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Pathology >  The Diagnosis of Lymphoma can be Challenging

Last update: 07/16/2012


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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

Abstract http://image.thelancet.com/


Lymphoma diagnosis integrates
- clinical (how it behaves and presents),
- morphological (appearance of cells under a microscope),
- immunophenotypical (cell differentiation – by cd expression), and
- molecular genetic features (such as deletions, transpositions), as shown in WHO classifications of lymphoid malignancies.

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 as lymphomas.

Anaplastic large-cell lymphoma variants that are positive for anaplastic lymphoma kinase, classical Hodgkin's lymphoma variants, and infarcted lymphomas might be misdiagnosed as reactive disorders.

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 strategies.

Full text not available online.

Summary of topics:
Reactive* lesions often misdiagnosed as lymphoma
Kikuchi lymphadenitis
Infectious mononucleosis and other causes of immunoblastic proliferation
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)
Classical Hodgkin’s
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, and panniculitis

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 studies

Up to 10% of cases may require clonality analysis to confirm a lymphoma.
False-negative PCR fro Ig gene clonal arrangement in b-cell lymphomas
False-negative PCR for TCR-gene clonal rearrangement in T-cell lymphomas
Cross-lineage gene rearrangement
Clonal Ig or TCR gene arrangement in non-neoplastic lymphoid lesions.

• Clonality – that all the proliferating cells are from the same cell of origin. A key characteristic of a cancer.

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