[Hypophyseal ACTH-cell carcinoma after several surgical interventions and radiotherapy]. / Hypophysäres ACTH-Zellkarzinom nach mehreren chirurgischen Eingriffen und Strahlentherapie.

HISTORY AND ADMISSION FINDINGS: A 56-year-old woman was admitted to our hospital with headache, especially on the left temporal side, dizziness and exercise intolerance. She had been operated three times and radiotherapy once because of pituitary adenoma with intermittend hypercortisolism. The clinical examination was without abnormal findings apart from left temporal pain on pressure on the top of the skull. INVESTIGATIONS: Blood tests were entirely normal. At cranial magnet resonance imaging (cMRI) a left temporal tumor of 10 mm diameter was diagnosed. TREATMENT AND COURSE: The first histological study of the excized lesion could not clarify the diagnosis completely. Because of a local recurrent tumor of 20 mm, a second operation was necessary two months later. Due to structural and immunohistological similarities this tumor was identified as a metastasis of a pituitary ACTH-cell carcinoma. The patient was given adjuvant stereotactic radiotherapy. Two years after the treatment, no tumor recurrence was seen by cMRI. CONCLUSION: Carcinomas of the pituitary are very rare. They can be diagnosed only by their metastases. The pathogenesis is still unclear. It is debatable, whether surgery and/or X-ray therapy in the past may influence tumor development.

Atypical tentorial meningioma 30 years after radiotherapy for a pituitary adenoma.

Although the human central nervous system used to be considered relatively resistant to the carcinogenic action of ionizing radiation, several lines of evidence now document a high incidence of secondary tumors in irradiated patients. The numerous reports of radiation-induced cerebral meningiomas generally distinguish those induced by high-dose radiation from those induced by low-dose radiation. We describe the case of patient who underwent subtotal resection of a chromophobe pituitary adenoma at the age of 18 years, who was successively treated by conventional fractionated radiotherapy with gamma rays emitted by a source of 60Co until a total dose of 41 Gy. Over the next 30 years the patient experienced all the known late effects of radiation, including panhypopituitarism, cranial-nerve deficits (II, III and VI), massive radiation necrosis involving the left cerebral hemisphere and causing right hemiparesis and aphasia and, ultimately, an atypical tentorial meningioma with early recurrence after total resection.

Non-functioning pituitary adenomas: indications for postoperative radiotherapy.

To determine the indications for postoperative radiotherapy after surgical resection of a nonfunctioning pituitary macroadenoma. A retrospective chart review of 72 patients with histologically proven chromophobe adenoma who presented for pituitary surgery between January 1985 and June 1998, with a minimum follow-up period of 12 months. The study endpoint was tumour recurrence or progression detected either by routine follow-up imaging or by clinical progression with subsequent confirmation by imaging. A proportional hazards model was used to determine independent prognostic factors. Mean follow-up was 64 months. In the radiotherapy group 13 of 50 recurred (or progressed) (26%), while in the nonradiotherapy group 10 of 22 recurred (46%), logrank test, P = 0.025. In patients assessed as having complete excision of tumour (n = 20) only two recurred (10%), both in patients without radiotherapy. No further treatment has been required in either case to date. In patients with residual tumour (n = 52), 41 had radiotherapy with 13 recurrences (32%), while 11 patients had no radiotherapy with eight subsequent recurrences (73%); logrank test, P = 0.007. Further treatment has been required in the majority of these cases. Cox's proportional hazards model analysis showed that only complete tumour removal and postoperative radiotherapy were independent favourable prognostic factors. The goal of surgery should be complete surgical excision where possible. The risk of recurrence in patients with no residual tumour on postoperative imaging is low enough to justify withholding routine postoperative radiotherapy in this group. In patients with residual tumour, conventional external beam radiotherapy administered within 12 months of surgery is effective at reducing recurrence or progression.

Intracranial dissemination of pituitary adenoma. Case report and review of the literature.

Leptomeningeal dissemination of pituitary adenoma is a very rare occurrence. The present report describes the case of a 28 year old man with a nonfunctioning pituitary adenoma which was operated on and irradiated. Eight years later, the patient developed Cushing's syndrome and multiple leptomeningeal masses were revealed by brain CT and MNR. The diagnosis was ACTH-cell adenoma, without malignant histological signs. The growth fraction of the tumor, detected by means of the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA), was 5.45% of cells; this figure is higher than that reported for non-recurrent pituitary adenomas. From a review of the reported cases, the possibility of predicting late malignant behaviour is discussed. The microscopic aspect has no prognostic value, since metastasizing cases are not overtly malignant in a histological or cytological sense. The application of methods aimed at detecting the growth fraction of the tumor may prove useful in the early identification of aggressive pituitary tumors.

Cervical lymph nodes metastases from a pituitary carcinoma.

The authors report a case of a pituitary carcinoma which was locally invasive and which metastasized to cervical lymph nodes more than 9 years after the initial presentation. Cells from the tumour and metastasis immunostained with antibodies to prolactin and growth hormone, even though there was no clinical or biochemical evidence that the tumour was secreting prolactin or growth hormone. In addition, ultrastructural studies showed a monomorphic tumour with secretory granules much smaller than those normally associated with prolactin and growth hormone secretion. The clinical and pathological features suggest that the tumour is probably an acidophil stem cell adenoma, which although known to be aggressive in its clinical behaviour has not been previously reported to metastasize.

Adenoma hipofisario no funcionante: aspectos clínicos y terapeúticos / Non-funtioning pituitary adenoma: clinical and therapeutical aspects

Se presentan las características clínicas y radiológicas de 20 pacientes (10 hombres y 10 mujeres) con diagnóstico de adenoma hipofisario no funcionante. El 85 por ciento presentó macroadenomas hipofisarios. El rango de edades estuvo entre 15 y 64 años. Los síntomas más frecuentes referidos fueron los trastornos visuales y la cefalea, con el 75 y 55 por ciento , respectivamente. Otros síntomas y signos encontrados fueron la pérdida de la libido, el retraso puberal, la amenorrea secundaria, los mareos y la obesidad. En 17 pacientes se observaron afectaciones en los estudios de campo visual, predominó la hemianopsia bitemporal en el 35 por ciento de los casos, la cuadrantanopsia temporal superior en el 15 por ciento y la reducción concéntrica unilateral. En los estudios radiológicos de silla turca se encontraron aumento de los diámetros anteroposterior y vertical de la silla, balonamiento, doble contorno del suelo y destrucción de éste, afinamiento o destrucción de las clinoides y porosis del dorso selar; mientras que en la tomografía computarizada fue más frecuente la presencia de masas hipodensas intraselares o con crecimiento supraselar. El hipopituitarismo parcial o completo se evidenció en 14 de los 20 pacientes y 4 de ellos presentaban diabetes insípida vasopresin sensible permanente. En cuanto al tratamiento, 18 enfermos fueron sometidos a cirugía transesfenoidal o transfrontal y 2 a tratamiento radiante exclusivamente. De los primeros, en 4 fue necesaria la reintervención quirúrgica en un período de 3 a 5 años. Se plantea la terapeútica más conveniente, y se reconoce la microcirugía transesfefnoidal como la de más baja morbilidad, así como la vigencia de la radioterapia sola o combinada con la cirugía, y se concluye señalando la importancia de los estudios por imágenes y neuroftalmológicos en el seguimiento evolutivo de estos pacientes

Adenoma hipofisario no funcionante: aspectos clínicos y terapeúticos / Non-funtioning pituitary adenoa: clinical and therapeutical aspects

Se presentan las características clínicas y radiológicas de 20 pacientes (10 hombres y 10 mujeres) con diagnóstico de adenoma hipofisario no funcionante. El 85 por ciento presentó macroadenomas hipofisarios. El rango de edades estuvo entre 15 y 64 años. Los síntomas más frecuentes referidos fueron los trastornos visuales y la cefalea, con el 75 y 55 por ciento , respectivamente. Otros síntomas y signos encontrados fueron la pérdida de la libido, el retraso puberal, la amenorrea secundaria, los mareos y la obesidad. En 17 pacientes se observaron afectaciones en los estudios de campo visual, predominó la hemianopsia bitemporal en el 35 por ciento de los casos, la cuadrantanopsia temporal superior en el 15 por ciento y la reducción concéntrica unilateral. En los estudios radiológicos de silla turca se encontraron aumento de los diámetros anteroposterior y vertical de la silla, balonamiento, doble contorno del suelo y destrucción de éste, afinamiento o destrucción de las clinoides y porosis del dorso selar; mientras que en la tomografía computarizada fue más frecuente la presencia de masas hipodensas intraselares o con crecimiento supraselar. El hipopituitarismo parcial o completo se evidenció en 14 de los 20 pacientes y 4 de ellos presentaban diabetes insípida vasopresin sensible permanente. En cuanto al tratamiento, 18 enfermos fueron sometidos a cirugía transesfenoidal o transfrontal y 2 a tratamiento radiante exclusivamente. De los primeros, en 4 fue necesaria la reintervención quirúrgica en un período de 3 a 5 años. Se plantea la terapeútica más conveniente, y se reconoce la microcirugía transesfefnoidal como la de más baja morbilidad, así como la vigencia de la radioterapia sola o combinada con la cirugía, y se concluye señalando la importancia de los estudios por imágenes y neuroftalmológicos en el seguimiento evolutivo de estos pacientes (AU)

Immunohistochemistry as a predictor of clinical outcome in patients given postoperative radiation for subtotally resected pituitary adenomas.

There is general agreement that postoperative radiation therapy is beneficial for patients with subtotally resected pituitary adenomas. We have identified 41 such patients treated during a 20-year period who received postoperative irradiation for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining, there were thirty-three chromophobe, seven eosinophilic, and one basophilic adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or adrenocorticotropin (ACTH) using the peroxidase-antiperoxidase immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of the IHC stain. While most patients with a known clinical endocrine syndrome stained positive on IHC for the suspected offending hormone, many patients without a clinical syndrome also stained positive indicating the presence of hormonally occult adenomas in this locally invasive group. The IHC stain results were compared to clinical outcome. The presence of positive GH IHC staining decreased the 15-year progression-free survival (PFS) from 100% to 64% compared to GH negative adenomas (p = 0.06). There was a trend toward decreased 15-year PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH, or TSH had no influence on the progression-free survival. We conclude that additional prognostic information can be obtained in this subset of patients (by performing IHC analysis) that is not known by the clinical presentation or appearance on H&E stain.

Stroke after pituitary irradiation.

BACKGROUND AND PURPOSE: Cranial irradiation may lead to accelerated atherosclerosis over several years. Stroke has been described after cranial irradiation administered for a number of conditions. However, pituitary irradiation has only rarely been associated with stroke. CASE DESCRIPTIONS: Two patients, 39 and 46 years of age, suffered strokes 13 and 20 years, respectively, after irradiation for pituitary tumors. Strokes were in the territories of small perforating arteries, but large vessels such as the carotid siphon and anterior cerebral arteries were also abnormal. Other risk factors for stroke were absent. CONCLUSIONS: It is suggested that pituitary irradiation increases the risk of subsequent stroke due to the known effects of ionizing radiation on vascular walls.

[Hypofunction of peripheral target-gland after radiotherapy of pituitary adenoma--an analysis of 140 cases].

One hundred and forty cases of pituitary adenoma, treated by surgery plus radiotherapy or radiotherapy alone from 1978 to 1985, were analysed as to the incidence of hypothalamo-pituitary and peripheral target-gland hypofunction after radiotherapy. The incidence of hypothyroidism, hypogonadism and hypoadrenalism was 51.7%, 61.4% and 17.8%, respectively. Thyroid and gonad were vulnerable following hypothalamo-pituitary hypofunction, and the incidence was 19.2% and 23.5% individually, and 27.1% simultaneously. The incidence of hypoadrenalism was 7.1%. The total incidence of target-gland hypofunction was 10.7%. Hypofunction of the posterior lobe of the pituitary often occurred after operation. For patients treated with radiotherapy alone, the incidence of hypothalamo-pituitary and target-gland hypofunction was high because of higher irradiation dose. Hormonotherapy was successful in the treatment of hypopituitarism and target-gland hypofunction. For radiotherapy of pituitary adenoma, DT 40-45 Gy and treatment field 4 x 4 cm are recommended.

[Tumors of the central nervous system induced by ionizing radiation. Update on their pathology and presentation of a case]. / I tumori del sistema nervoso centrale indotti da radiazioni ionizzanti. Up-to-date sulla patologia e presentazione di un caso.

Ionizing radiation-induced neoplasias are frequently described in literature but only 100 case about interested the central nervous system. The authors add a possible personal observation and line the main features of this association.

[Long-term results of radiation therapy for pituitary adenoma--analysis of 386 cases].

A total of 386 cases of pituitary adenoma treated in our hospital from Jan. 1963 to Jan. 1986 is reported. Of them, 117 were treated by operation alone, 97 by radiotherapy alone and 172 by operation plus radiotherapy. 119 cases (group A) treated before April 1980 were mostly diagnosed by pneumoencephalography or cerebral angiography, treated, by conventional operation, followed by radiation therapy with 60Co or linear accelerator. 267 cases (group B) treated after April 1980 arrived at the correct diagnoses by CT scan and endocrine assay, treated by microsurgery, followed by radiotherapy with linear accelerator. All patients were followed for 2-23 years. The response rates of groups A and B were 90.7% and 94%. The results were better in patients treated by surgery combined with irradiation. The recurrence rate of radiation or surgery alone was higher than that of combined therapy. It is indicated that the optimal treatment for pituitary adenoma is surgery combined with radiotherapy. Besides, the introduction of CT scan and microsurgery has improved the diagnosis and treatment results of pituitary adenoma.

Post-radiation cranial malignant fibrous histiocytoma studied by CT.

A 37-year-old woman presented with a proven case of malignant fibrous histiocytoma of the skull. This is thought to be a rare complication of post-radiation to a chromophobe adenoma which was treated by radiotherapy nine years previously. The radiation dose given to the sella region after the removal of the chromophobe adenoma was 4500 cGy.

Sequential growth hormone deficiency and acromegaly.

This is the case of a patient with a pituitary tumour presenting initially with growth hormone deficiency and requiring treatment with human growth hormone. Eight years later he represented with acromegaly. This sequence of events has not to my knowledge been reported previously.

Fibrosarcoma complicating irradiated pituitary adenoma.

Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.