An algorithmic approach to sellar region masses.

CONTEXT: Most sellar region masses (85%-90%) are pituitary adenomas; however, other neoplasms or even inflammatory or cystic nonneoplastic lesions may occasionally be encountered in this location. A practical, non-electron-microscopically based approach is essential for the daily practice of diagnosing and subclassifying adenomatous and nonadenomatous sellar region lesions. OBJECTIVE: To provide an algorithmic approach to sellar region masses for the pathologist and to formulate a cost-effective, limited panel of stains and immunostains that can be used in daily practice at most small to medium-sized centers. DESIGN: Pool collective experience of 3 neuropathologists practicing at academic medical centers with expertise in diagnosis and treatment of sellar region masses to craft a single-page algorithmic diagram and to liberally illustrate the range of lesions present in the sellar region. RESULTS: After formulating a differential diagnosis, the general pathologist can generate a confident final diagnosis of adenoma using 1 histochemical (reticulin) and 1 immunohistochemical (synaptophysin) stain, supplemented by 5 immunohistochemical stains (CAM5.2, follicle-stimulating hormone, growth hormone, prolactin, and adrenocorticotropic hormone), which provide subtyping of the adenoma in the overwhelming majority of examples. CAM5.2 and clinical information further help identify clinically aggressive variants such as sparsely granulated growth hormone adenomas and silent adrenocorticotropic hormone adenomas, respectively. MIB-1, thyroid transcription factor 1, and S-100 protein can be of further assistance in select cases where increased mitotic activity or possible nonadenomatous spindle cell lesions are suspected. CONCLUSIONS: Adenomas, normal anterior or posterior gland, and nonadenomatous masses can be easily diagnosed in a nontertiary pathology laboratory setting.

Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.

OBJECTIVE: To describe a multigenerational kindred with a frontotemporal dementia clinical syndrome (FTDS), extensive subcortical gliosis pathology, and autosomal dominant genetics. METHODS: Clinical, imaging, and pathologic evaluations of multiple family members. RESULTS: Symptom onset commonly occurred in the fifth or sixth decade, although some kindred members did not develop obvious symptoms until their eighth decade. White matter changes were prominent on both MRI and CT imaging. Results from six brain autopsy evaluations showed consistent but varying degrees of pathology that, while unique, share some histologic similarities with leukodystrophies. These brains were notably devoid of both tau- and ubiquitin-containing inclusions. CONCLUSIONS: Subcortical gliosis in this kindred arises from mutation of a novel gene or else represents a unique frontotemporal dementia clinical syndrome variant caused by mutation of an already known gene. Clinical relevance and research implications are discussed.

Differential expression of HOX genes in neoplastic and non-neoplastic human astrocytes.

HOX genes are a large family of regulatory genes implicated in the control of developmental processes. HOX genes are involved in malignant transformation and progression of different types of tumour. Despite intensive efforts to delineate the expression profiles of HOX genes in other cell types, nothing is known regarding the global expression profile of these genes in normal human astrocytes and astrocytomas. The present study has analysed the expression profile of the 39 class I HOX genes in normal human astrocytes (NHA and E6/E7), two well-established glioblastoma cell lines (U-87 MG and U-1242-MG), as well as neoplastic (WHO grades II/III and IV) and non-neoplastic temporal lobe specimens with hippocampal sclerosis and medically intractable epilepsy. RT-PCR, quantitative real-time PCR, immunocytochemistry, and western blot analyses revealed differential expression of nine HOX genes (A6, A7, A9, A13, B13, D4, D9, D10, and D13) in normal human astrocytic cell lines and non-neoplastic temporal lobe specimens. The data show that HOX genes are differentially expressed in neoplastic and non-neoplastic astrocytes and that multiple HOX genes are overexpressed in glioblastoma cell lines, astrocytomas (II/III), and glioblastoma multiforme. The differential expression of HOX genes in normal and neoplastic astrocytes suggests a role for these genes in brain tumourigenesis.

Challenging diagnosis: oligodendroglioma versus extraventricular neurocytoma.

Diagnosis of oligodendroglioma from other clear cell neoplasms of central nervous system (CNS) is still challenging despite advances in neuroradiology and molecular diagnostic tools. Herein, we present a 44-year-old male patient who had a diagnosis of right parietal oligodendroglioma grade II in 1994 which recurred in 2002. He presented with intratumoral hemorrhage and he underwent radical resection of tumor in 2003. Histopathological examination of the recurrent tumor showed anaplastic progression with confusing immunohistochemical (IHC) results; the tumor was positive for NeuN and synaptophysin staining. The question arisen was whether the recurrent tumor was an oligodendroglioma with neuronal differentiation or an extraventricular neurocytoma initially misdiagnosed as oligodendroglioma. Repeated IHC staining showed negative results for NeuN and synaptophysin. Chromosomal analysis revealed 1p/19q deletion, which led to the diagnosis ofanaplastic oligodendroglioma grade III. Accurate diagnosis of oligodendroglioma is crucial due to recent advances and promises in its treatment. Current diagnostic methods of oligodendroglial tumors are discussed in context of differentiating oligodendrogliomas from other clear cell neoplasms of CNS, especially from extraventricular neurocytomas.