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| Line 34: |
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| *** [[Peripheral T cell lymphoma]] | | *** [[Peripheral T cell lymphoma]] |
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| ==Genetics==
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| Different subtypes of non Hodgkin lymphoma and their genetic involvements::
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| {| class="wikitable"
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| |+
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| ! colspan="2" rowspan="2" |
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| ! rowspan="2" |Pathophysiology
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| ! rowspan="2" |Symptoms
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| ! rowspan="2" |Physical Examination
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| ! colspan="3" |Laboratory Findings
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| |-
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| !Immunochemistry
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| !Blood work
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| !Biospy
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| |-
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| |[[Diffuse large B-cell lymphoma]]
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| |Classified into 2 subtypes based on [[gene expression]] profiles:
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| *Germinal centre B-cell-like (GCB)
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| *Activated B-cell-like (ABC).
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| **B cell receptor (BCR) signalling
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| **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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| * Mass/Lump
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| :* Rapidly enlarging [[lymph nodes]].
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| :* Painless
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| :* May be present in neck, groin or abdomen
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|
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| :* It is not uncommon to have [[lymphoma]] in extranodal sites. B symptoms :
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| :* Fever
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| :* Night sweats
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| :* weight loss
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| :
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| *
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| * Non tender mass
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| *
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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]]
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| ** Immunoglobulin genes clonally rearranged and hypermutated
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| ** Mutation of ''BCL6'', ''MYC'', ''[[PAX5]]'', ''[[PIM1]]'', ''[[RhoH]]''/''TTFn'', ''[[TP53]]'' genes
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| ** Translocations involving ''c-MYC'', ''BCL6'', and ''IgH'' gene.
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|
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| *
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| * Neutropenia
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| * Anemia
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| * Hypergammaglobulinemia
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| * Screening tests for HCV, HBV and HIV.
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|
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| ====Centroblastic====
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| *Medium-to-large-sized [[Lymphocyte|lymphocytes]]
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| *Monomorphic
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| ====Immunoblastic::====
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| *> 90% immunoblasts
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| *Trapezoid shaped large lymphoid cells with significant [[basophilic]] cytoplasm
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| ====Anaplastic:====
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| *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.
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| |-
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| |[[Follicular lymphoma]]
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| * Reciprocal translocation t(14;18)(q32;q21).
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| *[[Fever]]
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| *[[Weight loss]]
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| *[[Night sweats]]
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| *[[Skin rash]]
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| *[[Chest pain]]
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| *[[Abdominal pain]]
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| *[[Bone pain]]
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| *[[Cough]]
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| *[[Dyspnea]]
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| *Painless swelling in the neck, axilla, groin, thorax and abdomen
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| * [[Lymphadenopathy|Central and peripheral lymphadenopathy]]
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| * [[Splenomegaly]]
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| * [[Hepatomegaly]]
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| * [[Abdominal tenderness]]
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|
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| * [[Seizures]]
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| |-
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| |[[Burkitt lymphoma]]
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| * Translocation of chromosome 8 ''[[myc]]'' locus with 3 possible partners (accounting for 90% of translocations):
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| ** The Ig heavy chain region on chromosome 14: t(8;14)
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| ** The kappa light chain locus on chromosome 2: t(2;8)
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| ** The lambda light chain locus on chromosome 22: t(8;22)
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| * [[Fever]]
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| * [[Night sweats]]
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| * Unexplained [[weight loss]]
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| * [[Swollen lymph nodes]] in the neck, axilla, or groin
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| * [[Proptosis]]
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| * Jaw mass
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|
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| * [[Abdominal mass|Abdominal masses]]
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| * [[Ascites]]
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|
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| * [[Lymphadenopathy|Peripheral lymphadenopathy]]
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| * [[CD19]]
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| * [[CD20]],
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| * [[CD22]]
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| * [[CD10]]
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| * BCL6.
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| * BCL2 and TdT.
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| :* 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]])
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| :* Round nucleus
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| :* Small nucleoli
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| :* [[basophilic]] cytoplasm
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| :* Brisk mitotic rate and [[apoptotic]] activity
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| :* Cellular outline usually appears squared off
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| :* "Starry-sky pattern":
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| :** The ''stars'' in the pattern are tingible-body macrophages (macrophages containing [[apoptotic]] tumor cells)
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| :** The tumour cells are the ''sky''
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| |-
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| | rowspan="25" |B cell lymphoma
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| |[[Mantle cell lymphoma]]
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| * [[CD5 (protein)|CD5]] positive antigen in pregerminal center of B-cell
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| * [[Chromosomal translocation]] at '''t(11:14)'''
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| ** Over-express [[cyclin D1]]
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| * Stage IV disease
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| * B symptoms,
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| * Generalized lymphadenopathy
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| * Abdominal distention
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| * Fatigue
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| * Night sweats
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| * Weight Loss
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| * Extranodal involvement of gastrointtestinal (GI) tract, lungs, and central nervous system (CNS)
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| * Generalized lymphadenopathy
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| * Hepato-splenomegaly
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| * Mental Retardation
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| * Less commonly
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| ** Palpable masses in skin, breast, and salivary glands
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| * CD5<sup>+</sup>
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| * B-cell antigen positive
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| ** CD19
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| ** CD20
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| ** CD22
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| * Cyclin D1 is overexpressed.
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| |CBC
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| * Anemia and cytopenias are secondary to bone marrow infiltration
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| * Lymphocytosis > 4000/µL
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| * Elevated LDH
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| *
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| * Germinal centers filled by small-to-medium atypical lymphocytes.
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| * Nodular appearance may be evident from expansion of the mantle zone in 30-50% of patients early in the disease.
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| |-
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| |[[Nodal marginal zone B-cell lymphoma]]
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| * Arise from memory B cells. Include
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| ** Splenic marginal zone lymphoma
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| ** Nodal marginal zone lymphoma
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| ** Extranodal marginal zone lymphoma.
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| * Stimulation of antigen receptor by autoantigen and co-stimulatory molecule CD40.
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| * Depends largely on its location
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| * Gastric marginal zone lymphoma
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| ** Dyspepsia
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| ** Abdominal pain
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| ** Hemorrhage
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| * Chronic infectious conditions or autoimmune processes, such as
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| ** ''H pylori'' gastritis
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| ** Hashimoto thyroiditis
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| ** Sjögren syndrome.
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| * AE1/AE3
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| * B-cell markers CD20, CD79a, CD10, CD23, and bcl-2 are expressed
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| * Follicular cells in reactive zone
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| * Centrocyte like cells in marginal zone lymphoma
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| |-
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| |[[Splenic marginal zone lymphoma]]
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| * Clonal rearrangements of the [[immunoglobulin]] genes (heavy and light chains) .
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| ** Deletion 7q21-32
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| ** Translocations of the CDK6 gene located at 7q21.
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| * [[CD20]]
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| * [[CD79a]]
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| * [[B-cells]] replace the normal [[white pulp]] of the [[spleen]].
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| * The neoplastic cells compromise
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| ** Small [[lymphocytes]]
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| ** Transformed blasts
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| * S[[Sinus|inus]] invasion
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| * Epithelial histocytes
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| * Plasmacytic differentiation of neoplastic cells.
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| * '''Splenic Hilar Lymph Nodes'''
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| ** Involved hilar [[lymph nodes]] adjacent to the [[spleen]] show an effaced architecture without preservation of the [[marginal zone]] seen in the spleen
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| * '''Bone Marrow Biopsy'''
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| ** Splenic marginal zone lymphoma in [[bone marrow]] displays a nodular pattern with morphology similar to what is observed in the splenic [[hilar]] [[lymph nodes]].
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| |-
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| |[[Hairy cell leukemia]]
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| * 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.
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| ** The ''p38-MAPK-JNK'' cascade
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| ** The ''MEK-ERK'' cascade
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| ** The ''Phosphatidylinositol 3 kinase (PI3K)-AKT'' cascade
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| * [[Fever]]
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| * [[Night sweat|Night sweats]]
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| * [[Fatigue]]
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| * Easy [[bruising]] or [[bleeding]]
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| * Generalized weakness
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| * [[Weight loss]]
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| * Recurrent [[Infection|infections]]
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| * Early satiety
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| * [[Pallor]],
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| * [[Petechiae]]
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| * [[Splenomegaly]]
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| * [[Annexin A1]]
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| * [[CD20]]
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| * [[CD25]]
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| * [[CD103]]
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| * [[CD19]]
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| * [[CD11c]]
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| * [[FMC7]]
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| * Tartrate-resistant acid phosphatase positive
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| * CBC
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| ** Decreased [[hemoglobin]] concentration
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| ** Decreased [[platelets]] count
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| **
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| :* Small cells with "fried egg"-like appearance
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| :* Well-demarcated thread-like [[cytoplasmic]] extensions
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| :* Clear cytoplasm
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| :* Central round [[nucleus]]
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| :* Peri-nuclear clearing ("water-clear rim" appearance)
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| |-
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| |[[Multiple myeloma|Plasma cell myeloma]]
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| |-
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| |[[Chronic lymphocytic leukemia]] / [[Chronic lymphocytic leukemia|small lymphocytic lymphoma]]
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| |-
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| |[[Monoclonal B-cell lymphocytosis]]
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| |[[B-cell prolymphocytic leukemia]]
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| |[[Waldenström's macroglobulinemia|Waldenström's macroglubulinemia]]
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| |[[Monoclonal gammopathy of undetermined significance]] (MGUS)
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| |-
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| |[[Heavy chain disease]]
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| |-
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| |Solitary plasmacytoma of bone
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| |Extraosseous plasmacytoma
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| |-
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| |Monoclonal immunoglobulin deposition diseases
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| |Extranodal marginal zone lymphoma of [[MALT lymphoma|mucosa-associated lymphoid tissue]] (MALT lymphoma)
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| |Large B-cell lymphoma with IRF4 rearrangement
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| |[[Primary cutaneous follicle centre lymphoma|Primary cutaneous follicle center lymphoma]]
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| |-
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| |T-cell/histiocyte-rich large B-cell lymphoma
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| |-
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| |[[Lymphomatoid granulomatosis]]
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| |[[Primary mediastinal large B-cell lymphoma|Primary mediastinal (thymic) large B-cell lymphoma]]
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| |[[Intravascular large B-cell lymphoma]]
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| |ALK1 large B-cell lymphoma
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| |Plasmablastic lymphoma
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| |[[Primary effusion lymphoma]]
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| |High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
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| | rowspan="6" |T cell lymphoma
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| |[[Mycosis fungoides]] / [[Sézary syndrome]]
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| * 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.
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| * 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.
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| * [[Epidermis (skin)|Epidermal]] [[atrophy]] or poikiloderma
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|
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| * Generalized [[itching]]([[pruritus]])
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| * [[Pain]] in the affected area of the skin.
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| * [[Insomnia]]
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| * Red ([[erythematous]]) patches scattered over the [[skin]] of the [[trunk]] and the [[extremities]]
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| * [[Weight loss]]
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| * [[Lymphadenopathy]]
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| * [[Malaise]] and [[fatigue]]
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| * [[Anemia]]
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| * May progress to [[Sezary syndrome]] (Skin involvement plus hematogenous dissemination)
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| * Cutaneous manifestaions
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| |[[T-cell granular lymphocytic leukemia]]
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| * Disregulation of signaling pathways:
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| ** FAS/FAS-L
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| ** Phosphatidylinositol-3 kinase (PI3K),
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| ** Mitogen-activated proteinkinase/extracellular signal-regulated kinase (MAPK/ERK)
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| Symptoms of T-cell large granular lymphocyte leukemia may include the following:
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| * Generalised weakness and [[Fatigue (physical)|fatigue]]
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| * [[Anorexia]]
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| * Joint pain
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| * Night sweating
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| * [[Epistaxis]]
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| * [[Bone pain]]
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| * [[Dyspnea]]
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| |
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| * Usually appear pale and malnourished.
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| * Cardiac flow murmur
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| * High-grade fever
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| * [[Hepatomegaly]]
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| * [[Splenomegaly]]
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| * [[CD3]]+
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| * [[TCR]]αβ+
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| * [[CD4]]-
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| * [[CD8]]+
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| |
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| * Neutropenia
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| * Anemia
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| * Hypergammaglobulinemia
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| :* Clonal rearrangements of the [[T-cell receptor]] (TCR) gene
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| :* Chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood
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| :* Large granular lymphocyte count greater than 2.0 × 109/L
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| :* Lymphocytosis (typically 2-20x109/L)
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| |-
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| |[[Subcutaneous panniculitis-like T-cell lymphoma]]
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| |}
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|
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|
| <references /> | | <references /> |
|
| |
|
| ==Associated Conditions==
| |
| Conditions associated with [disease name] include:
| |
|
| |
| *[Condition 1]
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| *[Condition 2]
| |
| *[Condition 3]
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|
| |
| ==Gross Pathology==
| |
| On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
| |
|
| |
| ==Microscopic Pathology==
| |
| On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
| |
|
| |
|
| ==References== | | ==References== |
| Line 591: |
Line 60: |
| **MLL2 | | **MLL2 |
|
| |
|
| ==Gross Pathology==
| |
| On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
| |
|
| |
| ==Microscopic Pathology==
| |
| On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
| |
|
| |
|
| ==References== | | ==References== |