Nodular Lymphocyte Predominant Hodgkin Lymphoma Flashcards
What are the basic defining features of
Nodular Lymphocyte Predominant
Hodgkin Lymphoma?
- B cell neoplasm
- nodular or a nodular/diffuse pattern of growth
- many small lymphocytes with scattered, large, neoplastic B cells
- LP cells or popcorn cells
- ringed by T lymphocytes
- neoplastic cells reside in large nodular meshworks of Follicular Dendritic cells
- contain histiocytes and non-neoplastic lymphocytes
Which malignancy can have morphologic overlap
with NLPHL?
- T-cell/histiocyte-rich large B cell lymphoma
How frequent is NLPHL and what population
is often affected?
- accounts for 10% of Hodgkin Lymphoma
- predominantly males
- 30-50 years old
What is the typical localization of
NLPHL?
- rare in the mediastinum, unlike CHL
- predominantly in:
- cervical
- axillary
- inguinal lymph nodes
- Note: mesenteric lymph node involvement can be seen
- sometimes spleen and bone marrow involved in advanced disease
What are the key clinical features of
NLPLHL?
- most patients have localized peripheral lymphadenopathy (Stage I or II)
- 20% have advanced stage disease
What is the typical morphology
on H&E of NLPLHL?
- small lymphocytes, histiocytes, epithelioid histiocytes and intermingled LP cells
- can grow in nodular, nodular diffuse, or diffuse patterns
- 6 distinct immunoarchitectural patterns
When there is a prominence of extranodular
LP cells, what is that associated with?
- propensity to develop a diffuse growth pattern and look similar to THRBCL
- this is often seen in patients with a recurrence
Note: if solid/diffuse growth is present, IHC is needed to ID the LP cells
- even if there is only one area, enough to exclude THRBCL
What is the classic morphology of
LP or popcorn cells?
- .large with a single nucleus and scant cytoplasm
- can resemble popcorn with cytoplasm (folded or multilobated
- nucleoli are usually multiple and basophilic
- smaller than those seen in CHL
- can be single and prominent though occasionally
Note: histiocytes and polyclonal plasma cells can be at the edge of nodules with LP cells
- Neutrophils and eosinophils rarely seen
Which precursor or simultaneous lesion
is often associated with NLPHL?
Progressive Transformation of
Germinal Centers
Note:
- vast majority of patients with reactive hyperplasia and progressive transformation of GC do not develop Hodgkin Lymphoma
What is the typical IHC of the LP cells
of NLPHL?
- positive:
- CD20, PAX5, CD79a, BCL-6
- CD45
- OCT2, BOB1
- CD75
- Note: remaining mantle zone B cells will be weakly positive for OCT2 and CD75, LP cells will be strong positive
- J chain and EMA positive (>50%)
What is the staining of LP cells
for CD15 and CD30?
- Negative for both markers
- CHL will be positive
Note: if there are scattered CD30+ cells these are likely to be reactive immunoblasts, unrelated to the LP cells
What is present in the follicular dendritic
meshwork of the nodules of NLPHL?
- FDC highlighted by CD21 or CD23
- predominantly filled by by stander B cells and T cells of the follicular helper type
- PD1 and CD57 positive
- form rosettes around LP cells
- T cells also express germinal center markers
- BCL6, IRF4/MUM1, and CD134
- don’t produce IL-2 or IL-4
What is an interesting flow finding of
T cells that are found in NLPHL?
- double positive for CD4 and CD8
IMP: on H & E for a diffuse growth pattern the finding of T cells double positive for CD4, CD8, PD1 and CD57 favors NLPHL
What combination of IHC findings in a
diffuse growth pattern would favor a
T cell histiocyte rich B cell lymphoma?
- total absence of small B cells
- low numbers of CD57 T cells
- dominant CD8+ cells and TIA+ cells
What is the postulated normal counterpart
of NLPHL?
- germinal center B cell
- centroblastic stage of development
What are frequent genetic alterations
encountered in NLPHL?
- LP cells harbour clonally rearranged IGHV genes
- can’t detect in whole tissue
- must isolate LP cells
- high load of somatic mutations, with ongoing mutations evident
- mutations functional = IG mRNA transcripts being produced
- BCL6 rearrangements in about 50%
- Aberrant somatic hypermutations in 80% of NLPHL cases, usually PAX5
What is the EBV status of
NLPHL?
- detected in LP cells in only 3-5% of cases
- both adults and children
- incidence may be higher in Asia
- EBV can involve some of the bystander B cells occasionally
What is the relationship between NLPHL
and THRBCL?
- LP cells similar to CHL and THRBCL by gene expression profiling
- partial loss of B cell phenotype
- deregulation of many apoptosis regulators and putative oncogenes
- NLPHL and THRBCL
- express BCL6, CD75, EMA, J chain
- THRBCL may be a variant of NLPHL or just a spectrum
- difference may lie in cellular environment
What is the genetic susceptibility to
NLPHL?
- some familial clusters seen
- Hermansky-Pudlak Syndrome
- type 2
- NK-cell and T cell defects in these patients
- Patients with autoimmune lymphoproliferative disorders with mutations in FAS
What is the prognosis of classic morphology
NLPHL?
- 10 year survival (stage I and II disease)- 80%
- develops slowly with frequent relapses
- remains responsive to therapy
- rarely fatal
What variant morphologies have a worse
prognosis in NLPHL?
- LP cells outside of nodules
- B-cell depletion
- THRBCL-like architecture/transformation
- indicates advanced disease with higher relapse rate
- good to put in report
What percentage of NLPHL
progress to DLBCL?
- 3-5% of cases
- cells can resemble LP cells, immunoblastic, centroblastic
- keep the LP cell immunophenotype
- some DLBCL have been found to precede NLPHL diagnosis
- if localized have a generally good prognosis
If you are thinking that NLPHL
is involving the bone what should you
consider?
- although rare, NLPHL can involve the bone marrow
- BUT must think of THRBCL as well or transformation
- If it is NLPHL involving the bone marrow then it is clinically aggressive with worse prognosis
What is the definition of progressive
transformation of germinal centers?
- Reactive hyperplasia of the follicles:
- large follicles: 4-5x normal with hyperplastic GC
- disruption of GCs due to infiltration of mantle zone B cells
- typically affected follicles are at different stages
- cause is unknown
- virus is suspected
What age groups are usually affected by Progressive Transformation
of Germinal centers and what locations does it occur in?
- can occur in any age but usually young adult males
- 20% occur in children
- usually involves peripheral lymph nodes
- cervical lymph nodes are the most common
- axillary and inguinal less common
- can be the predominant change occuring in the lymph node biopsy
What are the symptoms/clinical presentation of patients
with Progressive Transformation of the Germina centers?
- most patients are asymptomatic with localized lymphadenopathy
- generalized lymphadenopathy seen in:
- adolescents presenting with viral like illness
- patients with autoimmune diseases
- PTGC can be incidental finding in patients with lymphoma
- Usually spontaneously resolves but can recur in same or different lymph nodes
- NOT associated with HIV
What are the findings on histology of PTGC?
- large follicles, 4-5x normal with secondary reactive follicles
- usually focal, only involves few follicles in a lymph node
- process proceeds in stages
- initial: GC become hyperplastic, starry sky pattern
- 2-3 GCs per follicle, which fuse together
- Mantle zone B cells infiltrate and disrupt GC
- Eventually GC disappears
- IMP: follicles appear to be in different stages (asynchronous)
- almost always have interfollucular hyperplasia
- rarely can show Castlemann-like changes
What disease entities can PTGC coexist with?
- NLPHL (most common)
- Classic Hodgkin lymphoma
- Plasma cell myeloma
What is the cytology of PTGC?
- mixed population of small and large lymphocytes
- Small, round lymphocytes = Mantle zone B cells and reactive T cells
- Germinal centrocytes and centroblasts
- NO LP cells or RS cells
- No plasma cells, neutrophils or eosinophils
What are the immunohistochemical findings of
PTGC?
- GC
- B cell antigens (+): CD10, BCL6
- negative BCL2
- Disruption of the follicular dendritic cells: CD21 and CD23 +
- B cell antigens (+): CD10, BCL6
- Mantle Zone
- B cell antigens (+): IgD, BCL2
- Negative: CD10 and BCL6
- B cell antigens (+): IgD, BCL2
- relatively few T cells in PTGC
