A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.

The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG's consensus for the reporting of PitNETs and proposes a diagnostic algorithm.

From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

Phaeochromocytoma and Acromegaly: a unifying diagnosis.

UNLABELLED: A 52-year-old lady was referred after a 5 cm left adrenal mass was detected on computed tomography (CT) scanning. She was asymptomatic although was noted to have acromegalic facies. Blood pressure (BP) was normal but plasma normetanephrines were raised to 2.81 mmol/l (<1.09) and urinary normetadrenaline excretion 5.3 µmol/24 h (0-4.3). Adrenal biochemistry screen was otherwise normal. Metaiodobenzylguanidine (MIBG) scan demonstrated uptake in the adrenal lesion. Growth hormone (GH) nadir on oral glucose tolerance test (OGTT) was 2.2 ng/ml with an elevated IGF1 level of 435 ng/ml (72-215), confirming acromegaly biochemically. The remainder of the pituitary screen was normal. A magnetic resonance imaging (MRI) scan of the pituitary revealed an enlarged pituitary gland with a microadenoma/cyst of 2-3 mm in diameter. Alpha blockade was achieved with a titrated dose of phenoxybenzamine before a successful laparoscopic hand-assisted left adrenalectomy. Postoperative biochemical testing revealed a normal plasma normetanephrine level of 0.6 nmol/l (<1.09) and a metanephrine level of 0.35 nmol/l (<0.46 nmol/l). Nadir on OGTT was normal at 0.07 ng/ml with an IGF1 level within the reference range at 111 ng/ml (75-215). Histology demonstrated a well-circumscribed and encapsulated oval mass with microscopic features typical for a phaeochromocytoma. The sections stained strongly positive for GHRH in 20% of cells on immunocytochemistry. Genetic analysis showed no pathogenic mutation. This is a report of the rare condition of a phaeochromocytoma co-secreting GHRH resulting in clinical and biochemical acromegaly. Neuroendocrine tumours can stain positive for GHRH without coexisting acromegaly, but the resolution of patient symptoms and normalisation of serum GH and IGF1 levels following surgery imply that this was functional secretion. Pituitary surgery should be avoided in such cases. LEARNING POINTS: Incidental findings on imaging require thorough investigation to determine the presence of serious pathology.Acromegaly and phaeochromocytoma are rarely coincident in the same patient. If this occurs, co-secretion of GHRH from the phaeochromocytoma or the presence of underlying genetic abnormalities must be considered.Acromegaly is due to ectopic GHRH-secreting neuroendocrine tumours in <1% of cases, most commonly pancreatic or bronchial lesions.Co-secretion of GHRH from a phaeochromocytoma is extremely rare.In such cases, the pituitary gland may appear enlarged but pituitary surgery should be avoided and surgical treatment of the neuroendocrine tumour attempted.

Total hip revision using a cup design with a peg to treat severe pelvic bone defects.

When dealing with severe bone loss during acetabular revision of a total hip arthroplasty, it can be difficult to find a reliable anatomical structure to ensure high-quality primary fixation of the cup. Since 2003, we have been using an implant with a long peg that is anchored into the iliac isthmus. This structure is usually intact, even in the most severe situations of bone loss. The use of this specially designed component provides satisfactory mechanical reconstruction in cases that can be quite challenging (Paprosky and SOFCOT stage 3). The length and postoperative care for the procedure remain the same and early weight bearing is possible. The specific principles applying to this procedure, along with the anatomical features of the iliac isthmus, the implantation technique and our initial results are described in detail.

Downregulation of HMGA-targeting microRNAs has a critical role in human pituitary tumorigenesis.

Previous studies have demonstrated that high mobility group A proteins have a critical role on the onset of human pituitary adenomas. Indeed, both high mobility group A (HMGA) genes are overexpressed in pituitary adenomas, and consistently transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop mixed growth hormone/prolactin (GH-PRL)-secreting pituitary adenomas. Trisomy of chromosome 12, where HMGA2 is located, and/or amplification of the HMGA2 gene locus account for the HMGA2 overexpression in most human prolactinomas. Conversely, HMGA1 overexpression is not associated to any rearrangement or amplification of the HMGA1 locus. We have first identified micro RNAs (miRNAs) able to target both HMGA1 and HMGA2 messenger RNAs. Then, all of these miRNAs have been found downregulated in pituitary adenomas of different histotypes, compared with normal pituitary. Interestingly, their downregulation was also observed in nonfunctioning pituitary adenomas where HMGA2 overexpression is not associated to any alteration of the HMGA2 locus. Functional studies show that all these HMGA-targeting miRNAs inhibit the proliferation of the rat pituitary adenoma cell line GH3. Therefore, these results indicate that the downregulation of the miRNAs able to target the HMGA genes could contribute to increase HMGA protein levels in human pituitary adenomas, and then to pituitary tumorigenesis.

[Hypoplasia adrenal congenita of anencephalic type: two cases with pituitary abnormalities and review of literature]. / L'hypoplasie surrénale congénitale de type anencéphalique: deux cas avec anomalies hypophysaires, sans mutation de DAX-1 et SF-1 et revue de la littérature.

Hypoplasia adrenal congenita is an extremely uncommon disease of early onset. This condition can be lethal in the absence of treatment. Some forms are due to the congenital adrenal hypoplasia of anencephalic type whose origin is even unknown. Here, we present two cases of congenital adrenal hypoplasia of anencephalic type with pituitary abnormalities. The two male newborns died because adrenal insufficiency in the neonatal period. The adrenal glands were hypoplastic with a histological structure of anencephalic type Immunocytochemical study of the pituitary revealed an absence of the gonadotrophs. No mutation of DAX 1 and SF-1 was found.

[Endoscopy versus microsurgery: results in a consecutive series of nonfunctioning pituitary adenomas]. / Résultats comparés de la chirurgie endoscopique et de la microchirurgie dans une série consécutive de macroadénomes hypophysaires non fonctionnels.

Microsurgical removal of nonfunctioning pituitary adenomas (NFPAs) is often subtotal. Removing the blind spots as viewed through the microscope, endoscopic surgery may improve the quality of removal. Our purpose was to compare the results of the two techniques in a series of NFPA patients operated on by a single surgeon. Thirty-six patients with newly diagnosed NFPAs were operated on using a purely endoscopic procedure and 29 with a microsurgical technique. All patients were explored pre- and postoperatively (at 3 and 6 months and then every 12 months) by endocrine assays, ophthalmologic exam, and 3D MRI. The endocrine and ophthalmologic results as well as the quality of resection and the complications from the two techniques were compared. The follow-up duration and the mean tumor volume (higher in the microsurgical group) were the only differences observed between the two groups. Tumor height and the invasion of the cavernous sinus were not different. All patients with preoperative visual impairment in the endoscopic group improved, whereas in the microsurgical group 90.9% improved, 4.5% were stabilized, and 4.5% worsened (p=ns). Regarding anterior pituitary functions, 42.8% of the patients improved in the endoscopic group, 45.7% remained stable, and 11.4% worsened compared to, respectively, 31, 44,8, and 24.1% in the microsurgical group (p=ns). Gross total removal was achieved in 86.1% for the endoscopic group and in only 65.5% for the microsurgical group (p=0.075). Morbidity was similar in the two groups. This retrospective series showed that endoscopic surgery compared to microsurgery increases the quality of NFPA removal with similar morbidity.

Familial pituitary adenomas with a heterogeneous functional pattern: clinical and genetic features.

Familial pituitary adenoma is a rare syndrome which may present either as isolated lesions, or in association with other endocrine tumors, for example in the frame of multiple endocrine neoplasia (MEN-1) or Carney complex (CNC). The most frequently described forms of familial isolated pituitary adenoma (FIPA) are familial somatotropinomas or prolactinomas. Recently, some cases of familial isolated somatotropinoma have been associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The present report shows heterogeneous FIPA with 3 subtypes of tumor in 3 individuals of the same family: somatotropinoma in the proband, giant prolactinoma in a brother, and gonadotroph cell macroadenoma in the father. A prospective survey also suggested the occurrence of a silent microadenoma in the proband's sister. Clinical screening was performed in the 3 affected members, the 4th suspected case, and 9 additional, asymptomatic relatives. They had no clinical evidence of associated endocrine lesion suggesting MEN-1 or CNC. Genetic screening for germline mutation of the MEN-1, the gene encoding the protein kinase A (PKA) type 1 alpha regulatory subunit (R1 alpha) (PRKAR1alpha) and AIP gene was negative in 2 affected members. In conclusion, these data suggest that familial pituitary adenomas can occur with a heterogeneous functional pattern that is distinguished from MEN-1 or CNC. The absence of mutation of the recently described AIP gene suggests the implication of other predisposing gene(s). Collaborative, multicentric studies are needed to further define the location of gene(s) involved in heterogeneous FIPA.

B-RAF mutations are a rare event in pituitary adenomas.

Pituitary tumors are a relatively common neoplasia whose pathogenesis is still largely unknown. Recent studies have revealed frequent activating mutations of the gene for B-RAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies, including melanoma, thyroid, colorectal and ovarian cancer. However, analyses of B-RAF mutations in pituitary tumors have not been reported so far. Therefore, in the present study we have investigated the presence of the B-RAF mutations, by polymerase chain reaction (PCR) amplification of the hot spot exons 11 and 15, followed by direct sequencing, in 50 human pituitary adenomas, including 25 NFPA and 25 secreting adenomas (10 GH, 5 PRL, 6 LH and/or FSH, 4 GH/PRL). We found only one V600E mutation in a NFPA sample, suggesting that B-RAF mutations are a rare event in pituitary tumorigenesis.

[Nelson's syndrome: course of aggressive pituitary corticotroph adenoma]. / Syndrome de Nelson: évolution d'un adénome hypophysaire corticotrope agressif.

Nelson's syndrome was defined in 1958 as the association of an expanding pituitary tumor with high ACTH secretion after bilateral adrenalectomy for Cushing's disease. Pituitary MRI and ACTH measurements led to the definition of Nelson's syndrome as the proliferation of a corticotrophic microadenoma or an aggressive and highly proliferative tumor residue induced by the decreased glucocorticoid inhibition after bilateral adrenalectomy. Now, the problem is not the definition of Nelson's syndrome but rather the identification of markers predictive of tumor growth. Based on a typical case and a review of the literature, we point out some predictive markers of tumor growth after bilateral adrenalectomy: young age at diagnosis, presence of tumor residue on pituitary MRI before adrenalectomy, markers of tumor aggressiveness (Ki-67>3%, mitoses, nuclear PTTG) and increase of ACTH levels during the first months following adrenalectomy.

Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance.

BACKGROUND: Prolactinomas usually exhibit a benign course and can be safely and effectively managed by dopamine agonists (DA). However, some are locally invasive and may show resistance to DA therapy, and the management of such cases remains controversial. The aim of the present study was to determine whether histological features and markers of cell proliferation correlated to the clinical behaviour of prolactinomas and with DA resistance. METHOD: This retrospective study included 74 cases (36 men and 38 women) who had monohormonal prolactinomas removed by transsphenoidal surgery. The prolactinomas were categorized on the basis of tumour size (48 macroadenomas), invasion of the cavernous sinus (n = 31), and resistance to bromocriptine (BRC) therapy (n = 14). Group 1 consisted of non-invasive microprolactinomas (n = 24), group 2 of non-invasive macroprolactinomas (n = 19), group 3 of invasive non-BRC-resistant tumours (n = 19), and group 4 of invasive BRC-resistant tumours (n = 12). The later group included one case of carcinoma with bone and lung metastases. Seven additional parameters were studied, these being age, sex, basal prolactin (PRL) levels, the Ki-67 and PCNA labelling indices (LI), mitotic count, and cellular atypia. FINDINGS: Age and preoperative PRL levels did not correlate to the histological parameters studied. Tumour size and invasion were related to cellular atypia and the Ki-67 LI. BRC-resistant tumours were more frequently invasive (12/14) than BRC-responsive tumours (11/30; p = 0.002) and were more frequent in men than in women (33 versus 5%; p = 0.003). BRC-resistant tumours had a higher Ki-67 LI and mitotic count (4.2+/-2.0% and 4+/-1, respectively) than other tumours (0.7+/-0.2% and 1+/-0, respectively; p<0.05). The strongest correlations with tumoural staging were seen with male sex and high mitotic activity. Six out of the 12 invasive BRC-resistant macroprolactinomas, including the PRL secreting carcinoma, exhibited histological features of aggressiveness (a mitotic count >/=3 [i.e. in the fourth quartile] and/or a high Ki-67 LI and cellular atypia). CONCLUSIONS: In this surgical retrospective series, histological signs of aggressiveness are present in 50% of invasive and BRC-resistant prolactinomas, which are more frequent in men than in women. This fits with the behaviour of BRC-resistant prolactinomas, which can continue to grow despite DA treatment. These findings justify the long-term follow up of these tumours, and the use of surgery and/or radiotherapy if there is concern about the control of tumour growth.

[Development of the human adrenal glands]. / Le développement de la surrénale humaine.

The human adrenal is an endocrine gland located at the superior part of the kidney. Composed of the adrenal cortex of mesoblastic origin and the adrenal medulla of neuroectoblastic origin, the human fetal adrenal grows considerably during the first three months of development. From 12 to 18 weeks of development (WD), the weight of the adrenals increases seven-fold. The gland's weight doubles from 18 to 28 WD and from 28 to 36 WD. At birth, the two adrenals weigh on average 10 g. At the 8th week, two zones are individualized in the adrenal cortex: the definitive zone and the fetal inner zone. At the second trimester, according to ultrastructural and biochemical studies, a third zone, called the transition zone, is individualized between the definitive zone and the fetal inner zone. The definitive zone persists, but the origin of the three zones (glomerular, fascicular and reticular) of adult adrenal cortex is not known. The fetal inner zone regresses from the 5th month of gestation and disappears totally one year after birth. At the 8th week, the immature neuroblasts migrate to the definitive zone, then to the fetal inner zone to compose the adrenal medulla, which develops essentially after birth and during the first year. Before the 10th week, the human fetal adrenal is able to produce steroid hormones, in particular dehydroepiandrosterone sulfate (DHEA-S); the secretion of cortisol remains discussed. The development of the human fetal adrenal is complex and is under the control of hormones (ACTH, LH and betaHCG), growth factors (ACTH essentially) and transcription factors (essentially SF1 and DAX-1). Knowledge of morphological and molecular phenomena of this development permits to understand the pathophisiology of congenital adrenal deficiencies.

Antifungal treatment with carvacrol and eugenol of oral candidiasis in immunosuppressed rats

Carvacrol and eugenol, the main (phenolic) components of essential oils of some aromatic plants, were evaluated for their therapeutic efficacy in the treatment of experimental oral candidiasis induced by Candida albicans in immunosuppressed rats. This anticandidal activity was analyzed by microbiological and histopathological techniques, and it was compared with that of nystatin, which was used as a positive control. Microbiologically, carvacrol and eugenol significantly (p<0.05) reduced the number of colony forming units (CFU) sampled from the oral cavity of rats treated for eight consecutive days, compared to untreated control rats. Treatment with nystatin gave similar results. Histologically, the untreated control animals showed numerous hyphae on the epithelium of the dorsal surface of the tongue. In contrast no hyphal colonization of the epithelium was seen in carvacrol-treated animals, while in rats treated with eugenol, only a few focalized zones of the dorsal surface of the tongue were occupied by hyphae. In the nystatin treated group, hyphae were found in the folds of the tongue mucosa. Thus, the histological data were confirmed by the microbiological tests for carvacrol and eugenol, but not for the nystatin-treated group. Therefore, carvacrol and eugenol could be considered as strong antifungal agents and could be proposed as therapeutic agents for oral candidiasis.

[Therapeutic strategies in somatotroph adenomas with extrasellar extension: role of the medical approach, a consensus study of the French Acromegaly Registry]. / Stratégies thérapeutiques dans les adénomes somatotropes avec extension extrasellaire. Place du traitement médical. Etude consensus du Répetoire français de l'Acromégalie.

UNLABELLED: From the first 198 patient files included into the French Acromegaly Registry, we analyzed 68 patients harboring a somatotroph adenoma with extrasellar extension, after exclusion of those treated by stereotactic or conventional radiotherapy. In these patients (including 37 women), aged 21-77 yr. (45.7 +/- 13.3), GH concentrations ranged from 2-260 microg/L (38.6 +/- 44.3), and IGF I from 86-967% of age-matched upper limit of normal (303 +/- 164). Maximal diameter of the adenoma at MRI was 11-36.5 mm (20.4 +/- 6.5), with cavernous sinus involvement in 68% of cases. Three subgroups were defined: 20 patients treated by long-acting somatostatin analogs only (group M), for a mean duration of 3 yr. (extremes 1-7 yr.), 48 patients initially treated by transsphenoidal surgery (group C), of whom 21 were secondarily treated by long-acting somatostatin analogs (group CM) for a mean duration of 1.2 yr. (extremes 0.2-2 yr.). All 3 groups were not statistically different in terms of tumor mass and initial levels of GH and IGF-1. Patients from group M were significantly older than those of the other groups (p<0.05). RESULTS: 46% of patients from group C after surgery vs. 45% of patients from group M had a mean GH below 2.5 microg/L. Biochemical remission (GH<2.5 microg/L and normal IGF1 normal) was obtained in 31% of cases in group C, vs. 25% in group M. In this group, a decrease of the largest tumor diameter was observed in 10 patients (71.5%), ranging from 10-25% in 7 (50%) and exceeded 50% in 3 (21.5%). In group CM, the biochemical remission rate (42%) and final GH or IGF1 values were not significantly different from group M. In conclusion, these data suggest that surgery or long-acting somatostatin analogs have a comparable efficacy in terms of remission rates in somatotroph macroadenomas with extrasellar extensions.

[Pathology and pathogenesis of pituitary corticotroph adenoma]. / Histopathologie et tumorigenèse de l'adénome hypophysaire corticotrope.

Corticotroph adenoma is a benign tumor composed of adenohypophyseal cells; carcinoma with metastasis and ectopic adenoma have also been reported. In our pathological series, the frequency of this type of adenoma is 13% (250/1863 tumors removed between 1970 and 2001). Usually, corticotroph adenomas synthesize peptides derived from POMC maturation: ACTH, ss-endorphine, and ssLPH. In the great majority of cases, ACTH induces hypercorticism with clinical and biological signs of Cushing's disease. However, some tumors the pathologist identifies as corticotroph adenomas are not associated with clinical signs of hypercorticism (20% of the corticotroph adenomas in our series). Corticotroph adenoma is a basophilic or chromophobe tumor composed of cells which remain regulated by cortisol. This may explain the small size of this type of adenoma in 80% of the cases. In contrast, "silent" adenomas or macroadenonas which synthesize high-weight POMC are aggressive invasive tumors. Neurosurgery is indicated for the treatment of corticotroph adenoma. Recurrence is explained by incomplete removeal of the tumor. Peroperative studies may be necessary to find microadenomas. In some cases, the whole pituitary must be removed and cut in serial sections to find a tumor measuring<2 mm. In our opinion, the existence of corticotroph hyperplasia inducing Cushing's disease remains to be proven (we have never observed one). The pituitary origin of the tumor is based on its monoclonality. The general mechanism of tumorigenesis is known, but the specific factors involved and markers of aggressiveness remain to be discovered.

[Corticotroph microadenomas of the pituitary stalk. Diagnostic and therapeutic difficulties]. / Les adénomes corticotropes de la tige pituitaire.

Thirteen percent of the pituitary adenomas in our series have been corticotroph adenomas. Most have been microadenomas located in the adenohypophysis, more often laterally than posteromedially. In a few rare cases, the corticotroph cells of the pars tuberalis gave rise to an adenoma. Only 16 cases of pituitary stalk adenomas have been published to date. We report here three new cases among a series of 150 patients who underwent surgery for corticotroph adenomas (2% incidence as in the literature). There was no difference in the clinical or biological presentation of intrasellar and pituitary stalk adenomas. This location must be systematically searched on the MRI, but a negative exploration cannot excluded the diagnosis of pituitary stalk adenoma like in intrasellar ones. Two anatomical entities seems to be separated. Some stalk adenomas developed preferentially in the supradiaphragmatic space (one in our series) and are accessible for selective resection. Others develop within the pituitary stalk itself and sometimes in the pars distalis (two patients in our series) which requires section of the pituitary stalk with hypophysectomy if the lower limit is not clearly seen during surgery. The subfrontal or pterional access is the approach of choice for suprasellar tumors. These approaches remain controversial for pituitary stalk adenomas because of the poor visibility of the pituitary stalk and the floor of the third ventricle. The transnasosphenoidal approach with extension to the sphenoidal planum and opening of the optochiasmatic cisterna appears to be the best alternative for surgical removal of these adenomas.

[Indications for total hypophysectomy in Cushing's disease]. / Place de l'antéhypophysectomie totale dans le traitement de la maladie de Cushing.

OBJECTIVE: Transsphenoidal selective adenomectomy is the treatment of choice for Cushing's disease. In some patients, magnetic resonance imaging (MRI) fails to detect small pituitary ACTH-secreting adenomas. Total hypophysectomy can be performed when MRI appears normal. The aim of this paper is to study results and complications after total hypophysectomy for Cushing's disease. METHODS: Between July 1988 and May 1999, 49 patients underwent transsphenoidal surgery for Cushing's disease at our institution. The criteria for inclusion in this study were clinical and biochemical studies strongly suggestive of Cushing's disease with normal MRI. Total hypophysectomy was performed in 7 patients who fulfilled these criteria. Their results were analyzed retrospectively. RESULTS: The average age of the patients was 43 years; there were 7 women. Five adrenocorticotrophic hormone-secreting adenomas were proven histologically. Complications occurred in 6 patients (cerebrospinal fluid fistulas in 6 patients, loss of vision in 1 patient, meningitis in 5 patients, anterior pituitary insufficiency in 5 patients, diabetes insipidus in 5 patients). Six patients had sustained remission 36 months after surgery. CONCLUSION: Total hypophysectomy can be perform ed for Cushing's disease with normal MRI. Complications occurs frequently, especially cerebrospinal fluid fistulas. Inferior petrosal sinus sampling can be helpful in localizing the adenoma allowing hemihypophysectomy and thus reduced morbidity.

Antiproliferative effect of octreotide in somatotroph pituitary adenomas: discussion from a single case report.

The case of a 20-year-old man presenting with a rapidly expanding pituitary somatotrophic adenoma with a tumour volume doubling time of 426 days is reported. Preoperative octreotide therapy induced a 45% tumour shrinkage and proliferating cells were absent at the time of tumoural resection. The correlation between clinical and proliferation markers data in this single case report affords an opportunity to discuss the antitumoral effect of octreotide on somatotrophic adenomas which may result from a suppression of cell proliferation.

Visceral cancer metastasis to pituitary adenoma: report of two cases.

BACKGROUND: We report two cases of metastases from visceral cancers to pituitary adenomas, and review the literature. CASE DESCRIPTION: Two female patients, aged 75 and 87 years, underwent transesophageal surgery for presumably benign pituitary adenomas. Using extensive immunostaining studies, histopathological examination showed that the surgical specimens from both patients were composed of metastatic deposits within gonadotropin adenomas. Fourteen cases of metastases to pituitary adenomas have been mentioned in 11 reports in the literature. In all cases, the correct diagnosis was made after autopsy or histopathological studies, even in patients known to suffer from visceral malignancies. In our cases, immunohistochemical studies were conclusive in characterizing the two distinct tumor components. The pathogenetic mechanisms favoring the development of metastases in pituitary adenomas are discussed, especially those altering the normal hypophyseal circulation. CONCLUSION: Neurosurgeons performing pituitary surgery should be aware of the possibility of metastases in pituitary adenomas.

[Should silent corticotroph-cell adenoma be classified as a non-functional pituitary adenoma?]. / L'adénome corticotrope silencieux doit-il être classé dans le groupe des adénomes hypophysaires non fonctionnels?

A 45-year-old man underwent surgery for a silent corticotroph-cell pituitary adenoma which developed in 9 months. The tumor was termed silent because it exhibited increased corticotropic secretion without clinical signs of hypercorticism. This classes it as a non-functional adenoma. The non-functional group includes different types of adenomas such as gonadotroph and other silent thyreotroph and somatotroph adenomas with variable proliferative potential. Silent corticotroph-cell adenoma is considered as an aggressive tumor. In contrast, gonadotroph adenomas usually grow slowly and postoperative tumor remnants can remain stable for years. Because of this variability in tumor growth, the therapeutic decision is difficult if there is a postoperative remnant. No precise guidelines can be established. We suggest that non-functional pituitary adenomas should be considered separately, according to the histological type. This classification is essential for improving knowledge and specifying indications for radiotherapy.