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112 Cards in this Set

  • Front
  • Back
M-component can be seen in various entities including:
- Plasma cell myeloma
- MGUS
- LPL
- CLL
In the US, plasma cell myeloma is the __ common lymphoid malignancy in the Black population and __ in the White population
Black population: most common
White population: second most common
Median age for plasma cell myeloma
68-70
Plasma cell myeloma involves the __
- bone marrow (generalized, multifocal)
- plasmacytoma (intra- and extraosseous)
Sites of involvement by plasma cell myeloma in decending order of frequency
1. vertbrae
2. ribs
3. skull
4. pelvis (usually site for bx)
5. femur
6. clavicle
7. scapula
Major and Minor criteria of diagnosing plasma cell myeloma
Major:
1. marrow plasmacytosis (>30%)
2. plasmacytoma on biopsy
3. M-component
- serum:(IgG >3.5g/dl, IgA >2g/dl)
- urine: >1g Bence-Jones protein/24hr

Minor:
1. marrow plasmacytosis (10-30%)
2. M-component: present but less than above
3. lytic bone lesions
4. hypogammaglobulinemia (<50% normal):
- IgG <600mg/dl
- IgA <100mg/dl
- IgM <50mg/dl

Requires:
1. one major + 1 minor
2. three minors (must include marrow plasmacytosis 10-30% and M-component less than major)
PCM (plasma cell myeloma) is a disease of the ___
elderly (median age 66)

only 2% occur in patients under 40
The clinical consequences of PCM are related ___
1. space occupying, destructive bone lesions
- destroy medullary bone and erodes cortical bone (lytic bone lesions) BONE PAIN worsened by movement (most common presenting symptom)
- pathologic fractures
- hypercalcemia
- vertebral body collapse (common)
- anemia (fatigue)

2. high levels of M-component in serum

3. hypogammaglobulinemia and altered humoral immunity
- increased susceptibilty to bacterial infections
__% of patients with PCM have extramedullary disease. Most often involving__
70%

liver
spleen
lymph nodes

Note: organomegaly is RARE
Plasmacytomas (bone or soft tissue) are seen in __% of PCM cases
5%
In PCM, what is the relative frequency of the following:
anemia -
thrombocytopenia -
leukopenia -
anemia - common
thrombocytopenia - uncommon
leukopenia - uncommon
Anemia in PCM is multifactorial
1. replacement of erythroid elements of the marrow by myeloma
2. renal failure with decreased EPO production
Renal failure in PCM is due to:
Precipitation of monoclonal light chains (BJ proteins) in distal tubules and collecting ducts (MYELOMA KIDNEY)
Renal amyloidosis of the __ type is seen in some patients with PCM
AL type
__% of plasma cell myeloma cases are associated with a monoclonal protein in EITHER the serum or urine

___% with serum monoclonal protein

___% with urine monoclonal light chain

___% the only monoclonal protien detected is light chain detected in the urine

___% are nonsecretory myelomas
99%

80% with serum monoclonal protein

80% with urine monoclonal light chain

25% the only monoclonal protein detected is light chain detected in the urine

1% are nonsecretory myelomas
Prognosis in PCM
generally poor
median survival 3 years, despite ability to produce significant remissions
Serum monoclonal light chains are detected in the serum in __% of PCM patients
15%
Non-secretory myeloma is rare (___%), the tumor ___, but do not __
1%

synthesize Ig, but do not secrete Ig (detect monoclonal cIg)

Absence of M-component
The clinical features of non-secretory myeloma compared to plasma cell myeloma are generally ___
the same EXCEPT for less renal insufficiency!
For a diagnosis of plasma cell myeloma, clinically, the patients must be __
symptomatic and/or show evidence of progressive disease
In patients who meet criteria for PCM, but are asymptomatic, there are two clinical variants ___ and ___
1. Smoldering myeloma
2. Indolent myeloma

Disease may be stable for long periods of time

No treatment until symptomatic or progression
Diagnostic criteria of MGUS
1. M-component present, but less than myeloma levels

2. marrow plasmacytosis <10%

3. No lytic bone lesions

4. No myeloma-related symptoms

Note: these patients do not even meet minimal criteria for PCM (unlike for smoldering myeloma)
Diagnositc criteria for smoldering myeloma
Same as for MGUS but:
1. M-component at myeloma levels (major criteria for PCM)

2. marrow plasmacytosis 10-30% (minor criteria for PCM)

Note: patients meet minimal criteria for PCM, BUT are asymptomatic (NO anemia, NO renal insufficiency, NO hypercalcemia) and have NO lytic bone lesions
Criteria for indolent myeloma
Same as for PCM except:
1. M-component: (intermeidate levels)
- IgG <7g/dl
- IgA <5g/dl
2. Rare lytic bone lesions
- </= 3 lytic lesions
- NO compression fractures
- NO bone pain
3. Normal Hb, serum calcium, and creantinine
4. NO infections
If circulating plasma cells in the peripheral blood number >2 x 10^9/L or >20% of peripheral WBCs then the diagnosis is __
Plasma cell leukemia (PCL)
PCL (peripheral blood involvement by plasma cell myeloma) is rare __% of PCM cases.

It may be ___ or ___ PCL
2%

Primary PCL: at time of diagnosis

Secondary PCL: terminal complication of PCM
Plasma cell leukemia is more frequently associated with __
1. Light chain only myeloma
2. IgE and IgD myeloma

Less commonly with IgG or IgA myeloma
Compared to the clinical presentation of PCM, PCL is characterized by
1. less frequent lytic bone lesions and bone pain
2. more freqent lymphadenopathy and organomegaly

PCL is an aggressive disease with short survival
MGUS denotes the present of a ___ in a person without __, __, ___, or other related disorders
M-component (less than myeloma levels)

PCM, Waldenstroms macroglobulinemia, primary amyloidosis
Prevalence of MGUS is ___% in patients >50 years old and ___% in those over 70
1% in those >50
3% in those >70
Most M-components (paraproteins) of MGUS are Ig__
IgG 75%
IgM 15%
IgA 10%
20 year follow-up: __% of MGUS patients develop PCM, amyloidosis (AL), macroglobulinemia, or other lymphoproliferative disease
25%
For MGUS patients, the median interval from recognition to diagnosis of PCM, AL, or macroglobulinemia is __ years
10 years
MGUS plasma cells in the marrow are morphologically __ and comprise ___% of marrow nucleated cells
normal-appearing (no nucleoli)

<10%

May or may not detect a small monoconal plasma cell population
In bone marrow biopsy, normal or reactive plasma cells usually occur in ___ around __

Conversely, in PCM __
small clusters (5-6 plasma cells) around arterioles

PCM: Mass effect due to larger foci, nodules or sheets of plasma cells
Could a BM core biopsy with >50% plasma cells be benign?
rarely, reactive plasmacytosis can be this marked
On bone marrow aspirate, __% of PCM patients exhibit a plasmablastic morphology that is associated with __
10%

worse prognosis
Flame cells, in PCM, are__
vermilion glycogen-rich IgA containing plasma cells

it is the high sugar content of the IgA the results in the vermilion color

NOT specific for PCM
One of the more characteristic peripheral blood findings in PCM is
rouleaux formation

Note: circulating plasma cells or PCL is often a terminal event
Plasma cells with nucleoli are ___ neoplastic, while multinucleation and cytoplasmic inclusions are __ for neoplasia
most likely neoplastic

not specific for neoplastic plasma cells
Pattern of PCM involvement of the spleen, liver, and lymph nodes
spleen: red pulp process with compression of white pulp

liver: sinusioidal infiltration, especially around portal areas

LN: (common) with diffuse infiltration by sheets of plasma cells
Immunophenotype of plasma cells in PCM
express: CD38+. CD79a+, CD138+

neoplastic plasma cells often express: CD56

cIg+

Negative for:
sIg-
CD19-
CD20-
CD45-
Bence-Jones myeloma is __
light chain only disease (15% cases)
In PCM, molecular diagnositic assays (Southern blot, PCR) typically reveal a ___ monoclonal rearranged Ig band, however in __% of PCM cases there are ___ bands
single monoclonal Ig band

5% of cases - multiple rearranged Ig bands
cyclin D1/bcl-1 gene is located at what locus
11q13
Sometimes in tissue sections, plasmacytoid immunoblasts (DLBCL) may resemble plasmablasts. What IHC can help?
immunoblasts:
CD20+
LCA+

CD19+ (flow)
IgM M-component is __ in PCM
very rare!
Normal plasma cells are CD19?, while neoplastic plasma cells are CD19?
normal - CD19+
neoplastic - CD19-
Poor prognostic markers in PCM include
1. higher degree of marrow replacement by myeloma
2. plasmablastic morphology
3. deletions of 13q14 and 17p13
Estimation of the degree of marrow replacement by plasma cells in marrow core biopsy has prognostic significance: three stages I-III
I: <20%
II:20-50%
III:>50%
Plasmacytoma can be __ or __
1. osseous (solitary plasmacytoma of bone)

2. extraosseous plasmacytoma
Osseous plasmacytoma requires:
1. no other lytic lesion on complete skeletal survey
2. marrow away from the osseous plasmacytoma show NO plasmacytosis
Osseous plasmacytoma are rare (___% of plasma cell neoplasms)
5%
Frequency of M-component in patients with an osseous plasmacytoma
Uncommon!!

If present, it is usually low level and disappears after treatment
Treatment for plasmacytoma is__
typically radiation therapy
Prognosis for solitary osseous plasmacytoma:
At 10 years ___% appear cured, __% develop PCM, and __% have either local recurrence or another solitary plasmacytoma
35% cured
55% develop PCM (MOST)
10% local recurrence or new lesion
Patients with solitary plasmacytoma are generally __ compared to PCM patients
younger (median age 55 versus 68-70 for PCM)
Prognosis of solitary plasmacytoma is __ compared to PCM
better, with median survival of 7-9 years versus 3 years for PCM
Extraosseous plasmacytomas occur most commonly in the __ tract.
80% upper aerodigestive tract (oropharynx, nasopharynx, sinuses, larynx)

other sites: anywhere
For a diagnosis of extraosseous plasmacytoma there has to be __
1. no evidence of PCM in the marrow by histological or radiological examination
2. No anemia, hypercalcemia, or renal insufficiency
Some cases of extraosseous plasmacytoma occuring in the GI tract may actually be __
extranodal MZL with extreme plasmacytic differentiation
Extraosseous plasmacytoma has to be distinguished from a __ process
reactive process (plasma cell granuloma)

- polyclonal light chain expression
Typical treatment for extraosseous plasmactyoma is __
radiation therapy
Prognosis for solitary osseous plasmacytoma versus extraosseous plasmacytoma
osseous:
- 10% recurrence
- 55% develop PCM

extraosseous:
- 25% regional recurrence
- 15% develop PCM
Some cases of plasmacytoma may show cytokeratin positivity as well as some __ postivity
CK+ and EMA+
This plus CD45RB- could lead to incorrect diagnosis of carcinoma
CD56 expression in osseous versus extraosseous plasmacytoma
CD56+ is less common in extraosseous tumors, but 70% of osseous tumors are CD56+
Two monoclonal Ig deposition diseases (MIDDs) are __ and __
1. primary amyloidosis
2. light chain depostion disease (LCDD)
MIDDs are part of the spectrum of plasma cell myeloma, although these plasma cell neoplasms produce Ig that __ without a large ___
1. deposits into tissues leading to organ dysfunction

2. without a large tumor burden (without overt myeloma)
Primary amyloidosis and light chain deposition disease have different protein products
AL:
- MOSTLY lambda light chains
- fibrillary protein
- beta-pleated sheet structure
- binds Congo red with apple green birefringence
- contains amyloid-P component

LCDD:
- MOSTLY kappa light chains (80%)
- nonfibrillary protein
- NO beta-pleated sheet strucutre
- NO Congo red binding
- NO amyloid-P component
Primary amyloidosis develops in __% of PCM patients
15%
In primary amyloidosis, the plasma cell-related amyloid (AL) deposits in the: (list of sites and affects)
- heart: CHF
- liver: hepatomegaly
- kidneys: nephrotic syndrome and/or renal failure
- GI tract: malabsorption
- tongue: macroglossia
- nerves: peripheral neuropathy with loss of sphincter control
- bone
The sites for diagnostic biopsy for suspected amyloidosis include:
1. abdominal subcutaneous fat pad
2. bone marrow
3. rectum
4 major types of amyloidosis are categorized based on the type of ___ protein
fibrillary

1. primary amyloidosis
- Ig-light chain (AL)
amyloidosis (myeloma-
related)
2. secondary (AA) amyloidosis
- inflammation associated
3. familial (FA) amyloidosis
4. beta-2-microglobulin
amyloidosis
- hemodialysis-related
AL amyloid is composed of ___ secreted by __ and subsequently ___,___, and __ by macrophages into the __
1. intact Ig light chains
2. monoclonal plasma cells
3. ingested, processed and discharged by macrophages into the extracellular matrix
PCM with primary amyloidosis have a __ prognosis compared to PCM alone
worse (shorter survival)

about 15% PCM patients develop AL amyloidosis
Amyloid deposition into tissues, such as myocardium, cause ____ (gross appearance)
enlargement and a waxy consistency

WHO p.152
Monoclonal light and heavy chain deposition disease are very __ diseases that are non___ MIDD (type of __). They include:
rare (<70 reported cases!)

nonamyloid monoclonal Ig deposition disease (type of plasma cell neoplasm)

LCDD
HCDD
LHCDD
Light and/or heavy chain deposit disease leads to deposits in many tissues, including:
kidnesy: renal failure, nephrotic syndrome

Heart: CHF

Liver: factor X deficiency and coagulopathy

blood vessels
nerves

Tissues have a strong affinity for these free chains
___% of patients with monoclonal light and/or heavy chain deposition disease have a M-component in the serum
85% (majority)

15% few do not have a detectable M-component (reflects strong tissue binding of the aberrant Ig)
The basic problem leading to MIDD (LCDD, HCDD) is ___
a mutation or deletion involving the Ig gene leading to a structural change that results in premature secretion and tissue deposition
Compared to amyloidosis deposits in tissues, nonamyloid MIDD deposits in visceral tissues are ___ associated with plasma cells in the vicinity in tissue sections
not

WHO p. 153 glomerulsclerosis due to LCDD
In nonamyloid MIDDs, a bone marrow plasmacytosis is found in __%
50-60%
In LCDD, which light chain predominates?
Kappa (contrast with primary amyloidosis, in which lambda predominates)
The histologic hallmark of LCDD is ___
prominent, smooth, ribbon-like peritubular deposits of monoclonal Ig along the outer edge of the basement membrane (kidney)

see WHO p.153
In LCDD, the prognosis is generally __, with a fatal outcome within __
poor

1-2 years
Osteosclerotic myeloma is a plasma cell neoplasm characterized by ___ in the bone marrow biopsy and __ in the lymph nodes
1. plasma cell infiltrate with osteosclerosis (thickened bony trabeculae

2. changes resembling Castleman disease in the lymph node
Osteosclerotic myeloma is often a component of ____, which includes:
POEMS syndrome
1. polyneurotpathy (sensorimotor demyelination)
2. organomegaly (hepatosplenomegaly)
3. Endocrinopathies (DM, gynecomastia, testicular atrophy, impotence)
4. Monoclonal gammopathy
5. Skin changes (hyperpigmentation, hypertrichosis)

Plus, lymphadenopathy
The relationship between osteosclerotic myeloma and typical plasma cell myeloma is ___
unknown
Some reported cases of osteoslcerotic myeloma have been associated with what virus?
HHV8
Osteosclerotic myeloma is or is not associated with a M-component?
usually is! and it is usually low level (IgG or IgA, lambda)
Osteosclerotic myeloma in the bone marrow usually presents as either single or multiple ___ that histologically show
plasmacytoma(s)

osteosclerosis: focally thickened bone trabeculae with a cuff of fibrosis containing entrapped plasma cells

the marrow away from the osteosclerotic lesions usually have <5% mature plasma cells!
The survival for osteosclerotic myeloma is __ compared to typical plasma cell myeloma
better
Heavy chain disease is ___ the same as heavy chain deposition disease. Because __
NOT!!

HCD is not a true plasma cell neoplasm, but a group of lymphomas that represent variants of various typical lymphomas

HCDD is a ture plasma cell neoplasm
The three types of heavy chain disase include:

They represent variants of:
1. Gamma HCD: variant of LPL
2. Alpha HCD: extranodal MZL
3. Mu HCD: variant of CLL
The Ig produced in heavy chain diseases is usually a ___ that is incapable of full __; results in production of ___ sized Ig molecules
1. truncated heavy chain
2. assembly (lack light chain binding sites)
3. variably
The SPEP in the case of heavy chain disease may not show a ___
M-spike

- in this case, the monoclonal protein consists of variably sized molecules

- need IFE to detect and classify the IgH
Gamma heavy chain disease is also known as ____
Franklin disease
Pateints with Franklin disease usually present with ___
Very sick

systemic symptoms (anorexia, weakness, weight loss, FEVER, recurrent bacterial infections)

autoimmune manifestations (AIHA, autoimmune thrombocytopenia)

Splenomegaly, hepatomegaly

involvement of Waldeyer's ring!!

peripheral eosinophilia

circulating plasma cells and lymphs
The clinical presentation of Franklin disease can mimic a ___ process
infectious/inflammatory

-look at the clinical presentation (inlcudes fever, recurrent bacterial infections, peripheral eosinophilia....)

PLUS, the SPEP likely will not show a nice M-spike due the variable sized truncated heavy chain molecules, thus it may look normal or show a smear
Diagnosis of Franklin disease requires:
serum IFE demonstrating monoclonal heavy chain production without associated light chain
Similar to LPL, gamma HCD in the lymph node shows an inflitrate composed of ___
lymphs, plasmcytoid lymphs, plasma cells

IHC: no light chain with IgG heavy chain positivity
Mu heavy chain disease is extremely rare. It resembles ___, although the tumor cells are CD5__
CLL

CD5-
Mu HCD: in the marrow there are the classic ___ admixed with ____
1. plasma cells with vacuolated cytoplasm (WHO p.155)

2. small, round lymphs similar to those seen in CLL
Mu HCD clinically differs from CLL in that___
Mu HCD presents with hepatopslenomegaly and absence of lymphadenopathy
Alpha heavy chain disease is also known as ___ or ___, and is a variant of ___
1. IPSID (immunoproliferative small intestinal disease) OR Mediterranean abdominal lymphoma

2. extranodal MZL of MALT (GI tract)
Alpha HCD (IPSID) occurs in ___ and involves the ___ leading to ___
1. young adults (peaks in 20-30's)

2. GI tract

3. diarrhea and malabsorption
Alpha HCD sometimes begins as process that is potentially ___ with antibiotics, but may eventually lead to a ___
1. reversible

2. high grade lymphoma
IPSID is most common in areas bordering the __
Mediterranean
Alpha HCD (IPSID) involve mainly the ___ and ___
small intestine and mesenteric lymph nodes

usually NOT: bone barrow or other organs
The small bowel lamina propria in IPSID demonstrates
an infiltrate of plasma cells and small lymphocytes

marginal zone B cells may be present with lymphoepithelial lesion formation (LELs)

villous atrophy and separation of the crypts
The plasma cells and marginal zone B cells in IPSID express:
monoclonal IgA without light chain

pan B-cell antigens +

CD5-, CD10-
IPSID, in its early stages may be ___ with ___, but most patients __
reversibly with antibiotics

develop a high grade lymphoma (often a large B cell lymphoma) with a fatal outcome