Lymphomas 2-hd
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Transcript of Lymphomas 2-hd
Lymphomas – Hodgkin’s Disease
Dr.CSBR.Prasad, M.D.
Lymphoreticular system
Hodgkin’s disease
• B-cell neoplasm.• Characterised by the presence of RS-giant cells• RS-giant cells make only minor fraction of the
tumor.• Major fraction is formed by the cytokine recruited
inflammatory cells.• Age: Bimodel age distribution (2nd and 6th decade).
Patients usually present with a slowly expanding, non-tender lymph node, mostly cervical, axillary, or inguinal. Only rarely are axial abdominal and pelvic lymph nodes or Waldeyer's ring involved initially.
Hodgkin’s disease
Classification ( 5 types):1. Classic HD --Nodular sclerosing --Lymphocyte rich --Lymphocyte depletion --Mixed cellularity2. Nodular Lymphocyte predominant variety
Hodgkin’s disease
Nodular Lymphocyte predominant variety
In this variety RS cells have a characteristic B-cell immunophenotype distinct from that of the classical HD subtypes.
Hodgkin’s disease
RS-giant cell:-15-45µm in diameter.-Single or multiple nuclei-Each nucleus will have large inclusion, the
size of a lymphocyte / RBC.-Perinuclear halo / clearing.-Cytoplasm is abundant.-Positive for CD 15 and CD 30 and negative
for CD 45 and B&T markers.
Hodgkin’s disease
A patient of Dorothy Reed.
Hodgkin’s disease
Binucleate diagnostic Reed-Sternberg cells
Hodgkin’s disease
Size of the nucleolus is that of a lymphocyte (arrow) / RBC (circle)
Hodgkin’s disease
RS-giant cell
Diagnostic Reed-Sternberg cells
Hodgkin’s disease
RS-giant cell
Hodgkin’s disease
In this case CD30 (left) stains the cytoplasm of the Reed-Sternberg cells diffusely and also the perinuclear Golgi apparatus. CD15 (right) shows crisp membrane staining as well as Golgi staining.
Hodgkin’s disease IHC of Reed-Sternberg cell
Cytokines /chemokines and their possible main clinical and biological effects
Hodgkin’s disease
IL-1/TNF-alfa Systemic symptoms
IL-5 Eosinophilia
IL-6 Plasma cell response
IL-8 Neutrophil recruitment
TGF-ß Fibrosis & immunosupression
IL-13 & IL-9 Autocrine pathways
IL-7 Inflammatory infiltrate
Source: Hematol Oncol 2001; 19: 1-17
In fact to make the diagnosis of HL microscopically, two findings are needed:
1) Reed-Sternberg cells and variants and 2) an appropriate inflammatory background.
The inflammatory response is ultimately the result of cytokines produced by the tumor cells.
Hodgkin’s disease
LYMPHOCYTE PREDOMINANCE HODGKIN'S DISEASE
It is likely that this category of Hodgkin's disease contains two discrete entities:
1-Classic Hodgkin's disease, representing the end of the spectrum of mixed cellularity in which Hodgkin cells are relatively infrequent.
2-Nodular lymphocyte predominance in which nodularity is minimal or absent
There are two critical features for the diagnosis of this subtype:
1-the rarity of Hodgkin cells (RS-cells) and 2-the absence of fibrous bands (diagnostic of
nodular sclerosis)
LYMPHOCYTE PREDOMINANCE HODGKIN'S DISEASE
Small lymphocytes generally dominate the reactive element, although, contrary to what the name of the subtype might imply, the predominance of lymphocytes is not the defining feature. Histiocytes are variable in number; eosinophils are generally few in number.
LYMPHOCYTE PREDOMINANCE HODGKIN'S DISEASE
Mixed Cellularity Hodgkin Disease
1- Variety of different cell types in the background inflammatory component.
2- It lacks the fibrous bands (of the nodular sclerosis subtype)
3- Has more numerous Reed-Sternberg cells, and
4- Has a slightly worse prognosis.
The inflammatory infiltrate includes lymphocytes, eosinophils, neutrophils, and histiocytes. Though not seen here, plasma cells might participate also.
Mixed Cellularity Hodgkin Disease
Nodular sclerosis is a bit of a specialty item.
1-More common in women than men, and it 2-Very often presents with a mediastinal mass. 3-Named for the dense fibrous bands that subdivide
involved lymph nodes, 4-It has a prognosis slightly better than mixed
cellularity HL. 5-A morphologically variant Reed-Sternberg cell called
the "lacunar cell" is found (In formalin-fixed tissue)
Nodular sclerosis variety of Hodgkin Disease
Nodular sclerosis variety of Hodgkin Disease
Lacunar cells are a feature of nodular sclerosis Hodgkin disease and are not found in other subtypes. In formalin-fixed tissue, the cytoplasm around Reed-Sternberg cell nuclei retracts, leaving a cleared space possibly
spanned by a few shreds of cytoplasm. The nuclei are also contracted and have diminished nucleoli.
Nodular sclerosis variety of Hodgkin Disease
A diagnostic (multi-nucleated) Reed-Sternberg cell lies dead-center. Just below it is a non-diagnostic, uninuclear cell that has been called a "Reed-Sternberg variant" or a "Hodgkin" cell. Although this cell is characteristic of Hodgkin disease, the pathologist
who plays by the rules will scrutinize a node suspected of Hodgkin disease involvement until a diagnostic cell is found.
Nodular sclerosis variety of Hodgkin Disease
Lymphocyte Depletion Hodgkin Disease
Necrosis is prominent in the center, surrounded by many Reed-Sternberg cells. Some cases of lymphocyte depletion contain swarms of very atypical cells, sometimes sufficiently bizarre to merit the label of "sarcomatoid".
Nodular Lymphocyte-Predominance Hodgkin's Lymphoma
1-Have a B-cell immunophenotype (i.e. CD-20+)2-Negative for CD15 and CD30 3-Typical Reed-Sternberg cells are absent4-Polylobated variants called L & H cells
(Lymphocytic and/or histiocytic; colloquially "popcorn cells” are seen.
Additional distinctive clinical features setting apart nodular lymphocyte predominance HL include:
• an indolent though relapsing course with an excellent prognosis;
• occasional cases relapsing as high-grade B-cell non-Hodgkin's lymphoma;
• a peak incidence in males in their 30's and 40's, without the bimodal age pattern of classic HL;
• a greater tendency to be restricted to cervical lymph nodes.
Nodular Lymphocyte-Predominance Hodgkin's Lymphoma
L & H cells OR“Pop corn” cells
Nodular Lymphocyte-Predominance Hodgkin's Lymphoma
L & H cells
Nodular Lymphocyte-Predominance Hodgkin's Lymphoma
L & H cells
Nodular Lymphocyte-Predominance Hodgkin's Lymphoma
ImmunophenotypeThe immunophenotypes of the Reed-Sternberg cells and variants in the two subgroups of HL are mirror
images:
CD15 CD30 LCA(all
leukocytes)
CD20(B-
cells)
EMA
Classic Hodgkin + + – – –Lymphocyte Predominance
– – + + +
Hodgkin's Lymphoma (HL) Non-Hodgkin's Lymphoma (NHL)
Stage / Grade Because HL begins as a localized process that spreads slowly from one nodal region to another, stage (degree of spread) is important. In some cases grade may be significant, but it is mostly unremarked.
Because NHL is usually systemic from the get-go, grade influences prognosis and therapy more than stage.
Source of Mass Neoplastic cells are usually <1% of the mass, which is mostly benign inflammatory cells
Almost all the mass is neoplastic lymphoid cells
Immune Deficiency Usually cell-mediated (T-cell): mycobacterial, fungal, viral, & protozoal infections.
Usually humoral (antibodies from B-cells): bacterial infections.
GI / Waldeyer's Involvement Rare. Common.
Marrow Involvement Significant. In many cases not important.
Extra-Nodal Involvement 10% of cases 40% of cases.
Treatment HL is always treated, but milder, localized cases may receive only radiotherapy.
Indolent NHLs may remain untreated for years. Almost all treatment, however, is for systemic disease and thus utilizes chemotherapy. Radiotherapy may be an adjunct.
Ann Arbor Staging ClassificationStage I
Involvement of a single lymph node or extra-lymphatic site (IE) Stage II
Involvement of 2 or more lymph node regions on the same side of the diaphragm or localized involvement of an extra-lymphatic site (IIE)
Stage III Involvement of lymph node regions on both sides of the diaphragm or
localized involvement of an extra-lymphatic organ or site (IIIE) or spleen (IIIS) or both (IIISE)
Stage IV Diffuse or disseminated involvement of one or more extra-lymphatic
organs with or without associated lymph node involvement
The stage can also have a designation of "A" for asymptomatic or "B" for constitutional symptoms.
Hodgkin’s disease - staging
To make a patient "B", the patient must have one or more of the following:
1-Unexplained fever >38° C 2-Night sweats at least of moderate severity 3-Weight loss must be at least 10% of initial body weight
in the 6 months preceeding evaluation.
Other potentially important symptoms of HL such as fatigue, alcohol related pain or pruritus are not considered in the staging system.
----Hoffbrand's PG-Hematology 3rd Ed, 507p.
Hodgkin’s disease - staging
Prognosis is dictated by:
1-Bulk of the tumor2-Stage of the disease
Histological variety has very little role to play in determining the prognosis.
Hodgkin’s disease - staging
Which is a better term?
Hodgkin’s Lymphomaor
Hodgkin’s Disease ?
Hodgkin’s disease
E N D