Hemepath: Plasma Cell Neoplasms

Front 1

M-component can be seen in various entities including:

Back 1

- Plasma cell myeloma
- MGUS
- LPL
- CLL

Front 2

In the US, plasma cell myeloma is the __ common lymphoid malignancy in the Black population and __ in the White population

Back 2

Black population: most common
White population: second most common

Front 3

Median age for plasma cell myeloma

Back 3

68-70

Front 4

Plasma cell myeloma involves the __

Back 4

- bone marrow (generalized, multifocal)
- plasmacytoma (intra- and extraosseous)

Front 5

Sites of involvement by plasma cell myeloma in decending order of frequency

Back 5

1. vertbrae
2. ribs
3. skull
4. pelvis (usually site for bx)
5. femur
6. clavicle
7. scapula

Front 6

Major and Minor criteria of diagnosing plasma cell myeloma

Back 6

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)

Front 7

PCM (plasma cell myeloma) is a disease of the ___

Back 7

elderly (median age 66)

only 2% occur in patients under 40

Front 8

The clinical consequences of PCM are related ___

Back 8

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

Front 9

__% of patients with PCM have extramedullary disease. Most often involving__

Back 9

70%

liver
spleen
lymph nodes

Note: organomegaly is RARE

Front 10

Plasmacytomas (bone or soft tissue) are seen in __% of PCM cases

Back 10

5%

Front 11

In PCM, what is the relative frequency of the following:
anemia -
thrombocytopenia -
leukopenia -

Back 11

anemia - common
thrombocytopenia - uncommon
leukopenia - uncommon

Front 12

Anemia in PCM is multifactorial

Back 12

1. replacement of erythroid elements of the marrow by myeloma
2. renal failure with decreased EPO production

Front 13

Renal failure in PCM is due to:

Back 13

Precipitation of monoclonal light chains (BJ proteins) in distal tubules and collecting ducts (MYELOMA KIDNEY)

Front 14

Renal amyloidosis of the __ type is seen in some patients with PCM

Back 14

AL type

Front 15

__% 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

Back 15

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

Front 16

Prognosis in PCM

Back 16

generally poor
median survival 3 years, despite ability to produce significant remissions

Front 17

Serum monoclonal light chains are detected in the serum in __% of PCM patients

Back 17

15%

Front 18

Non-secretory myeloma is rare (___%), the tumor ___, but do not __

Back 18

1%

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

Absence of M-component

Front 19

The clinical features of non-secretory myeloma compared to plasma cell myeloma are generally ___

Back 19

the same EXCEPT for less renal insufficiency!

Front 20

For a diagnosis of plasma cell myeloma, clinically, the patients must be __

Back 20

symptomatic and/or show evidence of progressive disease

Front 21

In patients who meet criteria for PCM, but are asymptomatic, there are two clinical variants ___ and ___

Back 21

1. Smoldering myeloma
2. Indolent myeloma

Disease may be stable for long periods of time

No treatment until symptomatic or progression

Front 22

Diagnostic criteria of MGUS

Back 22

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)

Front 23

Diagnositc criteria for smoldering myeloma

Back 23

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

Front 24

Criteria for indolent myeloma

Back 24

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

Front 25

If circulating plasma cells in the peripheral blood number >2 x 10^9/L or >20% of peripheral WBCs then the diagnosis is __

Back 25

Plasma cell leukemia (PCL)

Front 26

PCL (peripheral blood involvement by plasma cell myeloma) is rare __% of PCM cases.

It may be ___ or ___ PCL

Back 26

2%

Primary PCL: at time of diagnosis

Secondary PCL: terminal complication of PCM

Front 27

Plasma cell leukemia is more frequently associated with __

Back 27

1. Light chain only myeloma
2. IgE and IgD myeloma

Less commonly with IgG or IgA myeloma

Front 28

Compared to the clinical presentation of PCM, PCL is characterized by

Back 28

1. less frequent lytic bone lesions and bone pain
2. more freqent lymphadenopathy and organomegaly

PCL is an aggressive disease with short survival

Front 29

MGUS denotes the present of a ___ in a person without __, __, ___, or other related disorders

Back 29

M-component (less than myeloma levels)

PCM, Waldenstroms macroglobulinemia, primary amyloidosis

Front 30

Prevalence of MGUS is ___% in patients >50 years old and ___% in those over 70

Back 30

1% in those >50
3% in those >70

Front 31

Most M-components (paraproteins) of MGUS are Ig__

Back 31

IgG 75%
IgM 15%
IgA 10%

Front 32

20 year follow-up: __% of MGUS patients develop PCM, amyloidosis (AL), macroglobulinemia, or other lymphoproliferative disease

Back 32

25%

Front 33

For MGUS patients, the median interval from recognition to diagnosis of PCM, AL, or macroglobulinemia is __ years

Back 33

10 years

Front 34

MGUS plasma cells in the marrow are morphologically __ and comprise ___% of marrow nucleated cells

Back 34

normal-appearing (no nucleoli)

<10%

May or may not detect a small monoconal plasma cell population

Front 35

In bone marrow biopsy, normal or reactive plasma cells usually occur in ___ around __

Conversely, in PCM __

Back 35

small clusters (5-6 plasma cells) around arterioles

PCM: Mass effect due to larger foci, nodules or sheets of plasma cells

Front 36

Could a BM core biopsy with >50% plasma cells be benign?

Back 36

rarely, reactive plasmacytosis can be this marked

Front 37

On bone marrow aspirate, __% of PCM patients exhibit a plasmablastic morphology that is associated with __

Back 37

10%

worse prognosis

Front 38

Flame cells, in PCM, are__

Back 38

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

Front 39

One of the more characteristic peripheral blood findings in PCM is

Back 39

rouleaux formation

Note: circulating plasma cells or PCL is often a terminal event

Front 40

Plasma cells with nucleoli are ___ neoplastic, while multinucleation and cytoplasmic inclusions are __ for neoplasia

Back 40

most likely neoplastic

not specific for neoplastic plasma cells

Front 41

Pattern of PCM involvement of the spleen, liver, and lymph nodes

Back 41

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

Front 42

Immunophenotype of plasma cells in PCM

Back 42

express: CD38+. CD79a+, CD138+

neoplastic plasma cells often express: CD56

cIg+

Negative for:
sIg-
CD19-
CD20-
CD45-

Front 43

Bence-Jones myeloma is __

Back 43

light chain only disease (15% cases)

Front 44

In PCM, molecular diagnositic assays (Southern blot, PCR) typically reveal a ___ monoclonal rearranged Ig band, however in __% of PCM cases there are ___ bands

Back 44

single monoclonal Ig band

5% of cases - multiple rearranged Ig bands

Front 45

cyclin D1/bcl-1 gene is located at what locus

Back 45

11q13

Front 46

Sometimes in tissue sections, plasmacytoid immunoblasts (DLBCL) may resemble plasmablasts. What IHC can help?

Back 46

immunoblasts:
CD20+
LCA+

CD19+ (flow)

Front 47

IgM M-component is __ in PCM

Back 47

very rare!

Front 48

Normal plasma cells are CD19?, while neoplastic plasma cells are CD19?

Back 48

normal - CD19+
neoplastic - CD19-

Front 49

Poor prognostic markers in PCM include

Back 49

1. higher degree of marrow replacement by myeloma
2. plasmablastic morphology
3. deletions of 13q14 and 17p13

Front 50

Estimation of the degree of marrow replacement by plasma cells in marrow core biopsy has prognostic significance: three stages I-III

Back 50

I: <20%
II:20-50%
III:>50%

Front 51

Plasmacytoma can be __ or __

Back 51

1. osseous (solitary plasmacytoma of bone)

2. extraosseous plasmacytoma

Front 52

Osseous plasmacytoma requires:

Back 52

1. no other lytic lesion on complete skeletal survey
2. marrow away from the osseous plasmacytoma show NO plasmacytosis

Front 53

Osseous plasmacytoma are rare (___% of plasma cell neoplasms)

Back 53

5%

Front 54

Frequency of M-component in patients with an osseous plasmacytoma

Back 54

Uncommon!!

If present, it is usually low level and disappears after treatment

Front 55

Treatment for plasmacytoma is__

Back 55

typically radiation therapy

Front 56

Prognosis for solitary osseous plasmacytoma:
At 10 years ___% appear cured, __% develop PCM, and __% have either local recurrence or another solitary plasmacytoma

Back 56

35% cured
55% develop PCM (MOST)
10% local recurrence or new lesion

Front 57

Patients with solitary plasmacytoma are generally __ compared to PCM patients

Back 57

younger (median age 55 versus 68-70 for PCM)

Front 58

Prognosis of solitary plasmacytoma is __ compared to PCM

Back 58

better, with median survival of 7-9 years versus 3 years for PCM

Front 59

Extraosseous plasmacytomas occur most commonly in the __ tract.

Back 59

80% upper aerodigestive tract (oropharynx, nasopharynx, sinuses, larynx)

other sites: anywhere

Front 60

For a diagnosis of extraosseous plasmacytoma there has to be __

Back 60

1. no evidence of PCM in the marrow by histological or radiological examination
2. No anemia, hypercalcemia, or renal insufficiency

Front 61

Some cases of extraosseous plasmacytoma occuring in the GI tract may actually be __

Back 61

extranodal MZL with extreme plasmacytic differentiation

Front 62

Extraosseous plasmacytoma has to be distinguished from a __ process

Back 62

reactive process (plasma cell granuloma)

- polyclonal light chain expression

Front 63

Typical treatment for extraosseous plasmactyoma is __

Back 63

radiation therapy

Front 64

Prognosis for solitary osseous plasmacytoma versus extraosseous plasmacytoma

Back 64

osseous:
- 10% recurrence
- 55% develop PCM

extraosseous:
- 25% regional recurrence
- 15% develop PCM

Front 65

Some cases of plasmacytoma may show cytokeratin positivity as well as some __ postivity

Back 65

CK+ and EMA+
This plus CD45RB- could lead to incorrect diagnosis of carcinoma

Front 66

CD56 expression in osseous versus extraosseous plasmacytoma

Back 66

CD56+ is less common in extraosseous tumors, but 70% of osseous tumors are CD56+

Front 67

Two monoclonal Ig deposition diseases (MIDDs) are __ and __

Back 67

1. primary amyloidosis
2. light chain depostion disease (LCDD)

Front 68

MIDDs are part of the spectrum of plasma cell myeloma, although these plasma cell neoplasms produce Ig that __ without a large ___

Back 68

1. deposits into tissues leading to organ dysfunction

2. without a large tumor burden (without overt myeloma)

Front 69

Primary amyloidosis and light chain deposition disease have different protein products

Back 69

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

Front 70

Primary amyloidosis develops in __% of PCM patients

Back 70

15%

Front 71

In primary amyloidosis, the plasma cell-related amyloid (AL) deposits in the: (list of sites and affects)

Back 71

- 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

Front 72

The sites for diagnostic biopsy for suspected amyloidosis include:

Back 72

1. abdominal subcutaneous fat pad
2. bone marrow
3. rectum

Front 73

4 major types of amyloidosis are categorized based on the type of ___ protein

Back 73

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

Front 74

AL amyloid is composed of ___ secreted by __ and subsequently ___,___, and __ by macrophages into the __

Back 74

1. intact Ig light chains
2. monoclonal plasma cells
3. ingested, processed and discharged by macrophages into the extracellular matrix

Front 75

PCM with primary amyloidosis have a __ prognosis compared to PCM alone

Back 75

worse (shorter survival)

about 15% PCM patients develop AL amyloidosis

Front 76

Amyloid deposition into tissues, such as myocardium, cause ____ (gross appearance)

Back 76

enlargement and a waxy consistency

WHO p.152

Front 77

Monoclonal light and heavy chain deposition disease are very __ diseases that are non___ MIDD (type of __). They include:

Back 77

rare (<70 reported cases!)

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

LCDD
HCDD
LHCDD

Front 78

Light and/or heavy chain deposit disease leads to deposits in many tissues, including:

Back 78

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

Front 79

___% of patients with monoclonal light and/or heavy chain deposition disease have a M-component in the serum

Back 79

85% (majority)

15% few do not have a detectable M-component (reflects strong tissue binding of the aberrant Ig)

Front 80

The basic problem leading to MIDD (LCDD, HCDD) is ___

Back 80

a mutation or deletion involving the Ig gene leading to a structural change that results in premature secretion and tissue deposition

Front 81

Compared to amyloidosis deposits in tissues, nonamyloid MIDD deposits in visceral tissues are ___ associated with plasma cells in the vicinity in tissue sections

Back 81

not

WHO p. 153 glomerulsclerosis due to LCDD

Front 82

In nonamyloid MIDDs, a bone marrow plasmacytosis is found in __%

Back 82

50-60%

Front 83

In LCDD, which light chain predominates?

Back 83

Kappa (contrast with primary amyloidosis, in which lambda predominates)

Front 84

The histologic hallmark of LCDD is ___

Back 84

prominent, smooth, ribbon-like peritubular deposits of monoclonal Ig along the outer edge of the basement membrane (kidney)

see WHO p.153

Front 85

In LCDD, the prognosis is generally __, with a fatal outcome within __

Back 85

poor

1-2 years

Front 86

Osteosclerotic myeloma is a plasma cell neoplasm characterized by ___ in the bone marrow biopsy and __ in the lymph nodes

Back 86

1. plasma cell infiltrate with osteosclerosis (thickened bony trabeculae

2. changes resembling Castleman disease in the lymph node

Front 87

Osteosclerotic myeloma is often a component of ____, which includes:

Back 87

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

Front 88

The relationship between osteosclerotic myeloma and typical plasma cell myeloma is ___

Back 88

unknown

Front 89

Some reported cases of osteoslcerotic myeloma have been associated with what virus?

Back 89

HHV8

Front 90

Osteosclerotic myeloma is or is not associated with a M-component?

Back 90

usually is! and it is usually low level (IgG or IgA, lambda)

Front 91

Osteosclerotic myeloma in the bone marrow usually presents as either single or multiple ___ that histologically show

Back 91

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!

Front 92

The survival for osteosclerotic myeloma is __ compared to typical plasma cell myeloma

Back 92

better

Front 93

Heavy chain disease is ___ the same as heavy chain deposition disease. Because __

Back 93

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

Front 94

The three types of heavy chain disase include:

They represent variants of:

Back 94

1. Gamma HCD: variant of LPL
2. Alpha HCD: extranodal MZL
3. Mu HCD: variant of CLL

Front 95

The Ig produced in heavy chain diseases is usually a ___ that is incapable of full __; results in production of ___ sized Ig molecules

Back 95

1. truncated heavy chain
2. assembly (lack light chain binding sites)
3. variably

Front 96

The SPEP in the case of heavy chain disease may not show a ___

Back 96

M-spike

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

- need IFE to detect and classify the IgH

Front 97

Gamma heavy chain disease is also known as ____

Back 97

Franklin disease

Front 98

Pateints with Franklin disease usually present with ___

Back 98

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

Front 99

The clinical presentation of Franklin disease can mimic a ___ process

Back 99

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

Front 100

Diagnosis of Franklin disease requires:

Back 100

serum IFE demonstrating monoclonal heavy chain production without associated light chain

Front 101

Similar to LPL, gamma HCD in the lymph node shows an inflitrate composed of ___

Back 101

lymphs, plasmcytoid lymphs, plasma cells

IHC: no light chain with IgG heavy chain positivity

Front 102

Mu heavy chain disease is extremely rare. It resembles ___, although the tumor cells are CD5__

Back 102

CLL

CD5-

Front 103

Mu HCD: in the marrow there are the classic ___ admixed with ____

Back 103

1. plasma cells with vacuolated cytoplasm (WHO p.155)

2. small, round lymphs similar to those seen in CLL

Front 104

Mu HCD clinically differs from CLL in that___

Back 104

Mu HCD presents with hepatopslenomegaly and absence of lymphadenopathy

Front 105

Alpha heavy chain disease is also known as ___ or ___, and is a variant of ___

Back 105

1. IPSID (immunoproliferative small intestinal disease) OR Mediterranean abdominal lymphoma

2. extranodal MZL of MALT (GI tract)

Front 106

Alpha HCD (IPSID) occurs in ___ and involves the ___ leading to ___

Back 106

1. young adults (peaks in 20-30's)

2. GI tract

3. diarrhea and malabsorption

Front 107

Alpha HCD sometimes begins as process that is potentially ___ with antibiotics, but may eventually lead to a ___

Back 107

1. reversible

2. high grade lymphoma

Front 108

IPSID is most common in areas bordering the __

Back 108

Mediterranean

Front 109

Alpha HCD (IPSID) involve mainly the ___ and ___

Back 109

small intestine and mesenteric lymph nodes

usually NOT: bone barrow or other organs

Front 110

The small bowel lamina propria in IPSID demonstrates

Back 110

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

Front 111

The plasma cells and marginal zone B cells in IPSID express:

Back 111

monoclonal IgA without light chain

pan B-cell antigens +

CD5-, CD10-

Front 112

IPSID, in its early stages may be ___ with ___, but most patients __

Back 112

reversibly with antibiotics

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