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Work-up of Lymphoma case

Posted Sept. 2, 2016. Pathology

1. Blood work up includes:

    • Total leucocytes (TLC).
    • Differential leucocyte count (DLC).
    • Hemoglobin
    • Erythrocyte sedimentation rate (ESR)
    • Platelet count.

2 Bipedal lymphangiogram. This is done for iliac and para aortic lymph nodes.

3. Staging laparotomy : Laparoscopy can be done for  splenectomy, liver biopsy, abdominal lymph nodes and bone marrow biopsy.

4.Clinical Examination : Do careful examination of lymph node, spleen, liver and etc.

5. Biochemical tests are needed are Liver function test (LFT) and lactate dehydrogenase (LDH).

6. Ultrasonography , CT scan and MRI are advised for further work up.

7. Advised liver and spleen scan.

Spleen 

25% positive in nonpalpable spleen by the pathologist.

50% negative in palpable spleen by the pathologist.

Bone Marrow

9 to 29% may show in the form of aggregates or diffuse infiltrate.

 

 


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.