1. The document discusses various subtypes of non-Hodgkin lymphomas including diffuse large B-cell lymphoma and its rare morphologic variants and molecular subgroups. 2. Burkitt lymphoma is summarized as a highly aggressive B-cell lymphoma characterized by a diffuse growth pattern, medium sized cells with distinctive features, and a t(8;14) translocation in the majority of cases. 3. Primary mediastinal large B-cell lymphoma is described as a subtype typically occurring in young adults that commonly presents as an anterior superior mediastinal mass.

1. 1
NON-HODGKIN LYMPHOMAS
PRESENTED BY - DEEPIKA

2. 2
A. LARGE CELL NHL – B LINEAGE
1) Diffuse large B-cell lymphomas (DLBCL)
[NOS, & other subtypes]
2) Plasmablastic lymphoma
3) Primary mediastinal (thymic) large B-cell lymphoma
4) Intravascular large B-cell lymphoma.
5) DLBCL a/w chronic inflammation.
6) Lymphomatoid granulomatosis.
7) ALK- positive LBCL
8) Large B-cell lymphoma arising in HHV8-associated
Castleman disease.
9) Primary effusion lymphoma.

3. 3
DIFFUSE LARGE B-CELL
LYMPHOMAS

4. Rare morphologic variants
 Myxoid
 Spindle
 Fibrillary matrix
 Signet ring cell morphology
 Alveolar
 Rosette formation
 Increased eosinophils
 Microvillous morphology
 Admixed crystal-storing histiocytosis
 lntrasinusoidal
Molecular subgroups
 GCB-Iike
 ABC-like
Immunohistochemical subgroups
 CD5-positive de novo DLBCL
 GCB-Iike
 Non-germinal center 8-cell--like

5. RARE MORPHOLOGIC
SUBTYPES

6. C: The lymphoma cells form an alveolar pattern defined by the fibrovamuscular
stroma. mimicking the architecture of rhabdomyosarcoma because of the alveolar
architecture
D: The lymphoma cells form an intrasinusoidal infiltrative pattern mimicking
metastatic carcinomas.

7. DLBCL with abundant myxoid stroma
mimicking extraskeletal myxoid
chondrosarcoma or myxofibrosarcoma
DLBCL with spindle morphology The large
lymphoma cells show elongated and
spindle nuclei, dense chromatin, indistinct
nucleoli, and a broad rim of cytoplasm.

8. DLBCL with fibrillary matrix. The large lymphoma
cells are associated with abundant eosinophilic
fibrillary matrix. The matrix is actually formed by
cell membrane materials from the lymphoma as
demonstrated by positive CD20 immunostaining.

9. g) signet ring cell features. The large lymphoma cells have eccentric
nucleus, dense
chromatin, indistinct nucleoli. and abundant eosinophilic cytoplasm.
h) DLBCL with rosette formation. The large lymphoma cells are associated
with rosette structures. The rosette matrix is actually formed by cell
membrane materials from the lymphoma cells, and is positive for CD20.

10. Molecular subtypes
Using GEP, DLBCL is divided into subgroups
reflecting different stages of B-cell differentiation:
germinal center B-cell-like (GCB)-DLBCL and
activated B-cell-like.
-GCB-DLBCL patients demonstrate a phenotype
or B cells in the dark zones or the GC, the
stage in which B cells undergo somatic mutations
in the variable region of the Ig gene.
-ABC-DLBCL cases do not have ongoing
mutations and are possibly derived from a late-
GC (light zone) or post-GC stage plasmablasts .

11. Germinal center B-cell like(GCB) molecular subtype.The lymphoma cells exhibit
typical centroblastic morphology.
b) Strong staining for CD 10

12. C: Strong staining
for Bcl-6. D. The
lymphoma cells are
not immuno-
reactive for MUM· I
and FOXP F) high
Ki-67 index of 70%
to 80%. G) ABC-
like or non-GCB
molecular subtype.
&: The lymphoma
cells show cleaved
or anaplastic
morphology . H)
The lymphoma
cells are not
immunoreactive for
CD-10.

14. Hans algorithm (three markers)

15. ADVERSE PROGNOSTIC
FEATURES

16. Differential diagnosis of DLBCL
 Infectious mononucleosis
 Kikuchi lymphadenitis
 Burkitt lymphoma
 Mantle cell lymphoma pleomorphic type
 Anaplastic plasmacytoma
 Classical hodgkin lymphoma
 Myeloid sarcoma
 Histiocytic sarcoma
 Peripheral T-cell lymphoma
 Non hematolymphoid malignancies(met. Melanoma or
ca)
 Nk-cell lymphoma

17. DIFFERENTIAL Dx OF DLBCL
A)Burkitt lymphoma. The lymphoma cells show monotonous cell size and
nuclear features.
The neoplastic cells are clonal with a CD45+, CD20+. Pax-5+. CD lO+, Bcl-2,
MUM-I-, Bcl-6+ immunophenotype, and a high proliferation index of 100% by Ki-
67 expression. B) Pleomorphic and blastoid MCL: The lymphoma cells are
medium sized and immunoreactive for CD20 and show a high proliferative
index. Staining for cyclin D1 is essential for differential diagnosis.

18. Infectious mononucleosis-subtotal effacement
of lymphoid tissue by large lymphoid cells, in
association with multifocal necrosis.
raising the consideration of DLBCL..
The tonsil is commonly involved and exhibits
ulceration and multifocal necrosis. C: There are
often many CD3+cells, including some large T
immunoblasts. The valuable clue to the correct
diagnosis of infectious mononucleosis is partial
preservation of normal lymphoid tissue architecture,
such as the sinuses and lymphoid follicles.

19. - Classical Hodgkin lymphoma. Findings to support the dx Include the +nce of mixed ICI
background, unique Hodgkin cell morphology and immunophenotype.
D: Peripheral T·cell lymphoma. The lymphoma cells may have
•centroblastic" features in a background of clusters of epithelioid histiocytes. The
lymphoma cells are medium sized and show clear cytoplasm with patchy distribution in
the lymph node.

20. : Nasal NK/T cell lymphoma. The lymphoma cells can form large aggregates with
clear cytoplasm,extending into the superimposed squamous epithelial cells. In this
case, the lymphoma cells are large sized, and possess eosinophilic cytoplasms and
2-3small prominent nucleoli.
F: Myeloid sarcoma-. The myeloid blasts show morphologic similarities to DLBCL.
Flndings to support the dlagnosis include the presence of intermingled eosinophilic
myelocytes and eosinophilic cytoplasm with granules. Myeloperoxidase and
nonspecific esterase stains highlight specific lineage of differentiating myeloid and
monocytic cells.

21. C: Chronic myelogenous leukemia and chronic myelomonocytic leukemia involving the
lymph node. The differentiating myeloid and monocytic cells show morphologic
similarities to diffuse B-cell lymphoma. Findings to support the diagnosis include the
presence of eosinophilic myelomonocytic cells, the eosinophilic cytoplasm with
granules. and other hematopoietic cells.
H: Histiocytic sarcoma-Findings to support the dx include the irregular nuclear features,
eosinophilic cytoplasm and inflammatory background.S-100 & CD 68 confirms cell
origin

22. 36
DEFINITION:
EBV+ clonal B-cell lymphoid proliferation that occurs in
patients >50 yrs. & without any known immunodeficiency
or prior lymphoma.
CLINICAL FEATURES & OUTCOME:
 In Asian countries accounts for 8–10 per cent of DLBCL
 20–25% of patients aged> 90 years (mean age 71 yrs)
 30% nodal, 50% nodal & extranodal; 20% extranodal
only
 Extranodal sites most commonly skin, lung, stomach &
EBV positive DLBCL of the elderly

23. 37
MORPHOLOGY:
 coagulative necrosis &
angiocentric-
angiodestructive growth
common.
 Polymorphic or
monomorphic.
 Some bizarre large cells,
may resemble RS cells.
IHC:
•Tumour cells usually
CD20 &/or CD79a.
•Large cells & RS-like cells
often CD30+ve but CD15-
ve.
•Tumour cells express

24. OTHER LYMPHOMAS OF LARGE B-
CELLS
38
1) Primary mediastinal (thymic) large B-cell
lymphoma
2) Intravascular large B-cell lymphoma.
3) DLBCL a/w chronic inflammation.
4) Lymphomatoid granulomatosis.
5) ALK- positive LBCL
6) Plasmablastic lymphoma
7) Large B-cell lymphoma arising in HHV8-associated
Castleman disease.
8) Primary effusion lymphoma.

25. Primary mediastinal (thymic) large B-cell
lymphoma
39
 Pred. in young adults
(median age~35 yrs). F>M
 Localised ‘bulky’ antero-
sup. mediastinal mass;
invading adjacent
structures.
 5-year survival 64% >
DLBCL (46%).
FIG (a) The tumor
frequently exhibits
prominent sclerosis,
resulting in a packeted
pattern.
FIG (b) presence of septa,
clear cells & admixed
lymphocytes can produce a

26. 40
FIG. (A) Lymphoma
cells are large,
possess round
nuclei,clear
cytoplasm; can be
mistaken for
seminoma cells.
FIG. (B) Chr. folded
nuclei &
abundant lightly
eosinophilic
cytoplasm.
Tumor traversed
by delicate
sclerotic bands.

27. Intarvascular large B- cell lymphoma
41
 Rare type of
extranodal
DLBCL.
 Pred. manifests
as neurological or
cutaneous
disease.
 Blood vessels,
esp. capillaries,
filled with large
mononuclear
cells. Some
lymphoma cells

28. DLBCL a/w chronic inflammation
42
 A/w long standing chr. Inflammatn,
EBV
 Mostly involve body cavities or
marrow spaces.
 Pyothorax associated lymphoma
(PAL) is the prototypic form.
Fig.A) CT scan showing
pleural tumor mass with
invasion of chest wall &
pleural effusion.
Fig. B) Lymphoma
comprises large cells
with moderate amount
of cytoplasm, which are
+ve for EBNA2 (inset).

29. Lymphomatoid granulomatosis
43  occurs in patients
with overt
immunodeficiency
or underlying
↓immune function;
EBV related.
 Mostly pulmonary
involvement; LN,
spleen usu. spared.
 EBV +ve large B-
cells admixed with
reactive T-cells.
 Patients with grade
III disease
regarded as having
FIG. In this lung lesion there is a
dense lymphoid infiltrate with central
geographic necrosis. The blood
vessels show mural invasion by the
lymphoid cells (angiocentric–

30. 44
FIG. -
Lymphomatoid
granulomatosis
type, grade III.
• Left: Many
large atypical
cells are
present, & the
cell
composition is
similar to that
of large cell
lymphoma.
• Right upper:
large number of
CD 20 +ve
neoplastic cells
(B lineage)
infiltrating the
blood vessel
wall.
• Right lower:

31. ALK positive LBCL
45
 V rare; LNP/ mediastinal
mass.
 ALK +ve monomorphic
large immunoblast-like B
cells, sometimes with
plasmablastic differentiatn.
FIG. A) - LN showing
characteristic sinus infiltration.
FIG. B) - Higher power view
showing regular rounded
immunoblastic cells with
prominent single central
nucleoli.

32. 46
FIG. - ALK-positive large B-
cell lymphoma stained for
ALK1. Note the granular
positivity characteristic of
the ALK1/clathrin gene
translocation.
FIG. – ALK +ve large B-
cell lymphoma stained for
CD138,
showing strong positive
staining of the tumour
cells.

33. DEFINITION
47
 It is a diffuse proliferation of large neoplastic cells
most of which resemble B immunoblasts, but in
which all tumor cells have the immunophenotype of
plasma cells.
CLINICAL FEATURES
• Uncommon; a/w HIV & may be other immunodef.
states.
• Mainly adults; mean age 50 yrs.
• Presents most frequently as a mass in the oral cavity.
• Also encountered in other extranodal areas- esp.
mucosal sites- e.g. sinonasal cavity, orbit.
• Most patients +nt at an advanced stage (III or IV).
PLASMABLASTIC LYMPHOMA

34. MORPHOLOGY
48
 Two histologic subtypes are recognized.
 Prototype:
 Chr. by large blastic cells showing a monomorphic
cohesive quality.
 Round to ovoid eccentric nuclei, with single central
large or several peripherally located nucleoli.
 Cytoplasm is abundant & basophilic to amphophilic,
with a prominent paranuclear hof.
 Apoptosis is prominent, & mitotic activity is brisk.
 TBM often present, imparting a starry-sky appearance.
 2ndsubtype: is chr. by presence of plasmacytic
differentiation. Immunoblasts & plasmablasts
predominate.

35. 49
FIG. - Plasmablastic lymphoma. The large lymphoma cells have
amphophilic cytoplasm & large nucleoli. Plasmacytic maturation is
present.

36. IMMUNOCYTOCHEMISTRY
50
 The tumour cells usually show loss of CD45 & CD20.
 Express plasma cell-associated antigens CD38 &
CD138
 EBER positive (50-74%).
 Ki67 index is often very high (>90%).
PROGNOSIS
• Usually locally invasive, shows early systemic
dissemination
• Poor response to therapy & short survival.

37. Primary effusion lymphoma
51  Usu. presents as
an serous
effusion without
solid tumour.
 Occurs in pts.
with immunodef.,
usu. AIDS.
 Universal a/w
HHV-8 (KSHV).
 2nd ry solid
tumors may
develop in
adjacent
structures, eg.
pleura.
FIG. - Primary effusion lymphoma
(Giemsa-stained smear of pleural
fluid). Huge cells with pleomorphic
nuclei & abundant basophilic

38. Burkitt lymphoma
Endemic Burkitt lymphoma
 Childhood predominance (peak age 4-7 yrs)
 a/w EBV in majority of cases
 M/F- 2:1
 Sites of involvement: jaws & other facial bones (orbit)
Sporadic Burkitt lymphoma
 Children and young adults
 EBV in 30%
 Sites of involvement: ileo-caecal region (M.C), abdomen
Immunodeficiency-associated Burkitt lymphoma
 Seen in a/w HIV infection
 EBV in 25-40% cases

39. Morphology
 Diffuse monotonous pattern of growth
 ‘Starry-sky’ pattern
 Medium sized cells
 Round nuclei, 2-4 nucleoli, coarsely granular
chromatin
 Strongly basophilic cytoplasm
 Cytoplasmic lipid droplets/vacuoles
 “Squaring” of cytoplasmic outline
 Many mitotic figures & apoptotic bodies
 Granulomatous reaction and plasmacytoid
differentiation

40. Monotonous lymphoid infiltrate with a starry-sky
appearance

41. The neoplastic cells are medium sized and show “squaring off” of
the nuclear membrane and cell membrane. Typical coarse chromatin,
multiple distinct nucleoli, and frequent mitoses. Many apoptotic
bodies are seen.

42. Immunophenotype
 CD19+, CD20+, CD10+,
BCL6+, CD5-, BCL2-
 Surface IgM positive
 Ki-67, approximately 100%
GENETICS
 t(8;14) in 80%
 t(2;8) or t(8;22) in 20%
Ki-67
PROGNOSIS
One of the most rapidly growing tumors
Intensive chemotherapy result in cure rate of 60-90%
Unresected tumor size >10cm & high serum LDH are
poor prognostic factors

43. Distinction Between Lymphoblastic and Burkitt
Lymphoma
Lymphoblastic Lymphoma Burkitt Lymphoma
Nuclei
Round or convoluted; usually no
significant molding
Usually round; prominent nuclear
molding, with “squaring” of
nuclear membrane
Chromatin
pattern
Fine, dusty Coarsely granular
Nucleoli Inconspicuous Distinct, 2-5 nucleoli,
Cytoplasm Scanty and barely visible.
Definite rim of basophilic
cytoplasm, with “squaring” of
cytoplasmic outline. Small lipid
vacuoles
Lineage
Usually T lineage, sometimes B or
NK lineage
Always B lineage