Within is a technical report on the challenges of correctly
diagnosing a lymphoma – showing that false positive, false
negatives, and incorrect subtype are all possible – for some
subtypes (histologies) more than for others.
Common misdiagnoses in lymphomas and avoidance strategies
Lymphoma diagnosis integrates
- clinical (how it behaves and presents),
- morphological (appearance of cells under a microscope),
- immunophenotypical (cell differentiation – by cd expression),
- molecular genetic features (such as deletions,
transpositions), as shown in WHO classifications of lymphoid
Diagnosis of lymphoma is challenging.
Reactive lesions such as Kikuchi lymphadenitis, infectious
mononucleosis, autoimmune lymphoproliferative syndrome, and
immunoglobulin G4-related sclerosing disease can be misdiagnosed
Anaplastic large-cell lymphoma variants that are positive for
anaplastic lymphoma kinase, classical Hodgkin's lymphoma
variants, and infarcted lymphomas might be misdiagnosed as
Difficulties with classification of lymphomas are also
encountered, such as the distinction of classical Hodgkin's
lymphoma from anaplastic large-cell lymphoma that is negative
for anaplastic lymphoma kinase.
Interpretation of immunophenotyping results is complicated in
some cases by aberrant or cross-lineage expression of lymphoid
antigens on lymphomas, and the occasional lymphoid antigen
expression on non-lymphoid malignancies.
Molecular analysis can help to define clonality (all from one
cell of origin) and lineage (cell type), but can be affected by
the sensitivity and specificity of tests and cross-lineage gene
rearrangement and pseudoclonality (false clonality).
To resolve these issues, a close collaboration between the
clinician, histopathologist, and molecular biologist is needed.
The aim of this review is to provide pathologists and clinicians
with a concise account of these pitfalls and avoidance
Full text not available online.
Summary of topics:
Reactive* lesions often misdiagnosed as lymphoma
Infectious mononucleosis and other causes of immunoblastic
Autoimmune lymphoproliferation syndrome
IgG4-related sclerosing* disease
* normal proliferation of immune cells in response to infection.
** pathological hardening of tissue especially from overgrowth
of fibrous tissue or increase in interstitial tissue; also : a
disease characterized by sclerosis
= or vice-versa:
Malignant lymphoma often diagnosed as reactive disorders
ALK-positive anaplastic large-cell lymphoma (ALCL)
Lymph node infarction
Difficulties and errors in classification of lymphoma
Classical Hodgkin’s versus ALK-negative ALCL
Lymphoplasmacytic lymphoma versus marginal zone lymphoma
Plasmablastic lymphoma versus anaplastic plasmacytoma
Burkitt’s lymphoma versus diffuse large b-cell lymphoma
Angioimmunoblastic T-cell lymphoma versus peripheral T-cell
lymphoma NOS and atypical lymphoid hyperplasia
Subcutaneous panniculitis-like T-cell lymphoma versus primary
cutaneous B T-cell lymphoma, extranodal NK or T-cell lymphoma,
Immunophenotyping Issues (cell differentiation CD markers)
Difficulties in diagnosing lymphoma
CD20 expression in non-B-cell lymphomas
Absense of CD20 in B-cell lymphomas
CD3 expression in non-T-cell lymphomas
Expression of pan-lymphoid markers on non-lymphoid malignancies
Difficulties in clonality* assessment with gene rearrangement
Up to 10% of cases may require clonality analysis to confirm a
False-negative PCR fro Ig gene clonal arrangement in b-cell
False-negative PCR for TCR-gene clonal rearrangement in T-cell
Cross-lineage gene rearrangement
Clonal Ig or TCR gene arrangement in non-neoplastic lymphoid
• Clonality – that all the proliferating cells are from the same
cell of origin. A key characteristic of a cancer.