10-28 Clone Wars - Attack of the T and B Lymphoid Drones Flashcards
(159 cards)
1
Q
What is this? What does Gomez have to say about this?
A
neoplastic lymphoid cells surround a small, atrophic germinal center, producing a mantle zone pattern of growth.
2
Q
You’re visualizing a Mantle Cell Lymphoma under high power. Dsecribe what you see?
A
a homogeneous population of small lymphoid cells with somewhat irregular nuclear outlines, condensed chromatin, and scant cytoplasm
(Large cells resembling prolymphocytes (seen in chronic lymphocytic leukemia) and centroblasts (seen in follicular lymphoma) are absent)
3
Q
What does MALT Lymphoma stand for? (softball card)
A
Marginal Zone Lymphoma
or
Mucosal-Associated Lympoid Tissue Lymphoma
4
Q
Why are marginal zone lymphomas named the way they are?
A
Initially recognized in mucosal sites and referred to as MALTomas or mucosal-associated lymphoid tissue lymphomas
5
Q
What are the body location(s) for marginal zone lymphomas?
A
Body Location and Morphology:
Extranodal (GI & Spleen) and/or lymph nodes
6
Q
Why do marginal zone lymphomas arise where they do?
A
Arise in tissues involved by chronic inflammatory disorders of autoimmune or infectious etiology
(Helicobacter pylori, Campylobacter jejuni, Sjogren syndrome, Hashimoto thyroiditis)
7
Q
What is the pathology behind the spread and possible regression of marginal zone lymphomas?
A
Remain localized for long periods, spreading systemically only late in course
If gastric, may regress if inciting agent (H. pylori) is removed
T-helper cell driven
8
Q
What is the immunophenotype of marginal zone lymphomas?
A
Positive CD19, CD79a, BCL2
Negative CD5, CD10, CD23, cyclin D1
9
Q
What’s this?
A
A type of marginal zone lymphoma, a gastric MALT lymphoma
10
Q
What sorts of translocations are associated with marginal zone lymphomas?
A
Genetics
No translocations initially but later can develop:
t(1;14) BCL10; IgH
t(11;18) MALT1;IAP2
t(14;18) IgH;IAP2
BCL10 and MALT1 activate NF-κB
11
Q
What is the prognosis associated with marginal zone lymphomas? What can these tumors progress to?
A
Excellent if inciting agent removed (80% 15 year survival)
If translocations occur then tumor does not regress with antibiotic treatment
May transform into diffuse large B-cell lymphoma
12
Q
What is the epidemiology of Hairy Cell Leukemia?
A
Rare, 2% of all leukemias
Predominately a disease of middle-aged Caucasian males (M:F 5:1)
13
Q
What is the immunophenotype associated with hairy cell leukemia?
A
CD19, CD20, CD79a, sIg, CD22, CD25, PAX5, CD11c , CD103, DBA.44, TRAP (tartrate resistant acid phosphatase)
also CD123, HC2, FMC7 and annexin A1
14
Q
What are the cytogenics behind hairy cell leukemia?
A
Cytogenetics/Molecular Genetics:
High incidence somatic hypermutation (post germinal center)
BRAF mutations
15
Q
What are the clinical features behind hairy cell leukemia?
A
Clinical Features:
Infiltration bone marrow, liver & spleen by neoplastic cells
Massive splenomegaly common
Pancytopenia with increased susceptibility to infection
Increased atypical mycobacterial infections
Leukocytosis only in 15-20%
16
Q
What is the prognosis associated with hairy cell leukemia?
A
Indolent course
Tumor cells “exceptionally sensitive” to chemotherapy
Long-lasting remission in majority of patients
17
Q
What’s this?
A
Hairy cell leukemia:
Phase-contrast microscopy shows tumor cells with fine hairlike cytoplasmic projections
18
Q
What’s this?
A
Hairy cell leukemia:
In stained smears, these cells have round or folded nuclei and modest amounts of pale blue, agranular cytoplasm
19
Q
What is often referred to as a plasma cell dyscrasia?
A
B-cell clone that usually synthesizes and usually secrets a single homogeneous immunoglobulin or its fragments
20
Q
What percentage of deaths do plasma cell neoplasms cause?
A
Cause 15% of deaths from white cell neoplasms
21
Q
We know that plasma cell dyscrasias usually synthesize and usually secrete a single homogeneous immunoglobulin or its fragments. What name do you use to refer to these components?
A
Monoclonal Ig in the blood is referred to as “M component”, monoclonal protein, dysproteinemia or paraproteinemia
22
Q
What is an important cytological finding in plasma cell dyscrasias?
A
Rouleaux in peripheral blood smear
23
Q
What’s this?
A
Plasma cell dyscrasia:
Rouleaux in peripheral blood smear
24
Q
What are Bence-Jones proteins? Where do they come from?
A
Neoplastic plasma cells often synthesize excess light or heavy chains along with complete immunoglobulins
•Free L (light) chains are known as Bence Jones protein that are primarily detected in the urine since blood levels are quickly eliminated in urine
25
Name the clinicopathological entities associated with monoclonal gammopathy.
Monoclonal gammopathy
Multiple Myeloma
Plasmacytoma
Smoldering myeloma
Heavy (Light) Chain Disease
Waldenstrom Macroglobulinemia
Primary or Immunocyte-Associated Amyloidosis
Monoclonal Gammopathy of Undetermined Significance (MGUS)
26
What is another name for multiple myeloma?
**Multiple myeloma** (plasma cell myeloma)
27
Where are plasmacytomas located? What is the prognosis?
**Plasmacytoma** (single mass)
Intraosseous – most eventually progress to multiple myeloma
Soft tissue – may be cured by local resection
28
What is the primary sign of a Smoldering Myeloma?
**Smoldering Myeloma** (asymptomatic with high plasma M component \> 3gm/dL)
29
What is the 'typical' progression of a smoldering myeloma?
**Smoldering Myeloma** (asymptomatic with high plasma M component \> 3gm/dL)
## Footnote
**~75% per progress to multiple myeloma within 15 years**
30
What is the typical finding associated with Heavy (light) chain disease?
**Heavy (Light) Chain Disease**: Secretes free H (L) chain fragments
31
What is the primary finding in Waldenstrom Macroglobulinemia?
**Waldenstrom Macroglobulinemia**: High levels of IgM
32
What is the primary finding in primary or immunocyte-associated amyloidosis?
**Primary or immunocyte-associated amyloidosis**:
free L chains leading to AL type amylodosis
33
What is the primary finding in MGUS? What is a progression sometimes associated with this cancer?
**Monoclonal gammopathy of undetermined significance (MGUS):**
M components \<3 gm/dL identified in blood, but no signs or symptoms
**~1% per year progress to multiple myeloma**
34
What would you expect to see on electophoresis with a case of MGUS? What about immunofixation?
Monoclonal Gammopathy of Undetermined Significance:
**Serum protein electrophoresis (Left)** showed a sharp peak in the gamma globulin region.
Immunofixation electrophoresis **(IFE, Right)** showed a monoclonal IgA, κ band.
35
What is the epidemiology associated with multiple myeloma?
* Incidence begins to increase substantially between ages 50 and 60 and peaks in 8th and 9th decade
* 1% US deaths caused by malignancy
* ~ 15% WBC malignancy deaths
* 10,000-12,000 cases of multiple myeloma/ year in U.S.
36
How does the incidence of mult myeloma vary by race, gender?
•Incidence varies by race; slightly higher incidence in males
## Footnote
**•9/100,000 Blacks**
**•4/100,000 Caucasians**
**•2.5/100,000 Chinese**
**•1.5/100,000 Japanese**
37
What age group is mult myeloma most frequently dx'ed in? What is median age at Dx?
Most frequently Dx'ed in age group 65-74
Median age at Dx: 69
38
What is a progression sometimes associated with mult myeloma?
Rarely develop **plasma cell leukemia** (MYC mutations)
39
What drives proliferation of mult myeloma?
**IL-6 drives proliferation**
Tumor M1P1α **upregulates RANKL** and inhibits osteoblasts (Wnt pathway)
40
What cell markers do mult myelomas often express?
**Express CD38, CD138, CD79a and cytoplasmic immunoglobulins**
(+/- CD56)
**Do not usually express CD19**
41
What signs can mult myelomas show on radiographs?
Radiographic punched-out lytic defects, usually 1-4 cm in diameter
Tumor M1P1α **upregulates RANKL** and inhibits of osteoblasts (Wnt pathway)
42
What's this?
Multiple myeloma of the skull (radiograph, lateral view).
The sharply punched-out bone lesions are most obvious in the calvarium
43
What are the common locations for mult myelomas?
Vertebrae 66%
Ribs 44%
Skull 41%
Pelvis 28%
Clavicle 10%
Scapula 10%
44
Of the plasma cell dyscrasias, which are the most prevalent by percent?
Mult myeloma --\> 80-90% PCD
Solitary Plasmacytoma --\> 5-10% PCD
Extramedullary Plasmacytoma --\> \<5% PCD
45
What is the average age of onset for mult myeloma, versus solitary plasmacytoma and extramedullary plasmacytoma?
MM - 59
SP - 56
EP - 59
46
What are the age ranges consistent for Dx of mult myeloma, versus solitary plasmacytoma versus extramedullary plasmacytoma?
MM --\> 30-80
SP --\> \<20 or \>80
EP --\> \<20 or \>80
47
What are the primary locations for mult myeloma versus solitary plasmacytoma versus extramedullary plasmacytoma?
MM --\> **Multiple bone marrow lesions**
SP --\> **Any bone;\>50% in vertebrae**
EP --\> **80-90% upper airway**
48
How often (as a percentage) are monoclonal proteins associated with mult myeloma versus solitary plasmacytoma versus extramedullary plasmacytoma?
mm --\> **99% (98-100%)**
SP --\> **43% (22-77%)**
EP --\> **27% (0-86%)**
49
Describe plasma cells seen in multiple myeloma?
Multiple myeloma (bone marrow aspirate).
Normal marrow cells are largely replaced by plasma cells, **including forms with multiple nuclei,** prominent nucleoli, and **cytoplasmic droplets containing Ig**.
50
What's this?
Plasma Cell Variants in Plasma Cell Dyscrasias "Flame Cell"
51
What's this?
Plasma Cell Variants in Plasma Cell Dyscrasias
52
What's this?
Plasma Cell Variants in Plasma Cell Dyscrasias "Russel Body" - Gihugnormous eosinophilic granule
53
What's this?
Neoplastic dysmorphic multiple myeloma plasma cells fill the marrow.
Sheets of atypical plasma cells (plasmablasts)
54
What would you expect to see on a serum protein electrophoresis for M-protein detection in mult myeloma versus a sample of normal serum?
Polyclonal IgG in normal serum (arrow) appears as a broad band; in contrast, serum from a patient with multiple myeloma contains a single sharp protein band (arrowhead) in this region of the electropherogram
55
What lab test is used to screen for suspected mult myeloma? What confirms it?
M protein detection in multiple myeloma. Serum protein electrophoresis (SP) is used to screen for a monoclonal immunoglobulin (M protein).
The suspected monoclonal Ig is confirmed and characterized by immunofixation.
56
You order an electrophoresis for a suspected mult myeloma case, which comes back positive. What do you order to confirm it, and what do you expect to see?
Polyclonal IgG in normal serum (arrow) appears as a broad band; in contrast, serum from a patient with multiple myeloma contains a single sharp protein band (arrowhead) in this region of the electropherogram.
The suspected monoclonal Ig is confirmed and characterized by immunofixation. In this procedure, proteins separated by electrophoresis within a gel are reacted with specific antisera. After extensive washing, proteins that are cross-linked by antisera are retained and detected with a protein stain. Note the sharp band in the patient serum is cross-linked by antisera specific for IgG heavy chain (G) and kappa light chain (κ), indicating the presence of an IgGκ M protein. Levels of polyclonal IgG, IgA (A), and lambda light chain (λ) are also decreased in the patient serum relative to normal, a finding typical of multiple myeloma.
57
What are the clinical features of multiple myeloma? What symptoms can they cause?
**Lytic bone lesions** → pathologic fractures and substantial bone pain
**Hypercalcemia** (metastatic calcification)
**Suppression of humoral immunity** recurrent infections
**Renal insufficiency**
58
What is the second most common cause of death in patients with multiple myeloma? What causes this morbidity?
Renal Failure
Second only to infection as cause of death
Due to toxicity of hypercalcemia and Bence-Jones proteins
59
In addition to lytic bone lesions, hypercalcemia, suppression of humoral immunity, and renal insufficiency; what are some other clinical features associated with multiple myeloma?
Increased immunoglobulins (AL amyloidosis) and Bence-Jones proteins
_Monoclonal Gammopathy:_
**IgG (60%)**\>IgA\>IgM/IgD/IgE
(15-20% produce only light chains)
Hyperviscosity with IgA, IgG3 and IgM subtypes:
Visual impairment, neurologic symptoms, bleeding, cryoglobulinemia
1% produce no monoclonal protein
60
What is the untreated prognosis for mult myeloma?
Untreated survival is 6 – 12 months from diagnosis
61
What is the prognosis for mult myeloma if treated with chemo?
With chemotherapy, median survival is 4-6 years
62
What means a good prognosis with mult myeloma?
Seems like a bit of an oxymoron, but:
Cyclin D1 translocations - good prognosis
63
What is the relative mortality of mult myeloma, by age group?
Mirrors incidence with only a shift to the right of 5-6 years
64
What is the lymphoid neoplasm that has a much higher incidence and death rate in african-americans than caucasians?
Mult myeloma
65
What are the 2 staging systems for mult myeloma? How many stages for each?
Salmon-Durie staging system
Stage I - Stage III, subclassification A and B too
International Staging System
Stages I - Stage III
66
When does lymphoplasmacytic lymphoma typically present?
B-cell neoplasm of older adults; presents in 6th & 7th decade
67
What is a common cause of Waldenstrom Macroglobinemia? What other Ig types are associated with this?
Lymphoplasmacytic Lymphoma:
Common cause of **Waldenstrom Macroglobulinemia (IgM)** but can also produce IgG or IgA
68
What are some common morphological findings associated with lymphoplasmacytic lymphoma?
Morphology: lymphocytes, plasma cells, and intermediate forms; Immunoglobulin inclusions
(Russell bodies –cytoplasm;
Dutcher bodies-nucleus)
69
What are the genetic and biochemical aberrations associated with lymphoplasmacytic lymphoma?
Genetics: MYD88 mutations leading to NF-κB activation
70
What cell markers/immunophenotype does lymphoplasmacytic lymphoma typically express?
Immunophenotype: Positive for CD19, CD79a, surface and cytoplasmic immunoglobulins (IgM, IgD, IgG or IgA); also variable CD20, and CD38
71
What are the clinical features of lymphoplasmacytic lymphoma?
**Lymphadenopathy, hepatomegaly and splenomegaly**
10% have RBC hemolysis
**~50% have Hyperviscosity Syndrome from high levels IgM**
72
What are the signs and symptoms of Hyperviscosity Syndrome?
**Hyperviscosity Syndrome from high levels IgM**
Visual Impairment
Neurologic problems: dizziness, deafness & stupor
Bleeding
Cryoglobulinemia
No lytic bone lesions
Usually no Bence-Jones proteinuria or amyloidosis
73
What is the prognosis for lymphoplasmacytic lymphoma?
Incurable with median survival 4-6 years from time of diagnosis
74
What's this?
Lymphoplasmacytoid Lymphoma
Bone marrow biopsy shows a characteristic mixture of small lymphoid cells exhibiting various degrees of plasma cell differentiation. In addition, a mast cell with purplish red cytoplasmic granules is present at the left-hand side of the field.
75
What are the peripheral T-cell neoplasms?
* Peripheral T-cell Lymphoma, unspecified
* Anaplastic Large Cell Lymphoma
* Adult T-cell Leukemia/Lymphoma
* Mycosis Fungoides/Sezary Syndrome
* Large Granular Lymphocytic Leukemia
* Extranodal NK/T-cell Lymphoma
76
What makes up 5-10% of non-Hodgkin lymphoma in US?
Peripheral T-cell and NK cell neoplasms
77
Compared to B-cell neoplasms, how do peripheral T-cell and NK cell neoplasms compare in terms of aggressiveness and prognosis?
**Much more aggressive neoplasms than B-cell neoplasms**
**Much worse prognosis than B-cell neoplasms**
****
78
Where do peripheral T cell and NK cell neoplasms occur, usually?
**Occur Predominately in Extranodal Sites**
79
How are peripheral T cell and Nk cell neoplasms Dx'ed?
**Diagnosis completely on flow cytometry marker studies**
Exhibit T-cell surface CD markers
Lack TDT
May or may not express CD4 or CD8
80
Characterize adult T cell leukemia/lymphoma according to:
cell of origin
genotype
salient clinical features
cell of origin - Helper T cell
genotype - **HTLV-1** provirus present in tumor cells
salient clinical features - Adults with cutaneous lesions, marrow involvement, and hypercalcemia; occurs mainly in Japan, West Africa, and the Caribbean; aggressive
81
Characterize peripheral T cell lymphoma, unspecified according to:
cell of origin
genotype
salient clinical features
cell of origin - Helper or cytotoxic T cell
genotype - No specific chromosomal abnormality
salient clinical features - Mainly older adults; usually presents with lymphadenopathy; aggressive
82
Characterize anaplastic T cell lymphoma, unspecified according to:
cell of origin
genotype
salient clinical features
cell of origin - Cytotoxic T cell
genotype - Rearrangements of ALK in a subset
salient clinical features - Children and young adults, usually with lymph node and soft-tissue disease; aggressive
83
Characterize extranodal NK/ T cell lymphoma according to:
cell of origin
genotype
salient clinical features
cell of origin - NK-cell (common) or cytotoxic T cell (rare)
genotype - **EBV**-associated; no specific chromosomal abnormality
salient clinical features - Adults with destructive extranodal masses, most commonly sinonasal; aggressive
84
Characterize mycosis fungoides/Sezary Syndrome according to:
cell of origin
genotype
salient clinical features
cell of origin - Helper T cell
genotype - No specific chromosomal abnormality
salient clinical features - Adult patients with cutaneous patches, plaques, nodules, or generalized erythema; indolent
85
Characterize large granular lymphocytic leukemia according to:
cell of origin
genotype
salient clinical features
cell of origin - Two types: cytotoxic T cell and NK cell
genotype - Point mutations in STAT3
salient clinical features - Adult patients with splenomegaly, neutropenia, and anemia, sometimes, accompanied by autoimmune disease
86
What is a way to break down all the different types of T cell lymphomas?
87
What does peripheral T cell lymphoma, unspecified usually present as?
•Present with lymphadenopathy and sometimes systemic signs (pruritis, fever, and weight loss)
88
What is peripheral t cell lymphoma, unspecified usually associated with?
**•T-cell lymphomas associated with lymph nodes**
89
How does the prognosis for peripheral T cell lymphoma, unspecified usually compare with B cell tumors? What is the typical survival?
•Significantly worse prognosis than comparable B-cell
## Footnote
**•Survival \< 1 year with treatment**
90
What cell surface proteins are typically expressed with peripheral T cell lymphoma, unspecified?
•CD2, CD3, CD5, αβ or γδ T-cell receptors, +/- CD4 or CD8
91
What's this?
Peripheral T-cell lymphoma, unspecified (lymph node).
A spectrum of small, intermediate, and large lymphoid cells, many with irregular nuclear contours, is visible
92
How much is lymphoma due to anaplastic large cell lymphoma, in kids and adults?
•Approximately 10-20% of childhood lymphoma and \<5% of adult lymphomas
93
What are the genetics associated with anaplastic large cell lymphoma?
ALK+ or ALK-
94
What is the pathogenesis behind ALK+ anaplastic large cell lymphoma?
* **ALK+ [anaplastic lymphoma kinase (ALK) gene** (2p23)]
* Rearrangement present more in children & young adults
* results in **fusion protein which activates tyrosine kinase (JAK/STAT)**
* Most common t(2;5) ALK and nucleophosmin (NPM) on chromosome 5
* **Excellent response to treatment when ALK+** (75% cured)
95
What is the prognosis associated with ALK- anaplastic large cell lymphoma?
* ALK-
* Usually in older adults
* poor prognosis ~other peripheral T-cell lymphomas
96
What are the cell surface markers typically associated with anaplastic large cell lymphoma?
•Markers – _CD30_, CD2, CD4, CD45, CD25, +/- CD25, _+/- ALK_
97
What's this?
Anaplastic large cell lymphoma
Several **“hallmark” cells** with horseshoe-like or “embryoid” nuclei and abundant cytoplasm lie near the center of the field.
98
What's this?
Anaplastic large cell lymphoma
Immunohistochemical stain demonstrating the presence of ALK fusion protein
99
When does adult T cell leukemia/lymphoma occur?
**Only in adults infected with human T-cell leukemia virus Type 1 (HTLV-1)**
100
What is the pathogenesis behind adult T cell leukemia?
•**Only in adults infected with human T-cell leukemia virus Type 1**
**(HTLV-1)**
•Virus encodes Tax protein activating NF-κβ
101
Where is adult t cell lymphoma endemic?
•Endemic in Southern Japan, West Africa & **Caribbean**
102
What are the signs associated with adult t cell lymphoma?
•Hepatosplenomegaly, lymphadenopathy, skin lesions, lymphocytosis, hypercalcemia
103
What is the progression and prognosis associated with adult t cell leukemia?
* Rapidly progressive; fatal within months
* Median survival 8 months
104
What is a characteristic finding in adult t cell leukemia?
•Characteristic cloverleaf nucleii
105
What's this?
cloverleaf nuclei, associated with adult t cell leukemia/lymphoma
106
What is a **CD4+ T cell lymphoma of the skin**? How does this happen?
mycosis fungoides
CLA, CCR4 & CCR10 expression leads to skin infiltration
107
What are the characteristic histological findings associated with Mycosis Fungoides?
Lymphoma cells with ceribriform nuclei
108
What are the clinical signs associated with mycosis fungoides? What is the typical prognosis?
Inflammatory (erythrodermic) pre-mycotic patch, plaque, & tumor phases
Aggressive neoplasm with median survival 8-9 years (M\>F)
109
What is Sezary Syndrome?
Mycosis Fungoides
**Sezary syndrome** is variant in which skin involvement is manifest as a **generalized exfoliative erythroderma**
110
What is a phase of Sezary syndrome? What is the survival?
Leukemic phase with **Sezary cell (cerebriform nuclei)** seen in Sezary syndrome and 25% of plaque
## Footnote
**→Survival \<3 years**
111
Describe the histological findings associated with large granular lymphocytic leukemia.
•Lymphocytes with abundant blue cytoplasm containing scattered azurophilic granules
112
What are the variants associated with large granular lymphocytic leukemia?
* Variants
* CD3+ T-cell (indolent)
* CD56+ NK cell (aggressive)
113
What are some clinical findings associated with large granular lymphocytic leukemia?
* Neutropenia & anemia despite scant marrow involvement
* Involves splenic red pulp and hepatic sinusoids (hepatomegaly)
* Associated with rheumatologic disorders
114
What is **Felty syndrome**?
Large Granular Lymphocytic Leukemia
•Associated with rheumatologic disorders - **Felty syndrome** in some (rheumatoid arthritis, splenomegaly and neutropenia)
115
What's this?
large granular lymphocytic leukemia
116
What are some other names for extranodal NK/T cell lymphoma?
•P.K.A. lethal midline granuloma, midline malignant reticulocytosis and angiocentric lymphoma
117
What happens, pathologically, in extranodal NK/T cell lymphoma?
* Most CD56+ NK cell
* Tumor cells typically surround and invade small vessels
118
What does extranodal NK/T cell lymphoma typically present as?
* Clinically presents as **sinonasal lymphoma**…..aggressive neoplasm poorly responsive to chemotherapy
* Sometimes midline skin or testes involved
119
What is an important association you should make with extranodal NK/T cell lymphoma?
**•EBV related**
120
How many different diseases make up Hodgkin Lymphoma? How do they differ?
Classical Hodgkin Lymphoma
Nodular Lymphocyte predominance
Differ in clinical features and behavior, morphology, immunophenotype, and composition of cellular background
121
How many subtypes make up classical hodgkin lymphoma? How are they different, and how are they the same?
* _Classical Hodgkin lymphoma (95%):_
* Nodular sclerosis (65-70%)
* Mixed cellularity (20-25%)
* Lymphocyte-rich (\<5%)
* Lymphocyte depleted (\<5%)
differ in their sites of involvement, clinical features, growth pattern, presence of fibrosis, composition of cellular background, number or degree of atypia of tumor cells, and frequency of EBV infection
same immunophenotype though
122
What's this?
5 cm lymph node (obviously from a patient with lymphadenopathy). The node should normally be soft, pink-tan & \< less 1 cm in size. This lymph node is involved with **Hodgkin Disease.**
123
What is the molecular pathogenesis of hodgkins lymphoma?
* Germinal center or post germinal center B-cell with V(D)J recombination and somatic hypermutation
* Aneuploid
* Activated transcription factor NF-κβ - NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells)
124
What are some cross-talk signals between Reed-Sternberg cells and surrounding normal cells in classical Hodgkin Lymphoma?
125
What is the common morphology and immunophenotype associated with nodular sclerosis subtype of Hodgkin Lymphoma?
Frequent lacunar cells and occasional diagnostic RS cells; background infiltrate composed of T lymphocytes, eosinophils, macrophages, and plasma cells; fibrous bands dividing cellular areas into nodules.
RS cells **PAX5+, CD15+, CD30+; 33% EBV+\***
126
What are the typical clinical features associated with the nodular sclerosis subtype of Hodgkin Lymphoma?
Where does it typically manifest?
What is the most common grade?
Most common subtype; usually stage I or II disease; frequent mediastinal involvement; equal occurrence in males and females (F = M), most patients young adults
127
What is the common morphology and immunophenotype associated with mixed cellularity subtype of Hodgkin Lymphoma?
Mixed cellularity (20-25%)
Frequent mononuclear and diagnostic RS cells; background infiltrate rich in T lymphocytes, eosinophils, macrophages, plasma cells;
RS cells **PAX5+, CD15+, CD30+; 75% EBV+**
128
What are the typical clinical features associated with the mixed cellularity subtype of Hodgkin Lymphoma?
In what population is this the most common Hodgkins lymphoma?
What grades are most common?
More than 50% present as stage III or IV disease; M \> F; biphasic incidence, peaking in young adults and again in **adults older than 55 MOST COMMON FORM OF HODGKIN LYMPHOMA IN PATIENTS\>50**
129
What is the common morphology and immunophenotype associated with Lymphocyte rich subtype of Hodgkin Lymphoma?
Lymphocyte rich (\<5%)
Frequent mononuclear and diagnostic RS cells; background infiltrate rich in T lymphocytes;
RS cells **PAX5+, CD15+, CD30+; EBV- (1 case)**
130
What are the typical clinical features associated with the lymphocyte rish subtype of Hodgkin Lymphoma?
Uncommon; M greater than F; tends to be seen in older adults
131
What is the common morphology and immunophenotype associated with Lymphocyte depletion subtype of Hodgkin Lymphoma?
Reticular variant: Frequent diagnostic RS cells and variants and a paucity of background reactive cells;
RS cells **PAX5+, CD15+, CD30+; 50% EBV+**
132
What are the typical clinical features of the lymphocyte depletion subtype of Hodgkin Lymphoma?
Uncommon; more common in older males, HIV-infected individuals, and in developing countries; often presents with advanced disease
133
What is the morphology and immunophenotype associated with the lymphocyte predominance subtype of Hodgkin lymphoma?
**Lymphocyte predominance (5%)**
Frequent **L&H (popcorn cell)** variants in a background of follicular dendritic cells and reactive B cells;
RS cells **CD20+, CD15-, C30-; EBV-, BCL6+**
134
What are the typical clinical features associated with lymphocyte predominance Hodgkin lymphoma?
In what body regions does this typically present?
**Lymphocyte predominance (5%)**
Uncommon; **young males** with cervical or axillary lymphadenopathy; mediastinal
135
What's this?
Diagnostic Reed-Sternberg cell, with two nuclear lobes, large inclusion-like nucleoli, and abundant cytoplasm, surrounded by lymphocytes, macrophages, and an eosinophil
## Footnote
**CD30+, CD15+, CD20-, CD45-, PAX5+, +/- EBV**
136
What's this?
Reed-Sternberg cell, mononuclear variant.
137
What's this?
Hodgkin lymphoma, nodular sclerosis type.
A low-power view shows well-defined bands of pink, acellular collagen that subdivide the tumor into nodules.
138
What's this?
Reed-Sternberg cell, lacunar variant (Nodular Sclerosis).
This variant has a folded or multilobated nucleus and lies within a open space, which is an artifact created by disruption of the cytoplasm during tissue sectioning
139
What's this?
Hodgkin lymphoma, mixed-cellularity type.
A diagnostic, binucleate Reed-Sternberg cell is surrounded by reactive cells, including eosinophils (bright red cytoplasm), lymphocytes, and histiocytes.
140
What's this?
Classical HL: Negative CD45 staining of RS cells and Variants
141
What's this?
Classical HL: CD30 membrane and paranuclear staining of RS cells and Variants
142
What's this?
Classical HL: Positive CD15 staining of RS cells and Variants
143
What's this?
Hodgkin disease, nodular lymphocyte-predominance
144
What's this?
Hodgkin lymphoma, lymphocyte predominance type.
Numerous mature-looking lymphocytes surround scattered, large, pale-staining lymphohistiocytic variants (“popcorn” cells).
145
What's this?
**Reed-Sternberg cell, lymphohistiocytic variant.**
**“Popcorn cell” of nodular lymphocyte predominance subtype !**
Several such variants with multiply infolded nuclear membranes, small nucleoli, fine chromatin, and abundant pale cytoplasm are present.
**CD20+, CD 45+, BCL6+, CD15-, CD30-, EBV-**
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What is the progression of clinical features of Hodgkin Lymphoma?
Lymphadenopathy at first
Later develop involvement of spleen, liver, marrow, etc.
B symptoms
LN, itching, abdominal pain, or vomiting with EtOH consumption
Cutaneous anergy (suppressed TH1 immune responses)
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What lymphodenopathies should you associate with each type of Hodgkin Lymphoma?
* Lymphadenopathy at first:
* _Classical Hodgkin lymphoma_
* Cervical, mediastinal, axillary, para-aortic
* Bimodal age distribution
* _Nodular lymphocyte predominance Hodgkin lymphoma_
* Cervical, axillary, inguinal
* Young males \< 35 years
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What do "B symptoms" include?
•Fever, drenching night sweats, weight loss
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What post treatment clinical features are associated with Hodgkin Lymphoma?
•Post-treatment develop myelodysplasia, leukemias, non-Hodgkin lymphoma, lung cancer, gastric cancer, sarcoma and melanoma
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What are the stages of Hodgkin and non-Hodgkin lymphomas?
Stages I-IV
All stages are further divided on the basis of the absence (A) or **presence (B) of the following symptoms: unexplained fever, drenching night sweats, and/or unexplained weight loss of greater than 10% of normal body weight**.
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What are the findings in stage I lymphoma?
Clinical Staging of Hodgkin and Non-Hodgkin Lymphomas (Ann Arbor Classification)
I
Involvement of a single lymph node region (I) or a single extra-lymphatic organ or site (IE).
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What are the findings in stage II lymphoma?
Clinical Staging of Hodgkin and Non-Hodgkin Lymphomas (Ann Arbor Classification)
II
Involvement of two or more lymph node regions on the same side of the diaphragm alone (II) or localized involvement of an extra-lymphatic organ or site (IIE).
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What are the findings associated with stage III lymphoma?
Clinical Staging of Hodgkin and Non-Hodgkin Lymphomas (Ann Arbor Classification)
III
Involvement of lymph node regions on both sides of the diaphragm without (III) or with (IIIE) localized involvement of an extra-lymphatic organ or site.
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What are the findings associated with stage IV lymphoma?
Clinical Staging of Hodgkin and Non-Hodgkin Lymphomas (Ann Arbor Classification)
IV
Diffuse involvement of one or more extra-lymphatic organs or sites with or without lymphatic involvement.
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What are the cure rates associated with stage I/IIA in Hodgkin Disease? Stage IV?
**Hodgkin Disease Cure Rate Stage I/IIA almost 90%;**
**Stage IV 5 year survival 60-70%**
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What are some major differences between Hodgkin and non-Hodgkin Lymphoma? Distinguish between:
age of onset
locality
spread
LNs involved
extranodal involvement
response to therapy
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What should you think of when asked about the age of initial diagnosis with Hodgkin Lymphoma?
**“Bi-Modal Peaks” 20-29 years, \> 70 years**
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What should you think of when asked about age of initial diagnosis for non-Hodgkin Lymphoma?
Large majority after age 50
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