Blood, Vol. 94 No. 4 (August 15), 1999:
pp. 1483-1484
CORRESPONDENCE
Fulminant Intravascular Disseminating Malignant Melanoma
Mimicking Acute Leukemia
 |
LETTER |
To the Editor:
A 48-year-old male patient with a previous history of 4 primary melanomas was admitted 1 year after the last melanoma excision because of recent onset of fatigue, weakness, weight loss, shortness of
breath, and limb pain. The initial hematological laboratory evaluation
disclosed moderate anemia, thrombocytopenia, and a marked
leukocytosis of 22.5 × 103 cells/µL, with 28%
atypical plasmacytoid cells, and acute leukemia was
suspected. Repeated Wright-Giemsa stains of peripheral blood smear
confirmed the presence of 30% to 40% abnormal, large pleomorphic cells, with abundant cytoplasm, eccentric nuclei, and marked
anisokaryosis (Fig 1A). These cells were
negative for myeloid-, T-, B-, and natural killer (NK)-cell markers.
Surprisingly, they were identified as circulating amelanotic melanoma
cells by their reactivity with S100 protein-, vimentin-, and
melanoma-specific HMB-45 monoclonal antibodies. Serum levels of the
melanoma tumor markers S100 and MIA protein were markedly
elevated, whereas polymerase chain reaction (PCR) for tyrosinase mRNA
was negative. Bone marrow biopsy showed an almost complete
replacement of hematopoiesis by HMB-45-positive melanoma cells. Chest
x-ray and abdominal ultrasound showed no further evidence of
macroscopic disease. The condition of the patient rapidly deteriorated
and, despite supportive measures, he died on the ninth hospital day.
Postmortem examination showed the presence of HMB-45-positive tumor
cell aggregates trapped in the microcirculation of the liver (Fig 1B),
the lungs, the kidneys, and the heart, with concomitant diffuse
infiltrates in the perivascular space. The spleen also showed diffuse
infiltration by tumor cells. The immediate cause of death was
plugging of the pulmonary vasculature resulting in congestive right
heart failure.
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| Fig 1.
Circulating amelanotic melanoma cells. (A) Wright-Giemsa
stain of peripheral blood smear shows large pleomorphic cells with
abundant cytoplasm, eccentric nuclei, and marked anisokaryosis. (B)
Paraffin-embedded liver tissue was stained with melanomaspecific
HMB-45 monoclonal antibody. Numerous melanoma cells are found in
hepatic sinusoids and hepatic veins without significant extravasation.
(C) Bone marrow biopsy stained with HMB-45 illustrates the significant
reduction of hematopoiesis and the dense infiltration by melanoma
cells.
|
|
Bone marrow infiltration of human melanoma is found in up to 7%
of in vivo staging procedures and in up to 45% of autopsy cases.1 So far, it has rarely been reported that
this would result in significant numbers of circulating melanoma cells
in peripheral blood.2 Usually, circulating melanoma cells
can only be detected on the submicroscopic level by methods such as PCR for tyrosinase melanoma associated antigen.3 It is not clear whether the massive load of tumor cells observed in the peripheral blood is caused by dissemination of melanoma cells from bone
marrow infiltration (Fig 1C) or whether the melanoma cells proliferated
autochthonously in the peripheral blood compartment. Although the first
possibility seemed to be more likely, we attempted to mimic
the in vivo situation by culturing whole blood cells or Ficoll
gradient-enriched mononuclear cells containing the tumor cells from
this patient. Even by using different growth media, the tumor cells did
not grow in suspension. However, when the cells were allowed to adhere
to plastic of culture flasks, a stable cell line could be established
that is now in culture for more than 1 year. This is the first report
of a melanoma cell line established from the peripheral blood
of a patient. To analyze the apparent reduced ability to transmigrate
and to form solid metastasis, we examined immunocytologically early
passage melanoma cells from the cell line for molecules relevant
for adhesion and migration. We found positive staining for integrin
subunits 
1 through 6 and 
1 as well as intercellular adhesion
molecule-1 (ICAM-1) and metastasis-promoting CD44 variant isoforms v5
and v6. There was no E-cadherin expression. Thus, the cells display a
pheno- type that is thought to be very compatible with progression of
melanoma and other solid tumors by increasing proliferation, invasion,
and/or metastasis.4,5
It has been calculated in an animal model of melanoma that 80% of
cells entering the microcirculation survive and extravasate by 24 hours.6 Because this patient had a calculated number of 5 × 1010 circulating melanoma cells without macroscopically
detectable metastases, it can be concluded that extravasation was
significantly reduced, which therefore represents a key stage of
metastatic control in this case. Alternatively, death of the patient
might have occurred before solid metastases developed. Cancer cells of
nonhematologic origin are only rarely seen on routinely prepared blood
smears. The term carcinocythemia had been introduced to describe rare
cases of disseminating carcinoma mimicking the clinical picture of
acute leukemia.2,7,8 We suggest describing the phenomenon in the presented case as melanocythemia.
Uwe Trefzer
Christina Schlegel
Wolfram Sterry
Department of
Dermatology and Allergy
Ernst Späth-Schwalbe
Kurt Possinger
Medical Oncology/Hematology
Carsten Denkert
Institute of Pathology
Medical Faculty Charité
Humboldt
University Berlin
Berlin, Germany
| |
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