Pituitary Chromophobe Adenoma Research Articles

Фактори ризику рецидиву неактивних аденом гіпофіза у хворих із дефіцитом гормона росту

Актуальність. На даний час залишається актуальним пошук діагностично значущих маркерів агресивності неактивних аденом гіпофіза (НАГ) для визначення подальшого прогнозу в постопераційному періоді. Аденоми гіпофіза, що не мають клінічних проявів гіперсекреції гіпофізарних гормонів, є формами доброякісних пухлин аденогіпофіза. У загальній популяції частота НАГ становить 50 випадків на 1 млн населення. Мета дослідження: визначити клініко­діагностичні маркери агресивності пухлини у хворих із НАГ і дефіцитом гормона росту і їх роль у формуванні тяжкості нейроендокринної симптоматики захворювання. Матеріали та методи. Під наглядом перебувало 87 хворих (із них чоловіків — 44, жінок — 43) із верифікованим діагнозом НАГ після трансназальної гіпофізектомії; період спостереження — від одного до трьох років. Результати. При розподілі хворих на групи залежно від гістологічної характеристики НАГ переважали пацієнти з крупноклітинною хромофобною аденомою гіпофіза (77,5 %). НАГ у жінок супроводжувалася ожирінням, первинним і вторинним гіпотиреозом, вторинним гіпогонадизмом, синдромом персистуючої галактореї — аменореї (симптоматична й ідіопатична форми), нецукровим діабетом, синдромом порожнього турецького сідла та ін. У чоловіків НАГ супроводжувалася ожирінням, первинним і вторинним гіпотиреозом, вторинним гіпогонадизмом, нецукровим діабетом, гінекомастією. Розроблена шкала маркерів агресивності НАГ дозволила ідентифікувати фактори за трьома ступенями і розробити комплекс профілактичних заходів, покликаних унеможливлювати рецидив зростання пухлини. Висновки. Маркерами агресивності перебігу НАГ є: молодий вік пацієнта, перші симптоми маніфестації хвороби, великі розміри пухлини, асиметричність і деформація гіпофіза, ознаки інвазії пухлини в сусідні тканини/артерії/кавернозний синус, наявність дрібноклітинних і/або темноклітинних хромофобних аденом, пангіпопітуїтаризм.

Pituitary carcinomas: review of the current literature and report of atypical case

Introduction: Pituitary carcinomas are poorly understood, rare entities. They are distinguished from adenomas not by histopathological features but rather by the presence of metastases.Objective: We discuss the diagnosis, mechanism of dissemination and pathogenesis based on a review of the literature and illustrated by a singular case.Case Report: A 59-year-old male presented with a dural-based posterior fossa lesion. He had been diagnosed with a pituitary chromophobe adenoma 43 years earlier that was treated at the time with surgery and radiation therapy. A presumptive diagnosis of a radiation-induced meningioma was made and surgery was recommended. At surgery the tumour resembled a pituitary adenoma. Histopathology, laboratory findings, and the patient’s medical history confirmed the final diagnosis of a prolactin-secreting pituitary carcinoma. To our knowledge, this is the longest reported interval between the pituitary adenoma and metastatic lesion diagnosis (43 years).Conclusion: Management should be tailored to individual patient and may include a combination of treatments (surgery, radiation therapy, chemotherapy, and hormone-targeted therapy). Functionally active tumours may be monitored with hormone levels as tumour markers.

Iatrogenic panhypopituitarism: how many puzzles you need to solve on your way to pregnancy: a clinical case

Introduction. Iatrogenic panhypopituitarism requires specific approaches to infertility treatment, prenatal care and childbearing. Aim: to show difficulties and peculiarities of infertility treatment of a patient with iatrogenic panhypopituitarism. Methods and materials. We present a clinical case of an infertile patient with panhypopituitarism followed the operation for a chromophobe pituitary adenoma. Results. The 31-year old infertile patient was operated at the age of 21 for pituitary adenoma, the surgery was followed by the hormone replacement therapy. At examination: Anti-Mullerian hormone - 0,28 ng/mL., uterine hypoplasia by ultrasound, hysterosalpingography showed that fallopian tubes were passable, normospermia. Three ovulation stimulations were performed: the first one - Menopur®, the step up protocol (after 44-day period one dominant follicle developed); the second - Menopur® step up (after 26-day period 4 follicles developed), both times - biochemical pregnancy; the third stimulation - 20 days using Gonal-F® 150 ME and Pregnyl 70 M.E., 4 follicles developed, childbirth went after pregnancy. During the stimulation, growth hormone, cortisol and low molecular weight heparin were added, with the extension of the growth hormone administration to the 36th week of gestation. Conclusion. Patients with hypogonadotropic hypogonadism are a population in which ovulation stimulation leads to folliculogenesis in 80 % of cases. The following questions remain debatable: Is the corresponding function achieved when solving the problem of uterine hypoplasia? Should we add growth hormone and for how long? How to evaluate the follicular reserve, and is Anti-Mullerian hormone accurate in such patients? What is the best compensation for luteinizing hormone activity? Is human chorionic gonadotropin the key to pregnancy?

Сatamnesis of organic hallucinosis case at pituitary macroadenoma.

The article describes a one-year follow-up study of the clinical case of organic hallucinosis that we have described in the previous article in the patient with pituitary macroadenoma. At primary admission to the hospital (one year earlier) the likelihood of permanent or recurrent nature of hallucinosis and absolutely poor prognosis for recovery and life without removal of the tumor was pointed out to the patient and his family. However, the patient and his relatives flatly refused to undergo neurosurgical intervention. The article describes the dynamics of psychopathological and somatic statuses of the patient during his readmission to a psychiatric hospital. The exciting cause of death on the 25th day of hospital stay was phenomenon of cerebral edema. By results of post-mortem studies the underlying cause of death was small cell chromophobe pituitary adenoma. There was a complete accuracy between clinical and post-mortem diagnosis. Absolutely unfavorable prognosis made before has been confirmed. The conclusion about the need of psychoeducational interventions with this contingent of patients and their relatives for prevention of an adverse disease outcome is made.

Acromegaly With an Ectopic Clival Pituitary Adenoma

Ectopic pituitary adenomas usually occur within the sphenoid sinus or nasopharynx and seldom within the clivus. In this report, we describe the fourth case of ectopic growth hormone (GH)-secreting adenoma in the clivus. A 49-year-old female patient was admitted with acromegaly and blurred vision. Biochemical evaluation revealed a notable elevation in the GH level at >40 ng/mL (normal range, 0.0 to 5.0 ng/mL). A magnetic resonance imaging scan of the pituitary showed a mass below the sellar turcica. The patient underwent an endoscopic transnasal transsphenoidal approach to the sella, and the tumor in the clivus was completely removed. The tumor was separated from the intrasellar contents by intact bone of the sella. Histologic examinations of the resected tumor showed a chromophobe pituitary adenoma, and immunocytochemistry was positive for GH adenoma. Including our case, only 16 reported ectopic adenomas have occurred in the clivus. Relevant literature is briefly reviewed.

Pituitary macroadenoma presenting as a nasal tumor: case report

Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass. The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases. Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present.

Pituitary macroadenoma presenting as a nasal tumor: case report Macroadenoma hipofisário, apresentando-se como um tumor nasal: relato de caso

CONTEXT: Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass. CASE REPORT: The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases. CONCLUSION: Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present.

Light microscopical morphometric classification of oncocytic and chromophobe pituitary adenomas.

Light microscopical morphometry was performed on 10 adenomas with oncocytic parts (26%-50% oncocytes, group I), on 9 oncocytic adenomas with 51%-75% oncocytes (group II), and on 12 oncocytic adenomas with 76%-100% oncocytes (group III). We measured the area and circumference of nuclei and areas of cells. Furthermore, shape factors for area and circumference of nuclei and the quotients of nuclei area/cell area were calculated. Data of about 40,000 single measurements were evaluated statistically. There is a clear positive correlation of cell areas compared to the proportion of oncocytes in the respective adenoma. A gradual, steady enlargement of cells can be observed, whereas enlargement of nuclei is seen to a much less extent. Consequently the quotients of area of nuclei/area of cells become smaller with increasing oncocytic transformation, evidence that enlargement of cells takes place in favour of cytoplasm. The three adenoma groups differ significantly from each other in their average cell sizes. Regarding nuclear sizes, the difference is mainly to be seen between group II and III. Comparison of adenomas containing oncocytes with large cell and small cell chromophobe adenomas also show significant differences in sizes of cells and nuclei. Large cell chromophobe adenomas show distinctly larger nuclei, which is looked upon as a display of their endocrine activity. On the other hand, oncocytic adenomas bear comparatively small nuclei in an extended cytoplasm which may well be related to their endocrine inactivity.

Immunohistochemical Analyses of Oncocytic and Chromophobe Pituitary Adenomas

Immunohistochemical analyses using antibodies against the major pituitary hormones, the alpha-subunit of glycoprotein hormones, chromogranin and synaptophysin were performed on 10 adenomas with oncocytic parts (26%-50% oncocytes, Group I), on 9 oncocytic adenomas with 51%-75% oncocytes (Group II), and on 12 oncocytic adenomas with 76%-100% oncocytes (Group III). Only 11 of the 31 investigated adenomas (35%) showed negative immunostaining for all major anterior pituitary hormones. FSH-content could be shown in 16 of 31 adenomas (52%), LH-content in 12 of 31 adenomas (39%), TSH-content in 3 of 31 adenomas (10%). Comparing all three groups of adenomas, there are no differences in the immunoreactivity to alpha-subunit (24 of 31 adenomas, 77%), chromogranin (26 of 31 adenomas, 84%), and of synaptophysin (13 of 31 adenomas, 42%). Considering the high percentage of cells of oncocytes showing alpha-subunit immunoreactivity we regard oncocytomas as originating very often from TSH-gonadotropin cell complexes of the anterior hypophysis. Alpha-subunit might become a reliable marker for oncocytomas. The finding of immunoreactivity to chromogranin in most cases confirms morphological studies that oncocytes contain some secretory granules. In most cases, the studied oncocytomas did not react to synaptophysin showing different results from other adenomas of the anterior hypophysis.

An Aged Bull with Concurrent Thyroid C Cell Carcinoma, Adrenal Pheochromocytoma and Pituitary Chromophobe Adenoma

A Japanese Black bull aged 20 years died following progressive loss of the body weight. Pathological examination disclosed multiple endocrine tumors including thyroid C cell carcinoma with metastases to the cervical lymph nodes and lung, adrenal pheochromocytoma and pituitary chromophobe adenoma in the pars distalis. The serum calcium content was as mildly low as 8.0 mg/dl at the terminal stage. The bull had daily ingested the ration containing 1.9 times the recommended calcium amount for 8 years and 120,000 units of vitamin D(3) for 5 years prior to death. The long-term dietary intake of moderately excessive calcium with vitamin D(3) might be related to the pathogenesis of the thyroid C cell carcinoma.

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.

Genetic heterogeneity and alterations in chromosome 9 loci in a localized region of a functional pituitary adenoma

The molecular alterations reported in pituitary adenomas include mutations at the G sα in somatotrophinomas, and hypermethylation of the p16 tumor suppressor gene. There are, however, no reports of genomic instability or intratumor genetic heterogeneity in pituitary adenomas. We have studied the microsatellite loci on the short arm of chromosome 9 (9p) and the DNA fingerprinting pattern, of adjacent compartments, about 2 mm across, in a functional chromophobe pituitary adenoma secreting growth hormone and prolactin. The microsatellite loci were studied by PCR amplification using locus specific primers, while the DNA fingerprinting pattern was studied by randomly amplified polymorphic DNA (RAPD) analysis. Normal leukocyte DNA was taken as control. Only one compartment (Ta) showed alterations in several of the microsatellite loci and in the RAPD pattern vis a vis corresponding normal DNA and also the other two compartments of the tumor. This provides evidence for the localized nature of genomic instability in this tumor.

Pituitary adenoma with neuronal choristoma: a report of two rare cases

Two rare cases of pituitary adenoma with neuronal choristoma are described. Both patients were female and presented with features of acromegaly with elevated growth hormone and prolactin levels. Radiologically, both lesions were predominantly intrasellar in location with extension into suprasellar region, but hypothalamus was not involved. Histopathological examination revealed a mixture of chromophobe pituitary adenoma cells and neuronal cells. In both cases, the adenoma component was positive for growth hormone and prolactin. Interestingly, immunopositivity for α-subunit, cytokeratin and prolactin was seen in the adenoma and neuronal cells in one case. Our findings support the hypothesis that the neuronal cells possibly arise from adenoma cells as a result of metaplasia.

Use of fluid attenuating inversion recovery, MR angiogram, and diffusion-weighted MRI techniques for assessment of pontine infarction in a patient treated with radiation therapy for pituitary neoplasm

Radiation exposure may lead to accelerated atherosclerosis. [1-3] We report a case in which magnetic resonance angiography (MRA), fluid attenuating inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) MRI assisted in the evaluation of a patient who had received radiation therapy for a pituitary adenoma. The patient was a 50-year-old man with a history of hypercholesterolemia and hypertension, treated with enalapril, who had undergone transphenoidal hypophysectomy with resection of a chromophobe pituitary adenoma in 1977 after presenting with bitemporal hemianopsia. In late 1982, the patient developed persistent headaches and decreased temporal vision in his left eye; a CT revealed recurrent pituitary adenoma and the patient underwent a second transphenoidal hypophysectomy. He received postoperative radiation therapy of 5,000 cGy to a 4.5 x 4.5-cm field by 360 degree rotational technique over 5 weeks and began hormone replacement with testosterone, L-thyroxine, and hydrocortisone. The patient was neurologically asymptomatic until March 1996 when he developed the acute onset of hiccups, dysarthria, dysphagia, unsteady gait, and mild left facial and left upper extremity weakness. On examination 2 days after the onset of his symptoms, he displayed an ataxic dysarthria and subtle left facial weakness. Tandem gait was unsteady and mild dysmetria of the left upper extremity was present. Conventional MRI sequences were performed …

Non-functional pituitary chromophobe adenoma in a calf

A 5-month-old male calf showed neurological signs, including circling, in-co-ordination, depression, blindness and eventual recumbency. On necropsy, a mass measuring 3.5 x 4.5 x 5 cm was found at the base of the brain, at the level of the pituitary gland. The hypothalamus and optic nerves were compressed by the dorsally expanding mass. Non-functional pituitary chromophobe adenoma was diagnosed from histochemical, immunohistochemical and electron microscopical findings.

Head and neck tumors after energetic proton irradiation in rats

This is a two-year progress report on a life span dose-response study of brain tumor risk at moderate to high doses of energetic protons. It was initiated because a joint NASA/USAF life span study of rhesus monkeys that were irradiated with 55-MeV protons (average surface dose, 3.5 Gy) indicated that the incidence of brain tumors per unit surface absorbed dose was over 19 times that of the human tinea capitis patients whose heads were exposed to 100 kv x-rays. Examination of those rats that died in the two-year interval after irradiation of the head revealed a linear dose-response for total head and neck tumor incidence in the dose range of 0–8.5 Gy. The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. The estimated dose required to double the number of all types of head and neck tumors was 5.2 Gy. The highest dose, 18 Gy, resulted in high mortality due to obstructive squamous metaplasia at less than 50 weeks, prompting a new study of the relative bological effectiveness of high energy protons in producing this lesion.

Background pathology in BDF1 mice allowed to live out their life-span

Fifty male and 50 female BDF1 mice were observed allowing them to live out their life-span. Mortality up to 104 weeks of age was higher in males (42%) than in females (34%), and the 50% survival age was 112 weeks for males and 118 weeks for females. Body weight reached the peak at 82 weeks of age in males and 92 weeks of age in females, showing the mean body weight of 54.3 g for males and 48.0 g for females. The incidence of calculi and proteinaceous casts in the kidneys, that were not associated with exposure to chloroform, cell-alteration in the adrenal cortex, and islet cell hyperplasia in the pancreas was significantly higher in males than in females. On the other hand, hyaline droplet degeneration of the renal tubular epithelium, spindle cell proliferation in the adrenal cortex and milk-retention in the mammary glands occurred at a significantly higher incidence in females than in males. Cerebral mineralization in both sexes, atrophy and calcification of the testes and enlargement of the seminal vesicles of males, as well as cyst-formations in the ovary and endometrium of females developed at a very high incidence. Frequent neoplasms in males were hepatocellular adenomas and carcinomas, blood vessel tumours, pulmonary adenomas and carcinomas, and malignant lymphomas. In females, malignant lymphomas were the most common neoplasm, followed by blood vessel tumours, chromophobe pituitary adenomas and hepatocellular adenomas. Hepatocellular carcinomas developed only in males, whereas the histiocytic and lymphocytic types of malignant lymphomas and chromophobe cell adenomas arose solely or at a significantly higher incidence in females than in males.

Response of dogs with functional pituitary macroadenomas and macrocarcinomas to radiation

ABSTRACTA prospective study was conducted to assess the use of radiation therapy for treatment of dogs with large, functional pituitary tumours and pituitary‐dependent hyperadrenocorticism. Four dogs received only pituitary irradiation, whereas two dogs received irradiation and concurrent mitotane treatment. Effects of radiation therapy on tumour size and function were assessed by sequential CT scans, ACTH assays and ACTH stimulation tests. Reduction in tumour size and resolution of neurological abnormalities occurred in all dogs. The mean and median survival time following irradiation for dogs in this report was 740 days and 743 days, respectively. Atnecropsy, a pituitary chromophobe adenoma was detected in three dogs, and a pituitary carcinoma in one dog; necropsy was not carried out on two dogs. Pituitary hypersecretion of ACTH persisted for at

Malignant pituitary tumors

Pituitary malignancies are rare. The definition of pituitary malignancy is still subject to debate. Three types of malignancy with the description of clinical course and complete autopsy were presented; i) true carcinosarcoma, ii) ectopic sphenoid invasive tumor, and iii) post-irradiation sarcoma. The first true carcinosarcoma had a long natural tumor history of 46 years, ending in malignant transformation with extracranial metastasis from a pituitary adenoma. The second ectopic sphenoid tumor was prolactin-producing, locally invasive, with the intact pituitary gland. The third post-irradiation sarcoma was followed by chromophobe pituitary adenoma. The interval between irradiation to the adenoma and malignant transformation to fibrosarcoma was about 14 years.

Computed tomography of hemorrhage in a pituitary adenoma without apoplexy

Hemorrhage in a pituitary adenoma is a rare occurrence. Before computed tomography became the primary imaging modality for the sella, hemorrhage in pituitary adenoma was always diagnosed during operations or at autopsy. A patient with subacute hemorrhage in a nonfunctioning chromophobe pituitary adenoma with computed tomography findings is reported. The clinical presentation was unlike a pituitary apoplexy.