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|[[Diffuse large B-cell lymphoma]]]
|Acute Lymphobalstic lymphoma
|Classified into 2 subtypes based on [[gene expression]] profiles:
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*Germinal centre B-cell-like (GCB)
* Precursor B-cell Lymphomas
*Activated B-cell-like (ABC).
 
**B cell receptor (BCR) signalling
 
**B cell migration/adhesion
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**Cell-cell interactions in immune niches
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**Production and class-switching of immunoglobulins
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|Follicular lymphoma
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* Mature B-cell Lymphomas
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|Mantle cell lymphoma
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* Mature B-cell Lymphomas
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* Mass/Lump
:* Rapidly enlarging [[lymph nodes]].
:* Painless
:* May be present in neck, groin or abdomen
:* It is not uncommon to have [[lymphoma]] in extranodal sites.  B symptoms :
:* Fever
:* Night sweats
:* weight loss
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* Non tender mass
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* [[Immunohistochemistry]](IHC)
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** CD20, CD3, CD5, CD45, CD10, BCL-2, BCl-6, MYC, IRF-4/ MUM-1, Ki-67
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* Flow Cytometry Panel
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** Kappa/ Lambda, CD3, CD5, CD45, CD10, CD19, CD20
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* [[Cytology]] (for primary CNS lymphoma only)
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* [[Genetic testing]]
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** 8q24/''MYC'' [[translocations]]
|Diffuse large B cell lymphoma
** Immunoglobulin genes clonally rearranged and hypermutated
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** Mutation of ''BCL6'', ''MYC'', ''[[PAX5]]'', ''[[PIM1]]'', ''[[RhoH]]''/''TTFn'', ''[[TP53]]'' genes
* Mature B-cell Lymphomas
** Translocations involving ''c-MYC'', ''BCL6'', and ''IgH'' gene.
* 8q24/''MYC'' [[translocations]]
 
* Hypermutated immunoglobulin genes  
* Mutation of ''BCL6'', ''MYC'', ''[[PAX5]]'', ''[[PIM1]]'', ''[[RhoH]]'' /''TTFn'', ''[[TP53]]'' genes
* Translocations involving ''c-MYC'', ''BCL6'', and ''IgH'' gene.
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* Fever
* Night sweats
* weight loss
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* Painless rapidly enlarging [[lymph nodes]]
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|Nl to ↓
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* Neutropenia
* Anemia
* Hypergammaglobulinemia
* Screening tests for HCV, HBV and HIV.
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====Centroblastic====
====Centroblastic====
*Medium-to-large-sized [[Lymphocyte|lymphocytes]]
*Medium-to-large-sized [[Lymphocyte|lymphocytes]]
*Monomorphic
*Monomorphic
====Immunoblastic::====
====Immunoblastic====
*> 90% immunoblasts
*> 90% immunoblasts
*Trapezoid shaped large lymphoid cells with significant [[basophilic]] cytoplasm
*Trapezoid shaped large lymphoid cells with significant [[basophilic]] cytoplasm
====Anaplastic:====
====Anaplastic:====
*Very large cells with a round, oval, or polygonal shape that may resemble Reed-Sternberg cells of Hodgkin's lymphoma or Anaplastic Large cell Lymphoma.
*Very large cells with a round, oval, or polygonal shape that may resemble Reed-Sternberg cells  
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* Hypergammaglobulinemia
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|Burkitt’s lymphoma
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* Mature B-cell Lymphomas
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|B cell chronic lymphocytic leukemia/small lymphocytic lymphoma
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* Mature B-cell Lymphomas
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|Marginal zone lymphoma
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* Mature B-cell Lymphomas
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|Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)
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* Mature B-cell Lymphomas
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Revision as of 19:30, 28 December 2018


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[2]

Category Disease Etiology Mechanism Clinical manifestations Paraclinical findings Gold standard Associated findings
Lab findings
Demography History Symptoms Signs CBC PBS LFT PT/PTT Immunochemistry Blood work Histopathology Other Imaging
Inherited Acquired Constitutional b symptoms Rash Abdominal pain Diarrhea V/S Mass LAP Hepatosplenomegaly Arthritis Other WBC Hb Plt
Hodgkin's Lymphoma
Acute Lymphobalstic lymphoma
  • Precursor B-cell Lymphomas


Follicular lymphoma
  • Mature B-cell Lymphomas
Mantle cell lymphoma
  • Mature B-cell Lymphomas
Diffuse large B cell lymphoma
  • Mature B-cell Lymphomas
  • 8q24/MYC translocations
  • Hypermutated immunoglobulin genes
  • Mutation of BCL6, MYC, PAX5, PIM1, RhoH /TTFn, TP53 genes
  • Translocations involving c-MYC, BCL6, and IgH gene.
  • Fever
  • Night sweats
  • weight loss
Nl to ↓

Centroblastic

Immunoblastic

  • > 90% immunoblasts
  • Trapezoid shaped large lymphoid cells with significant basophilic cytoplasm

Anaplastic:

  • Very large cells with a round, oval, or polygonal shape that may resemble Reed-Sternberg cells
  • Hypergammaglobulinemia
Burkitt’s lymphoma
  • Mature B-cell Lymphomas
B cell chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Mature B-cell Lymphomas
Marginal zone lymphoma
  • Mature B-cell Lymphomas
Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)
  • Mature B-cell Lymphomas
Follicular lymphoma
  • Reciprocal translocation t(14;18)(q32;q21).
Burkitt lymphoma
  • Translocation of chromosome 8 myc locus with 3 possible partners (accounting for 90% of translocations):
    • The Ig heavy chain region on chromosome 14: t(8;14)
    • The kappa light chain locus on chromosome 2: t(2;8)
    • The lambda light chain locus on chromosome 22: t(8;22)
  • Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells)
  • Round nucleus
  • Small nucleoli
  • basophilic cytoplasm
  • Brisk mitotic rate and apoptotic activity
  • Cellular outline usually appears squared off
  • "Starry-sky pattern":
    • The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells)
    • The tumour cells are the sky
B cell lymphoma Mantle cell lymphoma
  • Stage IV disease
  • B symptoms,
  • Generalized lymphadenopathy
  • Abdominal distention
  • Fatigue
  • Night sweats
  • Weight Loss
  • Extranodal involvement of gastrointtestinal (GI) tract, lungs, and central nervous system (CNS)
  • Generalized lymphadenopathy
  • Hepato-splenomegaly
  • Mental Retardation
  • Less commonly
    • Palpable masses in skin, breast, and salivary glands
  • CD5+
  • B-cell antigen positive
    • CD19
    • CD20
    • CD22
  • Cyclin D1 is overexpressed.
CBC
  • Anemia and cytopenias are secondary to bone marrow infiltration
  • Lymphocytosis > 4000/µL
  • Elevated LDH
  • Germinal centers filled by small-to-medium atypical lymphocytes.
  • Nodular appearance may be evident from expansion of the mantle zone in 30-50% of patients early in the disease.
Nodal marginal zone B-cell lymphoma
  • Arise from memory B cells. Include
    • Splenic marginal zone lymphoma
    • Nodal marginal zone lymphoma
    • Extranodal marginal zone lymphoma.
  • Stimulation of antigen receptor by autoantigen and co-stimulatory molecule CD40.
  • Depends largely on its location
  • Gastric marginal zone lymphoma
    • Dyspepsia
    • Abdominal pain
    • Hemorrhage
  • Chronic infectious conditions or autoimmune processes, such as
    • H pylori gastritis
    • Hashimoto thyroiditis
    • Sjögren syndrome.
  • AE1/AE3
  • B-cell markers CD20, CD79a, CD10, CD23, and bcl-2 are expressed
  • Follicular cells in reactive zone
  • Centrocyte like cells in marginal zone lymphoma
Splenic marginal zone lymphoma
  • Clonal rearrangements of the immunoglobulin genes (heavy and light chains) .
    • Deletion 7q21-32
    • Translocations of the CDK6 gene located at 7q21.
  • B-cells replace the normal white pulp of the spleen.
  • The neoplastic cells compromise
  • Sinus invasion
  • Epithelial histocytes
  • Plasmacytic differentiation of neoplastic cells.
  • Splenic Hilar Lymph Nodes
  • Bone Marrow Biopsy
    • Splenic marginal zone lymphoma in bone marrow displays a nodular pattern with morphology similar to what is observed in the splenic hilar lymph nodes.
Hairy cell leukemia
  • Production of cytokines, such as TNF alpha and IL-2R, provide important stimuli for malignant B cells proliferation in hairy cell leukemia.
    • The p38-MAPK-JNK cascade
    • The MEK-ERK cascade
    • The Phosphatidylinositol 3 kinase (PI3K)-AKT cascade
  • Tartrate-resistant acid phosphatase positive
  • CBC
  • Small cells with "fried egg"-like appearance
  • Well-demarcated thread-like cytoplasmic extensions
  • Clear cytoplasm
  • Central round nucleus
  • Peri-nuclear clearing ("water-clear rim" appearance)
Plasma cell myeloma
Chronic lymphocytic leukemia / small lymphocytic lymphoma
Monoclonal B-cell lymphocytosis
B-cell prolymphocytic leukemia
Waldenström's macroglubulinemia
Monoclonal gammopathy of undetermined significance (MGUS)
Heavy chain disease
Solitary plasmacytoma of bone
Extraosseous plasmacytoma
Monoclonal immunoglobulin deposition diseases
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)
Large B-cell lymphoma with IRF4 rearrangement
Primary cutaneous follicle center lymphoma
T-cell/histiocyte-rich large B-cell lymphoma
Lymphomatoid granulomatosis
Primary mediastinal (thymic) large B-cell lymphoma
Intravascular large B-cell lymphoma
ALK1 large B-cell lymphoma
Plasmablastic lymphoma
Primary effusion lymphoma
High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
T cell lymphoma Mycosis fungoides / Sézary syndrome
  • Cutaneous manifestaions
T-cell granular lymphocytic leukemia
  • Disregulation of signaling pathways:
    • FAS/FAS-L
    • Phosphatidylinositol-3 kinase (PI3K),
    • Mitogen-activated proteinkinase/extracellular signal-regulated kinase (MAPK/ERK)

Symptoms of T-cell large granular lymphocyte leukemia may include the following:

  • Neutropenia
  • Anemia
  • Hypergammaglobulinemia
  • Clonal rearrangements of the T-cell receptor (TCR) gene
  • Chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood
  • Large granular lymphocyte count greater than 2.0 × 109/L
  • Lymphocytosis (typically 2-20x109/L)
Subcutaneous panniculitis-like T-cell lymphoma