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`

review: Lymphoproliferative neoplasms..


(LPN)




list the leukemias


list 2 groups of lymphomas

LPN's:


1. def'n


2. sites of disease in Leukemia vs. Lymphoma

characteristics of transformed lymphoid cells 2

1. uncontrolled proliferation


2. failure to apoptose (for clearance of obsolete cells)

Normal Lymphocytes: review

characteristics of abnormal lymphocytes in lymphoma

tend not to die.. and will accumulate in all these lymphoid sites, leading to lumps and sometimes interfering with organ function and/or immunity

list the lymphoid "organs" 4 main




relevance: if you suspect a LPN, need to know where to look and the manifestations that an LPN in each system might have


LN's: review of clinical findings where you would suspect something



DDx for Localized Lymphadenopathy 4 categories



causes of generalized lymphadenopathy? 4 broad categories..



DDx lymph node enlargement..



H/P in abnormal LN's




note significance of ..


• smooth


• tender


• stony hard


• firm and rubbery


• fixed and matted



Investigations in Lymphadenopathy (LA)

Biopsy if no obvious cause, or very obviously neoplastic features, and the LN is persistent. 

Biopsy if no obvious cause, or very obviously neoplastic features, and the LN is persistent.

When to biopsy? 3ish

1. LN is persistent


2. cause is unclear


3. malignant features in Hx and physical

3 different types of biopsy

1. FNA


2. core


3. excisional (best if LPN suspected)

FNA: what can this tell us?

Can be done de visu orunder US or CT guidance. Material isspread on slides, architecture is not preserved and cells are somewhatdisorganized




Difficultto make a diagnosis with FNA for most lymphomas, butbecause architecture is not so important insolid tumors, FNAis often helpful '




(FNA is thus helpful in diagnosing solid tumors)

3 different types of biopsies for abnormal LN's



Utility of Core vs. Excisional biopsy

Whenwe think about lymphoma/LPN, core biopsy is often helpful, but excisionalbiopsy is preferred if possible because it permits to betterassess the pattern of involvement (architecture) and better define what subtypeof lymphoma there is. Ifsite of LN makes it difficult for an excisional bx (eg abdominal only LN that would require amajor surgery, retroperitoneal LN, ...), a core biopsy can beuseful (also, in today’s reality of difficulty getting OR time, if somethinghas to be done quickly because a patient is not well, a core will often beperformed to speed up the process)

Normal Size and weight of spleen?




and what would be abnormal findings...3



DDx splenomegaly


Neoplasm, infection, infiltration, other



workup of abnormal spleen.. H/P, investigations



note: spleen is not an easy site ot biopsy (it is very vascular and bleeds easily, so take from other sites)





eg blood smear, flow cytometry, or biopsy LN




bone marrow biopsy

Bone marrow:




what is normal wrt lymphoid cells


1. B:T cell ratio


2. overall proportion



Bone marrow: clues that LPN exists 3.

1. abnormal % lymphocytes


2. aggregates of lymphocytes seen in different pattern


3. qualitatively abnormal lymphocytes (abnormal B/T ratio, abnormal surface markers on flow cytometry)

Evaluation of lymphocytes:




what info do we get from blood smear?




from flow cytometry?

FIrst and foremost, QUALITATIVE DATA from both. 

blood smear: shape, morphology 

flow cytometry: cell surface markers, monoclonal antibodies, 

FIrst and foremost, QUALITATIVE DATA from both.




blood smear: shape, morphology




flow cytometry: cell surface markers, monoclonal antibodies,

how flow cytometry works..










How
it works is the cells are put in contact with monoclonal antibodies that will
attach to Ag on the surface of cells if present.  We usually identify t cell by tagging them
with an anti-CD3 if they are T, anti-CD19/20 if B...

Howit works is the cells are put in contact with monoclonal antibodies that willattach to Ag on the surface of cells if present. We usually identify t cell by tagging themwith an anti-CD3 if they are T, anti-CD19/20 if B cells, then can look atvarious CD expression on each of these B or T cells. That way, the percentage of B and T cells inthe blood is determined, and other markers can be looked at. Because we only have a few B cells incirculation normally, any excessive amount of B cells will be looked at, tryingto assess if they are clonal (all the same) and trying to identify the diseaseaccording to the specific CD expression.

example of markers that can be found on flow cytometry



1. List causes of benign lymphocytosis


2. duration ?


3. blood smear findings?


4. utility of flow cytometry?



causes of malignant lymphocytosis 4


duration?


blood smear findigns?


flow cytometry












Flow
cytometry is only useful if the problem is persistent and therefore thought to
be malignant (COSTLY and time consuming).  In contrast, blood smear is easy and not
expensive

Flowcytometry is only useful if the problem is persistent and therefore thought tobe malignant (COSTLY and time consuming). In contrast, blood smear is easy and notexpensive

example blood smear findings 

example blood smear findings



Causes of persistent lymphocytosis (4) along with flow cytometry findings



Most freuqent cause of persistent peripheral blood lymphocytosis?

CLL, mainly in elderly

Diagnosis of CLL? (smear and flow cytometry, + biopsy)



Other clinical manifestations of CLL



CLL: curable?

no, unless allogeneic stem cell transplant

Tx CLL



onto: approach to lymphoma

d

presentation of Lymphomas




1. physical findings 3


2. CBC findings


3. Sx


4. infections...



note: a fever due to lymphoma needs to be ...

unexplained, obvious, and persistent




if it's not severe, it's not a b symptom..

H/P for lymphoma

NB pruritis.. 

NB pruritis..

Lab investigations of lymphoma ?

higher LDH corresponds to more aggressive 

higher LDH corresponds to more aggressive

Lymphoma:




Staging, imaging, Bone marrow aspiration, LN biopsy



Staging of Lymphoma: Ann Arbor Staging System


4 stages + A/B + E + X



Dx of lymphoma subtype?

Excisional LN biopsy 

Excisional LN biopsy

Dx of lymphoma: things that you can look at in a biopsy (4)


There are MULTIPLE subtypes of Hodgkin and Non-hodgkin lymphomas

got it

Tx of Lymphoma (Hodgkin vs. NHL)



what can Rituximab treat?

CD20 positive NHL, this is the vast majority of B-cell NHLs





Pathology of NHL vs. Hodgkin's 

Pathology of NHL vs. Hodgkin's



how frequent are NHL and HD?

NHL: 18 cases per 100 000




HD: 3 cases per 100 000




incidence remains the same in males and females

age at diagnosis of NHL?












55)
NHL is a  disease of the elderly;
incidence increases after age 55-60. 
What about HD (younger patients, but bimodal F = 20-24
y of age

55)NHL is a disease of the elderly;incidence increases after age 55-60. What about HD (younger patients, but bimodal F = 20-24y of age

Clinical differences between HD and NHL


1. localized disease seen?


2. LN's involved


3. Extra-nodal involvement?


4. bone marrow involvement?


5. PB involvement?



difference in Tx of Hodgkin vs. NHL



Summary of Hodgkin's lymphoma


1. clinical presentation (age, involved nodes, sx)


2. pathology findings (key cell)


3. intent of treatment



survivorship in HL




explain the concept

also some toxicity from ABVD chemotx 

also some toxicity from ABVD chemotx

what is ABVD chemotherapy





d

NHL


1. cell of origin (B vs. T)


2. clinical behavior


3. median age


4. M;F ratio


5. nodes/ sites of disease










) If we summarize about NHL… It includes
a lot of different disease; B-cell NHL are far more common than T-cell NHL, it
is a disease of the older with slight male predominance, and widespread disease
is frequent, and it is ...

) If we summarize about NHL… It includesa lot of different disease; B-cell NHL are far more common than T-cell NHL, itis a disease of the older with slight male predominance, and widespread diseaseis frequent, and it is not rare to see extranodal and bone marrow involvement in patientwith NHL (compared to HD)

Frequency of NHL subtypes





d

B cell vs T cell NHL: markers



B cell NHL vs. T cell NHL differences




1. diagnostic markers


2. clinical presentation


3. tx


4. prognosis



B cell NHL: spectrum of behavior: 

B cell NHL: spectrum of behavior:

WHO B cell lymphoma classification 2001 (4)



Clinical behavior of agressive B-cell NHL


1. examples


2. other sites of disease


3. sx


4. tx intent


5. important complication...



tumor lysis syndrome


1. what causes it?


3. definition? 5 features



Tumor lysis syndrome: tx

hydration, allopurinol (xanthine oxidase inhib), rasburicase (changes uric acid into allantoin) and close monitoring

graphical summary of tumor lysis syndrome



Indolent B cell NHL


1. example


2. cure?


3. prognosis?


4. when to treat?





indolent B cell NHL: risk of transformation to...




(and when would we suspect this)



B-NHL: summary of aggressive NHL vs. Indolent NHL


1. most frequent type


2. goal of tx


3. when to treat?


4. when to use RT?



summary table of Lymphoproliferative neoplasms

DDx? 

DDx?

DDx anterior mediastinal mass 

DDx anterior mediastinal mass

approach to suspected LPNs


2 categories of investigations




(still on the mediastinal mass case)



note: in general, should chemo be started before the diagnosis is in?

NO. it is a big mistake to give chemo to a patient that doesn't have cancer.

note: presentation of SVC syndrome



Tx for suspected SVC syndrome from a lymphoma that we don't have a diagnosis for yet?

–Corticosteroids(dexamethasone or prednisone)»Alllymphomas are exquisitely sensitive to corticosteroids, and most rapidlyprogressive solid tumor too…

case: 57y F with 40 pack year history presents with isolated right (low) cervical LN . no sx. unremarkable lab workup.




DDx?



She is referred to ENT and FNA is performed




is this adquate?


ddx? possible sx? 

ddx? possible sx?

possible sx include B symptoms, pain from splenomegaly, pruritis, and sensitivity to EtOH, recurrent infections, .. 

possible sx include B symptoms, pain from splenomegaly, pruritis, and sensitivity to EtOH, recurrent infections, ..

investigation of generalized LA: diagnosis and staging



here's the CBC from our patient with generalized LA












(increased WBC, with absolute
lymphocytosis)







           DDx of peripheral blood lymphocytosis:
acute: mono,
other infections. Chronic: CLL       

(increased WBC, with absolutelymphocytosis)




DDx of peripheral blood lymphocytosis:acute: mono,other infections. Chronic: CLL

generalized LA case.. 

generalized LA case..

98)Remember... Treatment indications include significant LN, Bsymptoms and cytopenias (thepatient does not have any so far... But imaging should be done to help assesspossible abdominal disease)

Review: mono basics



conclusion slide