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{{CMG}}; {{AE}} {{Preeti}}
{{CMG}}; {{AE}} {{Preeti}}
{| class="wikitable"
|+
! colspan="2" rowspan="2" |
! rowspan="2" |Pathophysiology
! rowspan="2" |Symptoms
! rowspan="2" |History
! rowspan="2" |Physical  Examination
! colspan="3" |Laboratory Findings
|-
!Immunochemistry
!Blood work
!Biospy
|-
|
|[[Diffuse large B-cell lymphoma]]
|Classified into 2 subtypes based on [[gene expression]] profiles:
*Germinal centre B-cell-like (GCB)
*Activated B-cell-like (ABC).
**B cell receptor (BCR) signalling
**B cell migration/adhesion
**Cell-cell interactions in immune niches
**Production and class-switching of immunoglobulins
|
* 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
:
*
|
|
* Non tender mass
*
|
* [[Immunohistochemistry]](IHC)
** CD20, CD3, CD5, CD45, CD10, BCL-2, BCl-6, MYC, IRF-4/ MUM-1, Ki-67
* Flow Cytometry Panel
** Kappa/ Lambda, CD3, CD5, CD45, CD10, CD19, CD20
* [[Cytology]] (for primary CNS lymphoma only)
* [[Genetic testing]]
** 8q24/''MYC'' [[translocations]]
** Immunoglobulin genes clonally rearranged and hypermutated
** Mutation of ''BCL6'', ''MYC'', ''[[PAX5]]'', ''[[PIM1]]'', ''[[RhoH]]''/''TTFn'', ''[[TP53]]'' genes
** Translocations involving ''c-MYC'', ''BCL6'', and ''IgH'' gene.
*
|
* Neutropenia
* Anemia
* Hypergammaglobulinemia
* Screening tests for HCV, HBV and HIV.
|
====Centroblastic====
*Medium-to-large-sized [[Lymphocyte|lymphocytes]]
*Monomorphic
====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 of Hodgkin's lymphoma or Anaplastic Large cell Lymphoma.
|-
|
|[[Follicular lymphoma]]
|
* Reciprocal translocation t(14;18)(q32;q21).
|
*[[Fever]]
*[[Weight loss]]
*[[Night sweats]]
*[[Skin rash]]
*[[Chest pain]]
*[[Abdominal pain]]
*[[Bone pain]]
*[[Cough]]
*[[Dyspnea]]
*Painless swelling in the neck, axilla, groin, thorax and abdomen
|
|
* [[Lymphadenopathy|Central  and peripheral lymphadenopathy]]
* [[Splenomegaly]]
* [[Hepatomegaly]]
* [[Abdominal tenderness]]
* [[Seizures]]
|
|
|
|-
|
|[[Burkitt's lymphoma|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)
|
* [[Fever]]
* [[Night sweats]]
* Unexplained [[weight loss]]
* [[Swollen lymph nodes]] in the neck, axilla, or groin
|
|
* [[Proptosis]]
* Jaw mass
* [[Abdominal mass|Abdominal masses]]
* [[Ascites]]
* [[Lymphadenopathy|Peripheral lymphadenopathy]]
|
* [[CD19]]
* [[CD20]],
* [[CD22]]
* [[CD10]]
* BCL6.
* BCL2 and TdT.
|
|
:* 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''
|-
| rowspan="25" |B cell lymphoma
|[[Mantle cell lymphoma]]
|
* [[CD5 (protein)|CD5]] positive antigen in pregerminal center of B-cell
* [[Chromosomal translocation]] at '''t(11:14)'''
** Over-express [[cyclin D1]]
|
* Stage IV disease
* B symptoms,
* Generalized lymphadenopathy
* Abdominal distention
* Fatigue
* Extranodal involvement of gastrointtestinal (GI) tract, lungs, and central nervous system (CNS)
|
* History of Night sweats
* Weight Loss
|
* Generalized lymphadenopathy
* Hepato-splenomegaly
* Mental Retardation
* Less commonly
** Palpable masses in skin, breast, and salivary glands
|
* CD5<sup>+</sup>
* 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.
|
|
|
|
* [[CD20]]
* [[CD79a]]
|
|
* [[B-cells]] replace the normal [[white pulp]] of the [[spleen]].
* The neoplastic cells compromise
** Small [[lymphocytes]]
** Transformed blasts
* S[[Sinus|inus]] invasion
* Epithelial histocytes
* Plasmacytic differentiation of neoplastic cells.
* '''Splenic Hilar Lymph Nodes'''
** Involved hilar [[lymph nodes]] adjacent to the [[spleen]] show an effaced architecture without preservation of the [[marginal zone]] seen in the spleen
* '''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 [[Cytokine|cytokines]], such as [[TNF alpha]] and IL-2R, provide important stimuli for [[malignant]] [[B cell|B cells]] proliferation in hairy cell leukemia.
** The ''p38-MAPK-JNK'' cascade
** The ''MEK-ERK'' cascade
** The ''Phosphatidylinositol 3 kinase (PI3K)-AKT'' cascade
|
* [[Fever]]
* [[Night sweat|Night sweats]]
* [[Fatigue]]
* Easy [[bruising]] or [[bleeding]]
* Generalized weakness
* [[Weight loss]]
* Recurrent [[Infection|infections]]
* Early satiety
|
* Review occupational history related to sawdust exposure
* Review any exposure to radiations
* Review any exposure to herbicides or diesel
|
* [[Pallor]],
* [[Petechiae]]
* [[Splenomegaly]]
|
* [[Annexin A1]]
* [[CD20]]
* [[CD25]]
* [[CD103]]
* [[CD19]]
* [[CD11c]]
* [[FMC7]]
|
* Tartrate-resistant acid phosphatase  positive
* CBC
** Decreased [[hemoglobin]] concentration
** Decreased [[platelets]] count
**
|
:* 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)
|-
|[[Multiple myeloma|Plasma cell myeloma]]
|
|
|
|
|
|
|
|-
|[[Chronic lymphocytic leukemia]] / [[Chronic lymphocytic leukemia|small lymphocytic lymphoma]]
|
|
|
|
|
|
|
|-
|[[Monoclonal B-cell lymphocytosis]]
|
|
|
|
|
|
|
|-
|[[B-cell prolymphocytic leukemia]]
|
|
|
|
|
|
|
|-
|[[Waldenström's macroglobulinemia|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 [[MALT lymphoma|mucosa-associated lymphoid tissue]] (MALT lymphoma)
|
|
|
|
|
|
|
|-
|Large B-cell lymphoma with IRF4 rearrangement
|
|
|
|
|
|
|
|-
|[[Primary cutaneous follicle centre lymphoma|Primary cutaneous follicle center lymphoma]]
|
|
|
|
|
|
|
|-
|T-cell/histiocyte-rich large B-cell lymphoma
|
|
|
|
|
|
|
|-
|[[Lymphomatoid granulomatosis]]
|
|
|
|
|
|
|
|-
|[[Primary mediastinal large B-cell lymphoma|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
|
|
|
|
|
|
|
|-
| rowspan="6" |T cell lymphoma
|[[Mycosis fungoides]] / [[Sézary syndrome]]
|
* The [[tumor]] [[Cell (biology)|cells]] originate from [[memory T cells]] or [[skin]] homing [[CD4+ T cells]] expressing [[cutaneous]] [[lymphocyte]] [[antigen]] (CLA) and [[chemokine]] [[receptors]] [[CCR4]]<nowiki/>and CCR7.
* It is understood that cutaneous t cell lymphoma (maycosis fungoides, Sezary sydrome ) is the result of malignant T cell that derived from a mature CD41 CD45RO1 memory T cells.
|
* [[Epidermis (skin)|Epidermal]] [[atrophy]] or poikiloderma
* Generalized [[itching]]([[pruritus]])
* [[Pain]] in the affected area of the skin.
* [[Insomnia]]
* Red ([[erythematous]]) patches scattered over the [[skin]] of the [[trunk]] and the [[extremities]]
* [[Weight loss]]
* [[Lymphadenopathy]]
* [[Malaise]] and [[fatigue]]
* [[Anemia]]
* May progress to [[Sezary syndrome]] (Skin involvement plus hematogenous dissemination)
|
|
* 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:
* Generalised weakness and [[Fatigue (physical)|fatigue]]
* [[Anorexia]]
* Joint pain
* Night sweating
* [[Epistaxis]]
* [[Bone pain]]
* [[Dyspnea]]
|
|
* Usually appear pale and malnourished.
* Cardiac flow murmur
* High-grade fever
* [[Hepatomegaly]]
* [[Splenomegaly]]
|
* [[CD3]]+
* [[TCR]]αβ+
* [[CD4]]-
* [[CD8]]+
|
* 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]]
|
|
|
|
|
|
|
|}

Revision as of 14:48, 27 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]

Pathophysiology Symptoms History Physical Examination Laboratory Findings
Immunochemistry Blood work Biospy
Diffuse large B-cell lymphoma Classified into 2 subtypes based on gene expression profiles:
  • Germinal centre B-cell-like (GCB)
  • Activated B-cell-like (ABC).
    • B cell receptor (BCR) signalling
    • B cell migration/adhesion
    • Cell-cell interactions in immune niches
    • Production and class-switching of immunoglobulins
  • 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
  • Non tender mass
  • Immunohistochemistry(IHC)
    • CD20, CD3, CD5, CD45, CD10, BCL-2, BCl-6, MYC, IRF-4/ MUM-1, Ki-67
  • Flow Cytometry Panel
    • Kappa/ Lambda, CD3, CD5, CD45, CD10, CD19, CD20
  • Cytology (for primary CNS lymphoma only)
  • Genetic testing
    • 8q24/MYC translocations
    • Immunoglobulin genes clonally rearranged and hypermutated
    • Mutation of BCL6, MYC, PAX5, PIM1, RhoH/TTFn, TP53 genes
    • Translocations involving c-MYC, BCL6, and IgH gene.
  • Neutropenia
  • Anemia
  • Hypergammaglobulinemia
  • Screening tests for HCV, HBV and HIV.

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 of Hodgkin's lymphoma or Anaplastic Large cell Lymphoma.
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
  • Extranodal involvement of gastrointtestinal (GI) tract, lungs, and central nervous system (CNS)
  • History of Night sweats
  • Weight Loss
  • 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
  • Review occupational history related to sawdust exposure
  • Review any exposure to radiations
  • Review any exposure to herbicides or diesel
  • 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