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Leukemia Cutis

Synonyms: Cutaneous leukemia, extramedullary myeloid tumor

Etiology: Unknown

Associations: Systemic leukemia

Clinical: Erythematous patches, papules, nodules, hemorrhagic and
purpuric lesions, blue-green nodules

Histology: Malignant immature hematopoietic precursor cells in
dermis, diffusely or in patchy distribution

IHC repertoire: Lymphocyte surface markers and/or markers of specific
granules rarely necessary

Staging: Systemic work-up required

Prognosis: Poor, except for CLL

Adverse variables: Histologic subtype of high-grade leukemias

Treatment: No local therapy; systemic chemotherapy

Leukemia cutis is an uncommon cutaneous eruption that
may be difficult to diagnose. In the vast majority of
patients, there is a known history of leukemia at the time
of the skin manifestations. However, leukemia may have
its initial manifestation in the skin, in some cases with
simultaneous bone marrow involvement, or less com-
monly, in the absence of simultaneous marrow involve-
ment. (In these cases, the cutaneous eruptions have been
called extramedullary myeloid tumors (1)). In one series,
approximately 38% of patients had cutaneous findings at
the time of bone marrow diagnosis (2). In other series,
anywhere from 3% to 7% of patients had cutaneous lesions
prior to detection of marrow involvement (3). Patients
with all types of leukemia may demonstrate cutaneous
lesions. It has been reported in 2% to 3% of patients with
acute myelogenous leukemia (4). Cutaneous involvement
is less common in patients with acute lymphoblastic leu-
kemia (5). Chronic myelogenous leukemia patients have
skin manifestations in 6% to 20% of cases (6). The inci-
dence ranges from 4% to 20% in patients with chronic
lymphocytic leukemia (7).
The clinical manifestations of leukemia cutis are
protean. In some cases, the disparate clinical appearances
correlate with the subtypes of leukemia involved and the
systemic complications caused by these types of leukemia.
For instance, hemorrhagic lesions are commonly found in
the subtypes of leukemia that are associated with coagu-
lopathies (such as acute promyelocytic leukemia), but are
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rarely seen in patients with chronic lymphocytic leuke-
mia. Tumor nodules may occur in patients with any
subtype of leukemia, but are most commonly seen in
those with chronic myelogenous leukemia (Figure 5.1). In
other patients, diffuse erythematous papules and nodules
correlate with diffuse infiltrates of neoplastic cells
throughout the dermis. The etiology for bullae that have
been reported in rare patients is less well understood.
Some types of leukemia have more specific findings, such
as gingival hyperplasia associated with acute myelomo-
nocytic leukemia.
The histologic findings in leukemia cutis are varied. In
most cases, there is a diffuse infiltrate of atypical hema-
topoietic cells throughout the dermis (Figure 5.2).
In some cases, the neoplastic cells appear in such den-
sity as to form dermal tumor nodules. More commonly,
however, the cells are dispersed individually throughout
the dermis. The cells show little tendency for cohesion and
percolate between splayed collagen bundles. In some cases,
there is a predilection for aggregates of leukemic cells sur-
rounding the peri-eccrine vascular spaces (8).
The cytologic features of the infiltrating cells vary with
the type of leukemia. In acute myeloid leukemias, large,
immature precursor cells are present (Figure 5.3).
These cells are readily identified with routine sections
in most cases. In some cases, a chloroacetate esterase stain
or the use of an anti-myeloperoxidase antibody may be
helpful in identifying characteristic cytoplasmic granules.
5. Leukemia Cutis
FIGURE 5.1. Widely scattered viola-
ceous nodules of leukemia cutis.
Similarly, the chronic myeloid leukemias feature imma-
ture myeloid forms coursing throughout the dermis.
In these types of leukemia, abundant mitoses and indi-
vidual cell necrosis are common features. This subtype
of leukemia is usually straightforward to recognize in
the skin.
The lymphoid leukemias are more difficult to recognize
as involving the skin. In acute lymphoblastic leukemia
(ALL), large and atypical immature cells are present
FIGURE 5.2. Low power photomicrograph of dense dermal infil-
trate in leukemia cutis. Note the Grenz zone typical of this
condition.
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throughout the dermis. Abundant mitotic activity and
individual cell necrosis are commonly seen. These cells
are very difficult to classify based upon routine sections
or special stains; however, correlation with cytometric
studies is helpful, and in most cases, the patient’s prior
history makes the diagnosis straightforward. Chronic
lymphocytic leukemia (CLL) may also occur in the skin,
both in patients with long-standing disease, and as an
initial manifestation. In these cases, a de novo diagnosis is
difficult to make. The histologic findings include only a
monomorphous population of relatively small and unre-
markable lymphocytes within the dermis. The key obser-
vation is that the usual heterogeneity of cell type is absent,
as is the usual variation in lymphocyte size and shape.
Clonality can be ascertained in most cases, if the diagnosis
is entertained based upon routine sectioning. Some inves-
tigators have noted a tendency for the neoplastic lympho-
cytes in CLL to comprise the immune response underlying
primary keratinocytic neoplasms or infectious processes
(9,10). This may be the first clue to the diagnosis in some
patients.
The prognosis for patients with cutaneous involvement
by leukemia is generally poor. It suggests widely dissemi-
nated disease in most cases. However, for patients with
CLL, there is no evidence that the presence of neoplastic
lymphocytes within the dermis serves as any type of
adverse marker and long-term survival has been seen in
these patients.
There is no specific treatment for the cutaneous leuke-
mia other than palliation and symptomatic relief. Aggres-