Non-Hodgkin lymphoma (differentiating types of NHL)

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

Non-Hodgkin lymphoma (differentiating types of NHL)

Differentiating different types of Non-Hodgkin lymphoma.

Category	Disease		Etiology	Clinical manifestations						Paraclinical findings					Gold standard	Associated findings
										Lab findings
				Symptoms				Signs		CBC			Immunochemistry	Histopathology
				Constitutional symptoms	Rash	Abdominal pain	Diarrhea	Mass	Other	WBC	Hb	Plt
HL
	Hodgkin's Lymphoma
NHL
B Cell Lymphoma	B-lymphoblastic leukemia/lymphoma		Precursor B-cell Lymphoma Unknown Inherited mutations of PAX5, ETV6, and TP53	+	–	–	–		Bleeding Dyspnea Joint pain	↓	↓	Nl to ↓				Down syndrome
	Follicular lymphoma		Mature B-cell Lymphoma Reciprocal translocation t(14;18) Overexpression of BCL2	Only in 20% of patients: Fever Weight loss Night sweats	+	+	±	Painless peripheral adenopathy in the cervical, axillary, inguinal, and/or femoral regions Asymptomatic large abdominal mass	Seizures Chest pain Bone pain Cough Dyspnea	↓	↓	Nl to ↓	CD21 CD23	Nodular growth pattern	Lymph node biopsy	Most common clinically indolent NHL Peripheral nerve compression
	Mantle cell lymphoma		Mature B-cell Lymphoma CD5 positive antigen in pregerminal center of B-cell Chromosomal translocation at t(11:14)	Fatigue Night sweats Weight Loss		Abdominal distention		Palpable masses in skin, breast, and salivary glands Generalized lymphadenopathy	Extranodal involvement of GI tract, lungs, and CNS Mental Retardation	Lymphocytosis > 4000/µL	↓	Nl to ↓	CD5+ B-cell antigen positive Overexpression of Cyclin D1	Germinal centers filled by small-to-medium atypical lymphocytes Nodular appearance
	Diffuse large B cell lymphoma		Mature B-cell Lymphoma 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				Painless rapidly enlarging lymph nodes		↓	↓	Nl to ↓		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
	Disease		Etiology	Constitutional symptoms	Rash	Abdominal pain	Diarrhea	Mass	Other	WBC	Hb	Plt	Immunochemistry	Histopathology	Gold standard	Associated findings
	Burkitt lymphoma		Mature B-cell Lymphoma Translocation of chromosome 8 myc locus such as: t(8;14) t(2;8) t(8;22)	Fever Night sweats Unexplained weight loss				Swollen lymph nodes in the neck, axilla, or groin Jaw mass Abdominal masses	Ascites Proptosis				CD19 CD20 CD22 CD10 BCL6 BCL2 and TdT	Round and small nucleoli basophilic cytoplasm "Starry-sky pattern"
	B cell chronic lymphocytic leukemia/small lymphocytic lymphoma		Mature B-cell Lymphoma
	Marginal zone lymphoma	Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type	Mature B-cell Lymphoma
		Splenic marginal zone lymphoma	Mature B-cell Lymphoma Clonal rearrangements of the immunoglobulin genes (heavy and light chains) Deletion 7q21-32 Translocations of the CDK6 gene located on 7q21										CD20 CD79a	Small lymphocytes Transformed blasts Epithelial histocytes Plasmacytic differentiation of neoplastic cells
		Nodal marginal zone B-cell lymphoma	Mature B-cell Lymphoma Stimulation of antigen receptor by autoantigen and co-stimulatory molecule CD40		+				Hemorrhage Dyspepsia				Follicular cells in reactive zone Centrocyte like cells in marginal zone lymphoma			Chronic infectious conditions or autoimmune processes, such as H pylori gastritis Hashimoto thyroiditis Sjögren syndrome
	Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)		Mature B-cell Lymphoma
	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		Tartrate-resistant acid phosphatase positive CBC Decreased hemoglobin concentration Decreased platelets count			Annexin A1 CD20 CD25 CD103 CD19 CD11c FMC7	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)
T cell lymphoma	Precursor T-cell lymphoblastic leukemia/lymphoma		Precursor T-cell Lymphomas
	Adult T cell leukemia/lymphoma		Mature T-cell Lymphoma
	Anaplastic large cell lymphoma		Mature T-cell Lymphoma
	Cutaneous T-cell lymphoma	Mycosis fungoides / Sézary syndrome	Mature T-cell Lymphoma 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 manifestations
	Peripheral T-cell lymphoma	Subcutaneous panniculitis-like T-cell lymphoma	Mature T-cell Lymphoma
		Hepatosplenic gamma-delta T-cell lymphoma	Mature T-cell Lymphoma
		Enteropathy-type intestinal T-cell lymphoma	Mature T-cell Lymphoma
		Extranodal T-cell lymphoma, nasal type	Mature T-cell Lymphoma
		Angioimmunoblastic T-cell lymphoma	Mature T-cell Lymphoma
		Peripheral T-cell lymphoma, unspecified	Mature T-cell Lymphoma