Prognostic indicators in an aggressive pituitary Crooke's cell adenoma

OBJECTIVE: To investigate prognostic indicators in an aggressive Crooke's cell adenoma of the pituitary. METHODS: The surgically removed tumor was studied by histology, immunohistochemistry and transmission electron microscopy. RESULTS: An aggressive invasive sellar tumor removed by repeated surgeries from a 43-year-old woman with pituitary related Cushing's disease was classified as a Crooke's cell adenoma of the pituitary. The application of several cell proliferation markers confirmed the aggressive nature of the tumor. CONCLUSIONS: The investigation of the present case provides additional evidence that pituitary Crooke's cell adenomas may possess aggressive behavior.     

Paraganglioma in pituitary fossa

Paragangliomas are neuroendocrine tumors of paraganglionic tissue which are extremely rare in the sellar area. We present a case of sellar paraganglioma with parasellar and suprasellar extension in a 70‐year‐old man who presented with headache. CT demonstrated sellar mass with suprasellar and right parasellar extension. The lesion was removed subtotally via a trans‐sphenoidal approach. Histopathological diagnosis was paraganglioma. Differential diagnosis between paragangliomas and unusual types of pituitary adenomas, especially null‐cell adenomas, is made by presence of cell nests (Zellballen) in paraganglioma, lack of immunopositivity for pituitary hormones, cytoplasmic immunopositivity for chromogranin A and neuron‐specific enolase, and immunonegativity for cytokeratin 19, cytokeratin 20 and endomysial antibody. In the case of a mass in the sellar region, paraganglioma, although rare, should be included in the differential diagnosis.     

Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma

We report a case of a 60-year-old man who presented with weight gain, headaches, dizziness, erectile dysfunction and decreased libido. He was found to have elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma, marked by a proliferation of biphenotypic appearing cells, associated with a gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas are benign combination tumors that rarely occur in the sellar region. Adenomas in this setting are sometimes functional, and rare patients with mixed adenomas (adenomas secreting more than one hormone) have been reported. To our knowledge, there has been only one other report of a combined ACTH and prolactin-producing adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our patient, the immunohistochemical stains demonstrated that the bulk of the adenoma cells stained with prolactin antibody, and scattered clusters of cells within the adenoma stained positively for ACTH. The adenoma did not stain with antibodies to any of the other anterior pituitary hormones. Postoperatively, the elevated prolactin and ACTH levels returned to normal levels and there was no evidence of residual tumor. Adequate sampling and immunohistochemistry are important in rendering a correct diagnosis and in identifying the hormone status of mixed adenoma-gangliocytomas.     

Pituitary adenomas: clinicopathological and immunohistochemical study

The results of conventional histological staining, ultrastructural studies, and immunoperoxidase methods were compared in a study of 50 pituitary adenomas and correlated with clinical features. Final diagnosis was based on immunoperoxidase reactions and ultrastructural characteristics. There were 25 prolactin (lactotrophic) cell adenomas, 4 growth hormone (somatotrophic) cell types, 1 mixed growth hormone-prolactin cell tumor, 3 adrenocorticotropic cell tumors, and 17 undifferentiated cell adenomas. While serum hormone levels, immunoperoxidase reactions, and electron microscopic features generally correlated well with the clinical features, discrepancies emerged in several cases. Among the responsible factors were: (1) the small sample of tumor removed by transsphenoidal hypophysectomy; (2) uncertainty that the tumor was totally removed or that representative samples were furnished to the pathologist; (3) artifacts produced by electrocoagulation and surgical trauma; (4) inclusion in the biopsy of fragments of altered nonneoplastic adenohypophysis; (5) difficulty in distinguishing hyperplasia from adenoma in small fragments; (6) patchy or scattered immunoreactive cells within an adenoma; (7) the presence of a few cells immunoreactive for hormones other than the predominant one within an adenoma (e.g., cells immunoreactive for growth hormone within a prolactin cell adenoma); and (8) paradoxical serum hormone level abnormalities, especially prolactinemia in patients with undifferentiated cell adenomas and no endocrine symptoms. Biological complexity and technical problems associated with surgery for human adenohypophyseal disease result in continued failure to achieve precise diagnostic correlations with pituitary adenomas.     

Ganglion cell containing pituitary adenomas: signs of neuronal differentiation in adenoma cells

Ganglion cell containing pituitary adenomas are rare. They represent tumors originating in the sella turcica which are composed of adenomatous and neuronal components. Recently accumulated information suggests a common origin for their neuronal and pituitary constituents. The objective of this study was to report the clinical and morphologic findings of pituitary gangliocytomas and study their immunoprofile using neuronal markers. Seven cases of pituitary gangliocytomas retrieved from 1,322 sellar lesions were studied. All tumors were removed from patients with mild acromegaly. Histologically they were biphasic composed of pituitary adenoma and clusters of ganglion cells embedded in a variably dense neuropil substrate. All adenomas belonged to the category of sparsely granulated somatotroph adenoma and were positive for growth hormone, whereas in five tumors, a few adenoma cells were also positive for prolactin. Ganglion cells were immunoreactive for NSE, synaptophysin and neurofilament protein (NFP). NFP-reactive fibrils were observed in the neuropil substrate and varied in number among the cases. Interestingly, all tumors contained varying numbers of adenoma cells with NFP-positive, dot-like areas of cytoplasmic reactivity, mostly tiny paranuclear, a finding not previously reported in human pituitary gangliocytomas. The presence of NFP in pituitary adenomas indicates neuronal differentiation in adenoma cells, suggesting a common origin for neuronal and pituitary adenoma cell elements in gangliocytomas.     

T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra‐operative squash smear

We present a rare case of primary pituitary T cell lymphoma/leukemia (T‐LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55‐year‐old woman highlighting the importance of intra‐operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar‐suprasellar region with non‐visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra‐operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma‐like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T‐LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra‐operative cytology.     

MR imaging study of edema along the optic tract in patient with Rathke's cleft cyst]

We report an 80-year-old woman who was admitted to our hospital with symptoms due to diabetes insipidus. Magnetic resonance (MR) imaging demonstrated a sellar/suprasellar cystic lesion with marginal enhancement and the thick pituitary stalk. The MR imaging depicted edema spreading along the optic tract on fluid-attenuated inversion recovery (FLAIR) images. Upon neurological examination at the time of admission, there were no abnormal findings affecting the field of vision or visual acuity. In endocrinological examination, the basal plasma values of pituitary hormones were within normal range except for that of prolactin, which was 47.9 ng/ml. The preoperative diagnosis was craniopharyngioma, and the intrasellar mass was partially removed by the endoscopic transnasal transsphenoidal approach. Postoperative histopathological examination revealed Rathke's cleft cyst associated with squamous metaplasia. Lymphocytic infiltration was also confirmed in both the anterior and posterior pituitary lobe. The postoperative course was satisfactory. Edema spreading along the optic tract was reported as a characteristic MR imaging finding for diagnosis of craniopharyngiomas or optic nerve glioma. However, it is suggested that edema of the optic pathway seems to be caused not only by craniopharyngioma but also other suprasellar lesions. It was a rare case of secondary lymphocytic hypophysitis caused by Rathke's cleft with edema along the optic tract.     

Intrasellar dermoid cyst mimicking pituitary apoplexy: A case report and review of the literature

Intrasellar dermoid cysts are extremely unusual lesions, with only four cases reported to date, and have not been previously reported in association with sudden-onset symptoms. Here, we present the case of an intrasellar dermoid cyst with sudden-onset symptoms mimicking pituitary apoplexy in an elderly woman. A 69 year-old woman presented with sudden onset of headache, dizziness, and decreased visual acuity. Magnetic resonance imaging of the sellar region showed an intrasellar lesion, which showed mixed hyper- and hypointense signal on T1-weighted and T2-weighted images and enhanced peripherally. Endocrine workup showed pituitary hormones within normal levels. According to these findings, the initial diagnosis of nonsecreting pituitary macroadenoma apoplexy was made. Intraoperatively, a large amount of whitish-yellow purulent material was found in the mass and the lesion was partially removed, owing to tight adhesion between remanent mass and surrounding neurovascular structures. Pathology showed a dermoid cyst with abundant neutrophil infiltrations.     

Sellar neuroblastoma mimicking a pituitary tumour: Case report and review of the literature

Neuroblastomas of the sellar region are exceedingly rare. Only 2 cases have previously been reported. Management of these tumours depends on the tumour's primary site, the patient's age and histopathological features. We are reporting the case of a 43-year-old woman who developed progressive bitemporal hemianopsia and visual loss, accompanied by amenorrhea and hyponatremia. Laboratory findings revealed a slightly elevated prolactin level. Cranial MR-imaging displayed an intrasellar and suprasellar lesion with a maximum diameter of 2.5 cm that was suspicious for a pituitary adenoma or tuberculum sellae meningioma. The tumour was approached via a pterional trepanation. Intraoperatively, the tumour was highly vascularized and adhesive to the optic chiasm, the floor of the third ventricle, the hypothalamus and the hypophyseal stalk. Postoperatively, vision improved and prolactin dropped to normal values, but hyponatremia persisted. Histopathological examination revealed a neuroblastoma with strong positivity for synaptophysin and chromogranin, MAP-2 protein and NeuN-antigen in the immunohistochemistry. No pituitary hormone receptors were expressed. The MIB-1 labelling index was positive in 5% of the cell nucleoli. In the further course, the patient underwent radiotherapy of the neuroaxis.A brief review of the literature is presented.     

Pathological and experimental investigations in a case of gigantism

Summary A pituitary adenoma was transsphenoidally removed from a 4.5-year-old girl suffering from gigantism. Prior to the operation both the growth hormone (GH) and the prolactin (PRL) levels in the serum were elevated. By light microscopy the tumor appeared to be an acidophilic adenoma. Two distinct cell types, the densely granulated and the sparsely granulated cells, could be distinguished by electron microscopy. Double immunolabeling revealed the presence of GH alone in some densely granulated cells and PRL alone in some sparsely granulated cells, as well as GH and PRL co-localized in both of the morphologically distinguished cell types. Both cell types were identified in the monolayer and the suspension cultures by electron microscopy. GH and PRL concentrations in the culture media were measured by radioimmunoassay. The basal secretion of growth hormone was almost uniform during the 3-week cell culture period. GH and PRL release was significantly inhibited by bromocriptine. Our studies revealed a bimorphous and bihormonal mixed adenoma in childhood.     

Prolactin-producing pituitary adenoma with incomplete neuronal transformation: an intermediate adenoma–neuronal tumor

We present a unique case of a prolactin (PRL)-producing pituitary adenoma showing incomplete neuronal differentiation without ganglion cells. A 27-year-old man presented with nausea, headaches, and instability over the last 2 months. Clinical examination revealed obesity with no other endocrinological signs. His serum PRL levels were slightly elevated (38 ng/ml), whereas concentrations of the other adenohypophysial hormones were within normal range. Histology revealed an unusual pituitary adenoma containing many hypocellular areas with fibrillar appearance. The sizable tumor cells were polyhedral or elongated harboring an ovoid, vesicular nucleus with prominent nucleolus, lacking, however, the typical features of ganglion cells. By immunohistochemistry, many adenoma cells were positive for PRL. Immunostain for neurofilament protein revealed variable amounts of fibrils dispersed throughout the stroma, mostly in the hypocellular areas. In addition, neurofilament protein and chromogranin were strongly reactive in approximately 15% of the tumor cell population, whereas reactivity for synaptophysin was uniform throughout the tumor. These findings led to the conclusion that part of the tumor-cell population expressed a hybrid immunoprofile of adenoma–neuronal cell. Our case is the first PRL-producing pituitary adenoma showing incomplete neuronal differentiation lacking mature ganglion cells.     

Pituitary abscess in a pregnant woman.

Pituitary abscess is a rare and potentially lethal condition. Pituitary abscess in a pregnant woman has not been previously described. A 38-year-old pregnant woman (34 weeks gestation) with a pituitary mass complained of a progressive headache and sudden visual impairment. She was afebrile and had no inflammatory symptoms on admission. On MRI, the preoperative diagnosis was pituitary adenoma with sphenoid sinusitis. She underwent an uncomplicated transsphenoidal procedure for removal of the pituitary mass. The next day, labor commenced and a healthy preterm baby was delivered. Pathologic examination of the intrasellar mass showed polymorphonuclear cells, debris and no tumor cells. The sellar contents were cultured and Streptococcus viridans was grown. To our knowledge this is the first case of pituitary abscess reported during pregnancy. Although the patient was pregnant, the transsphenoidal approach was safe for the mother and the fetus. Surgical drainage and antibiotic therapy are required for the definitive treatment of this condition.     

Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy

Summary A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.Supported in part by Grant MT-6349 of the Medical Research Council of Canada     

A growth hormone‐secreting adenoma with incomplete nerve bundle formation

We present a unique case of an adenoma secreting growth hormone (GH), showing incomplete nerve bundle formation without ganglion cells. A 47‐year‐old man presenting with acromegaly was revealed to have high serum GH and IGF‐1 levels. The concentrations of the other adenohypophysial hormones were within the normal range. Histology revealed an unusual pituitary adenoma containing many nerve bundle‐like structures. Adenoma cells with ovoid or round hyperchromatic nuclei and eosinophilic cytoplasms lacked the typical features of ganglion cells. The nerve bundles consisted of slender elongated cells. These fibers were arranged into groups in a roughly parallel fashion. By immunohistochemistry, many adenoma cells were positive for GH, prolactin, thyrotropin beta, synaptophysin and chromogranin. Fibrous bodies revealed by keratin immunostaining were found only in adenoma cells. Scattered star‐shaped adenoma cells showed the same immunoreactivity as folliculo‐satellite cells. Adenoma cells, but not the bundle‐like structures, were also positive for Pit‐1. Immunostaining for neurofilament protein, GFAP, vimentin, and S‐100 protein revealed variable amounts of fibrils within the bundle‐like structures. Scattered immunoreactivity for myelin basic protein and synaptophysin was also found in the bundle area. Our case is the first GH‐secreting pituitary adenoma showing incomplete nerve bundle differentiation and lacking mature ganglion cells.     

Spindle cell oncocytoma of the adenohypophysis - a clinicopathological and ultrastructural study of two cases

Spindle cell oncocytoma (SCO) of the pituitary gland is a relatively recently established, very rare subtype of adenohypophysis tumours that was introduced as a distinct clinicopathological entity in the fourth edition of WHO classification of the central nervous system tumours (2007). It is non-endocrine neoplasm of the anterior pituitary that occurs in adults and usually follows a benign clinical course, corresponding to WHO grade I. Up to now, pituitary SCO have been reported occasionally and only 14 cases of SCO have been documented in the literature. Because of their rarity, the pathogenesis and natural history of these tumours have not been fully characterized. We report two additional cases of SCO occurring in females aged 63 years (Case 1) and 65 years (Case 2), who presented with pan-hypopituitarism, headache and visual field defect. In both cases, the magnetic resonance imaging showed solid sellar mass of moderate size with suprasellar extension. The clinical and radiological features suggested non-functioning pituitary macroadenomas without evidence of invasive growth. One patient presented with tumour recurrence 3 years after undergoing the previous surgical removal of tumour, which was initially misdiagnosed as schwannoma. The first tumour was removed by transsphenoidal surgery and the second one by frontal craniotomy. Histologically and immunohistochemically, both tumours displayed the features typical for SCO of the pituitary. They were composed of interwoven fascicles of spindle cells exhibiting abundant eosinophilic cytoplasm of oncocytic or granular appearance. Mitoses were rarely observed and necrosis was absent. In one case, the advanced lymphocytic infliltration was observed within neoplastic tissue. The tumour cells exhibited immunoreactivity for S-100 protein, galectin-3, vimentin and epithelial membrane antigen but they were negative for GFAP, anterior pituitary neuroendocrine markers (prolactin, growth hormone, TSH, ACTH, FSH, LH), chromogranin, synaptophysin, cytokeratin CK (AE1/AE3), smooth muscle actin, desmin, CD34 and CD68. MIB1 labeling index did not exceed 10%. Ultrastructurally, the tumour cells were rich in mitochondria with lamellar cristae. Moreover, in Case 2 some tumour cells showed a number of giant mitochondria with severely destructed internal matrix. Spindle cell oncocytoma of the anterior pituitary is often misdiagnosed entity of uncertain histogenesis. It should be considered in the differential diagnosis of various sellar-region lesions of oncocytic morphology.     

Secretion of neuron-specific enolase, prolactin, growth hormone, luteinising hormone and follicle stimulating hormone by "functionless" and endocrine-active pituitary tumours in vitro.

Secretion of the neuroendocrine marker neuron-specific enolase by 24 pituitary tumours was measured in maintenance tissue culture. Eleven endocrine-active and 13 "functionless" tumours were defined by measurement of prolactin, growth hormone, luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion rates in vitro and the corresponding plasma hormone levels. Measurement of prolactin secretion provided a clear distinction between true prolactinomas and "functionless" tumours causing hyperprolactinaemia by stalk compression (pseudoprolactinomas). A previous report of LH and/or FSH secretion by the majority of "functionless" tumours was confirmed, but plasma levels of LH and FSH were usually normal. It is argued that LH and FSH are not the major hormones secreted by "functionless" tumours. A high production rate of neuron-specific enolase appears to be characteristic of the cell type from which most "functionless" tumours derive.     

A case of pituitary metastasis from breast cancer that presented as left visual disturbance

Tumors that metastasize to the pituitary gland are unusual, and are typically seen in elderly patients with diffuse malignant disease. The most common metastases to the pituitary are from primary breast and lung cancers. We report a 65-year-old woman with pituitary metastasis from breast cancer who presented with recent-onset left progressive deterioration of visual acuity and visual field. The clinical diagnosis was made after brain and sellar magnetic resonance imaging showed a large sellar mass compressing the optic chiasm and invading the pituitary stalk. An otorhinolaryngology and neurosurgery team removed the tumor via a transsphenoidal approach, and this procedure obtained symptomatic relief. Postoperatively, metastasis from breast invasive ductal adenocarcinoma was confirmed histologically. We report this unusual case with a review of the relevant literature.     

Sella turcica metastasis from follicular carcinoma of thyroid

A case of metastasis to the sella turcica from a follicular adenocarcinoma of the thyroid gland is presented. Metastasis to this site is rare and review of the literature reveals only 12 cases of metastatic thyroid carcinoma involving the sella turcica and pituitary gland. The optimal treatment strategy is still to be determined. A 43-year-old woman presented with headache, nausea, visual impairment and galactorrhea. An MRI scan of the cranium revealed an enhancing destructive sellar lesion. The patient underwent transsphenoidal removal of the lesion to alleviate visual loss. The histological features of the sellar tumor were identical to those of a follicular adenocarcinoma partially removed from the thyroid gland 22 months earlier. Total thyroidectomy followed by three courses of iodine-131 ablation enhanced with synthetic thyrotropin and thyroid hormone suppression therapy was instituted. The post-operative course was satisfactory with improved vision and ceased galactorrhea. This case was successfully treated with a combination of surgical removal, iodine-131 ablation and hormone suppression therapy, which resulted in disease control duration of four years. Sella turcica metastases of thyroid carcinoma are exceedingly rare and currently there are no established therapeutic guidelines.     

Pituitary prolactin producing adenoma with ossification: A rare histological variant and review of literature

Pituitary adenoma with ossification is a rare histological variant. Previously there have been four cases reported in the literature. Here a case of pituitary prolactin‐producing adenoma with bone formation in a 21‐year‐old woman is described. The patient had irregular menstruation for three years. MRI revealed an unusual 1.5 cm³ ovoid nodule with partial shell‐like structure showing heterogeneous signals. The pre‐operative prolactin serum level was 258.78 ng/mL. The patient was operated through the trans‐sphenoidal pathway under general anesthesia. Histologically, the tumor was parenchymal and mostly replaced by the well‐differentiated lamellar bony tissue. Sheets of tumor cells interweaved with the mature lamellar bone trabeculae showing no cellular atypia. The cytoplasm of the adenoma cells was slightly eosinophilic and the myelo‐adipose metaplastic foci were also found within the parenchyma. Immunohistochemical staining of tumor cells showed positive expressions of prolactin, synaptophysin and chromogranin A in the cytoplasm of the tumor cells. Meanwhile, negative expressions of S‐100, epithelial membrane antigen, GFAP and other pituitary hormones were also demonstrated. As a rare histological variant of pituitary adenoma, the current case of pituitary prolactin producing adenoma with ossification is reported. It is speculated that the ossification may be derived from the osteo‐metaplasia of mesenchymal fibroblasts resulting from the effects of both secondary ischemia by the outgrowth of the tumor and/or the autocrine effect of prolactin in this case. The bony shell structure may limit the growth of pituitary adenoma.     

Pituitary adenomas: tumor cell growth by cluster formation. Pattern analysis based on immunohistochemistry

Summary The topographical distribution of adrenocorticotropic hormone, growth hormone and prolactin was studied in nine multihormonal pituitary adenomas and two normal adenohypophyses using quantitative immunohistochemical methods. For each pituitary hormone paraffin sections stained by antihormone antibodies were scanned with a light microscope equipped with a projection and scanning device. The number of immunoreactive cells of each square in the grid was counted and transformed into pseudocolors. In this way, the distribution of each hormone was documented. A chi-square test was applied to these distribution patterns to prove randomness. A nonrandom distribution of immunoreactive cells was observed in all pituitary adenomas and normal pituitary glands. Cluster formations of immunoreactive cells were found for each bormone. The clusters were surrounded by halo-like areas of decreasing number of immunoreactive cells from center to periphery. The cluster-halo type of immunoreactive cells was found not only in the adenomas but also in the normal pituitary gland. This may be explained by the similarity of biological processes during cell proliferation either in normal development or in adenoma formation. It can be concluded from our studies that pituitary adenomas in most cases develop by multicentric but not diffuse proliferation of cell clones of different endocrine activity.