Diffuse Large B Cell lymphoma Flashcards
What is DLBCL
A neoplasm of large B lymphoid cells with nuclear size equal to or exeeding normal macrophage nuclei or more than twice the size of a normal lymphocyte, and which has a diffuse growth pattern
Heterogenous group of lymphomas which has many subtypes. Those that have no clear criteria for subdivision are DLBCL NOS.
It includes: (1) the diffuse mixed cell form of follicular lymphoma; (2) peripheral T-cell lymphoma; (3) lymphoplasmacytic lymphoma with an increased number of immunoblasts (also known as polymorphic immunocytoma); (4) T-cell-rich large B-cell lymphoma; and (5) some examples of marginal zone B-cell lymphoma with an admixture of large cells; and probably others.
What characterizes DLBCLs?
It is characterized morphologically by large size of the cells, vesicular nuclei with prominent nucleoli, and relatively abundant cytoplasm, and immunophenotypically by expression of B-lineage markers
In which age group does DLBCL occur?
DLBCL occurs both in children and adults, but mostly in adults. The median age is 7th decade. It is slighly more common in men.
Where does it tend to present?
In comparison with most other types of lymphoma, it has a greater tendency for extranodal presentation and for being localized at the time of presentation.
Approximately 40% of the cases present in extranodal sites, most commonly stomach and ileocaecal region, but may involve any location.
Skin involvement is second most common extranodal site. BCL-2 expression is characteristic. Leg-type DLBCL commonest in elderly females
In more than half of the cases, the tumor is limited to one side of the diaphragm (40%, as opposed to 90% for follicular lymphoma).
Involvement of the bone marrow or liver is seen in 11-27% of cases, less common than in follicular or small lymphocytic lymphomas.
When the liver or spleen is involved, it is usually in the form of scattered large tumor masses instead of the multiple smaller nodules or miliary type seen with the group of lymphomas composed of small lymphocytes.
What do involved nodes look like?
The involved nodes are usually markedly enlarged, homogeneous, individualized, and with little or no necrosis
What does DLBCL in nodes look like microscopically?
Microscopically, the pattern of nodal involvement is by definition diffuse. However, it may be complete or partial, and on occasion it may be interfollicular or sinusal (see below). There is commonly extranodal extension, sometimes with accompanying sclerosis. Mitoses are numerous and a starry sky pattern may be present.
What are the subclassifications of DLBCL?
Centroblastic - medium sized to large lymphoid cells, oval vesicular nuclei, fine chromatin, 2-4 nucleoli. May be monomorphic or mixed iwth immunoblasts. Nuclei may be multilobated
Immunoblastic - over 90% cells are immunoblasts - centrally located nucleolus, basophilic cytoplasm, may have plasmacytoid differentiation. Sometimes need to distinguish it from a plasmablastic lymphoma or immature plasma cell myeloma
Anaplastic - very large round oval/polyganol cells with bizarre pleomorphic nuclei
Rare morphologic variants - myxoid or fibrillary matrix, pseudorosettes, spindle-celled, signet ring cells
Which subtype of DLBCL most commonly arises on a background of immunodeficiency or immuno-related diseases such as Hashimoto’s and Sjogren’s?
Immunoblastic
What is the immunoprofile of DLBCL?
B-lineage markers esp CD20, Igs (surface or cytoplasmic, IgM>IgG>IgA)
Follicle centre markers BCL-6 and CD10
in 60% and 40%
Some express post-germinal centre markers CD38, MUM-1, VS38
50% express BCL-2
A minority express CD30 (esp anaplastic variant)
CD5 expressed in 10% (usu de novo rather than arising from CLL/SLL)
Ki67 should be high
Rarely can express cytokeratin
What is the aetiology of DLBCL?
Transformation from a low grade lymphoma e.g. CLL/SLL, follicular, MZL, NLPHL
De novo
EBV driven (10% in non-immunosuppressed, more in immunosuppresesed)
How can DLBCL with CD5 +ve cells be distinguished from blastoid type of mantle cell lymphoma?
Cyclin D1
What is the proposed subgrouping of DLBCLs by immunophenotype?
Germinal centre-like:
CD10 +ve >30% of cells
CD10-ve, MUM1-ve, BCL-6 +ve
All other types regarded as non-GC type
The grouping does not alter therapy
What are the subgroups of DLBCL by gene expression profiling?
Germinal-centre B-cell-like: profile of germinal centre B cells. Some of these have the BCL-2 rearrangement
Activated B-cell-like: profile of activated peripheral B cells
Immunoblastic variant and centroblastic variant with more immunoblasts are more common in ABC subgroup, but the correlation between immunohistochemical grouping and genetic grouping is variable
What are unfavourable variables for DLBCL?
Age >60yrs
Poor performance status
Advanced Ann Arbor stage
Extranodal involvement at >2 sites
High serum LDH
What is Ann Arbor staging?
It is a staging system for lymphomas
Stage I indicates that the cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms.
Stage II indicates that the cancer is located in two separate regions, an affected lymph node or organ and a second affected area, and that both affected areas are confined to one side of the diaphragm - that is, both are above the diaphragm, or both are below the diaphragm.
Stage III indicates that the cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.
Stage IV indicates diffuse or disseminated involvement of one or more extralymphatic organs, including any involvement of the liver, bone marrow, or nodular involvement of the lungs.
