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]

Overview

Non-Hodgkin lymphoma (differentiating types of NHL)

Differentiating different types of Non-Hodgkin lymphoma. Gold standard for differentiation different types of Non-Hodgkin lymphoma is Biopsy.

Category	Disease		Etiology	Clinical manifestations						Paraclinical findings					Associated findings
				Clinical manifestations						Lab findings
				Symptoms				Signs		CBC			Immunochemistry	Histopathology
				Constitutional symptoms	Rash	Abdominal pain	Diarrhea	Mass	Other	WBC	Hb	Plt	Immunochemistry	Histopathology
	Hodgkin's Lymphoma^[1]^[2]^[3]^[4]^[5]		Activation of (NF-kB) Mutations in JAK-STAT pathway NF-kB leads to activation of many genes like: (ICAM-1) gene GM-CSF gene IL-6 gene IKBA gene Gain of function mutation of the MAP3K14 gene	Fever (Pel-Ebstein fever): persistent temperature >38°C (>100.4°F) Drenching night sweats Unexplained weight loss >10% of total body weight within the past 6 months	-	±	-	Painless lymphadenopathy with a rubbery consistency. Mostly above the diaphram	Pruritus Pain in lymph nodes after drinking alcohol Skin blushing or flushing Bone pain				CD45- CD30+ CD15+/-		EBV infection
Non-Hodgkin's Lymphoma
	Diffuse large B cell lymphoma^[6]^[7]^[8]^[9]^[10]^[11].		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	Extranodal involvement of GI tract, lungs, and CNS	↓	↓	Nl to ↓	CD20 CD3 CD5 CD45 CD10 BCL-2 BCl-6 MYC IRF-4/ MUM-1 Ki-67	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
B Cell Lymphoma	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
	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	Most common clinically indolent NHL Peripheral nerve compression
	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)
Category	Disease		Etiology	Constitutional symptoms	Rash	Abdominal pain	Diarrhea	Mass	Other	WBC	Hb	Plt	Immunochemistry	Histopathology	Associated findings
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

↑ Mauch PM, Kalish LA, Kadin M, Coleman CN, Osteen R, Hellman S (March 1993). "Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis". Cancer. 71 (6): 2062–71. PMID 8443755.
↑ Gobbi PG, Cavalli C, Gendarini A, Crema A, Ricevuti G, Federico M, Di Prisco U, Ascari E (December 1985). "Reevaluation of prognostic significance of symptoms in Hodgkin's disease". Cancer. 56 (12): 2874–80. PMID 4052959.
↑ Buri C, Körner M, Schärli P, Cefai D, Uguccioni M, Mueller C, Laissue JA, Mazzucchelli L (March 2001). "CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease". Blood. 97 (6): 1543–8. PMID 11238088.
↑ Peh SC, Looi LM, Pallesen G (March 1997). "Epstein-Barr virus (EBV) and Hodgkin's disease in a multi-ethnic population in Malaysia". Histopathology. 30 (3): 227–33. PMID 9088951.
↑ Andriko JA, Aguilera NS, Nandedkar MA, Abbondanzo SL (April 1997). "Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus". Mod. Pathol. 10 (4): 366–71. PMID 9110300.
↑ Colomo, L.; López-Guillermo, A; Perales, M; Rives, S; Martínez, A; Bosch, F; Colomer, D; Falini, B; Montserrat, E; Campo, E (2002). "Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma". Blood. 101 (1): 78–84. doi:10.1182/blood-2002-04-1286. PMID 12393466.
↑ Hans, C. P.; Weisenburger, D. D.; Greiner, T. C.; Gascoyne, R. D.; Delabie, J; Ott, G; Müller-Hermelink, H. K.; Campo, E; Braziel, R. M.; Jaffe, E. S.; Pan, Z; Farinha, P; Smith, L. M.; Falini, B; Banham, A. H.; Rosenwald, A; Staudt, L. M.; Connors, J. M.; Armitage, J. O.; Chan, W. C. (2004). "Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray". Blood. 103 (1): 275–82. doi:10.1182/blood-2003-05-1545. PMID 14504078.
↑ Muris, JJF; Meijer, Cjlm; Vos, W; Van Krieken, Jhjm; Jiwa, NM; Ossenkoppele, GJ; Oudejans, JJ (2006). "Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma". The Journal of Pathology. 208 (5): 714–23. doi:10.1002/path.1924. PMID 16400625.
↑ Korkolopoulou P, Vassilakopoulos T, Milionis V, Ioannou M (2016). "Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review". Adv Anat Pathol. 23 (4): 202–43. doi:10.1097/PAP.0000000000000117. PMID 27271843.
↑ Swerdlow SH, et al (editors). WHO classification of tumours of haematopoietic and lymphoid tissues. 4th edition. 2008. International Agency for Research on Cancer (IARC), Lyon, Franc
↑ Tilly H, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015; 26: v116-v125

[pmid8443755-1] Mauch PM, Kalish LA, Kadin M, Coleman CN, Osteen R, Hellman S (March 1993). "Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis". Cancer. 71 (6): 2062–71. PMID 8443755.

[pmid4052959-2] Gobbi PG, Cavalli C, Gendarini A, Crema A, Ricevuti G, Federico M, Di Prisco U, Ascari E (December 1985). "Reevaluation of prognostic significance of symptoms in Hodgkin's disease". Cancer. 56 (12): 2874–80. PMID 4052959.

[pmid11238088-3] Buri C, Körner M, Schärli P, Cefai D, Uguccioni M, Mueller C, Laissue JA, Mazzucchelli L (March 2001). "CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease". Blood. 97 (6): 1543–8. PMID 11238088.

[pmid9088951-4] Peh SC, Looi LM, Pallesen G (March 1997). "Epstein-Barr virus (EBV) and Hodgkin's disease in a multi-ethnic population in Malaysia". Histopathology. 30 (3): 227–33. PMID 9088951.

[pmid9110300-5] Andriko JA, Aguilera NS, Nandedkar MA, Abbondanzo SL (April 1997). "Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus". Mod. Pathol. 10 (4): 366–71. PMID 9110300.

[Colomo2003-6] Colomo, L.; López-Guillermo, A; Perales, M; Rives, S; Martínez, A; Bosch, F; Colomer, D; Falini, B; Montserrat, E; Campo, E (2002). "Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma". Blood. 101 (1): 78–84. doi:10.1182/blood-2002-04-1286. PMID 12393466.

[Hans2004-7] Hans, C. P.; Weisenburger, D. D.; Greiner, T. C.; Gascoyne, R. D.; Delabie, J; Ott, G; Müller-Hermelink, H. K.; Campo, E; Braziel, R. M.; Jaffe, E. S.; Pan, Z; Farinha, P; Smith, L. M.; Falini, B; Banham, A. H.; Rosenwald, A; Staudt, L. M.; Connors, J. M.; Armitage, J. O.; Chan, W. C. (2004). "Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray". Blood. 103 (1): 275–82. doi:10.1182/blood-2003-05-1545. PMID 14504078.

[Muris2006-8] Muris, JJF; Meijer, Cjlm; Vos, W; Van Krieken, Jhjm; Jiwa, NM; Ossenkoppele, GJ; Oudejans, JJ (2006). "Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma". The Journal of Pathology. 208 (5): 714–23. doi:10.1002/path.1924. PMID 16400625.

[pmid27271843-9] Korkolopoulou P, Vassilakopoulos T, Milionis V, Ioannou M (2016). "Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review". Adv Anat Pathol. 23 (4): 202–43. doi:10.1097/PAP.0000000000000117. PMID 27271843.

[10] Swerdlow SH, et al (editors). WHO classification of tumours of haematopoietic and lymphoid tissues. 4th edition. 2008. International Agency for Research on Cancer (IARC), Lyon, Franc

[11] Tilly H, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015; 26: v116-v125

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Non-Hodgkin lymphoma (differentiating types of NHL)

Overview

Non-Hodgkin lymphoma (differentiating types of NHL)

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