-

 Site of antigen recognition and processing / immunologic reaction

 Most are found in large draining areas like cervix/neck, inguinal area and internal
organs
 MALT have aggregates of lymphoid tissue
 Aggregates are the primary contact of antigen that drains to lymphoid tissue
 Lymphopoiesis
- Normal lymph node:
 Cortex
 Contains primary follicles that are aggregates of naïve B lymphocytes which are
Pan-B cell angtigen CD20,CD19, CD5+
 Secondary follicles w/ germinal center have CD21, Cd10, BCL6 and lack
antiapoptotic BCL2 protein
 Secondary lymphoid follicles are exposed to antigens
 Upon exposure to antigens, B cells transform, proliferate and differentiate
into plasma cells and memory B cells
 Naïve B cells are deposited at the periphery forming a mantle zone
 Centroblasts located in darkzones w/ large B cells w/ round vesicular nuclei
and small nucleoli
 Dark zones are sites of high proliferative activity and somatic mutations that
allows formation of Ig with best affinity to a particular antigen
 After darkzone, centroblasts become centrocytes located on the light zone
that are smaller cells w/ irregular nuclei and dense chromatin
 Centrocytes lose CD10 and BCL6 and differentiate into memory B cells
that are placed on the marginal zone and they gain BCL2
 Marginal zone lymphocytes have clear cytoplasm and indented nuclei
 Tingible body Macrophages w/ debris contribute a starry sky pattern of the
germinal center
 Plasma cells reside on medullary cords and also migrate to bone marrow
 Negative for pan-B cell antigens and surface Ig
 Positive for CD138 and 38
  Paracortex
 Separates follicles and medullary cords
 Occupied by immunocompetent T cells, interdigitating dendritic cells and high
endothelial venules
 T cells express pan-T cell antigens such as CD2,CD3,CD4 CD5,CD7,CD8
 HIE are gateways of lymphocytes in peripheral circulation to the lymph node
 T cells transform into effector cells in response to antigen stimulation
 They become immunoblasts that are large lymphoid cell with vesicular nuclei
and prominent nucleolus w/ abundant basophilia
 It also contains B immunoblasts

 Medulla
 Innermost portion srounding the hilum
 Composed of plasma cells in cords and medullary sinuses
 Sinuses
 Drains the lymph from afferent lymphatic vessels to efferent vessels at the hilum
 Formed by macrophages and histiocytes for antigen capture and processing
- Lymphadenopathy
1. Follicular pattern
 Most common form
 Seen in tonsils of children and adolescent in response to infection
 Prominent expansion of follicles beyond the cortex and medulla
 Secondary follicles retain hallmarks even in expansion
2. Paracortical pattern
 Associated with viral infection like infectious mono and drug reaction
 Also includes immunoblasts and vascular proliferation
 Associated with dermatopathic lymphadenopathy which manifests as
characteristic mottled appearance due to the increased number of large
histiocytes w/ abundant cytoplasm

 Monocytoid B cells can be detected that mimics HIV tand loxoplasma

lymphadenopathy
 Contains irregular nuclear outline and abundant cytoplasm

3. Sinusoidal pattern
 Commonly seen in draining limbs and inflammatory lesions or malignancies
 Manifests as expansion of Sinuses
 Lymph node is filled with histiocyte w/ abundant cytoplasm and small nucleus
4. Mixed pattern
 Commonly seen in Toxoplasma gondii infection that occurs after raw meat
ingestion of feco-oral contamination
  Follicular hyperplasia w/ irregular outline, Paracortical expansion, histiocyes in
the germinal center, and expanded sinuses w/ monocytoid B cells


- Lymphomas are neoplasms of lymphoid system
 Caused by altered immune function w/ immunocompromised patients or auto
immune patients
 Also caused by viruses, chemicals, and herbicides
- Rapapport classification – mas common
 Kiel and Working formulation is also considred
- Non-hodgkin’s lymphoma
 Mature B cell neoplasm
 Presents monoclonal light chains and Ig gene rearrangement
 Common manifestations due to light chains : Hypertension, hyperviscosity,
hypoxia, fatigue
 Occurs commonly in elderly
 Can also involve leukemic involvement
1. Chronic lymphocytic leukemia/ Small lymphocytic leukemia
 Accumulation of small lymphoid cells in peripheral blood and lymphoid
organs (memory B cells and mantle zone B cells/naïve B cells)
 5000/uL is diagnostic for CLL
 Blood and bonemarrow infiltration w/ coarse chromatin/ soccer ball
chromatin and absent nucleoli
 Bone marrow is infiltrated with small B lymphocytes


  Most are prolymphocytes
 Smudge cells is increased in number (due to increased fragility)
 Lymph nodes also contain soccer ball chromatin lymphocytes
 Presence of pseudo follicles w/ soccer ball cells is seen that is
pathognomonic to SLL
 Immunophenotypes: IgG, IgM,CD5, CD19,20,CD22,CD23, Kappa and lambda
light chains
 CD20 is expressed weakly
 Does not express FMC7, Cyclin D1 and SOX 11 that Is seen in mantle cell
lymphoma
 Usually asymptomatic (usually accidentaly findings)
 Generally affects adults
2. Prolymphocytic leukemia (derived from B or T cells)
 Mature lymphoid leukemia that involves blood, bone marrow, and spleen
 55% more than CLL requirement
 Blood involvement is more prominent
 Spleen involvement manifested as infiltration of white and red pulp
 Morphology
 B-cell PLL - medium sized punched out nucleolus ( twice as large as
normal lymphocyte
 Resembles Sezary cells
 punched out nucleolus separates PLL from CLL
 expresses Pan-B cell antigens w/ FMC7
 stronger CD20 density
 T-cell PLL – expresses CD2,3,4,5,7,8
 Lymph node involvement is more commonly seen in T cells
 Clinical features : prognosis is very poor due to aggressive malignancy
 3 years mean survival due to mutation of TP53 and unavailability of
therapy
 T-cell PLL can be treated w/ alemtuzumab
3. Hairy cell leukemia – malignancy of reticular endothelial system (fibrous tissue)
 Small B lymphocytes with abundant cytoplasm and fine hairy projections
 Cell of origin peripheral germinal center memory B cells
 Cells express pan-B cell w/ CD11c, 25, 103, and TRAP
 TRAP – ACP that resists tartrate therefore it stains positive for TRAP
 CD 123 and annexin A1 are the most specific marker of Hairy cell
leukemia
 Found in bone marrow and red pulp
 Preserves normal hematopoiesis
 Increases reticulin fibers due to fibrogenic cytokines of B cells
 May present myelofibrosis (secondary to PMF)
 TRAP – ACP that resists tartrate therefore it stains positive for TRAP
 Clinical features: Median age: 55 years
  Splenomegaly and consequent pancytopenia
 Conventional lymphoma therapy is not effective
 Usage of purine analogues for durable remissions
4. Mantle cell lymphoma
 Medium lymphocyte w/ irregular nuclear outline that comes from follicular
mantle zone
 Diffuse proliferation w/ monotonous cells
 Partial preservation of nodal structure w/ prominent mantle thickening
 Expresses pan B-cell w/ high density CD20 and light chains
 CD5 expression w/o CD23


 Main site: Lymph nodes Lymphadenopathy
 Involves GI and spleen (GALT involvement)
 Genetics : t(11;14) creation of Cyclin D1/BCL1 proto-oncogene that is
expressed
 Gene is involved in regulation of G1 to S phase
 Cyclin D1 negative cases are positive for SOX11 diagnostic for MCL
 Very aggressive lymphoma (antigen stimulated B cell)
 Median survival 3-5 years
 Bone marrow involvement and dissemintation
 Incurable w/ typical chemotherapy but SCT can be successful
5. Follicular lymphoma
 Develop from germinal center B -cell ( immature b-cells very fast to spread)
 Presence of numerous close spaced follicles that replace the nodal
architecture that may extend to perinodal adipose tissue
 Cells are composed of medium lymhpocytes that have indentations and
are similar to centrocytes w/ variable large lymhpoid cells like
centroblasts
 large lymphoid cells are more aggressive (Grade 3) treated
w/doxorubicin
 scattered large lymhphoid centroblasts (Grade1-2) are indolent
 Cells express CD 19,20, 10, BCL2, BCL6 and clonal immunoglobulin
 BCL2 is anti-apoptotic protein that allows B cell accumulation
 BCL2 is due to t(14;18) in BCL2
  Disseminated disease and bone marrow involvement
 Median age 59
 They keep their lymphoid organization when they invade organs (may
follicle sa kung ano anong organ
6. Extranodal marginal zone lymphoma of MALT
 Associated w/ autoimmune conditions or infections like Helicobater pylori
(bacilli) gastritis or hepatitis C
 Predominance of marginal zone cells w/ irregular nuclei
 Cells express normal CD markers w/o CD5 and CD10
 Persistent immune stimulation causes accumulation of reactive lymphoid
tissue and development of marginal zone lymphoma
 It did not mutate to begin with. This was caused by persistent infection
leading to altered immune response
 Occurrence of lympho-epithelial lesion that is caused by invasion of
lymphoids in the glandular epithelium

 GIT is the most common area of proliferation

 Confirmatory test: PCR, IgG, flow cytometry
 Give antibiotics to treat infection in order to remove stimulation of immune
system to allow remission
7. Plasma cell neoplasms
 Characterized by monoclonal proliferation of terminal B cells
 Large aggregates and sheets of plasma cells in bone marrow that form
clusters around vessels
 Cells have high N:C ratio w/ indistinct nucleoli
 Involves bone marrow and bone
 Accumulation of plasma cells in bone marrow presenting as lytic bone
lesions
 Monoclonal gammopathy is detected in serum and urine
 May be preceded by an MGUS condition w/ mild marrow plasmacytosis
  May present as solitary bone lesion or in extramedullary sites such as
pharynx and sinuses
 Different presence of flame cell (contains acid proteins) , grape cell, morula
cell, (russel bodies contain immunoglobulin)
 Absence of CD19 and CD20 (plasma cell differentiation)
 CD138 and 38 +
 CD56 and myeloid markers are present that are not expressed by normal
plasma cells
 Negative CD56 (blank orgin)
 Clinical features:
 Median age 70 y.o.
 Mean survival 3 years
 Bone pain and fractures
 Hypercalcemia
 Amyloidosis- Renal insufficiency due to obstruction or damage of IgG
 Cytopenia due to infiltration
 Coagulation cascade
 MM – bone resorption due to stimulation of macrophage by IgG
 WM – no bone lesions that manifest in hypervicous blood , B cell symptoms
(fatigue, fever, sweating) , Hyperviscous and hypertensive
 Rapdily progressive course ( plasma cells mitose very fast)
 Radiation theraphy can be responsive
8. Diffuse large B-cell lymphoma
 Most common non-Hodgkin’s
 Caused by diffuse proliferation of lymphocytes replacing nodal architecture
 Hallmark is large lymphocytes (twice as large) w/ multiple nucleoli
 Can originate from B cell development cells that expresses
CD5,CD10,BCL6,CD30 and CD138


 Neoplastic disease (nag mutate ung isang cell)
 Aggressive neoplasm w/ 40% proliferation rate
 Bone marrow involvement is rare
  Susceptible to multiagent chemotheraphy
 RCHOP – rimtuximab + chemotheaphy
9. Burkitt’s lymphoma/leukemia
 Proliferation of lymhpoid cells with basophilic vacuolated cytoplasm
 Hallmark: High proliferation rate due to MYC gene (cell cycle gate
keeping gene)
 Definitive diagnosis requires translocation of t(8;14), t(2;8), or t(8;22)
 Observance of Starry sky pattern by tangible macrophages that
phagocytose apoptotic debris from highly proliferative lymphocytes
 Lymphoma cells are highly basophilic with vacuolations

 Malignancy because of a viral infection (mutation) of EBV

 Occurs predominantly in HIV patients
 Pinakamabilis pumatay
 B-cell in origin and BCL6
 Endemic form- Common presentation is jaw mass (submandibular
lymphadenopathy) in children
 Sporadic form- abdominal mass in children
 Immunodeficient from – nodal disease
 Considered an emergency (pumapatay tumor lysis syndrome hyperurecimia)
10. Mature T cell and NK cell lymphomas
 Occurs more frequently in extranodal sites
11. Mycosis fungoides – skin manifestation
 Most common cutaneous lymphoma
 Small T-lymphocytes w/ irregular nuclear outlines
 Proliferates in the epidermis (dermotropism) and dermis
 Pautrier microabscesses are aggregates of neoplastic lymphocytes in the
skin and may appear as tumors
 Pan-T cell antigens w/ CD4 and absence of CD7
 

 Mukang skin infection of fungi (tinea , ringworms nagmumukang meron)

 Magakakron ng eosinophilic reaction- kakate
 Nareplace ung lahat ng squamous ng skin ng lymphocyte
 Epidermal- mild
 Dermal -severe
 Blood – Sezary syndrome
 Clinical features – incidence increases with age (55-60)
 Very slow dessimination of lymphoma
12. Sezary syndrome – systemic manifestation of erythoderma, lymphadenopathy.
And circulating Sezary cells (nuclei are cerebriform (mukang utak))
 Filled with monotonous lymphocyte infiltrates
 Evaluations:
 Atleast 1000 sezary cells
 CD4:CD8 ratio more than 10
 Loss of CD7 and CD26 on CD4 cells
 Give immune suppressants
Hodgkin’s lymphoma
13. Median age is 20-40
14. Nodular lymphocyte predominant lymphoma – popcorn cells that are mutated
but then are covered by lymphocytes that stimulated normal lymphocyte
proliferation
15. There is a cancer cell infected by epstein barr virus that cannot be removed and
lymphocytes normally proliferate as a normal immune reaction to that mutated
cell that causes organs to swell
16. Nodules of lymphocytes from normal proliferation causes the enlargement of
lymphnodes
Classic Hodgkin lymphoma
17. Presence of reed-sternbeg cell - comprosed of a group of lymphoid neoplasms
derived from the germinal center (parang same sa hodgkin’s pero reed-sternberg
cells ung present)
18. Positive for CD4 (T-cell in origin)
19. Mostly peripheral lymphadenopathy (usually is cervical lymphadenopathy)