CD30

What is CD30

The CD30 molecule and its ligand (CD30L) are newly

recognized members of the TNF receptor and TNF ligands
superfamilies

The biologic role of the CD30/

CD30L interaction is still largely unknown1

The soluble form of the CD30 antigen (sCD30) has

a smaller molecular weight (85 kD) than the membrane
bound form (120 kD), and is probably produced by proteolytic
cleavage of the membrane-bound CD302

CD30 shedding occurs as

an active process of viable CD30' cells and is not merely
caused by the release from dying or dead cells1

Ki-l (CD30) antigen is also expressed by highly activated

Band T cells and by certain large celllyrnphomas
(LCLs) of both T- and B-cell origin.3-8

Structure

The extracellular domain of CD30 has proved to be homologous

to that of the TNF receptor superfamily members6*
1's1(F2i g l), whose canonical motif is the presence of
several (usually three or four) cysteine-rich pseudorepeats,
each containing six cysteines and c40 amino acids in the
extracellular part of the molecule.9,10

CD30+ normal cells may represent activated proliferating lymphoid elements

of either B, T, or “null” type11

It has been shown that no other CD30-positive cells exist

in the human body1

Function

The CD30L induces pleiotropic biologic effects on human CD30+ cell lines; the specific
responses include differentiation, activation, proliferation,
and cell death, which depend on cell type, stage of differentiation,
transformation status, and the presence of other stimuli. 12

CD30 knock-out mice and

CD30L knock-out mice show no alteration of the immune
response whereas CD30L overexpression is a lethal mutation
(T. Mak and H.J. Gruss, personal communication, May
1 994).1

Detection of sCD30 could be used as a specific tool for CD30+ neoplasm 2

CD30 – clinical and therapeutic impact

The discovery that

the extracellular part of the membrane-bound CD30 antigen is
proteolpcally cleaved to produce a soluble form (sCD30) has
led to the development oef nzymelinked immunosorbent assays
(ELISAS) for the detction of sCD30 in the mum of patients
with CD30-expressing neoplasm2

the CD30 molecule appears to be an optimal target

for immune intervention with specific antibodies. 1
The Ber-H2 antibody, directed
against a fixative-resistant epitope of the CD30 molecule,
is particularly useful for the diagnosis of such entity.

CD30 role in disease

CD30 expression is also characteristic of ALCL, a recently

recognized type of lymphoma. The Ber-H2 antibody, directed
against a fixative-resistant epitope of the CD30 molecule,
is particularly useful for the diagnosis of such entity1

Mapping of the CD30 gene at lp36 excludes its

involvement in the (2;5) chromosomal translocation, which
has been found in a proportion of ALCL with T-cell phenotype.13

the CD30L has no effect on the HD-derived cell

lines with "B-cell-like'' phenotype (KMH2 and L-428) and
induces apoptotic cell death in the CD30+ ALCL cell lines12

previous studies have suggested

that patients with CD30-negative lymphomas have a
much worse prognosis than patients with CD30-positive
lymphoma14
However, the observation that four of five (80%)
patients with CD30-negative LCL with localized disease
at presentation died of progressive disease 4-46
months (median, 27 months) after diagnosis, compared
with 3 of 42 (7%) of the patients with CD30-positive
LCL, illustrates that CD30 expression is a much more
important prognostic parameter than is the extent of
skin disease at presentation.15

Unmodified anti-CD30 (Ber-H2 antibody)

Despite optimal in vivo targeting of tumor cells, none of our patients

with refractory HD showed a tumor regression in response
to the native Ber-H2 antibody

 Little/no competition with tumour sites for

binding of Ber-H2

This implies that, for therapeutic

purposes, anti-CD30 antibodies should be conjugated to cytotoxic
agents (either isotopes or toxins)16-20

Anti-CD30 immunotoxins
Because of their different mechanism of action (eg, killing of tumor
cells by inhibition
of protein synthesis) and nonoverlapping toxicity with chem~
therapy17'~an ti-CD30 immunotoxins may be expected to
be effective against chemoresistant and/or resting residual
CD30' tumor cells in this setting.

Systemic ALCL

Primary systemic ALCL, particularly of the common and

lymphohistiocytic types, frequently occurs in children and
young adults and is characterized in most cases by aggressive
clinical course, systemic symptoms, and multiple peripheral lymphadenopathy8,21

Cutaneous CD30+ disease

1. CD30+ lymphoproliferative disorder (pcALCL, LyP)
 2. Cutaneous CD30+ LCLs e.g. MF, LyP
3. Skin involvement with a primary non-cutaneous CD30+ LCL or Hodgkin’s disease

The treatment of these patients is unsatisfactory.

Topical or systemic steroids or antibiotics are not
effective. Aggressive treatment modalities such as
systemic polychemotherapy or total-skin electron beam irradiation may produce complete remissions,
but these are generally short-lived.

It is more likely that these lesions represent

only variants of the same disease entity and that the clinical
differences reflect the variability of the biological behavior
of this tumor entity.22

It is important to note that cutaneous

Ki-1 + ALC lymphomas do not only occur primarily,
but also arise secondarily from other types of lymphomas
such as MF, pleomorphic T cell lymphoma, T cell lymphoma
of angioimmunoblastic type, and Lennert's lymphoma,
as well as Hodgkin's disease.23

Anaplastic large cell lymphoma (ALCL)

strongly suggest that ALCL is a tumor of highly
proliferating activated lymphoid cells

Characterized by subtotal effacement of the lymph

node architecture, paracortical growth pattern, and spread to
the sinuses, polymorphic appearance, and expression of the
CD30 antigen by virtually all neoplastic cells.3

morphologically
distinct type of lymphoid large cell neoplasms
that was designated as Ki-I/CD30+ ALCL.24

occurs predominantly in adults (median age, 60 years)

as a solitary, asymptomatic tumor that remains restricted to
the skin for a long time (evolution to a systemic disease
occurring in only 25% of cases), responds well to local treatment
(surgery or electron-beam therapy), and is associated
with good prognosis (median survival 42 months)22,25

Clinical characteristics of these lymphomas

include presentation with solitary or localized skin lesions,
frequent cutaneous relapses (often with the same
morphology and in the same area as the initial skin
lesion), a peculiar tendency to spontaneous regression,
and a favorable prognosis15

Because of the potential risk for the development of

a systemic lymphoma, long-term follow-up is required,
in particular in patients in group II, who may
have an increased risk to develop persistent tumors
requiring additional radiotherapy.26

The results of this study indicate that

primary cutaneous CD30-positive LCL, regardless of
their morphologic classification (anaplastic or nonanaplastic)
can be considered as a distinct type of cutaneous
T-cell lymphoma. Recognition of this type of cutaneous
lymphoma is important because it may prevent patients
from unnecessary aggressive treatment.15

Treatment

However, the results of the current study indicate that systemic polychemotherapy as initial treatment does not
result in higher cure rates, longer disease-free periods, or less recurrences compared with local radiation therapy or
simple excision.15

Because of their cytomorphology and large growth

fraction, primary cutaneous Ki-1 ALC lymphomas are
grouped among cutaneous lymphomas of high-grade
malignancy by the EORTC Cutaneous Lymphoma Study
Group.28 Such a grouping has prompted clinicians to treat
these lymphomas with aggressive therapeutic protocols.
Our observations, however, do not justify such measures
because some patients are certainly overtreated.22

Lymphomatoid papulosis

LyP is defined as a chronic, recurrent, self-healing

papulonecrotic or papulonodular skin disease
with histologic features suggestive of a malignant
lymphoma27

 Type A – variable numbers of CD30+ large, atypical cells

 Type B – CD30- atypical cerebriform mononuclear cells similar to MF24

Immunohistochemical findings were consistent with an activated T-cell phenotype for the atypical cells of
lymphomatoid papulosis, the Reed-Sternberg cells of Hodgkin's disease, and the malignant cells of the T-cell
lymphoma.

A t(8;9) genetic translocation may be involved in the pathogenesis of lymphomatoid papulosis or its progression to
malignant disease28

the risk for these patients to develop

systemic lymphoma is extremely low

Overlapping spectrum

The borderline cases already described

clearly illustrate that the differences between
primary cutaneous CD30+ LCL and LyP are gradual
and suggest that these conditions form a continuous
spectrum, both clinically a nd histologically24

Distinction must be made between cutaneous

CD30-positive lymphomas that develop de novo in the
skin and cutaneous CD30-positive lymphomas that develop in patients with MF or other types of CTCL. Patients
from this latter category, who were excluded in
the current study, generally have a poor progn~sis
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