To the Editor:
We report the case of a 61-year-old Brazilian female who presented with cough,
hemoptysis, and fever for seven days prior to evaluation. Her previous medical history
revealed that she was a heavy smoker (80 pack-years) and had systemic arterial
hypertension. No occupational exposures were reported. Physical examination was
unremarkable. Blood workup revealed leukocytosis (white blood cell count, 15,000).
Chest
X-ray was also unremarkable, and the initial management was antibiotic treatment.
A CT
of the chest was requested, which revealed a spiculated tumor mass of 5 cm in diameter
in the right upper lobe, as well as mediastinal lymphadenopathy. The patient was then
submitted to bronchoscopy, which was negative for neoplasms. The decision was to perform
pulmonary lobectomy.
Gross pathology showed that the right upper lobe weighed 300 g and measured 18.5 ×
12.0
× 3.5 cm. The cut surface revealed a poorly circumscribed, tan-gray, hemorrhagic lesion
measuring 7.0 × 6.0 × 3.8 cm that infiltrated into the visceral pleura. Histologically,
the tumor was composed of spindle-shaped cells with marked pleomorphism and abnormal
mitosis. These tumor cells displayed a sarcoma-like growth pattern with scarce
multinucleated giant cells. Multiple foci of necrosis were present. Squamous cell
carcinoma or adenocarcinoma areas were not observed. Immunohistochemical studies were
performed using the avidin-biotin-peroxidase complex method. The tumor cells were
positive for pan-cytokeratin (AE1/AE3), CK7, and epithelial membrane antigen (Figure
1) but negative for other antibodies. The
pathology report revealed sarcomatoid carcinoma of the lung, with spindle cell features.
No lymph nodes were involved. The tumor-node-metastasis staging classification, based
on
the findings, was T2bN0Mx.
Figure 1
Photomicrographs of pathological and immunohistochemical studies. In A,
pan-cytokeratin cytoplasmic positivity of the tumor cells (AE1/AE3
immunostaining; magnification, ×400). In B, tumor cells showing diffuse
positivity for CK7 (CK7 immunostaining; magnification, ×100). In C, carcinoma
cells showing strong positivity for epithelial membrane antigen in contrast
with inflammatory adjacent non-tumoral tissue (immunostaining; magnification,
×100).
Immediately after the surgery, the oncological evaluation was completed. Abdominal
CT
and bone scintigraphy resulted normal. Chest CT scans revealed pneumothorax in the
right
upper lobe in the site of the resected tumor. Radiotherapy and chemotherapy were
proposed. However, the patient was lost to follow-up, and no adjuvant treatment was
performed.
After four months without any adjuvant therapy, the patient returned to the hospital
presenting with progressive, complete right hemiparesis and impaired verbal
expression/aphasia for 10 days. At admission to the neurosurgery ward, the patient
was
alert and cooperative, with a Glasgow Coma Scale score of 15, the pupils were isochoric
and reactive to light, and the patient presented with a grade-4 right hemiparesis
in
association with aphasia.
The patient was promptly submitted to a neuroimaging study, which revealed three images
(one in the left inferior frontal gyrus and two in the right parietal cortex) of lesions
with different dimensions in the brain parenchyma that resembled tumor invasion (Figure
2).
Figure 2
Neuroimaging scans. In A, a CT scan of the skull taken when the pulmonary
mass was discovered four months prior to the appearance of neurological
symptoms, which is apparently normal. In B, a CT scan of the skull taken four
months after readmission, when the patient presented with neurological
symptoms. In C-E, magnetic resonance imaging scans revealing details of the
metastatic spread and intense vasogenic edema.
The neurosurgery staff decided to perform microsurgery for the resection of the larger
lesion in the left frontal gyrus and adjuvant radiosurgery of the other lesions.
The resected specimen was sent to pathology. The microscopic findings were similar
to
the sarcomatoid carcinoma of the lung, characterized by the proliferation of pleomorphic
spindle-shaped cells. An immunohistochemical study was performed and revealed focal
positivity of the tumor cells for CK7 and diffuse positivity for epithelial membrane
antigen. The microscopic and immunohistochemical findings were consistent with
metastatic sarcomatoid carcinoma.
The patient was discharged without any postoperative complications; however, she was
rehospitalized one week later with progressive worsening of her general health status
and, two months after the surgery, she died, prior to performing any adjuvant
therapy.
Sarcomatoid carcinoma of the lung is a rare tumor, showing a male-to-female ratio
of
7.25:1.00. The mean and median age of the patients is 65 years, and the tumor accounts
for 0.1-0.3% of all lung cancers.(
1
-
4
) It arises
from the central airway in two-thirds of the patients and exhibits the morphology
of
polypoid airway lesions.(
3
)
Sarcomatoid carcinoma most often presents as solitary masses in the upper lobes, with
an
average size of 7 cm in diameter.(
4
,
5
) Parenchymal
masses appear as cavities with marked central necrosis and peripheral rim. The
association with smoking is strong.(
1
-
4
) The
treatment is essentially performed with surgical resection, chemotherapy and
radiotherapy being used as adjuvant therapy or in cases of poor surgical conditions,
since there seems to be little benefit.(
1
-
4
,
6
,
7
) The five-year survival for patients with sarcomatoid
carcinoma is approximately 20% (compared with 50% for those with non-small cell lung
cancer), and the median duration of survival is three months.(
1
,
2
,
5
,
7
)
The probable pathogenesis of sarcomatoid carcinoma includes malignant transformation
of
hamartoma, simultaneous malignant transformation of epithelial elements and stroma,
malignant transformation of cancer-derived stroma, sarcomatous change in carcinoma,
and
carcinomatous change in sarcoma.(
2
,
3
)
Although there are reports of systemic metastases, such as in the skin, stomach,
pancreas, esophagus, jejunum, rectum, kidneys, bones, and adrenal glands,(
4
-
10
) to our knowledge, only one report documented brain
metastases,(
1
) especially because
of the aggressiveness and low survival time.
Few reports have presented and discussed the presentation of metastatic sarcomatoid
carcinoma of the lung in the brain. In our case, we illustrate the presentation of
brain
metastases in a patient who had been previously treated for sarcomatoid carcinoma
of the
lung and highlight the need to consider the differential diagnosis of pulmonary cancer
and the aggressive features of sarcomatoid carcinoma. The treatment, in accordance
with
current therapies in metastatic brain disease, consisted of the surgical resection
of
the larger lesion and complementary radiosurgery in the surgical cavity, with the
resection of the two smaller lesions.(
1
,
2
,
10
) However, due to the progressive
worsening of the general status of the patient, the radiosurgical treatment was not
performed, and the patient died two months after being diagnosed with brain
metastases.
The early diagnosis and proper surgical and adjuvant therapy of the primary disease
might lead to prolonged survival, and physicians should be aware of the appearance
of
metastatic symptoms of sarcomatoid carcinoma, such as neurological symptoms, which
can
be prominent and misleading to other differential diagnoses.