Pituitary chromophobe adenomas consisting of prolactin cells

Summary Morphologic studies of pituitary neoplasms removed by surgery from 36 human patients revealed 8 chromophobe adenomas which differed clearly from the remaining tumors. The cytoplasm of the adenoma cells failed to stain with PAS, aniline blue, aldehyde fuchsin, aldehyde thionin, orange G or light green, but positively stained granules were found by using erythrosine or carmoisine. Immunoperoxidase technique disclosed the presence of prolactin in the cytoplasm of some adenoma cells. The adenoma cells exhibited distinct ultrastructural features such as well developed rough surfaced endoplasmic reticulum with Nebenkern formation, prominence of Golgi apparatus, presence of misplaced exocytosis as well as pleomorphism of secretory granules with a considerable variation of size ranging from 130 to 500 nm in diameter. Thus, by electron microscopy the adenoma cells showed a close resemblance to prolactin cells of the non-tumorous pituitary glands except for the reduced size and number of secretory granules.These chromophobe adenomas are regarded as representing a distinct pathological entity clearly distinguishable from other forms of pituitary neoplasms. In view of the morphologic findings and the elevation of blood prolactin level (measured in 3 patients) the term, sparsely granulated prolactin producing pituitary adenoma, appears to be the most appropriate one to designate these tumors.The authors wish to thank Dr. H. Friesen for providing the anti-human prolactin and Dr. L. A. Sternberger for the peroxidase-anti-peroxidase complex. The excellent technical assistance of Mrs. Gezina Ilse and Miss Nancy Macphail and the valuable secretarial help of Mrs. Maureen Rowling are appreciated.The work was supported in part by MA-552 grant of the Medical Research Council of Canada and by the St. Michael's Hospital Research Society.     

Effect of treatment with octreotide on the morphology of growth hormone—secreting pituitary adenomas: Study of 24 cases

Twenty-four acromegalic patients were treated with octreotide subcutaneously for periods of 3 to 6 weeks (group I, 12 cases) or 6 months (group II, 12 cases) before transsphenoidal surgery. Radiological studies performed in 19 patients before and at the end of this treatment period revealed no changes in 8 cases. In 8 other cases, a slight reduction in tumorsize was observed, and in 3 cases an important shrinkage was documented. At surgery, the adenomatous tissue appeared softer than in nonpretreated patients, facilitating the operation. Pathological examination revealed widening of perivascular spaces with accumulation of fibrous tissue and more crinophagy than in nonpretreated patients but failed to reveal morphologically pronounced cell involution as observed in prolactin-producing adenomas treated with dopamine agonists. No significant difference in frequency or extent of cellular changes was noted between the two groups. These morphological findings seem to be more consistent with a functional inhibition of growth hormone release than with cellular alterations induced by octreotide.     

Population differences in cardiovascular reactivity to the cold pressor test

The interaction of race and climatic adaptation on patterns of cardiovascular reactivity among young adult males was examined. Malay and Chinese subjects living in a tropical climate in the Orient and Caucasians living in a sub-tropical climate in North America were investigated. The cold pressor test with hand immersion in cold water was used as the stressor. Systolic and diastolic blood pressures, cardiac frequency, cardiac output, and stroke volume were measured. The results provided limited evidence for absence of differences in cardiac reactivity among racial groups and for greater vascular reactivity in the Caucasians. Cold immersion also elicited differential responses which could be partially attributed to differences in acclimatizations status. © 1995 Wiley-Liss, Inc.     

Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation

A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart.     

Pituitary pathology in erdheim-chester disease

Pituitary morphologic changes in patients with Erdheim-Chester disease have not been described in detail. We report here the histologic and immunohistochemical findings in the autopsy obtained pituitary of a 35-yr-old woman with extensively disseminated Erdheim-Chester disease. The posterior lobe was completely replaced by xanthogranulomatous infiltrates, providing an explanation for the patient’s diabetes insipidus. The anterior lobe was intact and immunohistochemistry demonstrated expression of GH, TSH, FSH, LH, and alpha subunit within the normal range. A clinically observed decrease of anterior pituitary function was interpreted as hypothalamic in origin due to massive destruction of the hypophysial stalk and compression of the hypothalamus. Prolactin immunoreactive cells were numerous, consistent with the view that prolactin cell hyperplasia resulted from the loss of hypothalamic dopaminergic inhibition. Massive Crooke’s hyalinization in the ACTH-producing cells was considered unrelated to Erdheim-Chester disease and was the consequence of treatment with pharmacologic doses of glucocorticoid hormones. It can be concluded that prolactin cell hyperplasia may be the only finding in the adenohypophysis of patients with disseminated Erdheim-Chester disease. It appears that in our patient the clinically apparent anterior hypopituitarism was not due to the lack of storage but rather to insufficient release of adenohypophysial hormones caused by the defect in hypothalamic regulation.     

Characteristics of very poor outcome schizophrenia

The authors compared 21 "Kraepelinian" schizophrenic patients who had been ill and dependent on others for the past 5 years with 76 chronic schizophrenic patients in remission or with exacerbations requiring hospitalization. The Kraepelinian patients met the criteria for schizophrenia by more diagnostic systems than the exacerbated patients, were less responsive to haloperidol, had more severe negative symptoms, and had similarly severe positive symptoms. They had cerebral ventricles that were more asymmetrical and a greater family history of schizophrenia spectrum disorders than the other chronic patients. These data suggest that patients with 5 years of illness and complete dependency on others may represent a subgroup of schizophrenia.     

Cerebral abscesses in children

Summary The authors analyze 81 cases of cerebral abscess in children admitted to the Clinic of Neurosurgery Bucharest, from 1936 to 1964; these cases represent 15 per cent of the total number of 542 cerebral abscesses treated in the clinic.A progressive increase was found in the incidence of cerebral abscesses during the last 10 years; an increase was also observed with the increase in age-group.Of the 81 cases 49 occurred in boys.In accordance with their origin there were: 56% contiguous cerebral abscesses (46% otogenic, 6% rhinogenic, 4% other causes); 17% were associated with the congenital cyanotic disease; 15% were post-traumatic abscesses and 12% of undetermined origin.The location was supratentorial in 56 cases, infratentorial in 23 cases and supra- and infratentorial in 2 cases. There were 17 frontal locations, 17 temporal locations, 4 parietal, 2 occipital; in 10 cases two lobes were involved, in 4 cases three lobes and in 1 case one of the cerebral hemispheres. There were 23 cerebellar abscesses and in 2 cases the abscess was supra- and infratentorial.The clinical picture was dominated by the syndrome of raised intracranial pressure (80 per cent of the cases); the evolution of almost half of the cases was afebrile.Among the clinical features of cerebral abscesses in children particular stress is laid on cerebral abscess in infants and on abscesses accompanying a congenital cyanotic cardiopathy.The difficulties of differential diagnosis with focal encephalities, cortical thrombophlebitis, otogenic hydrocephalus, cerebral tumour, etc. are discussed.The treatment of cerebral abscesses in children is considered by the authors as a neurosurgical emergency. They recommend total ablation of the abscess as the best method of treatment, because of the favourable, immediate and late results (the formation of a supple cicatrix) it offers. The surgical treatment was associated with antibiotics, antioedematous medication, corticotherapy and anticonvulsants.Of the 75 children operated on 42 recovered and 12 showed improvement. There was no lethal case in the 25 cerebral abscesses operated on during the last 5 years.

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Zusammenfassung Die Autoren geben eine Analyse von 81 Fällen kindlicher Hirnabszesse, die zwischen 1936 und 1964 in der Neurochirurgischen Klinik Bukarest beobachtet wurden. In dieser Zeit wurden insgesamt 542 Hirnabszesse behandelt. Die kindlichen machen davon 15% aus. Die Häufigkeit hat in den letzten Jahren zugenommen. Die Hirnabszesse sind bei älteren Kindern häufiger. Sie kommen bei Knaben häufiger vor als bei Mädchen.56% waren fortgeleitet entstanden (46% otogen, 6% rhinogen, 4% andere Ursachen). 17% traten im Verlauf angeborener Herzmißbildungen mit Zyanose auf. 15% entstanden posttraumatisch. Bei 12% war die Ursache nicht zu klären.56 Fälle lagen supratentoriell, 24% infratentoriell und 2 sowohl supra- als auch infratentoriell. 17 waren frontal, 17 temporal, 4 parietal und 2 okzipital lokalisiert. Bei 10 Fällen waren zwei Hirnlappen, bei 4 Fällen drei und bei 2 Fällen eine ganze Hirnhemisphäre befallen. Bei 23 Fällen fand sich der Abszeß im Kleinhirn.Das klinische Bild wurde von den Zeichen intrakranieller Drucksteigerung (80%) beherrscht. Beinahe 50% der Fälle verliefen afebril.Auf die Besonderheiten des Hirnabszesses bei Säuglingen und bei angeborenen Herzmißbildungen im Rahmen des Morbus Coerulius wurde eingegangen. Die Schwierigkeiten der Diagnose und der differentialdiagnostischen Abgrenzung von Herdenzephalitiden, kortikaler Thrombophlebitis, otogenem Hydrozephalus, Hirntumoren usw. wurden besprochen. Der diagnostische Wert von EEG, Angiographie und Kontrastdarstellung des Abszesses wurde betont.Als Behandlung der Wahl gilt die Totalexstirpation, weil sie die besten Früh- und Spätergebnisse gewährleistet und die resultierende Hirnnarbe weniger derb ist. Zusätzlich wurden Antibiotika, Osmotherapeutika, Kortikoide und Antiepileptika gegeben.Von 75 operierten Kindern genasen 42. Bei 12 weiteren wurde eine Besserung erzielt. In den letzten 5 Jahren wurde bei 25 operierten Kindern kein Todesfall mehr verzeichnet.

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Resumen Los autores presentan el análisis de 81 casos de absceso cerebral en niños, casos que se investigaron en la Clínica de Neurocirurgía de Bucarest entre los años 1936 y 1964 y que representan un 15% del total de los 542 abscesos cerebrales registrados en la clínica.Se comprueba un crecimiento progresivo de la frecuencia de los abscesos cerebrales en los últimos 10 años; se observa tambien que la frecuencia crece paralelamente al aumento de la edad de los niños.Predominan los abscesos cerebrales entre los varones (49 casos).Según su origen se encontraron: 56% abscesos cerebrales subyacentes (46% otógenos, 6% rinógenos, 4% debidos a otras causas); 17% abscesos asociados a la enfermedad cianógena congénita; 15% abscesos post-traumáticos y 12% abscesos de origen indeterminado.Desde el punto de vista de su localización, hubo 56 casos supratentoriales, 23 casos infratentoriales y 2 casos supra e infratentoriales. Con localización frontal hubo 17 casos, temporal 17 casos, parietal 4 casos y occipital 2 casos; en 10 casos, el absceso afectó 2 lóbulos, en 4 casos 3 lóbulos y en 2 casos un hemisferio cerebral. 23 abscesos fueron cerebelosos y 2 situados encima y debajo del tentorio.El síndrome de hipertensión intracraneana predominó en el cuadro clínico (80% de los casos); y casi la mitad de los casos evolucionaron sin fiebre.Entre las peculiaridades clínicas del absceso cerebral infantil se ponen de relieve los abscesos cerebrales entre los niños de pecho y los que se asocian a una cardiopatia cianógena congénita.Se discuten las dificultades que encuentra el diagnóstico del absceso infantil en comparación con la encefalitis en el foco, la tromboflebitis cortical, la hidrocefalia otógena, el tumor cerebral, etcétera.Los exámenes paraclínicos subrayan el valor de la electroencefalografia, de la arteriografia cerebral y de la abscesografia.El tratamiento de los abscesos infantiles impone, según los autores, la urgencia neuroquirúrgica; basados en su experiencia, ellos recomiendan como método exclusivo de tratamiento la ablación total del absceso, por dar este método los resultados más favorables tanto inmediatos como ulteriores (permitiendo la formación de una cicatriz cerebral más blanda. El tratamiento quirúrgico se asoció a una medicación antibiótica, antiedematosa, a la corticoterapia y al empleo de anticonvulsivos.De los 74 niños operados sanaron 42 y mejoraron 12. En los últimos 5 años, entre los 25 abscesos cerebrales infantiles operados, no se registró ningún caso de fallecimiento.

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Résumé Les auteurs présentent l'analyse clinique de 81 cas d'abcès cérébraux chez l'enfant, opérés dans la Clinique Neurochirurgicale de Bucarest (Roumanie), depuis 1936 jusqu'à 1964. Ces cas représentent 15% du nombre total de 542 abcès cérébraux hospitalisés dans cette période.On a pu constater, surtout dans les deux dernières années, une fréquence plus grande aussi bien qu'un accroissement du nombre des cas par rapport aux groupes d'âge des enfants.Le nombre de cas chez les garçons (49) l'a emporté sur ceux de l'autre sexe. La répartition des cas d'après leur origine fut la suivante: abcès de voisinage: 56% (dont 46% otogènes, 6% rhinogènes et 4% d'origine différente); abcès associes à une maladie cyanogène congénitale: 17%; abcès posttraumatiques: 15%; abcès d'origine indéterminée: 12%.La répartition des cas d'après la localisation: 56 cas furent des abcès supratentoriels, 23 cas soustentoriels et 2 cas mixtes. Parmi les 56 cas à localisation supratentorielle 17 étaient dans le lobe frontal; 17 dans le lobe temporal, 4 dans le lobe pariétal et 2 dans le lobe occipital; dans 10 cas l'abcès s'étendait à deux lobes, dans 4 cas à trois lobes et dans 2 cas l'abcès envahissait tout un hemisphère cérébral.Un syndrome d'hypertension intracranienne dominait l'aspect clinique dans 80% des cas et environ la moitié des cas eurent une évolution afébrile.Les auteurs insistent sur les particularités cliniques des abcès cérébraux chez le nourrisson et sur ceux accompagnant une cardiopathie cyanogène congénitale.On discute les difficultés diagnostiques de l'abcès cérébral chez les enfants surtout avec l'encéphalite en foyer, avec la trombophlébite corticale, l'hydrocéphalie otogène et les tumeurs cérébrales.Parmi les investigations paracliniques, on souligne la valeur de l'electroencéphalogramme, de l'angiographie cérébrale et de l'abcessographie.Les auteurs insistent sur le caractère d'urgence neurochirurgicale et, de par leur expérience, sont d'avis que le seul traitement qui puisse assurer les meilleurs résultats aussi bien immédiats que tardifs (cicatrice cérébrale plus souple) est l'ablation totale de l'abcès.Une médication antibiotique et antioedémateuse aussi bien qu'une corticotherapie et, des anticonvulsivants ont été constamment associées au traitement chirurgical.Du nombre de 75 enfants opérés, 42 ont été complètement guéris et 12 ameliorés. Dans les derniers 5 ans, il n'y eut aucun decès parmi les 25 enfants opérés pour abcès cérébral.

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Riassunto Gli AA. fanno l'analisi clinica di 81 casi di ascessi cerebrali nei bambini, osservati nella Clinica Neurochirurgica di Bucarest, dal 1936 al 1964, e scelti tra 542 casi di ascessi osservati nello stesso periodo.Si nota un accrescimento notevole della casistica negli ultimi 10 anni e con l'età del malato; il sesso maschile è stato molto più frequentemente colpito (49 casi).Dal punto di vista dell'eziologia sono stati riscontrati: 56% di ascessi per contiguità, tra cui: 46% ascessi otitici, 6% ascessi rinogeni e 4% da altre cause; 17% associati a cardiopatie cianogene congenite, 15% ascessi post-traumatici e 12% ascessi d'origine sconosciuta.La sede degli ascessi è stata molto variabile: 56 ascessi erano sopratentoriali, 23 ascessi sottotentoriali e 2 sopra- e sottotentoriali insieme. Tra gli ascessi sopratentoriali sono stati osservati: 17 casi in sede frontale, 17 in sede temporale, 4 in sede parietale e 2 in sede occipitale. In 20 altri casi risultavano lesi 2 lobi cerebrali, in quattro 3 lobi ed in un caso un emisfero intero.In quadro clinico era dominato dclla sindrome di ipertensione endocranica (80% dei casi); il 50% dei malati era apirettico.Tra le forme cliniche dell'ascesso cerebrale nei bambini, si mettono in rilievo quello del neonato e quello associato alla cardiopatia cianogena congenita.Vengono indicate inoltre brevemente le difficoltà di una diagnosi differenziale tra encefalite a focolaio, tromboflebite corticale, l'idrocefalia otitica ed i tumori cerebrali. Tra le indagini paracliniche si sottolinea l'importanza dell'elettroencefalografia, dell'angiografia cerebrale e dell'ascessografia con aria.La terapia degli ascessi cerebrali nei bambini costituiscono, secondo gli AA., una necessità neurochirurgica urgente e, come tale, il metodo chirurgico di elezione è l'asportazione totale dell'ascesso, visto che i risultati, tanto immediati quanto a distanza, sono migliori dopo l'operazione: per es. si ha una gliosi cerebrale meno retrattile e quindi una minore frequenza dell'epilessia.Alla cura chirurgica si è associato la terapia antibiotica, la medicazione dell'edema cerebrale, i cortisonici ed i farmaci anticonvulsivi.Tra i 75 casi operati si notano: 42 guarigioni e 12 miglioramenti clinici. Negli ultimi 5 anni non si deplora nessun caso mortale nei 25 ascessi cerebrali operati.