what is LCH that involves skin, bone and viscera
Chronic disseminated histiocytosis
(Hand-Schuller-Christian disease)
what is LCH that has Prominent cutaneous, visceral, and bone marrow involvement mainly in infants
Acute disseminated histiocytosis (letterer-Siwe disease)
in LCH, ___ is affected in 10-20% of all cases; dull pain and tenderness often accompany ___ lesions
jaw; jaw
what disease:
Ulcerative or proliferative mucosal lesions;
proliferative gingival mass develops if it breaks
out of bone
LCH oral manifestation
what disease:
Radiographically, lesions often appear as sharply punched-out radiolucencies without a corticated rim
LCH oral manifestation
what disease:
Bone involvement in the mandible is seen in the posterior areas; scooped out appearance is evident causing the teeth to appear as if they are floating in air
LCH oral manigestation
LCH tx
- Accessible bone lesions, such as those in the maxilla and mandible are treated by curettage
- Low dose of irradiation may be used for less accessible lesions
- Multiple chemotherapeutic agents are given in high-risk situations
what are tests for evaluating hemostasis
- prothrombin time (PT)
- partial thromboplastin time (PTT)
- test for platelet count
- test or platelet function
what does prothrombin time test
this test assesses the extrinsic
and common coagulation pathways
(PT = Play Tennis OUTSIDE)
prolonged PT can result from deficiency or dysfunction of what?
V, VII, X, prothrombin and fibrinogen
what does partial thromboplastin time test
this test assesses the intrinsic and common pathway
(PTT = Play Table Tennis INSIDE)
prolonged PTT can be due to deficiencies or dysfunction of what
V, VIII, IX, X, XI, XII, prothrombin or fibrinogen
what is reference range for testing platelet count to evaluate for hemostasis
Reference range is 150 x to 350 X 10^3/ μL
how to test for platelet function to evaluate for hemostasis
- At present no single test provides an adequate assessment of the complex function of platelets
- In clinical setting platelet aggregation measures the ability of platelets to adhere to one another in response to thrombin
what can excessive bleeding result from
- Increased fragility of vessels
- Platelet deficiency or dysfunction
- Derangement of coagulation
abnormal hemorrhage is due to what
- increase fragility of blood vessels
- inadequate hemostatic response due to either platelet deficiency or dysfunction
- derangement in clotting mechanism
what are clinical conditions in which vessel wall abnormalities cause bleeding disorders
Hereditary hemorrhagic telangiectasia
Perivascular amyloidosis
Drug reactions
Infections
Ehlers Danlos syndrome
Scurvy
(Harry Potter DIES)
what is bleeding related to reduced platelet number called
thrombocytopenia
reduction in platelet number constitutes an important cause of what
generalized bleeding
how many counts of platelets constitute THROMBOCYTOPENIA
Count <150,000 platelets /µL constitutes
thrombocytopenia
how many counts of platelets can aggravate POSTTRAUMATIC BLEEDING
Counts in range of 20,000 to 50,000
platelets/ µL can aggravate posttraumatic
bleeding
how many counts of platelets is associated with SPONTANEOUS BLEEDING
Count <20,000 platelets/ µL may be
associated with spontaneous bleeding
causes of thrombocytopenia
- decreased platelet production
- decreased platelet survivala
- sequestration
- dilution
what cause decreased platelet production
- Drug induced: alcohol, thiazides, cytotoxic drugs
- Infections: measles, HIV
- Nutritional deficiencies: B 1 2, folate,
- Leukemia, disseminated cancer, granulomatous diseases
what causes decreased platelet survival
- Immunologic destruction
- nonimune destruction
what diseases cause immunologic destruction that decrease platelet survival
- Chronic immune thrombocytopenic purpura
- acute immune thrombocytopenic purpura
what causes nonimmune destruction that decreases platelet survival
disseminated intravascular coagulation
what is characteristic in thrombocytopenia
small vessel bleeding
what does thrombocytopenia produce
petechia, purpura, and ecchymosis
