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Gastrointestinal (GI) lymphomas

Posted Sept. 1, 2016. Pathology

40% of the lymphomas are extra- nodal and Gastrointestinal (GUT) tract is the more common site.

1 to 4% malignancies of GUT are lymphomas.

Definition: Primary GI lymphoma shows no evidence of liver, spleen, or bone marrow at the time of diagnosis (regional lymph nodes may be involved).

GI lymphomas are seen in certain population like:

  1. Patients with helicobacter gastritis.
  2. Natives of mediterranean people.
  3. Patients with congenital immune deficiency.
  4. HIV- infected individuals.
  5. Patients with immunosuppressive therapy.
  6. Patient with sprue disease.

Sporadic  Lymphoma

  • This is termed as Western type lymphoma .
  • This arises from B - lymphocytes, mucosa associated lymphoid tissue (MALT).
  • These differ from nodal lymphoma:
  • Usually there is local disease, which may be resectable.
  • There may be relapse.
  • Genotype is different and unique 11:18 has been found in MALT (Translocation).

G I Lymphoma

Age : Usually affect adults.

Sex: There is no predilection.

Site: There is involvement of :

  • stomach = 55 to 60%
  • Small intestine = 25 to 30%
  • Proximal colon = 10 to 15%
  • Distal colon = upto 10%
  • Appendix and esophagus = Rare
H.Pylori Role: This bacteria produces cytokines which activates T-Helper cells and it leads to monoclonal proliferation of  B- lymphocytes.
  • Antibiotics treatment may cause regression of the tumor.

Sprue associated Lymphoma  the tumor in stomach.

  1. This will arise in some patients with long standing malabsorption syndrome.
  2. This is common in the younger age group 30 to 40 years of age.
  3. Most often seen in the proximal small intestine.
  4. This may be T - lymphocyte origin in response to gluten derived antigen.
  5. Overall prognosis is poor.

Mediterranean Lymphoma

  1. This is unusual intestinal B- lymphocyte lymphoma in patient with mediterranean ancestry.
  2. There is background of chronic diffuse mucosal plasmacytosis.
  3. This plasmacytosis produces abnormal IgA - heavy chain (V- portion deleted).
  4. There is history of malabsorption and now called as immunoproliferative small intestinal disease (IPSID)>
  5. There is response to antibiotics.

 


Childhood Lymphoma

Posted Sept. 1, 2016. Pathology

These lymphomas  are never nodular.

These are more aggressive lymphomas.

Majority become leukemic.

Burkitt’s Lymphoma

  • Age: Usually these lymphoma starts at 7 years.
  • Site: Common site is Jaws (mandible and maxilla).
  • EBV is associated in 98% of the cases.
  • EBV antibodies are seen in 100% of the cases.
  • Child when develop after the age of 13 years have poor prognosis then the younger patients.

Non-Burkitt’s Lymphoma

  • This is seen in 60% of the childhood lymphomas.
  • Age: Median age is 34 years. While it can be seen from 10 to 70 years of age.
  • Sex: male to female ratio is same.
  • Sites: This can be seen in lymph nodes, bone marrow, central nervous system, gastrointestinal system, liver and ovaries.
  • Histology: There is infiltrate of pleomorphic cells.
  • Majority are small non-cleaved cells.
  • There is less repose to treatment.
  • These lymphomas are treated aggressively like large cell lymphoma.

 


Large Cell Anaplastic lymphoma (Ki- I lymphoma

Posted Sept. 1, 2016. Pathology

  • This tumor is misdiagnosed as undifferentiated carcinoma.
  • This tumor is seen in young adults.
  • There are sheets of large pleomorphic cells.
  • These cells are  CD3+ and Ki- I antigen positive.
  • Prognosis is poor. 

 


Sezary Syndrome

Posted Sept. 1, 2016. Pathology

This is also cutaneous T cell lymphoma.

    • There is involvement of skin showing generalized exfoliative erythroderma.
    • Rarely there is tumor formation.
    • This condition is associated with Leukemia.
    • There are characteristic cells which are CD 4+ .
    • Median survival is 8 to 9 years.



 


Mycosis Fungoides

Posted Sept. 1, 2016. Pathology

This is Cutaneous T- cell Lymphoma. There is proliferation of CD4 + cells.

Clinically it is classified into :

Premycotic stage : 

  1. This is inflammatory condition. 
  2. Skin is erythematous, scaly, and pruritus.
  3. This gives picturs of chronic nonspecific dermatitis.

Mycotic stage:

  1. There is appearance of inflammatory plaques.
  2. There is polymorphous inflammatory infiltrate in the dermis.
  3. There are atypical histiocytes.
  4. Pautrier microabscess are seen which is infiltration of epidermis by the histiocytes.

Tumorous stage:

  1. Now atypical histiocytes predominates.
  2. In late stage lymph nodes are involved.
  3. There is also involvement of the viscera.

Median survival is 8 to 9 years.

 


Hodgkin's Lymphoma / Disease

Posted Aug. 31, 2016. Pathology

History

This was discovered by Sir Thomas Hodgkin in 1832. But no body gave any attention to this discovery.

Wilks rediscovered in 1856 this disease and gave his name.

Jackson and Parker divided Hodgkin's disease in 1944 into :

  • Paragranuloma
  • Granuloma
  • Sarcoma

Luke's et al gave another classification in 1966 which correlate with prognosis.

Criteria for Hodgkin's Lymphoma:

  1. This is morphologically distinct variety.
  2. It always arise in lymph nodes.
  3. There is contiguous spread.  
  4. There is no leukemic phase.
  5. There are typical cells called Reed Sternberg cells.
  6.  
  7. It has inflammatory infiltrate.
  8. Atypical Variant of Reed sternberg cells are:
    1. Cells with single nucleus.
    2. Cells with multiple nuclei.
    3. There are cells with lacunar nuclei.
  9. Reed Sternberg cells are also found in:
    1. Mycosis fungoides.
    2. Soft tissue sarcoma.
    3. Infectious mononucleosis.
    4. Lymphoma.
    5. Solid carcinoma.

 Reed Sternberg cell Origin

There are suggestion for origin of Reed Sternberg cells  from B cell or T cell or Histiocytes.

  • B - lymphocytes marker are seen as Ig, Kappa, and lambda, CD19 and CD20 positive.
  • T - lymphocyte markers are also seen as CD 3, CD 5 CD 2 and TCR / alpha and beta.
  • Histiocytes cells markers are also present.
  • So general consensus is origin from lymphocyte which may be activated B or T lymphocyte.
  • Origin from mononuclear phagocytic cell is not accepted.

Inflammatory cells accumulates due to production of cytokines by the Reed Sternberg cells.

Other cytokines detected are :

  • IL 4, IL 5, TNF-Image result for sign for alpha , GM-CSF, TGF- β.
  • IL -5 Correlates with increased eosinophils infiltrate.
  • TGF- β is fibrogenic cytokine found in the nodular sclerosis type.

Incidence

  1. This disease can be seen in any age.
  2. There are two peaks.
  3. There are rare before the age of 2 years.
  4. These are common after the age of 10 years.
  5. This disease is more common in male.
  6. Male to female ratio is 2:1 to 3:1.
  7. Nodular sclerosis type has equal male to female ratio.
  8. 0.7% are all new cases of cancer in USA (roughly 74000 / year).

Etiology

  1. This exactly not known.
  2. This was presumed as inflammatory onset and infection.
  3. There is different mode of presentation in different countries.
  4. In USA smaller peak is 15 to 34 years and larger peak is in older patient (50 years and above).
  5. This disease is rare in Japan.
  6. This is more common in male children of  the underdeveloped countries. Some believe it that this transmission of infection. 
  7. Report of Albany school, New york showed more incidence of this disease in that school.
  8. There are reports of familial outbreaks.
  9. T - cell dysfunction:
    1. Where Kaolan extracted immunosuppressive factor from these patients.
    2. There is cutaneous anergy.
    3. More chances to develop opportunistic infection.
  10. Viral hypothesis. EBV virus found in late stage.
    1. EBV- DNA found in some cases.

Classification of Hodgkin's Lymphoma

Jackson and Parker classified in 1944

  1. Paragranuloma
  2. Granuloma
  3. Sarcoma

Luke's et al classified in 1965 which was based on Lymphocytes and histiocytes.

  • Diffuse lymphocyte predominant
  • Diffuse histiocyte predominant
  • Nodular lymphocyte predominant
  • Nodular histiocyte predominant
  • Nodular sclerosis
  • Diffuse fibrosis
  • Reticular type

Rye Classification 1965

  • This is dependant upon:
    • The number of Reed Sternberg cells.
    • Number of lymphocytes.
  • The host response :
    • Hodgkin's lymphocytic predominant  10%
    • Hodgkin's lymphocytic depletion         10%
    • Hodgkin's mixed cell type                      20%
    • Nodular sclerosis                                     60%

Sign and Symptom

  1. Stage 1 and 11 may be symptoms free.
  2. Due to obscure or unknown mechanism there may be :
    1. Weight loss. 
    2. Fever.
    3. Night sweating.
    4. Pruritus.
    5. There is painless enlargement of the lymph node.
  3. Due to enlargement of lymph nodes there may be compression and lymphedema.
  4. Hematological findings are :
    1. Raised ESR.
    2. Anemia.
    3. Eosinophilia.
    4. Lymphopenia.
  5. Immunological disturbance leads to depression of T cell function. There are more chances for infection.
  6. Stage I and II have survival of 90% for 5 years.
  7. Stage IV A and IV B has survival 70% for 5 years.

Gross feature 

  1. This disease start in single lymph node and then spread to the adjacent nodes.
  2. This may start in spleen or thymus.
  3. Nodular sclerosis may start in thymus.
  4. On cut section lymphocytic predominant type has fish fleshy appearance.
  5. Mixed cell type may show foci of necrosis.
  6. Nodular sclerosis type has fibrous appearance.
Lymphocytic predominant type Mixed cell type Lymphocytic depletion type Nodular sclerosis
15%  30% 15% 40%
More in male <35 years of age More in male More in older male More in females and young adults
Mainly mature lymphocytes and variable histiocytes Lymphocytes are less in number Increased RS cells and less lymphocytes Fibrous bands. More collagen tissue
Reed Sternberg (RS) cells are rare RS cells are frequent Hypocellular RS cells are Lacunar cell  type
Little fibrosis Scanty fibrosis Diffuse fibrosis Fibrous bands and collagen
No necrosis Necrosis occasional Reticular type Lymphocytic predominant or mixed cell type
More lymphocytes Mimic granuloma More cellular, pleomorphic cells Classical RS cells are less common
Prognosis excellent Prognosis intermediate Prognosis poor. Aggressive tumor Prognosis excellent

Hodgkin's Lymphoma histology shown in the following table

  Reed sternberg cells Lymphocytes Collagen Diffuse fibrosis Eosinophils Plasma cells Frequency 5 years survival
Lymphocytic predominant rare ++ to +++++ 0 0 0 0 10% 90%
Mixed cellularity  +++ ++ to +++ 0 ++ ++ + 35 to 60% 70%
Lymphocytic depletion                
Diffuse type + to +++ 0 0 ++++ + + 5 to 10% 20%
Reticular type + to ++++ + 0 + ++ +    
Nodular sclerosis ++ Lacunar cells + to ++++ ++ to ++++ + + + 35 to 60% 50 to 70%

 Clinical Staging

 There is An Arbor staging system given in 1971 by Carbon, P.T. et al

Stage I: There is single lymph node or extra-nodal organ or site.

Stage II:Two or more lymph nodes region on the same site of diaphragm alone or with involvement of contagious extralymphatic organ or tissue (IIE)

Intestine with or without positive lymph nodes.

Stage III: Lymph nodes regions on both side of diaphragm which may include spleen (III S) and / or limited contiguous extra-lymphatic organs or site (III E S).

Stage IV: Multiple or disseminated involvement of one or more extra-lymphatic organs or tissue with or without lymphatic involvement.

Stage A and B are on the basis of sign and symptom like fever, weight loss 10% and night sweating.

 Host immune response depends upon the type of disease.

  • Good response in H.D lymphocytic predominant and Nodular Sclerosis.
  • Intermediate response in Mixed cell type.
  • Poor response in H.D lymphocytic depletion type.

There is long term survival due to radiation and chemotherapy.

These patients may develop other malignancies like cancer of lung, stomach,and melanoma.


Lymph node, Lymphomas, Non-Hodgkin lymphoma Part 3

Posted Aug. 16, 2016. Pathology

Malignant Lymphoma

The lymphomas  are monoclonal in origin.

 Definition:

 Rappaport 1996 Defined that It is neoplastic proliferation of Lymphocyte, Histiocytes and reticulum cells in lymphoid tissue in the body. It is most common in Lymph Node.

Various names:

    • These lymphomas are also called Immunoproliferative disorders.
    • Britisher calls it Reticulosis,  or Reticuloendothelial.

Lymphoma:

 This is a Misnomer because it spreads from single Lymph Node to chain of Lymph Node and distant nodes. It also spreads to liver, spleen and Bone marrow where it gives leukemia phase.

 Lymphosarcoma:

It is a special variant of NHL (PDL)

Lymphomas are classified into :

1.     Non-Hodgkin’s lymphoma

2.     Hodgkin’s lymphoma

 Confusion for classification is due to:

1.     Histogenesis.

2.     Degree of differentiation.

3.     Failure to differentiate between Lymphocyte and Epithelial cells.

4.     Difficult to differentiate  malignant or hyperplastic lesion.

Non-Hodgkin’s lymphoma (NHL)

  1. Non-Hodgkin lymphoma may be localized or generalized.
  2. 2/3 of Non-Hodgkin lymphoma are primary origin from lymph nodes  while 1/3 or extranodal and they may originate from bone marrow, Oropharynx, Gastrointestinal Tract and skin.
  3. 3% of all malignancies in western countries are non-Hodgkin lymphomas.

 Reason for classification of NHL:

    •  Categorization to know response to treatment.
    • Should be easy to be followed by pathologist.

       Well known classification of NHL are :

    •     Rappaport                               1996
    •     Bennett                                    1974
    •     Dorfman                                  1974
    •       Lukes and Collin                    1974  
    •     Lennert         
    •     Mathew                                   1976
    •     Working formulation           1982
    • Real classification (Revised European-American classification of lymphoid neoplasm) 1994

 Non-Hodgkin’s Lymphoma:

  •   Majority (80-85%) are B-Lymphocyte origin.
  •    Rest non-Hodgkin’s lymphoma are T-Lymphocyte
  •     Histiocytic in origin are uncommon.
  • Non-Hodgkin’s lymphoma 2/3 are nodal in origin including Hodgkin’s lymphoma while 1/3 are extra-nodal e.g. skin, stomach and brain.

Rappaport Classification:

Given in 1966 and modified in 1978.

Criteria of classification:

  1. This depends upon;
    1. Nodular or diffuse
    2. Cell Morphology, where we look for:
      1.  Size of cells.
      2. Nuclear shape.
      3. Nucleoli.
      4.  Cytoplasm.
      5.  Chromatin
      6.  Mitosis.
    3. Two cell subset (Lymphocytes and Histiocytes).
    4. Degree of differentiation of cells.

Classification of lymphomas by Rappaport

Nodular type   Diffuse type  
Poorly differentiated     24% well differentiated lymphocytic 5 %
Mixed cell type 12 % Poorly differentiated  16 %
Histiocytic 3 % Histiocytic  28 %
    Mixed cell type 6 %
    Lymphoblastic <5 %
    Undifferentiated (Burkitt's type)  
    Undifferentiated (Non-Burkitt's)  

       Good Points of Rappaport:

  1.  Nodular (follicular) or diffuse : This is easy to appreciate and has good prognosis.
  2. Easy to follow histologically.

Drawbacks:

  1. Type of cells are not mentioned either B or T-Lymphocyte.
  2. Transformed activated B-Lymphocytes looks like histiocytes.
  3. Small B-Lymphocyte end-stage is incorrect.

Rappaport classification is based on cytologic cell division like :

  1. Small lymphocytes.
  2. Histiocytes which are 2 to 3 times than the small lymphocytes with 2 to 5 nucleoli and abundant cytoplasm.
  3. Then are the undifferentiated cells.

 Nodular Type Non-Hodgkin's Lymphoma 

  1. These are 40% of the lymphomas.
  2. These are the tumor of old age and rear before the age of 20 years.
  3. Sex ratio is female to male is equal.
  4. These lymphomas have better prognosis.
  5. These tumors can transform into diffuse form which take at least 8 years.
  6. These tumors needs to be differentiated from follicular hyperplastic changes in the lymph node.
  7. Mitosis are rare.
  8. The cells are Follicular small cell (FSC)  and mixed cells are Small cleaved (SC) and large cleaved cells (LC)>
  9. Surface markers are :
    1. Positive surface Ig.
    2. Positive pan B CD molecule 19 +.
  10. 75% of the cases bone marrow is involved.
  11. Extranodal spread is rare.
  12. Median survival is 7 to 9 years.

Diffuse well differentiated lymphocytic lymphoma  

  1. These  are low grade and are 5% of the lymphomas.  
  2. 40% are the transform into chronic lymphocytic leukemia.                                                         
  3.  There are small B- lymphocytes with compact nuclei.
  4. The mitosis are rare.
  5. These are the tumor of old age.
  6. There is monoclonal gammopathy.
  7. Tumor marker shows surface Immunoglobulin Igm and IgD.
  8. These cells are CD19 + cells.
  9. Bone marrow is almost always positive.
  10. These are the low grade lymphomas.

Poorly differentiated Lymphoma (PDL)

  1. These can be :
    1. Nodular 
    2. Diffuse
  1. Age is middle and older age group.
  2.  These are 30% of the lymphomas.
  3. Multiple lymph nodes are involved.
  4. There may be enlargement of spleen and liver.
  5. There is infiltration of the bone marrow.
  6.  Nucleus has variable morphology.
  7. Mitosis are rare.
  8. When involve the blood and bone marrow looks like acute lymphocytic leukemia.
  9. These are also called  lymphosarcoma.

       Histiocytic Lymphoma

  1. These may be:
    1. Nodular
    2. Diffuse:
  2. These are 31% of the Rappaport lymphomas.
  3. Extranodal form is more common.
  4. Leukemic form is uncommon.
  5. Nucleus is vesicular.
  6. There are 2 to 5 nucleoli.
  7. These are large noncleaved cells.
  8. There are areas of necrosis.
  9. Prognosis is poor. 

     Mixed cell type lymphoma

  1. These are more in nodular form.
  2. In this variety histiocytes are 30 to 50%.
  3. These lymphomas may start as nodular and transform into diffuse form.

Lymphoblastic Lymphoma

  1. These are <5% of the Lymphomas.
  2. These are considered to be  T-lymphocytes.
  3. Age : These are more common in the young patients.
  4. Sex : The male to female ratio is 6 : 1.
  5. There is mediastinal mass presentation in 50 to 70% of the cases.
  6. There is early involvement of the bone marrow.
  7. Surface markers: These cells are CD 4, CD 8, CD 2, CD 5 and CD 7 positive.
  8. In these cases nucleus is lobulated.
  9. Increased number of mitosis gives starry sky appearance.
  10. These lymphomas are treated like acute lymphoblastic lymphoma.
  11. These are to be considered as high grade.

Undifferentiated Non Hodgkin's Lymphoma

Burkitt's Type

  1. This group includes Burkitt's and Non Burkitt's.
  2. This variety is more common in African countries and is endemic in form.
  3. In these patients Epstein barr virus (EBV) is positive in 98% of the cases while antibody positive in 100% of the cases.
  4. This is the disease of young children.
  5. Cell is large with size of 10 to 25 micron in diameter.
  6. There are 2 to 5 nucleoli.
  7. There are increased number of mitosis.
  8. The common site and presentation is mandible and maxilla.
  9. There is long survival in 50% of the cases.
  10. Response to treatment is good.

Non Burkitt's or American type 

  1. These are more common in the older age group and around 34 years.
  2. There is involvement of the gastrointestinal tract, ovaries and peritoneum.
  3. The cell morphology is pleomorphic.
  4. These tumors are less responsive to treatment.
  5. These are high grade lymphomas.

                                       Luke's and Collins classification lymphoma 1974

  • This classification was given on the basis of origin of the cells like B or T lymphocytes.
  • Second criteria was the cell morphology considering cells size, shape and nucleus.

Table showing various type of Lymphomas according to Lukes and Collins Classification

B - lymphocytes origin  65% T - Lymphocyte origin 20% Histiocytic origin  0.2% U - cell origin 14.8%
Small cell 9% small lymphocyte 2%        
Follicular small cleaved 28%

Convoluted lymphocyte

cut.T cell lymphoma

10%        
Follicular large cleaved 5% Lymphoma 2%        
Follicular small non-cleaved 7% Immunoblastic cells 4%        
Follicular large non-cleaved 6%            
Immunoblastic cells 3%            
Plasmacytoid cells 7%            

Drawbacks of above classification are :

  1. There is no mention of nodular type or diffuse form.
  2. This classification is difficult to follow.

                                                Working Formulation - 1982

This classification has very strong clinical significance.

 These lymphomas are divided into grades on the basis of survival of the patient.

There is consideration of B and T lymphocytes.

Following diagram  shows the differentiation of the cells when stimulated by antigenic stimulation.

 

 

Table showing Working Formulation

Low grade Intermediate grade High grade
5 years survival 50 to 70% 5 years survival 35 to 40% 5 years survival 23 to 32%
10 years survival 45% 10 years survival 26% 10 years survival 23%
Small lymphocytes B-L (SLL) Follicular predominantly large cells (LC + LNC) Large cells Immunoblastic cells (B and T cells origen)
Follicular predominantly small cleaved (SC) Diffuse small cells (SC) Lymphoblastic cells
Follicular mixed (SC + large cells) Diffuse mixed cells (SC + large cells ) Small non-cleaved (Burkitt's and non-Burkitt's)
  Diffuse large cells (LC + LNC ) Miscellaneous (Mycosis Fungoides, Sezary syndrome, Histiocytosis and HTLV-leukemia)

                                                LOw Grade Lymphomas

Small lymphocytic lymphoma (SLL)

  1. These are 4% of the lymphomas.
  2. These are well differentiated lymphocytic non-hodgkin's lymphoma.
  3. These are old age group lymphomas. 6th to 7th decadesis common.
  4. There is generalized enlargement of the lymph nodes.
  5. There is mild enlargement of liver and spleen.
  6. These lymphomas have indolent course, but difficult to eradicate owing to low proliferative index.
  7. There is no follicular pattern and these are always diffuse .
  8. These are B - Lymphocytes (95%)  with surface marker of IgM, IgD, and CD19+.
  9. While T - Lymphocytes are 5% in origen.
  10. There is compact nucleus and mitosis are rare.
  11.  40 to 60% transform into chronic lymphocytic lymphoma.
  12. Bone marrow involvement is common.
  13. Some of these lymphomas produced IgM is called Waldenstrom's Macroglobulinemia.
  14. There is prolonged survival .

Follicular Lymphoma 

 These are 40% of the adult Non-Hodgkin's lymphoma.

There are types of :

  1. Small Cleaved cell
  2. Mixed cells type consists of Small cleaved, Large cleaved and Large non-cleaved.

Follicular Small cleaved cell Lymphoma

  1. These are most common. These are 60% of the adult Non-Hodgkin's lymphoma.
  2. This more common in the middle aged and the elderly people.
  3. Nucleoli are indistinct and mitosis are rare.
  4. There are Large cleaved and Large non-cleaved cells are present but these are <20%.
  5. Median survival is 10 years.

Follicular Mixed Cell Lymphoma

  1. These are more common in the older age group (50 to 60 years).
  2. Male, female ratio is equal.
  3. There is painless enlargement of the lymph nodes.
  4. Bone marrow involvement is common, seen in 75% of the cases.
  5. These are >20% and <50% are large cells. There are large cleaved and large non-cleaved cells.
  6. Transition to diffuse form takes roughly 8 years.
  7. There are >20% and <50% of the large cells.
  8. Lymphoma cells show surface markers of Ig, and CD10, CD20 and CD21. 
  9.  Median survival is 7 to 9 years.
  10. Some believes that hands off.

                                                      Intermediate Grade  Lymphoma

 Follicular Predominantly large cells.

  1. These are uncommon lymphomas <15%.
  2. There are increased mitosis.
  3. They change into diffuse form.
  4. Prognosis is poor because they early transform into diffuse .
  5. Majority of the large cells are large cleaved and large non-cleaved.

Diffuse Small Cleaved cells lymphoma

  1. Age is around 60 years.
  2. There is increase male to female ratio.
  3. There are increased mitosis.
  4. Nucleoli are indistinct and coarse chromatin.
  5. Surface Ig and pan B- antigen (CD19 and CD20) are positive.
  6. Rarely CD10 may positive.
  7. Prognosis is poor and median survival is 3 to 4 years.

Diffuse Mixed Cell Type Lymphoma

This lymphoma consists of Small cleaved (SC), Large cleaved (LC), and large non-cleaved (LNC).

Large cleaved cells are larger than normal histiocytes or endothelial cells.

Chromatin is dispersed and nucleoli are indistinct.

Large non cleaved cells are four times the size of small lymphocytes.

Nucleoli are prominent and are 1 to 2.

Nucleus is vesicular and cytoplasm is pale.

Diffuse large cell Lymphoma

  1. This consists of large cells and Large non-cleaved cells.
  2. These are most common.
  3. There is increased male to female ration.
  4. Median age is 60 years.
  5. Extranodal signs and symptoms are more common. There is involvement of skin, gastrointestinal tract, bone and brain.
  6. There is involvement of waldeyer's ring in more than 50% of the cases.
  7. There may be diffuse masses in liver, spleen.
  8. Aggressive chemotherapy  is needed. 
  9. Remission may be seen in 60 to 80%.
  10. 50% of the patient may be symptoms free.
  11. 70% of the cases there are B- lymphocytes and 30% has T- lymphocyte.

                                                                High Grade Lymphoma

These are aggressive lymphomas. Often cured by chemotherapy.

There is high proliferative index which make more susceptible to cytotoxic drugs.
Small Noncleaved Non Hodgkin.s lymphoma are Burkitt's and Non Burkitt's lymphoma .

Large Cell Immunoblastic lymphoma

There are wide morphologic changes.

B - Immunoblastic Lymphoma:

  1. There the cells are 4 to 5 times of the small lymphocytes.
  2. There is vesicular nuclei  and 1 to 2 nucleoli.
  3. Cytoplasm is deep staining.
  4. Surface marker is CD19 and CD20 positive.
  5. 50% has history of  autoimmune diseases like Sjogren's syndrome and Hashimoto's thyroiditis and AIDs.

T - Immunoblastic lymphoma:

  1. These are seen in 5th decades.
  2. These are more common in the male.
  3. The cells have clear cytoplasm and polymorphous nuclei.
  4. These represents 20% of the childhood lymphoma.

Lymphoblastic Lymphoma:

  1. These are most common before the age of 20 years.
  2. Male : female ratio is 2 : 1.
  3. In children 40% Non Hodgkin's lymphoma falls in this group.
  4. There is early bone marrow , and meninges involvement.
  5. There may be leukemic phase looks like Acute lymphocytic leukemia.
  6. There are T - lymphocytes and looks like  T- L acute lymphocytic leukemia.
  7. Cells have uniform and scanty cytoplasm.
  8. Nucleus is lobulated and nucleoli not prominent.
  9. Increase mitosis give rise to starry sky appearance.
  10. Surface markers are CD2, Cd5, CD7 are positive. Some cells show Cd4 and CD8 positive. CD3 is positive/negative.
  11. Treatment is judt like acute lymphocytic leukemia (ALL) .  Aggressive treatment is effective.