Invasive thymoma metastatic to the cavernous sinus.

BACKGROUND: Thymomas are typically benign tumors of thymic epithelium. Metastases to distal sites, particularly intracranial locations, are extremely rare. Herein, we present the third case of thymoma and the second invasive thymoma to metastasize to the cavernous sinus, adjacent to the pituitary. CASE DESCRIPTION: A 41-year-old female patient presented with headaches, stuffy nose, and drooping of the right face. A magnetic resonance imaging scan revealed a complex, multilobulated mass centered upon the right cavernous sinus. The mass was removed via transsphenoidal surgery, and histopathological investigation confirmed the diagnosis of metastatic thymoma. A positron emission tomography-computed tomography scan demonstrated a large anterior mediastinal mass. A biopsy confirmed the diagnosis of invasive thymoma morphologically identical to the World Health Organization type B2 sellar region metastasis. CONCLUSION: Although rare, thymomas can metastasize to the central nervous system. Our case is the second invasive thymoma to metastasize to the cavernous sinus, adjacent to the pituitary.

Tumefactive demyelination and glioblastoma: a rare collision lesion.

OBJECTIVE: Inflammatory demyelination occasionally forms a solitary mass lesion clinically and radiographically indistinguishable from glioma, replete with enhancement and mass effect. Termed "tumefactive demyelination" it often prompts a brain biopsy. DESIGN: We undertook neuroimaging and morphologic analysis of a unifocal demyelinating lesion intimately associated with glioblastoma. MRI characteristics of the lesion were assessed as were biopsy and resection specimens by both histological and immunohistochemical methods. RESULTS: The patient, a 49-year-old woman, presented with subacute onset headaches. An MRI T1W scan revealed a hemispheric mass with centrally reduced signal and ring enhancement. T2W images showed increased central signal with a rim of reduced signal co-localized to the enhancing ring. A biopsy was initially misinterpreted as demyelination alone, given abundance of histiocytes, the presence of hypertrophic astrocytes with micronuclei ("Creutzfeldt-Peters cells"), and occasional mitoses. Upon consultative review, two histologically distinct components, one inflammatory demyelination and the other an anaplastic astrocytoma were revealed. Subsequent complete resection of the abnormality demonstrated a WHO grade IV astrocytoma (glioblastoma multiforme). CONCLUSION: Our experience underscores the importance of adequate tissue sampling during biopsy for suspected glioma, and confirms the fact that active inflammatory demyelination may coexist with a high-grade glioma. Despite detailed study, the basis for the association remains elusive.

Dysembryoplastic neuroepithelial tumor and calcifying pseudoneoplasms of the neuraxis: a collision of two seizure-associated lesions.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm typically associated with intractable, partial complex seizures in children and young adults. The authors present a case in which a DNET in a 45-year-old male was accompanied by a so-called "calcifying pseudoneoplasm of the neural axis" (CPNA), a rare tumefactive lesion considered reactive in nature. An MRI scan of the brain revealed a right temporal lobe abnormality with characteristics of DNT but no apparent calcification. Histologically, it exhibited classic features of DNET and an overlying meningeal- based, partially ossified, chondrocalcific lesion morphologically characteristic of CPNA. The association of DNET and CPNA has not been previously reported. The literature relevant to these two seizure-associated lesions is reviewed.

Transformation of low grade glioma and correlation with outcome: an NCCTG database analysis.

Glioblastomas (GBM) may originate de novo (primary), or following transformation from a lower grade glioma (secondary), and it has been postulated that these tumors may have different biological behaviors. We performed a correlative analysis involving 204 patients with glioma treated prospectively on NCCTG clinical trials. Central pathology review of tumor tissues taken at the time of initial diagnosis and at recurrence were performed in all patients. Tumors progressed from low (WHO grade 2) to high (grade 3-4) at recurrence in 45% low grade oligodendroglioma patients, in 70% with low grade oligoastrocytoma, and 74% with low grade astrocytoma (P = 0.031). Median overall survival (OS) from initial diagnosis varied by histology: oligodendroglioma, 8.8 years; (95% CI 5.7-10.2); oligoastrocytoma, 4.4 years (95% CI 3.5-5.6); astrocytoma grade 2 3.1 years (astrocytoma grade 2-4, 2.1 years) (95% CI 1.7-2.5, P < 0.001). Mean time to recurrence (TTR) also varied between patients with de novo GBM, those secondary GBM, and those that remained non-GBM at recurrence (1.1 ± 1.1 vs. 2.9 ± 1.8 vs. 4.0 ± 2.9 years, respectively, P < 0.001). Median OS from time of recurrence also varied between these three categories (0.7 years, 95% CI: 0.5-1.1 vs. 0.6 years, CI: 0.5-1.0 vs. 1.4 years, 95% CI: 1.1-2.0, respectively) (P < 0.001). At time of relapse, transformation to higher grade is frequent in low grade pure and mixed astrocytomas, but is observed in less than half of those with low grade oligodendroglioma. From time of recurrence, OS was not significantly different for those with primary versus secondary GBM, and it may thus be reasonable include patients with secondary GBM in clinical therapeutic trials for recurrent disease.

Anaplastic astroblastoma-sarcoma in neurofibromatosis Type 1.

Astroblastoma is a distinctive brain tumor when its histologic features occur in pure form. More often, the tumor pattern is seen to emerge in infiltrative astrocytic tumors. The former are rare. Astroblastoma as a de novo component of gliosarcoma has not previously been described. Furthermore, astroblastoma has only once been reported to occur in the setting of neurofibromatosis Type I (NF1), a condition more often associated with pilocytic and diffuse or infiltrative astrocytic tumors. Herein, we describe a unique case of anaplastic de novo astroblastoma-sarcoma, in essence a variant of gliosarcoma, occurring in a 50-year-old female with documented NF1. Genetic study (fluorescence in situ hybridization) demonstrated no chromosomal losses or gains. Testing for abnormalities of chromosomes 7, 9, 10, 12, 17, 19 and 20, including the EGFR, p16, PTEN, MDM2 and NF1 gene regions, we found the tumor to exhibit a deletion of PTEN, monosomy 17 and gains of chromosomes 19 and 20q. The latter alterations, having been reported in astroblastoma, were noted in both tumor components, thus confirming the common origin of the glial and sarcomatous elements.

Concurrent solitary fibrous tumor and low-grade fibrillary astrocytoma of the cerebellum.

OBJECTIVE: We report the clinicopathologic features of a solitary fibrous tumor (SFT) having undergone malignant transformation and being intimately associated with a WHO Grade II astrocytoma. CLINICAL PRESENTATION: A 7-month old patient presented with delayed motor development and hydrocephalus. INTERVENTION: Histologic and immunocytologic methods were applied in the study of the tumors. Resection was initially employed and the SIOP protocol employing vincristine and carboplatin was applied upon tumor recurrence. CONCLUSION: The biologic basis for the association of SFT and astrocytoma is unknown. The complex lesion differs substantially from WHO Grade IV gliosarcoma and from gliofibroma, lesions in which the disparate elements are linked by metaplasia. Indeed, it may represent a collision tumor. Lastly, induction of the glioma by the solitary fibrous tumor, a mechanism invoked to explain the poorly understood "sarcoglioma," deserves consideration.

Endoglin and CD-34 immunoreactivity in the assessment of microvessel density in normal pituitary and adenoma subtypes.

UNLABELLED: Vascularization is a prerequisite of tumor growth, invasion and metastasis. In the present work, microvessel density was assessed by quantitating using two different endothelial cell biomarkers, endoglin (CD-105) and CD-34. Fifty endocrinologically active and 36 clinically nonfunctioning pituitary adenomas, all surgically resected, as well as 10 autopsy-derived normal adenohypophyses were investigated by immunohistochemistry. The results showed that in every pituitary adenoma type endoglin, an assumed biomarker of proliferating endothelial cells, immunostained fewer vessels than CD-34 which revealed immunopositivity in all capillaries. Differences in endoglin versus CD-34 immunoexpression indicate varying degrees of vascularity in pituitary adenoma subtypes. The low levels of endoglin immunoexpression in pituitary tumors exposed to long-acting somatostatin analogs and dopamine agonists are consistent with the view that these agents inhibit angiogenesis. KEYWORDS: immunohistochemistry, endoglin, CD34, microvascular density, angiogenesis, pituitary.

Estrogen receptors alpha and beta immunohistochemical expression: clinicopathological correlations in pituitary adenomas.

AIM: We investigated the immunohistochemical expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) in pituitary adenoma subtypes combined with clinicopathological factors. MATERIALS AND METHODS: Pituitary adenomas (n=75) were immunostained for ERalpha and ERbeta using the streptavidin-biotin-peroxidase complex method with a monoclonal ERalpha antibody and polyclonal ERbeta antibody. RESULTS: Nuclear immunoreactivity for both receptors was highest among PRL, FSH/LH, null cell, and GH adenomas. ACTH, silent subtypes I and II corticotrophs, and subtype III adenomas were the least immunoreactive for both receptors. ACTH adenomas expressed significantly less ERalpha than FSH-LH, GH, and null cell adenomas. A significantly elevated ERalpha expression was observed in macroadenomas compared to microadenomas and non-invasive compared to invasive tumors. CONCLUSION: ERalpha and ERbeta are differentially expressed in the various pituitary adenoma subtypes suggesting a cell-specific function for these receptors. To elucidate the role of ERalpha in tumor size and invasiveness, additional studies are required.

Identification and consequences of galectin-3 expression in pituitary tumors.

Although the mechanisms regulating pituitary tumor development and progression are still unclear, new information on the molecular mechanisms involved in the pathogenesis of human pituitary tumors have accumulated. Recent evidence suggests that galectin-3 plays an important role in pituitary tumorigenesis and in tumor progression. Galectin-3 is expressed in a variety of tumors and the intensity of expression and localization depend on tumor progression, invasiveness and metastatic potential. Galectin-3 expression has been used as a potential diagnostic and/or prognostic marker in a variety of neoplasms. This review summarizes existing information regarding the structural and functional properties of galectin-3 protein as well as the LGALS3 gene in pituitary tumorigenesis. Given its role in pituitary tumor cell proliferation and in apoptosis, galectin-3 may be a target for the treatment of aggressive pituitary tumors.

Expression of diagnostic neuronal markers and outcome in glioblastoma.

BACKGROUND: High-grade gliomas featuring giant cells, often demonstrate immunoreactivity for neuronal markers, a finding prognostically significant according to some studies. We investigated this event in glioblastomas (GBM). METHODS: Immunoexpression for synaptophysin, neurofilament protein, neuronal nuclear antigen, chromogranin and glial fibrillary acidic protein was analysed in 82 GBM including 11 fibrillary, 8 gemistocytic, 40 giant cell and 23 small cell examples. Survival was compared between tumours exhibiting (GBMpos) or lacking (GBMneg) neuronal markers and also between tumours expressing only one vs. two or more neuronal markers. RESULTS: Forty-five of the 82 tumours (54.8%) including 5 fibrillary, 5 gemistocytic, 30 giant cell and 5 small cell GBMs expressed at least one neuronal marker, synaptophysin being the most frequent (96%). There was no statistically significant difference in survival between GBMpos and GBMneg tumours, all cytologic subtypes combined (P = 0.22). The same was true when cytologic categories were compared. When only GBMpos tumours were analysed, there was a marginally significant difference in outcome between tumours positive for one vs. multiple markers (P = 0.05). This difference was influenced primarily by giant cell GBMs among which the survival time was significantly shorter in the multiple vs. single marker category (median 123 vs. 295 days, P = 0.014). This difference was not observed in the other GBM cell types. Ultrastructurally, rare neurosecretory granules in glial filament-rich cells were identified in one of four tumours studied. CONCLUSIONS: Neuronal marker expression is a frequent feature of GBM. Its prognostic significance is limited to the giant cell GBMs expressing two or more neuronal markers, these being associated with shorter survival.

Intraosseous soft tissue perineurioma: report of a vertebral example.

OBJECTIVE: To describe a unique intraosseous perineurioma affecting the L2 vertebral body and pedicle of a 28-year-old female. MATERIAL: A lytic, expansive lesion virtually limited to bone was gross totally excised; only minimal epidural extension was noted. METHODS: Histologic, immunohistochemical and ultrastructural studies were performed. RESULTS: The tumor was partially encapsulated, moderately cellular, and showed classic features of benign soft tissue perineurioma, being composed of interlacing fascicles of spindle cells with undulating nuclei and long, very narrow, cytoplasmic processes. Immunohistochemistry showed reactivity for EMA, Glut-1, claudin, collagen-4 and CD34; no S-100 or neurofilament protein staining was seen to suggest an origin in nerve. CONCLUSION: Perineurioma, a tumor affecting soft tissue, and presumably nerve-unassociated, may affect bone. No prior entirely osseous examples have been reported. This tumor expands the differential diagnosis of spindle cell tumors of bone.

Oncocytic choroid plexus carcinoma: case report.

Herein, we report an unusual choroid plexus carcinoma with extensive oncocytic transformation. A 13-month-old girl presented with acute lethargy which quickly progressed to coma. A CT scan of the head revealed impending herniation due to hemorrhage within an intracranial tumor. An MRI scan showed a large, partly cystic and highly vascular left lateral ventricular mass. A near total resection was achieved. Microsections revealed a WHO Grade III choroid plexus carcinoma with extensive oncocyti c transformation. A minor portion of the moderately to poorly differentiated tumor exhibited classical microscopic features of choroid plexus carcinoma, including marked nuclear atypia, brisk mitotic activity (78/10 HPF), a high MIB-1 labeling index (44%) and zones of necrosis. In contrast, the large, eosinophilic, cytologically malignant but granular-appearing oncocytes comprising the majority of the lesion showed scant (1/10 HPF) mitotic activity and only a low MIB-1 labeling index (5%). A subsequent recurrence at 1 year consisted entirely of non-oncocytic tumor. Choroid plexus carcinoma with oncocytic transformation has not been previously reported. The remarkable extent of this alteration and its clinical significance remains to be determined.

Plurihormonal gonadotroph cell pituitary adenoma: report of a unique case.

OBJECTIVE AND IMPORTANCE: Pituitary adenomas producing primarily FSH and to a lesser extent GH, LH, alpha-subunit, TSH and PRL without clinical or laboratory evidence of increased hormone release have not previously been reported. Our aim was to obtain some insight into the possible cytogenesis of this unusual tumor. CLINICAL PRESENTATION: A 65-year-old woman presented with headaches. Magnetic resonance imaging (MRI) demonstrated a sellar mass. Pituitary hormone assays showed normal blood levels. The tumor was removed by the transsphenoidal approach. RESULT: By light microscopy, the adenoma was chromophobic, weakly PAS-positive, and immunoreactive mainly for FSH (85%) and to a lesser extent for GH (30%), LH (15%), alpha-subunit (3%), TSH (2%), and PRL (1%). Although double immunostaining showed hormone reactivities to be localized largely in separate distinct cells, the tumor was ultrastructurally monomorphous, i.e., consisted of a single-cell type, resembling gonadotrophs. CONCLUSION: The cytogenesis of plurihormonal pituitary adenomas is not fully understood. Further investigations are required to clarify the basis for their plurihormonality despite an ultrastructural gonadotroph phenotype.

Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment.

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.

Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis.

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as 'tumefactive multiple sclerosis'. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2 : 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing-remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5-12), with a discernible size of 2.1 cm (range 0.5-7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

Ganglioglioma of the neurohypophysis.

The normal infundibulum and neurohypophysis consist entirely of neuronal processes, the neuronal cell bodies of which lie within the supraoptic and paraventricular nuclei of the hypothalamus and supportive glial cells or pituicytes. The finding of neurons within the neurohypophysis is exceedingly rare, as are ganglion cell tumors at this site. In this paper, we report a ganglion cell tumor of the neurohypophysis found incidentally at autopsy. Despite chronic hypertension and the finding of some vasopressin immunoreactivity in lesional neurons, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was excluded on the basis of normal serum sodium levels. The morphologic and immunohistochemical features of the tumor are presented, cytogenetic considerations are discussed, and literature regarding neuronal lesions of the pituitary gland is reviewed.

Collision lesions of the sella: co-existence of craniopharyngioma with gonadotroph adenoma and of Rathke's cleft cyst with corticotroph adenoma.

Collision lesions of the sellar region are relatively uncommon. Most contributions include a pituitary adenoma or a cyst/cystic tumor, particularly a Rathke cleft cyst. The association of craniopharyngioma with an adenoma is particularly rare. Among reported cases, some have included secondary prolactin cell hyperplasia due to pituitary stalk section effect. Herein, we report two collision lesions, including a gonadotroph adenoma with adamantinomatous craniopharyngioma and a corticotroph adenoma with Rathke's cleft cyst. Clinicopathologic correlation and a review of the literature are undertaken.

Adrenomedullin expression in pituitary adenomas and nontumoral adenohypophyses.

Adrenomedullin (ADM) is a novel peptide originally identified in extracts of human pheochromocytoma. It is produced by several tissues, including the pituitary gland. The presence of ADM has been immunohistochemically demonstrated in pathologic pituitary glands, but no systematic study of ADM expression in human pituitary adenomas has been reported. Thus, we investigated ADM immunoexpression in 88 various hormone-secreting and clinically nonfunctioning pituitary adenoma types as well as 30 nontumoral adenohypophyses. Furthermore, ADM immunoreactivity was assessed on a 0 to +3 scale in all samples. We found strong immunoreativity for ADM in normal gonadotrophs also expressing FSH and LH whereas in the other adenohypophysial cell types expression of ADM was mild. Results showed that normal adenohypophyses were strongly immunopositive for ADM (2.18+/-0.11). Our findings demonstrate that ADM expression in the anterior pituitary is diminished in tumors as compared to the normal gland. The physiologic function of ADM is unknown, but it could act as a paracrine or autocrine factor in the adenohypophysis.

Infiltrative chordoid meningioma of the pineal region: a study of 2 cases.

OBJECTIVE: Meningiomas involving the pineal region are rare. Herein we describe two cases of chordoid meningioma with histologic evidence of pineal gland infiltration. MATERIALS AND METHODS: Clinical histories were abstracted from chart review and consultation letters. HE-stained slides were reviewed in both cases. Selected immunohistochemical stains were performed. RESULTS: the patients included a 44-year-old male and a 37-year-old female who presented with symptoms of intracranial tumor referable to the pineal region. On magnetic resonance imaging (MRI), both lesions demonstrated heterogeneous contrast enhancement. Histologically, the tumors were characterized by strands and cords ofmeningothelial cells arranged in a mucinous stroma. In addition, obvious meningothelial cytology as well as focal osseous metaplasia (Case 1), and transitional histology (Case 2) were also noted. Tumor cells demonstrated EMA and focal S100 protein immunoreactivity, but lacked cytokeratin AE1/AE3 and glial fibrillary acidic protein (GFAP) staining. Synaptophysin and neurofilament protein highlighted the overrun pineal gland parenchyma. MIB1-proliferative index was 8.4 and 20.1%, respectively. CONCLUSIONS: Chordoid meningioma, although rare, may occur in the pineal region. The differential diagnosis of this meningioma subtype in this location is discussed.