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Non-Hodgkin’s Lymphoma

Lymphomas – are an array of heterogenous malignancies that originate in the lymphocytes , NHL make around 90 % of the lymphomas and Hodgkins lymphoma ( HL ) about 10 % Differentiation between NHL and HL is based on different clinical characteristic and the absence of Reed- Steenberg cells and Cd15 and Cd30 staining on histology Classification of NHL is complex and ever-evolving with more than 50 types described by the WHO classification


The subtypes have distinct genetic , morphological and clinical features and can vary by age , sex , ethnicity and geographic region In the Western world – Diffuse Large B – cell lymphoma ( DLBCL ) is the most common subtype constituting about 25 % to 30 of all adult NHL’s DLBCL are aggressive high grade tumours Based on cell of orgin majority > 90 % are from B- lymphocytes and < 10 % are of T-cell or NK cell derived.


NHL is the most common haematological malignancy in the world – it accounts for about 3 % of cancer diagnoses and death Incidence of NHL has increased globally ( for e.g doubled over the past 2 decades in US ) NHL’s are more common in developed countries Globally men have double the cumulative risk of developing NHL Overall common in age 65-74 , with median age being 67 yrs Wide geographic variations for e.g Burkitt lymphoma widespread in Africa with a peak incidence in children between to 7 yrs In the US , NHL has become the 5th most common diagnosed malignancy In the UK , Cancer Research reports that NHL is the 6th most common cancer accounting for about 4 % of all new cancer cases in 2017 Oropharyngeal lymphomas are the 2nd most common malignant disease in the oral region after SCC.


Aetiology is not fully understood Most lymphomas would not have a single identifiable cause but several well defined associations have been noticed Like other cancers it is thought that NHLs arise by a multistep accumulation of genetic aberrations that induce a selective growth advantage of the malignant clone mechanisms involved can include
○ dysregulation of cell growth
○ cell signaling pathways and programmed cell death chromosomal translocation or mutation/ deletion – leads to activation of proto-oncogenes and tumour suppressor genes are inactivated The t ( 14 ; 18 ) translocation is the most common chromosomal abnormality Other important causes include
○ immunosuppression ○ oncogenic viruses ○ direct carcinogenesis by environmental factors ○ autoimmune diseases ○ familial risk


Ascertaining risk factors for an illness with 50 + subtypes has been challenging . InterLymph ( International Lymphoma Epidemiology Consortium ) was formed in 2001 to look ino identifying risk factors which are both shared by and particular to specific NHL subtype


numerous environmental , lifestyle , medical , genetic risk factors have been identified a family h/o haematological malignancy has been identified as a risk factor across all subtypes of NHL immunosuppression ( for ae,g immunosupressant medications , AIDS) UV radiation Viruses and other pathogens ( EBV , HTLV , HHV 8 , Hepatitis C , SV 40 , Helicobacter pylori , HIV ) Autoimmune and chronic inflammatory disorders as rh arthritis , Sjogren’s syndrome, SLE Radiotherapy treatment Occupational exposure to certain chemicals , pesticides , organophosphates ( working in a farm , painter ) Autologous stem cell transplant along with multi agent ante-retroviral therapy Congenital immunodeficiency states as Wiskott- Aldrich syndrome , SCID Tobacco smoking conflicting results List of probable and possible risk factors is growing.


Indolent NHL’s – Chronic lymphocytic leukaemia / small lymphocytic lymphoma
( CLL / SLL ) Follicular lymphoma Lymphoplasmacytic lymphoma / Waldenstrom macroglobulinemia Marginal zone lymphoma Mycosis fungoides


Aggressive NHL’s Diffuse large B cell lymphoma Anaplastic large cell lymphoma Burkitt/ Burkitt like lymphomas Angioimmunoblastic T cell lymphoma Mantle cell lymphoma Peripheral T cell lymphoma Sézary syndrome.

painless peripheral lymphadenopathy fever , weight loss or night sweats ( B -symptoms ) based on site involved for e.g extranodal disease -stomach or skin
( lymphomas can happen anywhere ) based on subtype based on indolent or aggressive indolent lymphomas can present with widespread slowly progressive disease without significant systemic symptoms aggressive lymphomas may present with rapidly enlarging lymph nodes often with B symptoms pay attention to node bearing areas , including Waldeyer ring and to size of liver and spleen.


FBC – may reveal anaemia , thrombocytopenia , leukopenia , pancytopenia , lymphocytosis, thrombocytosis U&E, LFT,Bone profile , LDH , immunoglobulins ,electrophoresis ( paraprotein M in SLL anf FL ) Beta 2 microglobulin ( prognostic value ) Viral serology ( hepatitis , HIV ) urine for Bence Jones protein Core or excision biopsy Imaging CT scan of neck , chest , abdomen , pelvis or PET scan Bone marrow biopsy and aspirate.


Diffuse B cell lymphoma – most common subtype makes up to 25 % to 30 % of all adult NHLs in western world typical presentation is rapidly growing mass or enlarging lymph nodes in nodal or extranodal sites / B symptoms extranodal involvement is quite common ( stomach and GI tract quite common other sites kidney , lung , bone or bone marrow ) lack of specific symptoms , haematogenous spread often leads to a delay in diagnosis & late presentation incidence increases with age , median age presentation is 64 yrs due to malignant proliferation of B cells during their various stages of development diagnosis is made based on biopsy of a surgical specimen / excisional lymph node or extranodal tissue treatment is based on staging , type of the disease and the molecular subtype


Follicular lymphoma – accounts for about 15 % to 20 % of all NHL’s indolent clinical course with less extranodal involvement common in middle and old age ( median 55 yrs ) graded as 1-3 ( low to high grade ) diffuse lymphadenopathy , bone marrow involvements and splenomegaly lymphadenopathy is painless and can be waxing and waning in nature common sites of involvement are the axillary , cervical , femoral and inguinal regions in children FL tends to affect the lymphoid tissues ( tonsils and lymph nodes ) originates from germinal / follicular center B cells majority of cases have the characteristic t ( 14;8 ) translocation involving the IgH/bcl-2 genes cytopenias ( can occur ) but constitutional symptoms are less common diagnosis is based on histology from a lymph node or other affected tissue LDH may be raised in 20 % of presentations prognosis has improved ( based on assessment of risk factors which can include parameters as Beta2 microglobulins , bone marrow involvement , Hb , diameter of the largest node involved node and age )


Chronic lymphocytic leukaemia / small lymphocytic

lymphoma – often grouped as type of NHL’s indolent malignancy defined by increased production of mature bu dysfunctional B lymphocytes that are smudge cells as noted in peripheral smear these accumulate in the blood , bone marrow , secondary lymphoid tissues leading to lymphocytosis , leukaemia cell infiltration of the marrow , lymphadenopathy and splenomegaly CLL is the most common adult leukaemia in the western world and relatively uncommon in Asian countries Seen rarely in children – incidence increases rapidly with increasing age with an average age of diagnosis at 70 yrs runs in families ( has a genetic basis- chromosomal alterations , mutations , alterations in the expression of mi RNA and epigenetic modifications ) mostly asymptomatic and picked up on routine FBC testing with abnormal lymphocytosis some patients may c/o fatigue , involuntary weight loss , excessive night sweats , abdominal fullness with early satiety and ↑↑ frequency of infections which may be associated with hypogammaglobulinaemia and enlarged lymph nodes at cervical , axillary and inguino-femoral regions clinical course can be highly variable – some patients remain free of symptoms and can be fully active for decades whereas others may rapidly develop symptoms or develop high risk disease requiring early treatment



Burkitts lymphoma – highly aggressive rapidly growing NHL which accounts for about 1 % to 5 % of all NHL’s associated with Epstein Barr Virus ( EBV ) , human immunodeficiency virus ( HIV ) and chromosomal translocations that cause the overexpression of oncogenic c-myc ( translocations of chromosomes 8 and 14 → upregulation of the c-myc protein transcription factor with upregulation of cell proliferation ) three variants – sporadic , endemic and immunodeficiency associated
○ sporadic type seen in USA and western Europe ( accounts for 30 % of Paediatric lymphomas )
- primary site of involvement is abdomen but H&N may also be involved
○ endemic found in equatorial Africa and New Guinea & accounts for nearly 50 % of all childhood cancer in equatorial Africa ( e.g facial tumour associated with EBV )
- head and neck involvement is common in endemic form
○ Immunodeficiency associated BL- seen in HIV patients , allograft recipients and patients with congenital immunodeficiency presentation may vary based on subtype , age and site presentation may be a with a rapidly growing mass ↑ LDH and ↑ uric acid levels treatment is with chemotherapy.


Hodgkin’s lymphoma EBV infection SLE Solid tumour malignancies -Metastases Malignancies or lymphoproliferative disorders like granulocytic sarcoma Benign lymph node infiltration or reactive follicular hyperplasia secondary to infection as TB , other bacterial , fungal and rarely viral infections


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