Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development).

PURPOSE: Malformations of cortical development (MCD) (cortical dysplasias) are well-recognized causes of intractable epilepsy. Although a histologic classification system for MCD has been proposed by Palmini et al. (Neurology; 2004; 62:S2), studies to date have not assessed reproducibility. The purpose of this study was to analyze inter- and intraobserver agreement among eight experienced neuropathologists (NPs) with respect to this classification system. METHODS: Sections from 26 epilepsy resections were selected to represent the range of pathologies described by Palmini et al. Recuts of single sections from each case were sent to the NPs to classify. The slides were resent at a later date for reclassification. Kappa analysis for both inter- and intraobserver concordance was performed. RESULTS: Interobserver agreement was moderate (kappa = 0.4968). There was > or =62.5% (5 of 8 NPs) agreement for 19 of 26 cases. The greatest concordance was present when making focal cortical dysplasia (FCD) types IIA/B classifications (12 of the 14 cases with > or =75% consensus). Mild MCD (types I/II) and FCD types IA/B classifications were the least reproducible, and used most frequently in cases without consensus. Intraobserver concordance was moderate to very good (range kappa = 0.4654-0.8504). The category with the fewest classification changes made on reevaluation was FCD type IIB (4.2%), whereas that with the most changes was mild MCD (types I/II) (52.9%). DISCUSSION: Interobserver concordance using this approach was moderate. The classification categories with the greatest concordance were FCD type IIA/B, and the least, mild MCD and FCD types IA/B. In addition, difficulty in differentiating Mild MCD/FCD type I lesions from normal and/or gliotic tissue was noted.

Isolated cardiac involvement in primary amyloidosis: presenting as sick sinus syndrome and heart failure.

Cardiac amyloidosis is an infiltrative cardiomyopathy with a grave prognosis. Its clinical manifestations include restrictive cardiomyopathy, diastolic heart failure, conduction defects, and arrhythmias. Isolated cardiac involvement and significant conduction disturbances are reported very infrequently. We report a rare case of isolated cardiac involvement in primary amyloidosis, in a 76-year-old man who initially presented with sick sinus syndrome that necessitated permanent pacemaker insertion. Subsequent symptoms of heart failure led to additional evaluation, including an endomyocardial biopsy that revealed primary cardiac amyloidosis. Medical therapy improved the patient's symptoms, and he was discharged from the hospital in stable condition. In addition to discussing the patient's case, we review the relevant medical literature.

Clear cell meningioma: a clinicopathologic study of 18 tumors and examination of the use of CD10, CA9, and RCC antibodies to distinguish between clear cell meningioma and metastatic clear cell renal cell carcinoma.

Clear cell meningiomas (CCM) can be difficult to distinguish from metastatic clear cell renal cell carcinomas by standard light microscopy. Distinction is important in deciding patient management and establishing prognosis. The purpose of this study is to evaluate the use of immunomarkers CA9, CD10, and RCC in differentiating between CCM and clear cell renal cell carcinoma. The study retrospectively reviewed the clinicopathologic features of 18 patients with CCM (9 females, 9 males; age range at the time of surgery 16 to 86 y) including immunostaining results with antibodies to CA9, CD10, and RCC. Immunostaining results were compared with those found in 26 cases of clear cell renal cell carcinoma. The most common sites of origin for the CCM included the meninges overlying the frontal lobe (n=7), cavernous sinus (n=3), and cerebellopontine angle/posterior fossa (n=2). All tumors had at least a 10% clear cell component (mean 41%). All tumors showed a sheet-like growth pattern. Other commonly observed morphologic features included increased cellularity (n=12), nucleolation (n=8), small cell change (n=6), microcalcifications (n=5), and necrosis (n=5). A mean of 1.9 mitotic figures per 10 high-power fields and a mean Ki-67 labeling index of 12.1% were observed. Seven tumors (38.9%) showed CA9 immunoreactivity, 5 tumors (27.8%) CD10 staining, and 0 cases showed RCC staining. Immunostaining results observed in the clear cell renal cell carcinoma group included 93.8% CA9 staining (15/16 cases evaluated), 100% CD10 staining (15/15 cases), and 36.4% RCC staining (4/11 cases). Follow-up was available in 16 CCM patients (mean follow-up of 58.9 mo); 10 patients (62.5%) developed at least 1 recurrence requiring surgical intervention. In conclusion, meningiomas with at least a 10% clear cell component tend to behave in a more aggressive fashion with increased risk of recurrence. Immunohistochemical staining with antibodies to CA9, CD10, and RCC are potentially useful in differentiating CCM from metastatic renal cell carcinoma. In the majority of cases in which immunostaining was observed in meningiomas, staining was focal (involving <5% of neoplastic cells) in comparison with CA9 and CA10 immunostaining in renal cell carcinomas in which more than 50% of tumor cells stained the majority of cases.

Focal cortical dysplasia type II (malformations of cortical development) aberrantly expresses apoptotic proteins.

bcl-XL, bax, bcl-2, and p53 are apoptotic proteins essential to normal neural development. Aberrant expression of these proteins has been observed in several central nervous system neoplasms. Immunoexpression of these markers is studied in 21 patients with focal cortical dysplasia type II (Taylor-type cortical dysplasia; malformations of cortical development) who had undergone lesionectomy for treatment of pharmacoresistant epilepsy. Paraffin immunohistochemistry using standard methodology was performed on representative sections using antibodies to bcl-XL, bax, bcl-2, and p53. Aberrant expression of bcl-XL, bax, bcl-2, and p53 was observed in the majority of cases, with dysmorphic neurons staining positively for bcl-XL, bax, and bcl-2 in 71%, 76%, and 24% of cases, respectively, and balloon cells staining positively for bcl-XL, bax, and bcl-2 in 89%, 78%, and 17% of cases, respectively. Most cases (86%) showed some expression of p53, with the majority showing expression of p53 most prominently in balloon cells. Previous work has shown gangliogliomas and dysembryoplastic neuroepithelial tumors, both dysplasia-associated neoplasms, to demonstrate aberrant expression of apoptotic markers, suggesting a possible common mechanism of development for these 2 processes in patients in whom they coexist.