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Case Report
Rapid onset of myelodysplastic syndrome after treatment for anal cancer: A case report
1Department of Oncology, McGill University Health Centre, Montreal, QC, Canada;
2Department of Medicine, McGill University Health Centre, Montreal, QC, Canada
J Gastrointest Oncol 2010; 1: 120-121. DOI: 10.3978/j.issn.2078-6891.2010.016
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Anal cancer is a highly curable disease. Chemoradiotherapy
has superseded surgery since it results in an equivalent
survival with the benefit of a better functional outcome,
as there is no need for colostomy. However, the long-term
complications of definitive chemoradiotherapy for anal
cancer have not been systematically described. In this report,
we present the case of a woman who presented with therapyinduced
myelodysplasia within a year after treatment for anal
cancer.
A 58-year-old woman with no significant past medical
history was diagnosed with squamous-cell carcinoma of the
anal canal, during a work-up for hematochezia. She regularly
drank moderate amounts of vodka in the evening, and was
a heavy smoker. The anal cancer was treated in standard
fashion with chemoradiation, the chemotherapy consisting
of 5-fluorouracil and mitomycin C. Follow-up physical
examination and imaging studies revealed a complete
response, as well as a normal complete blood count (CBC)
during the following months. One year after the end of
treatment, a CBC performed 2 days
prior to a scheduled visit revealed a platelet count of 15 x
109/L. The patient was immediately called to the clinic for an
evaluation.
She denied any complaint. One to two weeks before the
visit, she had been scratched by a pet cat. This was followed by
fever, and swelling of the right hand. She was in good general condition, with normal vital signs. A tender right axillary
adenopathy was felt. The remainder of the examination was
normal.
The CBC showed the following values: white blood cell
count 7.3 x 109/L, with a normal differential; hemoglobin 129
g/L, hematocrit 38.2 %, mean corpuscular volume 116 fL,
platelet count 15 x 109/L. The blood smear was unremarkable,
except for thrombocytopenia. Coagulation parameters
were normal, as was serum creatinine level. Liver function
tests results showed nonspecific abnormalities, consisting
of elevation of aminotransferases and alkaline phosphatase
levels. Total serum protein level was high at 87 g/L (normal
60 g-80 g/L), with normal albumin at 42 g/L.
The patient denied any excess of alcohol consumption.
Vitamin B12 and folic acid levels were 434 pmol/L (normal
greater than or equal to 133 pmol/L), and 17.2 nmol/L
(normal greater than or equal to 11.8 nmol/L), respectively.
A serum protein electropheresis (SPEP) showed no
monoclonal peak. The diagnosis of an immune mediated
thrombocytopenia (ITP), either idiopathic or secondary to
an infection, was entertained. Given the patient’s exposure
to a cat, she was tested for Bartonella henselae antibodies.
Antibody titers were high, 1:640 the week of the consultation,
1:1280 two weeks later. No response of the platelet count was
observed after steroid and immune globulin therapy.
A bone marrow aspiration-biopsy showed hypercellularity
with megaloblastoid changes, micromegakaryocytes, and
a normal blast count of 2%. Cytogenetics revealed trisomy
8. No tumor cells were seen in the biopsy specimen. The
diagnosis of myelodysplastic syndrome was made. The
previous exposure to radiotherapy and chemotherapy
suggested therapy-related MDS (t-MDS). Although not
entirely ruled out, a concomitant diagnosis of myelodysplasia
and anal cancer appears unlikely, given the entirely normal
values of the CBC at the patient’s first consultation. In
addition, we cannot entirely rule out that this patient presented sequentially two diseases that were not connected.
As no family match for stem-cell transplantation was
identified, she was started on azacytidine, with normalization
of the platelet count after six cycles. The duration of the
remission after the end of treatment was only four months.
T-MDS is a rare but serious complication of chemotherapy
and radiotherapy, resulting from DNA damage in the
hematopoietic cells. It can be considered a consequence of
the lack of selectivity of these therapeutic modalities, since
they affect both normal and malignant cells. However, the
exact pathogenic mechanism of this adverse reaction is not
fully known.
Two classical presentations have been described in
association with chemotherapy:
1. An earlier form, usually occurring within 3 years of exposure to inhibitors of topoisomerase II (1), and with typical abnormalities of chromosomes 11 and 21. Topoisomerase II inhibitors can cause DNA double-strand breaks within the loci of hematopoietic transcription factors (2).
2. A later form, associated with alkylating agents (3), with median time of onset of about 5 years after treatment. Many chromosomal abnormalities have been described, including trisomy 8. After formation of adducts by alkylators in the hematopoietic cells, faulty DNA repair mechanisms are postulated to lead to DNA double-strand breaks and chromosomal instability.
Radiotherapy-induced MDS typically appears several
years after treatment, and is also associated with variable
karyotypes (4). DNA damage in stem cells is probably the
most important pathogenic mechanism, but aberrant signals
to the stem cells from the irradiated microenvironment may
also play a role (5). Although chemotherapy and radiotherapy
exhibit synergistic effects in the treatment of some cancers,
no published data suggest that combined-modality therapy
necessarily results in a higher risk of myelodysplasia.
A particular feature of this case is the shortness of the
latency period, not characteristic of radiotherapy nor of
the specific chemotherapy she received (6). Although
antimetabolites such as 5-fluorouracil have only rarely
been associated with myelodysplasia, it is thought that they
can contribute to it by depleting cells of folates, which are necessary to nucleotide biosynthesis, and, therefore, DNA
repair (2).
Additional research is needed to estimate the prevalence
of myelodysplasia in patients treated with chemoradiotherapy
for anal cancer, as well as the individual contribution of
different chemotherapeutic drugs and radiation techniques
to this complication. Last but not least, an instructive
feature of this case was the intercurrent cat-scratch disease, a
confounding circumstance that had the potential of delaying
diagnosis and initiation of effective therapy. In the setting
of myelodysplasia, cat-scratch disease has been reported
to present with widespread skin manifestations and late
seroconversion, unlike what was observed in our case (7). At
any rate, this case reminds us that coincidence is not always
synonymous with causality.
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References
Cite this article as:
Alcindor T. Rapid onset of myelodysplastic syndrome after treatment for anal cancer: A case report. J Gastrointest Oncol. 2010;1(2):120-121. DOI:10.3978/j.issn.2078-6891.2010.016
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