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PAPER SPOTLIGHT
What To Call What We Treat, Part I
WHO Releases Updated Classification of
Lymphoid Neoplasms
After nearly a decade since its last
iteration, the World Health Organization (WHO) has revised its
2008 classification of lymphoid
neoplasms, updating the current
classification categories and adding new classification categories
for neoplasms in certain disease
states.
“In addition to adding a limited number of new provisional
entities, the modifications impact
the diagnostic criteria for some
entities related to important
prognostic or predictive factors,”
Steven H. Swerdlow, MD, from
the University of Pittsburgh
School of Medicine in Pennsylvania, and lead author of the monograph told ASH Clinical News in a
joint statement with co-authors
Elias Campo, MD, PhD, from the
University of Barcelona in Spain,
and Elaine S. Jaffe, MD, from
the National Cancer Institute in
Bethesda, Maryland.
To develop this new monograph, the WHO convened a clinical advisory committee that met
in 2014 to gain input, advice, and
consent from clinical hematologists/oncologists, pathologists,
and other physicians. The 2016
monograph features a review of
the major changes in the understanding of lymphoid, histiocytic,
and dendritic neoplasms that
have been published in the years
since the earlier edition.
“We have seen new insights
into the biology and management of both clonal proliferations with limited malignant
potential,” the authors wrote, “as
well as the aggressive lymphoid
neoplasms where more targeted
and effective therapies are being
investigated.”
The 2016 WHO classification
and associated monograph will
provide updated diagnostic categories and criteria, together with
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ASH Clinical News
biological and clinical correlates,
and facilitate state-of-the-art
patient care, future therapeutic
advances, and basic research in
this field.
“The updated classification
will allow physicians to better tailor therapies to the very specific
type of neoplasm that a patient
has,” said Drs. Swerdlow, Campo,
and Jaffe. “We are far beyond the
point where one regimen or drug
fits all patients.”
“Furthermore, [the revised
classification] facilitates communication between pathologists
and clinicians,” Dr. Swerdlow and
colleagues continued. “Evaluation of lymphomas requires a
pathologist who understands
what is needed to diagnose these
neoplasms. In addition, the need
for a multifaceted approach to
diagnosis requires sufficient tissue biopsies.”
Read below for some of the
major and proposed changes to
the classification. For the full
updated classification, visit
www.bloodjournal.org.
Mature B-Cell Lymphoid
Neoplasms
The many updates in the classification of small B-cell lymphomas
result from the “explosion of new
clinical, pathologic, and genetic
data” on these diseases, including
the following:
Chronic lymphocytic leukemia
(CLL)/small lymphocytic leukemia
(SLL): Cytopenias or disease-related symptoms are now insufficient to make a diagnosis of CLL
with <5x109/L peripheral blood
CLL cells. The monograph also
recognizes mutations of potential
clinical relevance (TP53, NOTCH1,
SF3B1, ATM, and BIRC3).
Hairy cell leukemia: BRAF
V600E mutation occurs in a vast
majority of cases with MAP2K1
mutations in most cases that use
IGHV4-34 and lack BRAF mutation.
Follicular lymphoma (FL): Pediatric FL will become a definite
entity in the 2016 classification
but is now known as pediatrictype FL because similar lymphomas may occur in adults. The
mutational landscape is better
understood, but the clinical impact remains to be determined.
In situ FL will be referred to
as in situ follicular neoplasia to
reflect the low risk of progression
to lymphoma.
Mature T-Cell and NK-Cell
Neoplasms
Advances in the classification
of nodal and extra-nodal T- and
NK-cell neoplasms have occurred
since the previous WHO classification, prompting revisions and
additions to this section. Many
of these changes, the authors
noted, are the result of genomic
studies that have examined
gene-expression profiling and the
genetic landscape of T-cell and
NK-cell neoplasms.
Nodal T-cell lymphomas with
T follicular helper (TFH) phenotype: This umbrella category was
created to highlight the spectrum
of nodal lymphomas with a TFH
phenotype, including angioimmunoblastic T-cell lymphoma,
follicular T-cell lymphoma, and
other nodal peripheral T-cell
lymphoma (PTCL) with a TFH
phenotype. Overlapping recurrent
molecular and cytogenetic abnormalities have been recognized
that could impact therapy.
Anaplastic lymphoma kinase
(ALK)-negative anaplastic large
cell lymphoma (ALCL) is now a
definite entity that includes cytogenetic subsets that appear to
have prognostic implications.
Breast implant–associated
anaplastic large cell lymphoma
(ALCL): A new provisional entity
distinguished from other ALKALCL, ident ified as a non-invasive
disease associated with excellent
outcome.
Nodular lymphocyte predominant Hodgkin lymphoma (HL):
Variant growth patterns should
be noted in diagnostic report, if
present, due to their clinicopathologic associations.
Cytotoxic T-Cell Lymphomas
and Leukemias
In this heterogeneous group of
diseases, the revised monograph
reflects new data about certain
neoplasms published since 2008.
Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and primary cutaneous
acral CD8-positive (CD8+) T-cell
lymphoma: These provisional
entities are both clonal disorders, usually composed of CD8+
T cells, with an indolent clinical
course.
Newly identified recurrent
mutations affecting the JAK/
STAT pathway: STAT3 mutations
are common in large granular
lymphocyte leukemia of both Tand NK-cell types, while STAT5B
mutations are more uncommon
and associated with more clinically aggressive disease. These
findings have led to changes in
the categorization of intestinal
T-cell lymphomas.
Epstein Barr Virus–Positive TCell and NK-Cell Lymphomas
The updated monograph delineates the different clinical
presentations and biology in Epstein Barr virus–positive (EBV+)
T-cell lymphomas and leukemias.
Specifically, EBV-associated Tand NK-cell lymphoproliferative
disorders among the pediatric
age group are now classified as
chronic active EBV-infection and
systemic EBV+ T-cell lymphoma
of childhood, which is no longer
referred to as a lymphoproliferative disorder.
Hodgkin Lymphoma
Although the classification of HL
has not changed, the monograph
updates the nodular lymphocyte
May 2016