Case presentation:
A 55-year-old Tunisian female presented to the hospital with confusion,
aphasia, and a Glasgow Coma Scale (GCS) of 12/15. A Computed Tomography
(CT) scan head revealed two well-defined adjacent lobulated intra-axial
lesions in the left occipital lobe. MRI head detected multiple left
cerebral lesions in the temporo-occipital area. A stereotactic biopsy of
one of the lesions was performed, and histopathology revealed Anaplastic
Astrocytoma World Health Organization (WHO) grade 3. The tumor cells
were strongly positive with Glial Fibrillary Acidic Protein (GFAP),
Oligodendroglial Lineage Marker (OLIG-2), while negative with CD20 and
CD30. Few scattered lymphocytes were seen within the tumor cells
staining with CD3, CD8, CD45, and CD4. Ki-67 index was high, reaching
50% in some areas. Isocitrate Dehydrogenase (IDH) 1 and 2, P53, and
BRAF mutations were negative, whereas the ATRX nuclear staining was
retained. The patient underwent excision of the tumor after two weeks.
Histopathology results of excision biopsy revealed Glioblastoma, WHO
grade 4, with wild type IDH – 1, P – 52, and ATRX and a 50 %
proliferative index of Ki – 67. Post-operation, she had two episodes of
generalized tonic-clonic seizures and was started on levetiracetam 500
mg twice daily. She also developed pulmonary embolism, for which she was
started on enoxaparin twice daily.
One–month post-surgery, she was started on partial brain radiotherapy
and concurrent chemotherapy with Temozolomide at a dose of 144mg for six
weeks with the plan to maintain on Temozolomide alone afterward.
During concurrent -chemo-radiotherapy; after 19 sessions patient
presented with bleeding from injection sites on her thigh and bruises on
her upper and lower limbs for one day. She did not complain of headache,
fever, or bleeding from any other site. The patient was on enoxaparin
and levetiracetam at the time of admission with bleeding and bruises
from injection sites. Enoxaparin was withheld due to the bleeding. On
examination, she was vitally stable, and apart from limb bruises and
oozing blood from the injection site, her physical examination was
unremarkable. Blood profile revealed pancytopenia with a white blood
cell (WBC) count of 0.2 x10^3/uL (normal range: 4 – 10 x10^3/uL),
hemoglobin of 8.5 gm/dL (normal range: 12 – 15 gm/dL ), platelet count
of 7 x10^3/uL (normal range: 150 – 400 x10^3/uL) and absolute
neutrophil count of 0.0 x10^3/uL (normal range: 2 – 7 x10^3/uL).
Temozolomide was discontinued as it was suspected to be the underlying
cause of her pancytopenia. Her absolute reticulocyte count was 0.2
(normal level: > 2), indicating a hypo proliferative
marrow. Peripheral smear showed marked pancytopenia, but no abnormal
cells were visualized. She was initiated on Filgrastim 300 mcg
subcutaneous daily and received multiple platelet infusions without any
ANC or platelet count improvement. The patient developed febrile
neutropenia three days after admission, secondary to the right axillary
cellulitis. Swab culture grew Pseudomonas Aeruginosa for which
intravenous cefepime was given for ten days. The patient became afebrile
after completion of cefepime but remained pan cytopenic despite platelet
and Filgrastim transfusions. Radiotherapy sessions were also held since
this admission due to critically low platelet and WBC counts.
Given the non resolving pancytopenia without an apparent cause, a bone
marrow biopsy was performed. Bone marrow aspirate showed few tiny
particles with hypocellular smear and markedly decreased trilineage
hematopoiesis, many scattered lymphocytes and relatively increased
plasma cells (28%) with no increase in blasts. Bone marrow biopsy
showed pronounced hypocellularity (5%-15%) with a remarkably decreased
trilineage hematopoiesis and a relative increase in plasma cells .
[Figure 2].Flow cytometry on bone marrow aspirate showed
approximately 50% T-cells, 3% B-cells, and increased plasma cells
(15%) with no immunophenotypic evidence of monotypic B-cell or plasma
cell populations. The bone marrow did not show any evidence of
paroxysmal nocturnal hemoglobinuria in flow cytometry analysis.. As the
patient took Temozolomide, which was recently started, she was diagnosed
with aplastic anemia secondary to it.
Two days after the bone marrow biopsy, the patient developed left facial
swelling with fever. A CT scan of the face revealed a subtotal
opacification of the anterior left nasal cavity with low soft tissue
density, extending to the left cheek medially. There was also a partial
opacification of both maxillary sinuses, noted more on the left side,
with hyperdense foci. The collective picture was suggestive of suspected
fungal infection. She was started on IV Meropenem 1 gm 8 hourly and
Amphotericin – B 435 mg daily, empirically, and cultures were sent to
the lab. However, the patient remained febrile and pan
cytopenic.[Figure.1].Treatment options for AA were discussed with
the hematology team; however, she was not a candidate for Anti thymocyte
globulin (ATG) or cyclosporin or eltrombopag because of underlying
malignancy and pulmonary embolism. A trial of IV Immunoglobulin was
given with no improvement in counts. The cheek swelling worsened
involving the left eye, and an urgent debridement was performed. The
infected area’s biopsy revealed necrotic tissue, heavily infiltrated by
fungal organisms, compatible with aspergillosis. Although the necrotic
tissue was debrided, and she was on appropriate antifungal medication,
the facial cellulitis did not respond to the treatment, and she
deteriorated with desaturation, hypotension, and confusion. On the
38th-day post-admission, the patient was transferred
to the Medical Intensive Care Unit (MICU) and was intubated to protect
the airways and started on vasopressors for her septic shock. The
patient remained transfusion-dependent and was sedated and intubated for
a total of 10 days. Eventually, the patient developed a cardiac arrest
with asystole and succumbed to the sepsis and pancytopenia with a
complicated and prolonged hospital stay of 47 days. Over the course of
her hospital stay, the patient had bacteremia with Multi-Drug Resistant
Organisms (MDRO) including Stenotrophomonas, Enterococcus casseliflavus
and Achromobacter xylosoxidans, and fungemia with Aspergillus flavus.