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)


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.


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

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.


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.


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.


L & H cells OR“Pop corn” cells


L & H cells


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.


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.


Which is a better term?

Hodgkin’s Lymphomaor

Hodgkin’s Disease ?

Hodgkin’s disease

lymphomas 2-hd

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