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Lymphoma - Non B cell neoplasms

Post-transplantation lymphoproliferative disorders (PTLD)

WHO Classification of post-transplant lymphoproliferative disorders

Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 24 October 2011, last major update September 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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1. Early Lesions¹
Plasmacytic hyperplasia
Infectious mononucleosis-like lesion

2. Polymorphic PTLD

3. Monomorphic PTLD²
B-cell neoplasms
     -Diffuse large B-cell lymphoma
     -Burkitt lymphoma
     -Plasma cell myeloma
     -Plasmacytoma-like lesion
     -Other³

T-cell neoplasms
     -Peripheral T-cell lymphoma, NOS
     -Hepatosplenic T-cell lymphoma
     -Other

4. Classical Hodgkin lymphoma-type PTLD

¹Some mass-like lesions in the post-transplant setting may have the morphologic appearance of florid follicular hyperplasia or other marked but non-infectious mononucleosis-like lymphoid hyperplasias.
²ICD-O codes for these lesions are the same as those for the respective lymphoid or plasmacytic neoplasm.
³Indolent small B-cell lymphomas arising in transplant recipients are not included among the PTLD.

Charts
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Pathologic evaluation of speciments for the diagnosis of PTLD
(from WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, Lyon 2008)

Method of evaluation	Necessity	Purpose
Histopathology	Essential	Evaluate architecture and cytologic features, required for classification
Immunophenotype	Essential	Assess possible light chain class restriction* and basic lymphoid subsets, required for classification
EBER-ISH	Essential**	Most sensitive method for assessing if PTLD is EBV-positive, aids in diagnosis and possibly prognostication, useful in differential diagnosis with rejection in allograft (if positive)
Genetic/Cytogenetic studies	Variable	Determine clonality, lineage of clonal population(s), chromosomal and oncogene abnormalities, may be needed for classification
EBV clonality	Not required	Identification of minor clones
*Paraffin section immunohistochemistry will often fail to demonstrate monotypic B-cell populations, even if present, unless there is plasmacytic differentiation. **If the less sensitive EBV-LMP1 stain is positive, EBER-ISH is not required.

Criteria used in the categorization of PTLD
(from WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, Lyon 2008)

Pathologic category	Histopathology		Immunophenotype/in situ hybridization	Genetics
	Architectural effacement	Major findings		IgH@TCR	Other abnormalities
Early lesions	Absent	Small lymphocytes, plasma cells, +/- immunoblasts, +/- hyperplastic follicles	Pcl B cells & admixed T cells; often EBV+	Pcl or very small mcl B-cell population(s)	None
Polymorphic PTLD	Present	Full spectrum of lymphoid maturation seen	Pcl or mcl B cells & admixed T cells; often EBV+	Mcl B cells, non-clonal T cells	Some have BCL6 somatic hypermutations
Monomorphic PTLD	Usually present	Fulfils criteria for a NHL (other than one of the indolent B-cell neoplasms) or plasma cell neoplasm	Varies based on type of neoplasm they resemble. EBV more variable than in other categories	Clonal B cells and/or T cells (except for rare NK cases)	Usually present
Hodgkin lymphoma type PTLD	Present	Fulfils criteria for CHL	Similar to other CHL; EBV+	IgH will not be easily demonstrated	Not known
Pcl, polyclonal; Mcl, monoclonal; NK, natural killer; TCR, T-cell antigen receptor.

Notes
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● According to some authors, MALT lymphomas should be considered M-PTLD: may be EBV+ and may regress after reduction in immunosuppression
● PTLD at relapse may differ from initial PTLD in morphology, EBV status and lineage
● B-cell and T-cell PTLD can occur in the same patient; most commonly B precedes T, but simultaneous or vice versa also possible

Additional references
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● Medeiros; Diagnostic Pathology: Lymph Nodes and Spleen with Extranodal Lymphomas, 2011
● Review articles: Arch Pathol Lab Med 2007;131:1209, J Clin Oncol 2010;28:1038, Oncologist 2006;11:674

End of Lymphoma - Non B cell neoplasms > Post-transplantation lymphoproliferative disorders > WHO Classification of post-transplant lymphoproliferative disorders

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