Sandbox:Preeti

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	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 Medium-to-large-sized 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	Central and peripheral lymphadenopathy Splenomegaly Hepatomegaly Abdominal tenderness Seizures
	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 masses Ascites 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
B cell lymphoma	Mantle cell lymphoma	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 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.			CD20 CD79a		B-cells replace the normal white pulp of the spleen. The neoplastic cells compromise Small lymphocytes Transformed blasts Sinus 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 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	Fever Night sweats Fatigue Easy bruising or bleeding Generalized weakness Weight loss Recurrent infections Early satiety	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)
	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	The tumor cells originate from memory T cells or skin homing CD4+ T cells expressing cutaneous lymphocyte antigen (CLA) and chemokine receptors CCR4and 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.	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 Anorexia Joint pain Night sweating Epistaxis Bone pain Dyspnea	Usually appear pale and malnourished. Cardiac flow murmur High-grade fever Hepatomegaly Splenomegaly	CD3+ TCRαβ+ 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