Departments of Medicine (M.A., N.G.), Neurosciences (I.K.), Radiology (A.R.), and Pathology (A.T.), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Address all correspondence and requests for reprints to: Mohammed Ahmed, Department of Medicine (Mail Box Code-46), King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
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Case Report |
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Laboratory data
Random GH was >200 (reference range, 07 µg/L). GH monitoring following 75 g of oral glucose loading showed: time (min), 0, 30, 60, 90, 120; GH (µg/L), 134, 74, 90, 39, 31.4; blood sugar (mmol/L), 5.9, 11, 15, 15.3, 12.3.
Other serum hormone levels were: PRL, 80 and 105 (reference range, 020 µg/L); testosterone, 4.16 (10.441.6 nmol/L); LH, <1 (520 IU/L); FSH, 15.2 (419 IU/L); total T4, 114.5 (68.2160 nmol/L); T3 resin uptake, 0.27 (0.250.35); Free thyroxine index (FTI), 30.9 (1756 nmol/L); TSH, 2.7 (1.17.2 mU/L); cortisol morning sample, 220.7 (193689.7 nmol/L); and cortisol afternoon sample, 187.6 (55.2193 nmol/L).
Imaging data
A skull x-ray showed massive enlargement of the sella turcica with
destruction at the base of the skull. Computerized tomography (CT) scan
of the head showed an invasive pituitary tumor with suprasellar
extension involving the hypothalamus and optic chiasma, with parasellar
extension into both cavernous sinuses and inferiorly into the sphenoid
and ethmoid sinuses with diffuse bone destruction (Fig. 1).
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External radiotherapy (RT) by linear accelerator (8 MeV) was used to administer 5040 cGy over 42 days in 28 fractions to the right and left lateral pituitary fossa in a parallel pair. Post-RT, signs of acromegaly relented gradually, and clinical improvement was noticed. Multiple GH levels monitored over the next 67 months showed normal values ranging from <0.52.5 µg/L and serum insulin-like growth factor-I (IGF-I) levels ranging from 229352 (100558.6 µg/L).
A follow-up CT scan 9 months post-RT showed an impressive decrease in
tumor size to half the original bulk, and at 17, 27, and 38
months (Fig. 2) post-RT
there was continuing decrease in the suprasellar extension of the
tumor; however, the inferior portion of the tumor remained unchanged,
and invasion of the floor of the middle fossa with bone destruction
continued, as well as invasion of the left parasellar and ethmoidal
sinuses. A follow-up CT scan 22 months later showed no further change.
BC was continued in a dose of 5 mg twice daily; replacement
hydrocortisone and T4 were added to provide coverage for
radiation treatment related hormonal deficiencies.
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Ophthalmological evaluation revealed bilateral blindness secondary to pressure effect on the optic chiasma; he had bilateral optic atrophy. There was paralysis of the left lateral rectus and the right inferior rectus muscles.
Differential diagnosis and literature review
The differential diagnosis at this time included conditions that
would cause an acute increase in the volume of the adenoma. About 10%
of pituitary adenomas undergo acute or subacute changes in the form of
hemorrhage, necrosis, or edematous swelling, with clinical signs and
symptoms of a change in the pattern of headache, which often becomes
severe in nature and frontal in location, a rapid deterioration in
vision, and ophthalmoplegia (1). An appropriate diagnosis may be
elusive and a high index of suspicion is necessary to arrive at the
correct diagnosis. The clinical course of our patient at the last
presentation was certainly compatible with an acute ischemic or
hemorrhagic insult insofar as he harbored a large tumor, had a recent
change in the pattern of headache, visual loss, and ophthalmoplegia;
these findings are most consistent with pituitary apoplexy, necrosis,
or infarction of the pituitary tumor. Pituitary apoplexy is a rare
disorder; in our experience it has occurred in 13 out of 300 patients
with pituitary tumor (2). Commonly misdiagnosed conditions include
ruptured intracranial aneurysm, meningitis, or sphenoid mucocele. The
CT/magnetic resonance imaging is especially helpful in arriving at the
right diagnosis. The finding of acute or subacute bleeding within an
enlarged sella is highly suggestive of pituitary apoplexy. We have
detailed previously the CT scan findings in patients with apoplexy (2).
These consist of fluid-fluid level, or hyperdensity, without contrast
and hypodensity, or ring enhancement, with contrast administration. As
seen in Fig. 3, such findings were not
evident on the CT scan of this patient, which instead showed a
significant increase in the size of an invasive pituitary tumor
compared with the study done 19 months previously. These findings raise
a real possibility of tumor recurrence, notwithstanding the fact that
the patient had received radiation therapy previously, which does
indeed appear to reduce the recurrence rate of pituitary adenoma (3).
Tumor recurrence is by far the commonest cause of visual deterioration,
as had occurred in this patient. Recurrence of visual failure can be
accounted for by other conditions as well, such as arachnoid adhesions
associated with progressive empty sella, however, a finding of empty
sella was not evident on the CT scan of this patient. Another cause of
recurrence of visual failure in this setting is delayed radionecrosis
resulting in optic nerve and chiasmal damage. This can occur as a late
complication of radiation treatment (4).
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Follow-up course
At follow-up serum hormone levels were: GH 1.3, <0.25 µg/L, IGF-1, 352 µg/L; PRL, 120 µg/L; cortisol (1600 h), 110.4 nmol/L; free T4, 55.3 (1036 pmol/L); T3, 55 (65162 nmol/L); and TSH, 1.7 mU/L. A bilateral cerebral angiogram showed findings of a hypovascular pituitary tumor with an associated thrombus in the left internal carotid artery proximal to its bifurcation into the cavernous sinus. There was marked narrowing of the parasellar portion of the right carotid artery and the proximal anterior cerebral arteries bilaterally caused by encasement by the tumor.
The aforementioned results of the GH and IGF-I levels make it clear that the recurrent tumor was not a GH-secreting tumor. What was its precise nature?
Further clinical course
Three days following admission, the patient underwent transsphenoidal surgery and partial removal of the tumor was achieved. There was some destruction of the posterior part of the sphenoid sinus by the tumor, which was protruding and destroying the base of the sphenoid sinus. The tumor was necrosing and it had destroyed the skull base intra- and extrasellarly, as well as the posterior ethmoid sinuses. Tumor that had invaded laterally into the cavernous sinuses was not removed at operation.
Histological examination (Fig. 4) showed
fragments of normal pituitary tissue, and those of a moderately
cellular tumor composed of spindle cells arranged in intersecting
fascicles. Remnants of normal pituitary glandular epithelium were also
seen scattered diffusely among the tumor cells. These remnants stained
strongly positive focally with immunohistochemical stains for FSH and
PRL in a nonuniform manner and stained negative for human growth
hormone. The spindle cells in the tumor showed moderate nuclear
pleomorphism, and several mitoses were seen (Fig. 5
). Immunohistochemically, the tumor
cells were positive for vimentin only and were negative for ACTH, TSH,
LH, FSH, HGH, and cytokeratin. Ultrastructural studies showed cells
with enlarged, irregular nuclei. Dilated cisternae of rough endoplasmic
reticulum and prominent Golgi complexes were seen within the cytoplasm.
These features supported a diagnosis of spindle cell sarcoma most
compatible with fibrosarcoma of intermediate grade.
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Discussion |
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Goldberg et al. (6) suggested that multiple courses of radiation treatment could be a risk factor for developing sarcoma. However, most cases subsequently reported, including the present one, have had a single course of radiation (10, 11, 12, 13, 14). Although the majority of reported cases have undergone orthovoltage radiation, the more recent ones have had the higher energy radiation of cobalt-60, betatron, linear accelerator therapy, or the heavy particles of cyclotron radiotherapy (10, 11, 12). Notwithstanding the lack of information on the use of gamma-knife, it is obvious that all other current forms of radiation therapy used in the treatment of pituitary adenoma have the potential to induce fibrosarcoma in susceptible individuals.
The lesion typically begins as a pituitary adenoma, and serial biopsies have shown the presence of increasingly bizarre fibroblastic proliferation (13). There has been a unanimity in interpreting the spindle-cell sarcomatous element as diagnostic of fibrosarcoma (13). In the reported cases, it is stressed that none of these lesions metastasized, and atypical cytological changes in adenoma do not necessarily indicate metastatic potential (9, 13).
In summary, a fibrosarcoma developed in the pituitary gland of a patient who had been irradiated 79 months previously for treatment of a GH-secreting adenoma. The neoplasm was a large, aggressively growing, spindle cell tumor that eroded the surrounding structures. The lesion developed in the path of irradiation after a long latent period, with no apparent metastases, contained histologically identifiable benign appearing pituitary tissue interspersed within the spindle cell tumor, and resulted in the patients death.
Because irradiation is an effective treatment for pituitary adenoma and the occurrence of fibrosarcoma is only a rare complication, its use will continue. It is therefore important to be aware of such an occurrence. A rapidly growing, locally destructive pituitary lesion, associated with changes in vision and/or visual field, in a patient who had been previously irradiated for a pituitary adenoma, should alert one to the possibilities of not only apoplexy or a recurrence but, albeit more unusually, of a fibrosarcomatous degeneration. These conditions require prompt attention. Early diagnosis may render surgery feasible, as the only hope for palliation in a case of pituitary sarcoma.
The final diagnosis for this patient was pituitary sarcomatous degeneration of a previously irradiated GH-secreting tumor.
Received January 6, 1997.
Revised June 5, 1997.
Accepted June 11, 1997.
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References |
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