Non-Hodgkin lymphoma (differentiating types of NHL)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[3], Kamal Akbar, M.D.[4]

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.

Disease Etiology Clinical manifestations Paraclinical findings Associated findings
Lab findings
Symptoms Signs Immunochemistry Histopathology
Constitutional symptoms Rash Abdominal

pain

Diarrhea Mass Other
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:
- ± -
  • Painless lymphadenopathy with a rubbery consistency.
  • Mostly above the diaphram
Nodular lymphocyte predominant
  • Effacement of the lymph node architecture by Reed-Sternberg cells .
  • Reed-Sternberg cell is a large often bi-nucleated cells with prominent nucleoli and an unusual immuno phenotype.
Non-Hodgkin's Lymphoma (B Cell 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.
- + +
  • CD20
  • CD3
  • CD5
  • CD45
  • CD10
  • BCL-2
  • BCl-6
  • MYC
  • IRF-4/ MUM-1
  • Ki-67

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
_
Mantle cell lymphoma
[12][13][14][15][16]
+ +
  • CD5+
  • B-cell antigen positive
  • Overexpression of Cyclin D1
  • Germinal centers filled by small-to-medium atypical lymphocytes
  • Nodular appearance
Abdominal distention
B-lymphoblastic leukemia/lymphoma
[17][18][19]
  • Precursor B-cell lymphoma
  • Unknown
  • Inherited mutations of PAX5, ETV6, and TP53
+
  • CD20+
  • CD10+
  • Consists of small to medium-sized lymphoid cells with blastic nuclear chromatin and a high mitotic rate.
Follicular lymphoma
[20][21][22][23][24]
  • Mature B-cell lymphoma
  • Reciprocal translocation t(14;18)
  • Overexpression of BCL2
20% of patients present with: + + ±
  • CD21
  • CD23
  • Nodular growth pattern
  • Most common clinically indolent NHL
  • Peripheral nerve compression
Burkitt's lymphoma
[25][26][27][28][29][30][31][32]
  • Mature B-cell lymphoma
  • Translocation of chromosome 8 myc locus such as:
    • t(8;14)
    • t(2;8)
    • t(8;22)
+
  • Round and small nucleoli
  • basophilic cytoplasm
  • "Starry-sky pattern"
B cell chronic lymphocytic leukemia/small lymphocytic lymphoma
[33]
  • Mature B-cell Lymphoma
  • Ch 13 abnormalties

33% of patients present with:

  • CD5
  • CD38
  • Monoclonal small well differentiated B cells.
  • Significant number of smudge cells or basket cells.
Marginal zone lymphoma Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type
[34][35][36][37][38][39][40][41][42][43]
  • Mature B-cell lymphoma
  • Recurrent translocation of such as:
    • t(1;14)(p22;q32)
    • t(11;18)(q21;q21)
    • t(14;18)(q32;q21)
    • t(3;14)(p14.1;q32)
  • B symptoms may or may not be present
± + + B-cell associated antigens that co-express

Negative for:

  • Presence of dense diffuse lymphoid infiltrate of marginal‐zone cells in lamina propria
  • Prominent lymphoepithelial lesions and consisting of small atypical cells with monocytoid features.
Splenic marginal zone lymphoma
[44][45][46][47][48][49][50]
  • 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
+ +
  • Small lymphocytes
  • Transformed blasts
  • Epithelial histocytes
  • Plasmacytic differentiation of neoplastic cells
Nodal marginal zone B-cell lymphoma
[51][52]
  • Mature B-cell Lymphoma
  • Stimulation of antigen receptor by autoantigen and co-stimulatory molecule CD40
  • Mutations in KMT2D, PTTPRD, NOTCH2, KLF2
+
  • Follicular cells in reactive zone
  • Centrocyte like cells in marginal zone lymphoma
Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)
[53][54][55][56][57]
+ Express pan B-cell antigens

Variable expression of

Majority express:

  • IgM surface immunoglobulin

Fewer express

  • Russell bodies (intracytoplasmic inclusions) and Dutcher bodies (intranuclear inclusions)
  • Prominent epithelioid histiocytes
Hairy cell leukemia
[58][59][60][61][62]
  • 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
+
  • N/A
  • 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)
Disease Etiology Constitutional symptoms Rash Abdominal pain Diarrhea Mass/Lesion Other Immunochemistry Histopathology Associated findings
Non-Hodgkin's Lymphoma (T Cell Lymphoma)
Precursor T-cell lymphoblastic leukemia/lymphoma
[63][64]
  • Precursor T-cell lymphomas
+ - -
T-cell granular lymphocytic
[65][66][67]
- - - May be associated with the following conditions:
T-cell prolymphocytic leukemia
[68]
  • Abnormal proliferation of mature T cells (post thymic)
+ - -
  • Lymphocytes with abundant basophilic, nongranular cytoplasm, atypical nucleus
  • Cytoplasmic protrusions (blebs)
Adult T cell leukemia/lymphoma
[69][70][71]
+ - -
  • Charecterstic leukemia cells with sharp nuclear indentations and a prominent nucleoli
  • "Cloverleaf" or "flower" cells
Anaplastic large cell lymphoma
[72][73][74][75]
  • Mature T-cell lymphoma
+ + -

Painless swelling in :

Strongly immunoreactive for :
  • Nucleoli tend to be more prominent
  • The cytoplasm may be either basophilic or eosinophilic and the cell might have many nuclei with dispersed or clumped chromatin
  • May be caused by textured breast implants
Cutaneous T-cell lymphoma Mycosis fungoides / Sézary syndrome
[76][77][78]
+ + -
  • Cutaneous manifestations
  • Polymorphous inflammatory infiltrate in the dermis that contains small numbers of frankly atypical lymphoid cells
  • These cells may line up individually along the epidermal basal layer
  • The presence of spongiosis is highly suggestive of mycosis fungoides
Peripheral T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma
[79][80][81]
  • Mature T-cell lymphoma
- - - Painless swellings on:
  • Extremities
  • Trunks
Positive for:
Hepatosplenic T-cell lymphoma
[82][83][84]
+ + - Painless swelling in :
  • Intermediate sized tumor cells with clear cytoplasm, oval nuclei, slightly dispersed condensed chromatin, inconspicuous nucleoli
  • Patients with inflammatory bowel diseases taking immunosuppressant and anti-tumor necrosis factor-α agent are also have a higher risk for developing hepatosplenic T-cell lymphoma
Enteropathy-type intestinal T-cell lymphoma
[85][86][87]
  • Mature T-cell lymphoma
+ + + Painless swelling in the :
  • Lymphomatous infiltrate with neoplastic large cells
  • May have pleomorphic, multinucleated cells
  • Adjacent mucosa shows villous atrophy, crypt hyperplasia, increased inflammatory cells
  • Lymphocytosis
  • Mostly diagnosed in the small intestine
Extranodal T-cell lymphoma, nasal type
[88][89][90]
  • Mature T-cell lymphoma
+ - - Painless swelling in :
  • Medium sized tumor cells and polymorphic infiltrate of non-neoplastic inflammatory cells
  • Lymphoma cells may be admixed with a polymorphic infiltrate of non-neoplastic inflammatory cells
Angioimmunoblastic T-cell lymphoma
[91][92][93]
  • Mature T-cell lymphoma
+ + -
Peripheral T-cell lymphoma, unspecified
[94][95]
  • Mature T-cell lymphoma
- + -
  • Clear cytoplasm, resemble Reed-Sternberg cells, with irregular, pleomorphic, hyperchromatic or nuclei
  • A lot of mitotic figures; very broad cytologic spectrum

References

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