Hemepath: Mature B Cell Neoplasms (Excluding Plasma Cell Neoplasms) Ii/ii

Front 1

Diseases with prominent splenic involvment include:

Back 1

- SMZL
- HCL
- hepatosplenic T cell lymphoma
- Mastocytosis
Rarely:
- LPL
- FL

Front 2

Splenic MZL is an ___ low grade B cell lymphoma with primary presentation in the __

Back 2

uncommon

spleen

Front 3

SMZL is characterized by neoplastic small lymphocytes that surround and ___ the splenic white pulp germinal centers. These neoplastic small lymphs efface the ___ and merge with __

Back 3

- surround and replace the splenic white pulp germinal centers
- efface the follicle mantle zone and merge with a peripheral marginal zone of larger cells (marginal zone-like cells - not true marginal zone)

Front 4

SMZL often involves (sites of involvement):

Back 4

spleen
splenic hilar lymph nodes (not peripheral lymph nodes)
bone marrow
blood (villous lymphocytes)

Front 5

Virtually all patients with circulating villous lymphocytes have __, while not all patients with ___ have circulating villous lymphocytes

Back 5

SMZL

Front 6

Most patients with SMZL are ___(age)

Back 6

over 50 (median age 68)
older adults

Front 7

Pateints with SMZL present with __ without ___

Back 7

splenomegaly without peripheral lymphadenopathy

spleen is large (often >1kg)

Front 8

The clinical course of SMZL is ___ with a 5 year survival of __. Median time to progression is __

Back 8

indolent

65-78%

5 years

Front 9

Treatment of choice of SMZL is __

Back 9

Splenectomy

Front 10

In SMZL, gross cut surface of the spleen shows __

Back 10

miliary small nodules

Front 11

In SMZL, the splenic white pulp shows __

Back 11

- nodular expansion with an APPARENT marginal zone pattern
- nodules may coalesce
- BIPHASIC PATTERN: small lymphs replace the white pulp germinal centers (may see residual GC centrally) with a rim of medium-sized cells, with more dispersed chromatin and abundant pale cytoplasm resembling normal marginal zone cells

- occasional transformed large cells in the peripheral rim

Front 12

In SMZL, the splenic red pulp shows__

Back 12

- prominent infiltration by small lymphs with micronodular aggregates of medium-sized cells

- red pulp is always involved

Front 13

Less common findings in a spleen involved by SMZL include ___ and __

Back 13

- plasmacytic differenitation
- epithelioid granulomas

Front 14

Splenic hilar lymph nodes involved by SMZL show __

Back 14

- stiking nodular pattern with dilated sinuses (WHO p136)
- as in the spleen, the nodules are formed on pre-exising lymphoid follicles, may see residual GC's
- HOWEVER, in the LN: the small lymphs replace the follicules with few interspersed transformed cells, BUT, no distinct marginal zone pattern is seen

Front 15

Bone marrow involvment by SMZL shows a __ pattern

Back 15

interstitial nodular pattern with intrasinusoidal infiltration

Front 16

Immunophenotype in SMZL

Back 16

- express B antigens: CD20+, CD22+, sIg+
- Bcl-2+ (but Bcl-6-, CD10-)

- negative for: CD5, CD10, CD23, CD43, CD103, Bcl-6, and cylcin D1

- absence of CD5 and CD43 help exlcude CLL and MCL (cyclin D1)
- absence of CD103 helps exclude HCL
- absence of CD10 helps exclude FL

Front 17

SMZL differs from extranodal and nodal MZL

Back 17

SMZL:
- lacks a true marginal zone growth pattern
- frequently express IgD (not seen in the others)
-

Front 18

Difference between SMZL and splenic involvement by extranodal MZL, which is uncommon

Back 18

In extranodal MZL, there is a true marginal zone pattern of involvement with preservation of the mantle zone and central GC

Front 19

Hairy cell leukemia (HCL) is an ___ mature B cell lymphoma that manifests in the ___, ___, and ___

Back 19

indolent

bone marrow, spleen, and blood

Front 20

HCL is not responsive to standard NHL therapies, but __

Back 20

long term remissions can be induced with HCL therpay

Front 21

HCL is rare with only __ cases per year in the US

Back 21

600-800

Front 22

Typical patient with HCL

Back 22

- middle aged (50 years old)
- male (M:F ration 4:1)

Front 23

HCL presents with:

Back 23

- splenomegaly (80% cases) with abdominal fullness
- pancytopenia (50%) (almost always monocytopenia)(25% present with only 1 or 2 cell lines suppressed)
- >50% have thrombocytopenia
- most have a normocytic, normochromic anemia
- hepatomegaly uncommon (20%)
- lymphadenopathy is rare

or

- asymptomatic

Front 24

HCL typically involves the __ and ___, with typically small numbers of __

Back 24

bone marrow and spleen

few circulating hairy cells in the blood (rarely frankly leukemic)

Front 25

Bone marrow biopsy: HCL is often associated with a ___

Back 25

dry tap due to reticulin fibrosis

Front 26

Hairy cell morphology

Back 26

- small lymphs (1-2 times the size of small lymphs)
- round, oval, or reniform nuclei
- chromatin is less dense than normal lymphs
- inconspicuous nucleoli
- abundant cytoplasm (clear to light blue) with circumferential hairy projections

Front 27

In bone marrow core biopsy, the appearance of HCL

Back 27

- usually hypercellular (but may be normo- or hypo-)
- intersitial, patchy to diffuse
- NO NODULAR AGGREGATES, if seen, suggest an alternate diagnosis
- "fried egg" appearance due to abundant cytoplasm
- reticulin fibrosis invariably
- extravasated RBCs often present

Front 28

HCL can result in a hypocellular marrow that resembles __

Back 28

- 10-20% have hypocellular marrow

- some cases are markedly hypocellular and resemble aplastic anemia due to cytokine production by the tumor cells

- avoid misdiagnosis by detection of CD20+ hairy cells

- typically other hematopoietic cells are almost always decreased in HCL; the granulocytes are most severely depressed

Front 29

Cytochemical staining for __ is positive in most cases of HCL

Back 29

TRAP
- tartrate-resistant acid phosphatase
- typically performed on blood smears, bone marrow aspirate smears or touch preps of bone marrow

- there is an immunostain for TRAP in paraffin-embedded tissue

Front 30

HCL in the spleen primarily involves the ___ pulp

Back 30

- red pulp, with atrophy of the white pulp
- Grossly, the splenic parenchyma is diffusely dark red and the spleen is markedly enlarged
- blood-filled pseudosinuses (blood lakes) lined by tumor cells are highly characteristic

Front 31

Characteristic EM finding in HCL

Back 31

ribosome lamellar complexes

Front 32

Immunophenotype of HCL

Back 32

bright CD45+ with increased forward and side scatter

CD19+
CD20+
CD22+
CD79a+

coexpress: CD103, CD25, FMC-7, and CD11c

monotypic Ig+

tyically CD5-
usually CD10-

Front 33

In paraffin-embedded tissue, __ is a highly sensitive marker for HCL

Back 33

DBA.44

- it is NOT specific for HCL

Front 34

Hairy cell variant is a rare variant: similarities and differences

Back 34

- in both: pateints present with anemia, thrombocytopenia, and splenomegaly, BUT, in HCLv there is a HIGH white cell count and NO monocytopenia

- HCLv cells resemble prolymphs with hairy projections:
1. are a little bigger
2. may have bilobed nuclei
3. coarse chromatin (compared to finer)
4. prominent nucelolus (versus inconspicuous nucleoli in classic HCL)
5. basophilic cytoplasm (compared to clear to light blue)

HCLv cell immunophenotype/cytochemical staining:
1. TRAP negative (typically)
2. CD25-, CD103-

Bone marrow:
1. only moderated reticulin fibrosis
2. aspirates obtained easily (NO dry tap)

Front 35

HCLv is resistant to therapy including __ while classic HCL is responsive

Back 35

IFN-alpha

Front 36

SLVL(SMZL) vs. HCL

Back 36

1. the villous projections of villous lymphocytes are often polarized
2. villous lymphs have less cytoplasm than hairy cells
3. Bone marrow involvement by SLVL is characterisitcally nodular and interstitial (NO! nodules in HCL)
4. Villous lymphs are CD103- and CD25-

Front 37

In HCL, cyclin D1 is overexpressed in 50-75% of cases, but __

Back 37

this is NOT associated with t(11;14)

Front 38

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprised of morphologically _____ small B cells including:

Back 38

heterogeneous

- marginal zone cells (monocytoid B cells)
- small lymphocytes
- scattered immunoblasts
- varible plasma cells

Front 39

In extranodal MZL of MALT, the infiltrate is within the ___

Back 39

marginal zone of reactive B-cell follicles!! (unlike SMZL, with infiltration of the germinal center and a marginal zone-like pattern)

Front 40

In MZL of MALT, the neoplastic cells typically infiltrate the ___ forming ___

Back 40

epithelium

LELs

Front 41

A special type of MALT lymphoma occuring more commonly in young adults near the Mediterranean is known as ___

Back 41

IPSID (alpha heavy chain disease)

Front 42

MALT lymphoma is a disease of ___, comprising __% of B-cell lymphomas, but __% of primary GASTRIC lymphomas

Back 42

adults (median age 63)

7-8% of B-cell lymphomas

up to 50% primary gastric lymphomas

Front 43

Many cases of MALT lymphoma are associated with a prior history of ___ with the development of ___

Back 43

prior chronic inflammation often with autoimmune disorders
-H.pylori gastritis
-Sjogrens syndrome
-Hashimoto thyroiditis

= development of extranodal lymphoid tissue (MALT)

Front 44

In MALT lymphomas, the neoplastic cells may colonize the germinal centers, morphologically this detected by the absence of a ___ in the GCs

Back 44

starry sky (TGM's are normally present in uninvolved reactive GCs)

Front 45

Patients with ___ and ___ are at an increased risk of developing MALT lymphoma

Back 45

1. Sjogrens/lymphoepithelial sialadenitis(SS/LESA)
- 85% of lymphomas developing in this setting are MALT lymphomas
- have a 44-fold increased risk of lymphoma!!

2. Hashimoto thyroiditis
- 3-fold increased risk of lymphoma in general
- 70-fold increased risk of thyroid lymphoma
- 94% of patients with thyroid lymphoma have thryoiditis in the adjacent gland tissue

Front 46

IPSID may be associated with chronic ___

Back 46

intestinal infection

- some cases are reversible with antibiotic therapy early in the course

Front 47

MALT lymphoma most commonly occur in the ___, however other sites include:

IPSID occurs in ___

Back 47

GI tract 50% (stomach most common site in GI tract 85%)

IPSID typically involves the small intestine and colon

other sites include:
- lung 14%
- ocular adnexae
- head and neck
- breast
- thyroid
- skin

Front 48

MALT lymphomas: bone marrow involvement is __

Back 48

uncommon (20%)

Front 49

Plasmacytic differentiation can be seen in MALT lymphomas, and a serum paraprotein (M-component) is ___ present. What about IPSID?

Back 49

rarely (despite plasmacytic differentiation)

exception: IPSID aka alpha HCD!! produces truncated IgA heavy chain that is detectable in the serum

Front 50

In H. pylori-related gastric MALT lymphomas, the proliferation of the neoplastic B cells requires ___

Back 50

activate T cells, stimulated by H. pylori antigens

Front 51

In some cases of cutaneous extranodal MZL, ___ is a possible source of antigenic stimulation driving the lymphoma

Back 51

Borrelia burgdorferi

Front 52

MALT lymphoma cells infiltrate around ___ B-cell follicles, external to a ___, from which they ___

Back 52

1. reactive
2. preserved mantle zone (unlike SMZL, loss of the mantle zone)
3. spread out to form large confluent areas of lymphoma that eventually overrun most of the follicles

Front 53

Characteristic marginal zone B cell morphology

Back 53

- small to medium-sized, slightly irregular nuclei
- inconspicuous nucleoli
- moderately abundant pale cytoplasm (gives the monocytoid appearance)

Note: they may just resemble small lymphocytes too!!

Front 54

lymphoepithelial lesion (LEL) is defined as an aggregate of __ or more ____ cells within the epithelium, resulting in __

Back 54

aggregate of 3 or more marginal zone B cells within the epithelium, resulting in distortion and destruction of the epithelial cells

epithelial cells often show eosinophilic degeneration

Front 55

In a MALT lymphoma, in which the lymphoma cells colonize the germinal centers, this can sometimes resemble___

Back 55

follicular lymphoma

Front 56

MALT lymphomas are by definition a ___ cell lymphoma, if there are large aggregates or sheets of transformed cells then it should be designated __

Back 56

small cell lymphoma

DLBCL with note of accompanying MALT lymphoma

Front 57

Morphologically, IPSID and typical MALT lymphomas are ___

Back 57

similar

Note: IPSID may have striking plasmacytic differentiation

Front 58

MALT lymphoma can involve lymph nodes?

Back 58

YES

-as usual, the lymphoma cells infiltrate the marginal zone of reactive follicles
- aggregates of marginal zone cells in the paracortical areas and perisinusoidal areas

- varying degress of plasmacytic differentiation too

Front 59

Characteristic immunoprofile for MALT lymphoma?

Back 59

NO!

Absence of characteristic marker of other B cell neoplasms is useful

CD21 and CD35 will highlight tumor cells plus show the FDC meshwork of residual/colonized germinal centers

Front 60

Two common cytogenetic abnormalities in MALT lymphoma

Back 60

1. trisomy 3 (most common) 60%

2. t(11;18)(q21;q21)
API2/MLT fusion
- apoptosis inhibitor gene (API2)
- associated with resistance to H. pylori therapy

Front 61

t(11;18)(q21;q21) in gastric MALT lymphomas is good or bad?

Back 61

Not so good.
Associated with resistance to H. pylori therapy

Front 62

Prognosis for MALT lymphoma

Back 62

indolent (slow to disseminate)

risk of transformation to large B-cell lymphomas

Front 63

MALT lymphoma is sensitive to ___

Back 63

radiation therapy

Gastric MALT lymphoma - H. pylori treatment

Front 64

Criteria for differential diagnosis of gastric MALT lymphoma

Back 64

see WHO p. 160
includes:

Score 0(nml) to 5 (MALT lymphoma)

0: normal

1: chronic active gastritis without lymphoid follicles or LELs

2: chronic active gastritis with florid lymphoid follicle formation No LELs!!

3: suspicious lymphoid infiltrate, probably reactive

4: suspicious lymphoid infiltrate, probably lymphoma

5: MALT lymphoma - see dense, diffuse infiltrate of marginal zone cells in lamina propria w/ prominent LELs

Front 65

Nodal MZL lymphoma is ___. It is a primary nodal B cell neoplasm that morphologically resembles___ but without__

Back 65

Rare (1.8% of lymphoid neoplasms)

nodal involvement by SMZL or extranodal MZL (MALT lymphoma), but without extranodal disease

Front 66

There are two morphologic types of nodal MZL described:

Back 66

1. resembles nodal involvement by SMZL

2. resembles nodal involvement by MALT lymphoma

Front 67

In patients with MALT lymphoma, Hashimoto thyroiditis, or Sjogrens syndrome, instead of a diagnosis of nodal MZL, the diagnosis should be __

Back 67

MALT lymphoma with secondary lymph node involvement

Front 68

Follicular lymphoma (FL) makes up __% of NHL in the US, and __% of low grade B-cell lymphomas.

Back 68

35%

70%

Front 69

Follicular lymphomas is a disease of ___ people, median age __. Rarely, it occurs in __

Back 69

middle age to older
59 years old
<20 years old

Front 70

Follicular lymphoma: site(s) of involvment: predominately ___, but also __

Back 70

1. lymph nodes
2. spleen, bone marrow (40% at diagnosis!!), blood

3. uncommon in extrahematopoietic tissues, but if so it is usually associated with widespread lymph node involvement too!!

Front 71

Follicular lymphoma in the skin?

Back 71

FL is the one of the most common primary cutaneous B cell lymphoma

Front 72

Patients with FL usually present with __

Back 72

- widespread disease with BM involvement in 40% and splenomegaly is common.

- despite widespread disease, patients are usually asymptomatic other than LAD

- LAD may wax and wane

- some patients present with constitutional symptoms

Front 73

Follicular lymphomas has at least a partially ____ pattern. The pattern is described as ___

Back 73

1. follicular

2. pattern:
- follicular (>75% follicular)
- follicular and diffuse (25-
75% follicular)
- minimally follicular (<25% follicular)

There is at least some follicular pattern present

Front 74

In FL, the neoplastic follicles are:

Back 74

1. poorly defined
2. often lack a mantle zone
3. are closely packed
4. efface the nodal architecture, with occasional perinodal extension
5. nonpolarized
6. lack a starry sky appearance (tingible body macs)
7. follicles are often smaller than reactive follicles

Front 75

In FL, the neoplastic cells can infiltrate the ___ areas, however this does not qualify as a ___ pattern

Back 75

interfollicular areas

diffuse

Front 76

Most cases of FL are composed of two cell types

Back 76

1. centrocytes (cleaved FCC)
- small to medium-sized cells
- nuclei can be angulated, elongated, twisted, or cleaved
- inconspicuous nucleoli
- scant pale cytoplasm

2. centroblasts (noncleaved FCC)
- large transformed cells
- usually round or oval nuclei
- vesicular chromatin
- one to three peripheral nucleoli
- narrow rim of cytoplasm

Front 77

In FL, the ___ usually predominate.

Back 77

-centrocytes predominate, however, centroblasts are always present in the minority

Front 78

FL is graded (WHO recommendation) using a 3-tiered system, based on ___

Back 78

1. proportion of centroblasts

Histologic grading can predict clinical outcome

Count 10 hpf's: 1 hpf for 10 separate follicles.

grade 1: 0-5 centroblasts/hpf
grade 2: 6-15 centroblast/hpf
grade 3: >15

Front 79

In FL, if a discrete area of grade 3 is present in a background of grade 1 or grade 2, then the diagnosis should reflect:

Back 79

each grade, giving the relative proportion for each grade

Front 80

The follicles selected for grading FL should be __

Back 80

representative

Not those with the most centroblasts!!

Front 81

In FL, when looking for centroblast (in grading), be sure not to count __ or __as centroblasts

Back 81

1. follicular dendritic cells
WHO p.164
- often binucleated
- central esoinophilic nucleolus (versus multiple distinct nucleoli often peripherally located)
- CD21+ CD23+
2. large centrocytes (larged cleaved cells)

Front 82

FL, for research purposes, grade 3 can be divided into

Back 82

grade 3a
- centrocytes present
grade 3b
- solid sheets of centroblasts

Front 83

Any areas of DLBCL within FL is considered__

Back 83

transformation to a higher grade lesion

report the relative proportions of FL and DLBCL

Front 84

Immunophenotype for FL

Back 84

sIg+
pan B antigen +
CD10+
Bcl-2+
Bcl-6+

CD5-
CD43- (see note)

CD21+ CD23+ FDCs present in follicular areas

Note: some grade 3 FL are CD43+

Front 85

Cutaneous follicular lymphoma is frequently Bcl-2___

Back 85

Bcl-2 negative!!

Front 86

The most common cytogenetic abnormality in FL __

Back 86

t(14;18)(q32;q21)
BCL2/IgH

Front 87

In FL, histologic grade correlates with prognosis

Back 87

grade 1 and 2: indolent, not curable

grade 3: more aggressive with potential for cure with aggressive therapy (similar to DLBCL)

Front 88

Grade 3, FL has a ___ prognosis compared to DLBCL

Back 88

slightly better

- grade 3, FL is treated similar to a DLBCL

Front 89

In FL, how does the presence of large diffuse areas in grade 1 or 2 lesions effect prognosis?

Back 89

It does not.

But: in grade 3, it is more common to find large diffuse areas, and SOME studies show a worse prognosis

Front 90

___% of FL cases transform or progress to LBCL most often DLBCL

Back 90

25-35%

Front 91

Cutaneous follicle center lymphoma is often Bcl-2 __ and typically involves the __ region of the body

Back 91

- Bcl-2 negative
- head and neck
- remain localized!! amenable to local therapy

- true relationship with nodal FL is unknown

Front 92

Diffuse follicle center lymphoma is __

Back 92

- a FL without a follicular pattern!!
- so we cannot call it a FL
- rare
- has the mix of centrocytes with minor component of centroblasts
- both the small and large cell must have the SAME immunophenotype as a typical FL

Front 93

Diffuse follicle center lymphoma (FCL) should be grade similar to FL, but one big difference is __

Back 93

1. grade similar to a FL for grades 1 and 2, BUT:
- IF centroblasts predominate ((OR)) the small lymphs turn out to be T cells!! then it is a DLBCL

Front 94

In FL, how does bone marrow involvement effect prognosis?

Back 94

It does not seem to effect prognosis.

Front 95

FL is rare in children, but if it occurs, it is similar to ___

Back 95

primary cutaneous FL
BOTH:
- usually lack BCL2 gene rearrangement and are Bcl-2-
- head and neck region involved
- disease is apparently curable

Front 96

In FL, the neoplastic follicles ___ the nodal architecture, with occasional __

Back 96

efface

extension into perinodal tissue

Front 97

In FL, the small cleaved cells are still __X the size of small lymphocytes

Back 97

2X

slightly larger abnormally shaped cells

Front 98

Bone marrow involvement by FL characteristically occurs in a ___ location

Back 98

paratrabecular

Front 99

Grade 3b FL is a special category that differs from other FL's

Back 99

- less often CD10+ (50% vs 100%)
- t(14;18) less common (22% vs 73%)
- appears to be more biologically related to DLBCL

BUT: there is no difference in survival between grade 3a and 3b

Front 100

FL with diffuse component: for grade 1 and 2, diffuse component does not seem to effect ___ (unless it occupies __%), but in grade 3___ (from Fletcher)

Back 100

1. prognosis
2. 25-50% diffuse
3. in grade 3 FL, any area of diffuse should lead to a diagnosis of "FL with DLBCL" instead of "FL, grade 3, follicular and diffuse"

Note: Contrast with WHO:
- even large diffuse areas in a grade 1 or 2 does not seem to affect prognosis; but it says that some studies do show the degree of nodularity does have an impact on survival, so they recommend reporting the % of diffuse and follicular components

Front 101

In situ follicular lymphoma?

Back 101

- partial node involvement
- usual reactive follicles present
- some follicles have germinal centers with aggregates of bcl-2+ follicle center cells (monoclonal)
- some pts have FL in other nodes, if not, 23% will develop FL

- may represent early involvement by FL or a preneoplastic event

Front 102

sIg can be negative in some cases of FL, especially if composed of mostly __

Back 102

large cells

Front 103

Bcl-2 is postivie in ___% of FL cases, it is more likely to be negative in __

Back 103

85% bcl-2+

cases composed predominately of large cells are more likely to be negative

Front 104

Ki-67 (proliferation) index is usually __ in FL compared to reactive follicular hyperplasia

Back 104

lower

Front 105

In FL, deletions of __ and __ are associated with __

Back 105

6q and 17p

- shorter survival
- higher probability of transformation to DLBCL

Note: only 10% of FL cases have t(14;18) as the sole abnormality.

Front 106

FL, with marginal zone differentiation

Back 106

- at periphery of the follicles there is a pale rim of monocytoid B cells
- these cells are CD10- and bcl-6-
- not clear whether or not it is clinically significant

Front 107

In MALT lymphoma, multifocal disease (involving more than on mucosal or extramucosal sites) is associated with what cytogenetic abnormalities?

Back 107

- gastric lymphomas: t(11;18)(q21;q21)

- extragastric lymphomas: trisomy 18

NOTE: there is no significant differences in survival between localized and disseminated disease!!

Front 108

___% of gastric MALT lymphomas associated with H. pylori show complete remission with antibiotics

Back 108

70-80%

- regression usually occurs within a few weeks (up to 1 year in some)

- NOTE: molecular evidence residual tumor lags behind clinical remission and may persist

Front 109

In gastric MALT lymphomas, bcl-10 aberrant nuclear positivity is associated with ___

Back 109

t(11;18) and lack of a response to anti-Helicobacter therapy

In normal B lymphocytes, including those lacking t(11;18), bcl-10 immunoreactivity is limited to the cytoplasm

Front 110

extranodal MZL is bcl-2__, in cases of colonization of ___, this may resemble FL

Back 110

bcl-2+

germinal centers by MZL

BUT: CD10-, bcl-6-

Front 111

t(11;18)(q21;q21)

Back 111

- gastric MALT lymphomas
- lack of response to anti-Helicobacter therapy
- API2 gene on 11q21 fused with MALT1 gene on 18q21
- fusion protein directly activates NFkB, bypassing normal signaling pathways

Front 112

t(11;18) in gastric MALT lymphomas and transformation to a large cell lymphoma?

Back 112

t(11;18) seems to protect it from large cell transformation

Front 113

Mantle cell lymphoma (MCL) has a striking ___ predominance (gender)

Back 113

male (7:1)

Front 114

patients with mantle cell lymphoma often present with

Back 114

lymphadenopathy, often with extranodal involvement (spleen and GI)

Front 115

lymphomatous polyposis

Back 115

ileocecal involvement by MCL, with formation of multiple polyps

Front 116

Lymph nodes with MCL show a

Back 116

- diffuse, vaguely nodular to nodular, or mantle zone pattern
- NO proliferation centers
- NO (or minimal) transformed cells
- scattered, solitary epithelioid histiocytes are an IMPORTANT clue to MCL
- blood vessels often hyalinized

- monotonous lymphoma cells with folded nuclei

Front 117

immunophenotype of mantle cell lymphoma

Back 117

B-antigen positive
CD5+
CD23-

CD10-
bcl-6-

Cyclin D1+

Front 118

Cyclin D1 can be seen in:

Back 118

-MCL
-rare CLL/SLL
-some HCL
-some plasma cell myeloma/plasmacytoma

Front 119

Cylcin D1 negative (by IHC)MCL?

Back 119

7% cases
Dx based on:
- morphology
- CD5+
- expression of other cyclins

Front 120

In MCL, the Ig genes can be mutated (20-30%) or unmutated (70-80%), but unlike CLL/SLL___

Back 120

In MCL, there is no clinical difference between the two

Front 121

__% of MCL exhibit t(11;14)

Back 121

50-65% although >90% are positive for cyclin D1 by IHC!!

Additonally, by FISH for 11q13 translocations, practically all cases are positive

Suggests that cryptic translocations or other mechanisms are involved in CYCLIN DI dysregulation

Front 122

cyclin D1 is also known as __

Back 122

bcl-1
PRAD1

Front 123

Blastoid/pleomorphic MCL has a __ prognosis compared to classic MCL

Back 123

worse

Front 124

blastoid MCL is TdT__

Back 124

negative

distinguishing it from B-LBL

Front 125

MCL is characterized by a ___ population of ____ to ___-sized B lymphocytes with ___ nuclei. NO ___ are present.

Back 125

- monomorphous
- small to medium
- irregular

- NO proliferation centers (pseudofollicles), transformed neoplastic cells (centroblasts), or paraimmunoblasts

Front 126

Most commonly involved extranodal sites for MCL are ___and ___

Back 126

GI tract and Waldeyer's ring

Front 127

Lymphomatous polyposis can involve __ part of the GI tract

Back 127

any!!

Fletcher (ileocecal)

Front 128

MCL often presents with __ splenomegaly

Back 128

massive

LAD, hepatosplenomegaly, bone marrow involvement

Front 129

Some patients with MCL have a marked lymphocytosis that can mimic __

Back 129

prolymphocytic leukemia
- the circulating MCL cells can be morphologically indistinguishable from prolymphocytes!!

Front 130

MCL is characterized by a ___ population of ____ to ___-sized B lymphocytes with ___ nuclei. NO ___ are present.

Back 130

- monomorphous
- small to medium
- irregular

- NO proliferation centers (pseudofollicles), transformed neoplastic cells (centroblasts), or paraimmunoblasts

Front 131

Most commonly involved extranodal sites for MCL are ___and ___

Back 131

GI tract and Waldeyer's ring

Front 132

Lymphomatous polyposis can involve __ part of the GI tract

Back 132

any!!

Fletcher (ileocecal)

Front 133

MCL of presents with __ splenomegaly

Back 133

massive

LAD, hepatosplenomegaly, bone marrow involvement

Front 134

Some patients with MCL have a marked lymphocytosis that can mimic __

Back 134

prolymphocytic leukemia

Front 135

Is mantle cell lymphoma graded?

Back 135

No
But, if blastoid features are present, it is noted in the diagnosis

Front 136

In mantle cell lymphoma, transformation to a typical large cell lymphoma ___ occur

Back 136

does NOT

- but may see subsequent blastoid variant with recurrence

Front 137

CD5- MCL cases may be more ___

Back 137

indolent than typical CD5+ MCL

Front 138

the most consistently reported adverse histopathological prognositic finding in MCL is

Back 138

a high mitotic rate (not well defined!!)

high mitotic rate: >10/10hpf to 20-30/10hpf

Front 139

MCL, blastoid variant has two subtypes:

Any difference in survival?

Back 139

1. Usual
- resembles lymphoblasts (high mitotic rate >10/10hpf, usually at least 20-30/10hpf)

2. Pleomorphic
- heterogenous cells

Front 140

B symptoms in a pt with CLL at presention

Back 140

predicted to have a shorter survival.

- remember, many patients are incidently discovered

Front 141

The ddx in young patients with suspected CLL is with NLPHL

Back 141

the lymphs in NLPHL do not express CD5 and CD43 and are polytypic not monotypic as in CLL

Front 142

DLBCL, the lymphoma cells are equal to or exceed the size of a ___

Back 142

normal macrophage!! or 2X the size of a normal lymphocyte

Front 143

DLBCL sites of involvment:

Back 143

1. extranodal:
- most common site is GI (stomach and ileocecal region)
- any site could be the primary
- up to 40% of cases, the disease is limited to extranodal sites
2. nodal
3. bone marrow
- primary BM or PB involvement is RARE!!

Front 144

Most DLBCL arise __

Back 144

de novo

But, can represent progression or transformation of a less aggressive lymphoma

Front 145

DLBCL that arise in the setting of immunodeficiency are often ___-related

Back 145

EBV

- immunodeficiency is a risk factor

Front 146

DLBCL patterns of involvement within nodal and extranodal tissues

Back 146

variety
- complete to partial effacement
- interfollicular
- sinusoidal

- often infiltrates perinodal tissues

- +/- broad bands of sclerosis

Front 147

DLBCL is composed of large __ lymphoid cells

Back 147

transformed

Front 148

The DLBCL variants are described but not very reproducible, therefore, the pathtologist can use the term __

Back 148

DLBCL only or use one of the variant types

Front 149

The most common morphologic variant of DLBCL is the ___

Back 149

centroblastic variant
- medium to large cells
- oval to round, vesicular nuclei
- fine chromatin
- 2-4 membrane bound nucleoli
- scant cytoplasm

Front 150

Immunoblastic DLBCL:
- features
- DDX

Back 150

- majority (>90%) of the cells have a single, central, nucleolus
- moderate basophilic cytoplasm
- NOTE: centroblasts MUST be <10% of cells

DDX: plasmablastic variant of plasma cell myleoma

Front 151

T-cell/histiocyte rich DLBCL
- majority of the cells are __

Back 151

- majority of the cells are T-cells w/ or w/out histiocytes
- <10% large neoplastic B cells!!!

Front 152

t-cell/histiocyte rich DLBCL can raise a DDX including:

Back 152

1. NLPHL
- in T-cell/histiocyte rich DLBCL, small B cells are rare, but if present, along with fewer large neoplastic B cells and a vague nodularity, may suggest NLPHL
2. HL

Front 153

The pleomorphic variant of DLBCL can mimic __

Back 153

1. carcinoma (if growing in cohesive pattern, especially if there is a sinusoidal pattern of growth)
2. RS cells of HL
3. ALCL ( T cell lymphoma)

Front 154

Immunophenotype of DLBCL

Back 154

1. express various pan B markers
- may lack one or more too!
2. sIg+ 50-75%
3. cIg+ in ones with plasmacytic differentiation
4.+/- CD30+!!! (as is ALCL)
5. +/- CD5+ (these are cyclin D1 negative distinguishing them from blastoid MCL)
6. many are bcl-6+
7. occasionally CD138+ (if immunoblastic variant, could be confused with plasmablastic variant of plasma cell myeloma)
8. Ki-67 index is high >40%, upto >90% in some cases

Front 155

Most anaplastic DLBCL variants are CD30__.

Back 155

CD30+

- as is ALCL

Front 156

___% of DLBCL exhibit t(14;18)

Back 156

20-30%

Front 157

Bcl-2+ is seen in ___% of DLBCL and may be associated with __

Back 157

30-50% cases are bcl-2+

worse prognosis

Front 158

Bcl-6 translocation in DLBCL may be associated with a __ prognosis

Back 158

better

Front 159

Plasmablastic variant of DLBCL is ___ and typically presents in the __, in the setting of __.

Back 159

RARE

oral cavity

HIV infection

- 60% EBV+
- lymphoma cells are CD20- and CD45-
- they are CD138+

Front 160

How can you distinguish a plasmblastic DLBCL from a variant of plasma cell myeloma?

Back 160

In plasmablastic DLBCL
- CD20- (vs CD20+)
- CD45-
- CD138+
- lack of mature monoclonal plasma cells
- high proliferation index
- clinical picture (HIV, oral cavity)

Front 161

DLBCL usually presents with __, but __ is common

Back 161

lymphadenopathy, but extranodal presentation is common too

Front 162

If DLBCL is detected in a staging marrow, it is IMPORTANT to determine __

Back 162

- is it marrow involvement by DLBCL or is it involvement by an occult follicular lymphoma

REASON:
- marrow involvement by DLBCL is a dismal px (stage IV)
- marrow involvement by FL DOES NOT affect the prognosis, BUT it suggests that the disease is more likely to relapse after complete remission, in the form of FL

Front 163

DLBCL is an aggressive disease that is fatal if untreated, but __

Back 163

- is potentially curable with aggressive therapy
- 50% cases can achieve long term disease-free survival

Front 164

DLBCL treatment includes:

Back 164

1. CHOP:
- cyclophosphamide
- doxorubicin
- vincristine
- prednisone

2. CHOP + rituximab

Front 165

Morphologically, a DLBCL and peripheral T cell lymphoma can __ be distinguished

Back 165

can NOT!

Front 166

__% of DLBCL are bcl-6+ and CD10+

Back 166

40% CD10+
60% bcl-6+

- follicle center cell origin

Front 167

DLBCL: __% are bcl-2+ and are associated with __

Back 167

50% bcl-2+
associated wtih resistance to CTX

Front 168

3 molecular pathways to the development of DLBCL

Back 168

1. transformation pathway
- involves activation of BCL-2 w/ or w/o P53 mutation

2. de novo pathway involving BCL-6 rearrangement

3. de novo pathway with retained germline BCL-6 and BCL-2, via some unknown mechanism

Front 169

Immunophenotypic findings with poor prognostic significance in DLBCL

Back 169

- bcl-2 + (single strongest independent unfavorable prognostic factor)

- bcl-6-

- CD5+

- HLA-DR-

- ki-67+ >60-80%

Front 170

Germinal center cell differentiation in DLBCL is associated with a __ prognosis

Back 170

better

What about t(14;18)?

Front 171

3 subtypes of DLBCL with distinct features include:

Back 171

1. mediastinal (thymic) large B-cell lymphoma (Med-DLBCL)

2.Intravascular large B-cell lymphoma

3. Primary effusion lymphoma

Front 172

Med-DLBCL occurs in which age group and gender?

Back 172

young women

30-50's

F>M

anterior mediastinal mass

Front 173

Med-DLBCL are EBV__

Back 173

EBV negative

Front 174

Med-DLBCL consists of __

Back 174

variably sized neoplastic B cells with abundant pale cytoplasm and sclerosis

- classic clear cell appearance and delicate interstitial fibrosis

Front 175

Med-DLBCL may contain eosinophils, fibrosis, and interspersed benign lymphs suggesting a dx of __

Back 175

HL (NS type)

- NOTE: the lymphoma cells are often CD30+ (often weak), BUT CD45+, CD20+, CD15- and EBV- !!

Front 176

Immunophenotype of Med-DLBCL

Back 176

CD19+, CD20+
CD10-
CD5-
CD30+ (70%)(patchy and weak, focal to diffuse)
CD15-

CD23+ (70%)

Front 177

In med-DLBCL (thymic large B-cell lymphoma) a cytokeratin can highlight __

Back 177

- thymic remnants infiltrated by tumor cells

- WARNING: thymic remnants may appear n clusters mimicking carcinoma

Front 178

Unlike most lymphomas, med-DLBCL may spread to the __

Back 178

CNS (26% cases either at presentation or relapse)

Front 179

Med-DLBCL therapy is different compared to DLBCL

Back 179

- it is not as responsive to standard DLBCL therapy (CHOP)
- require multimodality therapy often with XRT
- can achieve 10 yr disease-free survival up to 78%

Front 180

Med-DLBCL consists of __

Back 180

- medium to large cells
- mod to abundant pale, clear, or amphophilic cytoplasm
- intermingled RS-like cells, highly pleomorphic cells, and small lymphs

Front 181

the sclerosis in med-DLBCL leads to a ___ pattern that can mimic __

Back 181

compartmentalized pattern

mimic carcinoma or seminoma

NOTE: sclerosis is NOT essential for the diagnosis

Front 182

CD23 and sIg are typically __ in med-DLBCL and __ in non-mediastinal DLBCL

Back 182

med-DLBCL CD23+ (70%) and sIg-

nonmed-DLBCL CD23- (only 10% CD23+) and sIg+

Front 183

med-DLBCL distinguished from a mediastinal lymph node invovled by DLBCL

Back 183

LN w/ DLBCL
- M>F
- older age
- sIg+
- CD23-

med-DLBCL:
- young women
- CD23+
- sIg-

Front 184

DDX of med-DLBCL

Back 184

1. thymoma, thymic carcinoma
- presence of well-formed Hassall corpuscles favor lymphoma!! Rarely seen in thymoma

2. germinoma
- due to the packeted pattern and clear cell morphology
- absence of glycogen!! and marked nuclear irregularities favor lymphoma

3. syncytial variant of NS Hodgkin lymphoma

Front 185

Intravascular large B-cell lymphoma is a ___ disease characterized by the presence of ___ cells within the lumina of __

Back 185

extremely rare (only a few cases reported!!)

lymphoma cells only in the lumina of small vessels, particularly capillaries

Front 186

Intravascular large B-cell lymphoma can involve any __ site. It is a subtype of ___ DLBCL. Sites involved include __

Back 186

- any extranodal site
- it is a subtype of extranodal DLBCL
- brain, bone marrow, skin,...

Front 187

intravascular large B-cell lymphoma is aka ___

Back 187

- intravascular lymphomatosis
- malignant angio-endotheliomatosis

Front 188

In cases of intravascular large B-cell lymphoma, despite the almost exclusive intravascular proliferation, there usually is no __

Back 188

circulating lymphoma cells in the PB

Front 189

bone marrow morphologic examination for intravascular large B-cell lymphoma is often __, however ___ is often ___

Back 189

negative

molecular evidence is often present

Front 190

In intravascular large B-cell lymphoma the tumor cells plug the lumina of __

Back 190

small and medium-sized vessels

vascular occlusion leads to infarcts in multiple organ systems

Front 191

TCRBCL (T cell rich large B cell lymphoma): the __ cells make up >90% of the cells

Back 191

T-cells

in cases with a rich histiocyte or epithelioid histiocyte component, the term T-cell rich/Histiocyte rich B-cell lymphoma is used

Front 192

In TCRBCL the background T-cells are often CD__+

Back 192

CD8+

Front 193

Primary effusion lymphoma (aka__) is a type of __ without a ___

Back 193

body cavity-based lymphoma

large B cell lymphoma without a detectable tumor mass and presenting as a serous effusion

HHV8+

a/w immunodeficiency

Front 194

primalry effusion lymphoma most often occurs in two patient populations:

Back 194

1. young HIV+ homosexual men with HHV8
2. non-immunodeficient elderly men in areas with high HHV8 prevalance (Mediterranean)

Front 195

Primary effusion lymphoma most commonly involves the __, __, and __ cavities

Back 195

pleural, pericardial, and peritoneal

other sites: soft tissues, GI tract, other

Front 196

Primary effusion lymphoma cells are positive for ___ and often coinfected with ___

Back 196

HHV8+

EBV

Front 197

In cytology, primary effusion lymphoma cells appear __

Back 197

- large cells
- prominent nucleoli
- nuclei round to irregular
- cytoplasm can be abundant, deeply basophilic, and contain vacuoles!!

Front 198

Immunophenotype for primary effusion lymphoma

Back 198

CD45+
CD19-
CD20-
CD22-
CD79a-
CD3-
CD138+
+/-CD30 (activation marker)
+/-HLA-DR (activation marker)
CD10-
bcl-6-
The B cell nature is supported by Ig gene rearrangements

Front 199

primary effusion lymphoma typically remains ___

Back 199

localized to the body cavity or origin

Front 200

median survival for primary effusion lymphoma is

Back 200

6 months

Front 201

In cases of primary effusion lymphoma, a pleural biopsy may show__

Back 201

- lymphoma cells adherent to the pleural surface often embedded in fibrin and occasionally invading the pleura

Front 202

In primary effusion lymphoma, abberrant CD3__ has been reported

Back 202

CD3+

- in combination with the often absent pan B cell markers, this can make assigning the appropriate lineage difficult

Front 203

Although the majority of primary effusion lymphomas remain localized to the ___, there have been reported cases of ___

Back 203

- body cavity of origin

- extracavitary solid form, WITHOUT effusion, involving lymph nodes or extranodal sites

Front 204

Main differences between classic primary effusion lymphoma and the extracavitary solid form are __

Back 204

- slightly higher frequency of B cell antigen and sIg expression
- better survival (but still poor px) 11 mos vs 3 mos

Front 205

Primary effusion lymphoma is a very aggressive disease, with a median survival of __ and __% 1 year survival

Back 205

- 6 months
- 39%

Front 206

Primary effusion lymphoma cells are large cells with voluminous, ___ ____ and a pale ___.

Back 206

- voluminous basophilic cytoplasm
- pale Golgi zone

Front 207

Using gene expression profiling, primary effusion lymphoma closely resembles that of a ___

Back 207

- malignant plasma cells
- may be a form of malignant plasmablastic neoplasm

Front 208

HHV8+ germinotropic large B cell lymphoma:
- occurs in __ host
- presents with __
- has a ___ response to CTX and/or XRT
- lymphoma cells infiltrate and replace ___
- immunophenotype __

Back 208

- occurs in immunocompetent hosts
- present with LAD
- favorable response to CTX and XRT
- prexisting follicles are partially or completely replaced by large, pleomorphic lymphoma cells
- plasmablastic immunophenotype:
CD20-
CD79a-
CD10- (germinal center marker)
bcl-6- (germinal center marker)
-Ig light chain restricted

Front 209

HHV8-associated lymphomas include:

Back 209

- primary effusion lymphoma (HHV8+EBV)
- germinotropic large B cell lymphoma (HHV8+EBV)
- plasmablastic lymphoma associated with multicentric Castleman disease (HHV8)
- some cases of sporadic plasmablastic lymphoma

Front 210

Lymphomas associated with HHV8 tend to have ___ features

Back 210

plasmablastic

Front 211

ALK+ large B-cell lymphoma is a __ disease. Occurs mostly in __ ___. It presents with __. It has a ___ clinical course

Back 211

- very rare!
- adult men
- marked LAD in multiple sites
- very aggressive clinical course

Front 212

As with ALCL, ALK+ large B cell lymphoma obliterates the lymph node architecture with frequent involvement of the ___. The lymphoma cells are ___ and may appear __, mimicking a __

Back 212

- sinusoids (sinusoidal pattern)
- lymphoma cells are large, with large vesicular nuclei, prominent nucleoli and abundant amphophilic cytoplasm
- may appear cohesive, mimicking a carcinoma!!

Front 213

Immunophenotype of ALK+ large B cell lymphoma

Back 213

CD45+ (68%)
CD20+ (5%)
CD79a+ (10%)
- variably positive for pan B-cell markers (more often negative)

IgA+ (50%)
CD138+ (100%)
EMA+ (100%)

ALK+ (100%)
CD30+ (24%) (unlike ALCL)
CD4+(71%)

B cell nature supported by finding Ig gene rearrangment

Front 214

ALK staining in ALK+ large B-cell lymphoma is __

Back 214

- CYTOPLASMIC and granular
- rarely nuclear and cytoplasmic

Front 215

ALK expression in ALK+ large B cell lymphoma is most often due to t(__,__)

Back 215

- t(2,17), rarely t(2,5)
- contrast with t(2,5) in ALCL

Front 216

Large B cell lymphomas with plasmablastic features are CD20__

Back 216

CD20-

Front 217

Plasmablastic lymphoma is an uncommon and highly aggressive form of ___ that encompasses ___

Back 217

- large B-cell lymphoma
- encompasses more than one entity (heterogeneous group)

Front 218

Originally defined cases of plasmablastic lymphoma were thought to occur in two settings__

Back 218

1. oral cavity and jaw of HIV+ pts
2. in setting of multicentric Castelman disease

NOW:
- can occur in both immunocompromised and immunocompetent hosts
- involves lymph nodes and extranodal sites (GI, upper respiratory tract, bone, soft tissues)

Front 219

4 types of large B-cell lymphoma with plasmablastic features include:

Back 219

1. plasmablastic lymphoma
2. primary effusion lymphoma
3. ALK+ large B-cell lymphoma
4. HHV8+ germinotropic large B-cell lymphoma

Front 220

Two histologic types of plasmablastic lymphoma are__

Back 220

- prototype characterized by large blastic cells only
-- eccentric, vesicular, round to ovoid nuclei with prominent nucleoli
-- abundant cytoplasm and a paranuclear hof

- second type has evidence of plasmacytic differentiation
-- immunoblasts and plasmablasts
-- some plasma cells present

Front 221

plasmablastic lymphoma immunophenotype

Back 221

- usually CD20- and PAX-5-
- +/- CD45, CD79a, Ig, and EMA
- CD38+
- CD138+
- MUM-1+

- Ki-67+ >90%!!

Front 222

plasmablastic lymphoma:
EBV__
HHV8__

Back 222

- EBV+ in many cases (50-74%)
- HHV8+ in only some sporadic cases
- NOTE: plasmablastic lymphoma associated with multicentric Castleman is HHV8+!!

Front 223

Distinguishing plasmablastic lymphoma from the plasmablastic type of plasmacytoma/myeloma?

Back 223

- can be difficult
- plasmablastic lymphoma is closer to lymphoma than myeloma and is NOT associated with a M-spike

Front 224

Two histologic types of plasmablastic lymphoma are__

Back 224

- prototype characterized by large blastic cells only
-- eccentric, vesicular, round to ovoid nuclei with prominent nucleoli
-- abundant cytoplasm and a paranuclear hof

- second type has evidence of plasmacytic differentiation
-- immunoblasts and plasmablasts
-- some plasma cells present

Front 225

plasmablastic lymphoma immunophenotype

Back 225

- usually CD20- and PAX-5-
- +/- CD45, CD79a, Ig, and EMA
- CD38+
- CD138+
- MUM-1+

- Ki-67+ >90%!!

Front 226

plasmablastic lymphoma:
EBV__
HHV8__

Back 226

- EBV+ in many cases (50-74%)
- HHV8+ in only some sporadic cases
- NOTE: plasmablastic lymphoma associated with multicentric Castleman is HHV8+!!

Front 227

Distinguishing plasmablastic lymphoma from the plasmablastic type of plasmacytoma/myeloma?

Back 227

- can be difficult
- plasmablastic lymphoma is closer to lymphoma than myeloma and is NOT associated with a M-spike

Front 228

Burkitt lymphoma (BL) is a __ lymphoma that often presents at ___ or as an __

Back 228

- aggressive
- extranodal sites or as an acute leukemia

Front 229

There are __ clinical variants of Burkitt lymphoma

Back 229

3 clinical variants of BL:

1. endemic BL
- equatorial Africa and Papua New Guinea
- most common malignancy in chldren in these regions
- peak incidence 4-7 yo
- M:F 2:1

2. sporadic BL
- worldwide
- mainly children and young adults
- 30-50% of childhood lymphomas
- median age of adults pts: 30 yo

3. immunodeficiency associated
- associated with HIV
- EBV+ in 25-40% of cases

Front 230

Burkitt lymphoma often presents in __ sites; a three clinical variants are associated with a risk of __ involvement

Back 230

- extranodal sites with some variation according to the clinical variants
- all three variants are at risk for CNS involvement

1. endemic BL:
- present in jaw and other facial bones (orbits) in 50% cases

2. sporadic BL:
- majority present with abdominal masses (ileo-cecal most common)

3. immunodeficiency-associated BL
- lymph node and bone marrow involvement are common

NOTE:
- RARE for BL to present as pure acute leukemia (Burkitt leukemia)
- leukemic phase usually seen with bulky disease

Front 231

Most patients with BL present with a __ tumor burden, due to __

Back 231

- high tumor burden
- short doubling time of the tumor

Front 232

Bone marrow involvement by Burkitt lymphoma is a __

Back 232

- poor prognostic sign
- seen in pts with high tumor burden

Front 233

Patients with BL who have bulky disease will have the following serum marker abnormalities

Back 233

- high uric acid
- high LDH

Front 234

BL is clinically staged. Most patients present with __ stage disease

Back 234

- advanced stage disease III and IV/IV

Front 235

With the start of therapy for BL, patients are at risk for __

Back 235

- tumor lysis syndrome
- release of intracellular components

- severe hyperkalemia with possible cardiac arrest
- hyperphosphatemia with secondary hypocalcemia
- precipitation of uric acid, xanthine, and/or phosphate in renal tubules causing severe renal failure

Front 236

EBV is positive in % of endemic, sporadic, and immunodeficiency-associated BL cases

Back 236

- endemic: 100%, EBV+ in the majority of tumor cells too!

- sporadic: <30% (EBV is less commonly associated with sporadic cases)

- immunodeficiency-associated: 25-40%


EBV is not essential for the development of BL, but likely plays a co-factor role

Front 237

Genetic abnormalities involving the __ gene at locus __ is essential for BL pathogenesis

Back 237

- MYC
- 8q24

Front 238

Classic Burkitt lymphoma cells are ___ in size and shape, the nuclei contain ___, and the nuclear diameter is approximately that of __

Back 238

- uniform in size and shape
- multiple small basophilic nucleoli
- starry sky histiocyte nucleus

Front 239

On touch imprints, classic Burkitt lymphoma cells have cytoplasm that is __ and contains __

Back 239

- deeply basophilic cytoplasm
- abundant lipid vacuoles in the cytoplasm

Front 240

Nodal involvement is __ in endemic and sporadic BL

Back 240

- RARE!!
- can see uninvolved nodes surrounded by tumor

Front 241

Morphologic types of Burkitt lymphoma include (3)

Back 241

- Classical BL
- BL with plasmacytoid differentiation
- atypical Burkitt/Burkitt-like

Front 242

Classical BL morphology

Back 242

- medium-sized cells (about the size of a starry sky histiocyte nucleus)
- DIFFUSE monotonous pattern of infiltration
- rounded nuclei with clumped chromatin
- mutiple basophilic nucleoli
- deeply basophilic cytoplasm with lipid vacuoles

- extremely high proliferation index

- starry sky pattern

Front 243

BL with plasmacytoid differentiation is characterized by __ and is seen more common in ___ BL

Back 243

- some tumor cells with plasmacytoid features: eccentric nucleus with a single central nucleolus and monotypic intracytoplasmic immunoglobulin

- seen more commonly in immunodeficiency-associated BL

Front 244

Atypical Burkitt/Burkitt-like lymphoma is characterized by ___ and requires ___

Back 244

- predmoninantly MEDIUM-sized cells
- high proliferative index (nearly 100% required)
- greater nuclear pleomorphism
- fewer more prominent nucleoli
- less consistent starry sky pattern
- DX requires proven or strong presumptive evidence of MYC translocation

Front 245

Immunophenotype of BL

Back 245

sIgM+ (monoclonal)
CD19+
CD20+
CD22+
CD79a+

CD10+
Bcl-6+

CD21+ (endemic BL, but usually CD21- in sporadic BL)

In cases of BL with plasmcytoid differentiation: monotypic cIg+

Ki-67+ (nearly 100% of cells)

CD5-
CD23-
Bcl-2- (cells are growing fast and dying fast)

In contrast to blasts of precursor B-ALL, BL has a mature B-cell phenotype

bright CD45+
CD34-
TdT-
sIg+
mature B-cell markers (CD19+, CD20+, CD22+, CD79a+)

Front 246

somatic mutations of the Ig genes in BL is consistent with a __ stage of differentiation

Back 246

germinal center

Front 247

Translocations associated with Burkitt lymphoma

Back 247

- all cases involve MYC gene (8q24) translocations
- t(8;14)(q24,q32) MOST COMMON
- t(2;8) and t(8;22) are less common

Front 248

MYC translocations are __ specific for BL

Back 248

- NOT entirely
- seen in some cases of secondary B-LBL following follicular lymphoma

Front 249

BL presenting with CNS and/or bone marrow involvement is stage __

Back 249

stage IV/IV

Front 250

endemic and sporadic BL is a highly aggressive but potentially __ disease

Back 250

- curable
- with intensive CTX: 80-90% survival
- children do better than adults

Front 251

Poor prognositc findings in BL

Back 251

- CNS and/or BM involvement
- high serum LDH
- unresected tumor >10cm

- still potentially curable

Front 252

Relapse of BL typically occurs within __ yr(s), after __yr(s) without relapse, the patient can be considered cured

Back 252

- 1yr if it is going to happen
- after 2 yrs of no replapse = cure!

Front 253

Burkitt lymphoma is one of the most rapidly growing human tumors, with a potential doubling time of __

Back 253

24-48hours

Front 254

BL makes up a __ proportion of NHL cases in AIDS patients compared to the general population

Back 254

- higher %
- 24-40% of NHL in AIDS vs <5% of NHL in general pop

Front 255

BL morphology is characterized by __

Back 255

- a monotonous infiltration of medium-sized cells with round nuclei, coarse chromatin, 2-5 basophilic nucleoli and an appreciable rim of basophilic cytoplasm
- frequent mitotic figures
- apoptotic cells
- TBM

- nuclear and cytplasmic borders often show molding and squaring off (distinctive feature) - best seen in formalin fixed tissue

- some cases show necrosis and granulomatous response

Front 256

Granulomatous response in Burkitt lymphoma is associated with EBV_, __stage disease, and __ px

Back 256

- EBV+
- early stage
- good px

Front 257

CD21 is the __ receptor

Back 257

C3d/EBV receptor

Front 258

Lymphomatoid granulomatosis (aka___) is an __ and __ lymphoproliferative disease involving __ sites

Back 258

- LYG (aka angiocentric immunoproliferative lesion)
- angiocentric and angiodestructive lymphoproliferative disease
- extranodal sites

Front 259

LYG is dominated by reactive __

Back 259

T-cells

Front 260

LYG can evolve into a __

Back 260

EBV+ DLBCL

Front 261

LYG must be distinguished from __, which also has an angiodestructive growth pattern and EBV+

Back 261

extranodal NK/T cell lymphoma, nasal-type

Front 262

Lymphomatoid granulomatosis is a __ rare disease the mainly affects __

Back 262

RARE
- mostly adults (can be seen in immunodeficient children)
- M:F 2:1

Front 263

Lymphomatoid granulomatosis most often involves __, but other sites include___

LYG RARELY invovles __ and __

Back 263

- lung (MOST COMMON)
- brian, kidney, skin, GI, upper respiratory tract

RARE: lymph node and spleen

Front 264

LYG usually present with __

Back 264

- symptoms related to pulmonary involvement (cough, CP, dyspnea)
- constitutional symptoms are common (fever, malaise, weight loss, GI)

- RAREly asymptomatic

Front 265

Lymphomatoid granulomatosis is a __-driven lymphoproliferative disorder. Patients who are __ are at increased risk of developing LYG

Back 265

- EBV-driven
- immunodeficient (including iatrogenic and hereditary causes)

Front 266

LYG most commonly present with ___

Back 266

- mulitple pulmonary nodules that vary in size
- larger lesions may exhibit central necrosis and cavitate
- lesion usually involve mid and lower lung fields

Front 267

Morphologically, LYG is charactrerized by __

Back 267

- angicentric and angiodestructive POLYMORPHOUS lymphoid inflitrate
- admixed plasma cells, immunoblasts, and histiocytes
- NO SIGNIFICANT NEUTROPHILIC OR EOSINOPHILIC COMPONENT
- NO WELL-FORMED GRANULOMAS
- SMALL number of EBV+ B cells in a prominent inflammatory background
- vascular changes: lymphocytic vasculitis, which can lead to tissue necrosis

Front 268

The EBV+ B cells in LYG may resemble __

Back 268

- RS cells, but classic RS should NOT be seen in LYG

Front 269

Grading of lymphomatoid granulomatosis is based on the proportion of __ relative to __

Back 269

- EBV+ B cells to reacitve background lymphocytes

Front 270

LYG is graded I-III

Back 270

Grade I
- large transformed lymphoid cells are RARE to ABSENT
- ISH: EBER1/2 probe - detect infrequent EBV+ cells (<5/hpf); some cases EBV-
- NO prominent necrosis

Grade II
- occasional large transformed lymphoid cells or immunoblasts seen
- polymorphous background
- necrosis more commonly seen
- ISH: readily detected EBV+ cells (5-20/hpf)

Grade III
- readily identified histologically as MALIGNANT
- numerous large lymphoid cells
- STILL MAINTAINING INFLAMMATORY BACKGROUND
- may see markedly pleomorphic and RS-like cells
- ISH: extremely numerous EBV+ cells (may see sheets of cells!)
- BASICALLY A SUBTYPE OF LARGE B-CELL LYMPHOMA

Front 271

Grade III LYG should be considered a ___, however some cases may __

Back 271

- type of large B cell lymphoma
- some cases may spontaneous regress with immunotherapy or alteration in immune status

Front 272

LYG immunophenotype

Back 272

EBV+ cells:
CD20+
CD79a+/-
CD30+/- but CD15-

LMP-1+

Background lymphocytes:
CD3+ T cells (mostly CD4+)

Front 273

By molecular techniques, most grade II or III LYG demonstrate __

Back 273

- PCR: CLONALITY (sometimes different clones in different anatomic sites)
- southern blot analysis: clonality of EBV

Front 274

In cutaneous LYG a ___ response is more commonly seen; the infiltrate is seen in the __

Back 274

- granulomatous
- infiltrate present in subcutis +/- fat necrosis

Front 275

LYG: demonstration of clonality seen in __ cases of grade II and III disease. What about grade I disease?

Back 275

- most cases of grade II and III disease exhibit clonality

- less consistent in grade I disease

- NOTE: some cases may be polyclonal

Front 276

Postulated cell of origin for LYG

Back 276

Mature B lymphocyte, transformed by EBV

Front 277

Natural history of LYG is ___.

Back 277

VARIABLE
- may wax and wan, with spontaneous remission without therapy
- MOST cases - the disease is aggressive with median survival less than 2 yrs

Front 278

Most common cause of death secondary to LYG

Back 278

progressive pulmonary involvement

Front 279

Grade III LYG show some response to ___ CTX, while grade I and II disease may respond to ___

Back 279

- aggressive CTX for grade III disease
- interferon alpha 2b for grade I and II