bromochloroacetic-acid and Hemangioblastoma

Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.

Topics: Alkaline Phosphatase; Carcinoma, Renal Cell; Central Nervous System Neoplasms; Diagnosis, Differential; Germinoma; Glial Fibrillary Acidic Protein; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Meningioma; Mucin-1; Oligodendroglioma; S100 Proteins; Synaptophysin; Vimentin; Xanthomatosis

Hemangioblastoma is a benign tumor that can occur sporadically, or in association with von Hippel-Lindau disease in approximately one-quarter of the cases. Only exceptionally does it occur outside the central nervous system. This report describes 2 cases of sporadic renal hemangioblastoma, with 1 patient presenting with hematuria and polycythemia, and the other low back pain. Histologically, the tumors were circumscribed, and composed of sheets of large polygonal cells traversed by arborizing thin-walled blood vessels. Many of the tumor cells showed pleomorphic nuclei, but the mitotic figures were rare. The cytoplasm was eosinophilic, and occasionally finely vacuolated indicating the presence of lipid. The diagnosis of hemangioblastoma was confirmed by negative immunostaining for cytokeratin, and positive staining for α-inhibin, S100, and neuron-specific enolase. This benign neoplasm which can be mistaken for various malignancies such as renal cell carcinoma, epithelioid angiomyolipoma, adrenal cortical carcinoma, and paraganglioma, deserves wider recognition for its occurrence as a primary renal tumor.

Topics: Biomarkers, Tumor; Female; Hemangioblastoma; Hematuria; Humans; Immunohistochemistry; Inhibins; Keratins; Kidney Neoplasms; Low Back Pain; Male; Middle Aged; Nephrectomy; Phosphopyruvate Hydratase; Polycythemia; S100 Proteins

Distinguishing hemangioblastomas from metastatic clear-cell renal cell carcinomas (CCRCCs) in the brain is a diagnostic challenge owing to similar clinical and morphologic presentations. Inhibin-alpha and aquaporin1 were shown as positive markers of hemangioblastoma, but are not totally reliable distinguishing hemangioblastoma from metastatic CCRCC. This study shows that the diagnosis can be achieved using a combination of markers. To identify the panel of markers useful for this differential, 67 hemangioblastomas and 34 metastatic CCRCCs were analyzed using a panel of antibodies including aquaporin1, inhibin-alpha, D2-40, cytokeratin AE1/AE3, epithelial membrane antigen, and CD10. The study confirms the usefulness of aquaporin1 (97% sensitivity, 83% specificity) and inhibin-alpha (88% sensitivity, 79% specificity) as positive markers of hemangioblastoma and shows that aquaporin1 is a superior positive marker versus inhibin-alpha for the differential. Positivity of tumor cells with cytokeratin AE1/AE3 is the signature of a metastatic CCRCC (100% specificity, 88% sensitivity) and CD10 expression as well (100% specificity, 79% sensitivity). The combined use of aquaporin1 and AE1/AE3 yields a high degree of sensitivity and specificity to differentiate between hemangioblastoma and metastatic CCRCC. All tumors but one aquaporin1 positive and cytokeratin AE1/AE3 negative (65/66) correspond to hemangioblastomas (97% sensitivity, 97% specificity, 98.5% diagnostic positive predictive value). Tumors with the opposite profile, aquaporin1 negative, and cytokeratin AE1/AE3 positive, (25/25), correspond to metastatic CCRCC (74% sensitivity, 100% specificity, 100% diagnostic positive predictive value). In summary, aquaporin1 is the most sensitive positive marker of hemangioblastoma. Despite its moderate specificity, when used in combination with epithelial marker AE1/AE3, it allowed to reliably distinguish hemangioblastoma from metastatic CCRCC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aquaporin 1; Biomarkers, Tumor; Brain Neoplasms; Carcinoma, Renal Cell; Child; Diagnosis, Differential; Female; Hemangioblastoma; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged

Hemangioblastomas are intracranial and intraspinal tumors arising sporadically or in patients with von Hippel-Lindau disease. To date, hemangioblastomas have not been described in the skin. Proliferating clear cells with a variable vascular component are found histologically. These clear cells stain for neuron-specific enolase but not cytokeratin or epithelial membrane antigen, allowing them to be differentiated from metastatic renal cell carcinoma.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Renal Cell; Diagnosis, Differential; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Nose Neoplasms; Phosphopyruvate Hydratase; Skin Neoplasms

Here we report tumor-to-tumor metastases identified in two patients with von Hippel-Lindau (VHL) disease. The first patient had bilateral renal carcinomas and multiple cerebellar hemangioblastomas, and the second patient had a renal carcinoma and multiple hemangioblastomas in the retina, cerebellum and spinal cord. A cerebellar lesion from the first patient and a spinal lesion from the second patient contained two distinct components. The inner part of these tumors consisted of a nested mass of polygonal clear cells that expressed cytokeratin and epithelial membrane antigen, while the outer part of the tumors showed proliferation of capillaries and intervening foamy stromal cells that were negative for cytokeratin and epithelial membrane antigen. The tumors were thus considered to be hemangioblastomas complicated by metastatic lesions of renal cell carcinoma of clear cell type. These cases indicate that tumor-to-tumor metastasis should be considered when hemangioblastoma contains a clear cell carcinoma component in the setting of VHL disease, and that immunohistochemical staining for cytokeratin and epithelial membrane antigen is useful for the diagnosis.

Topics: Biomarkers, Tumor; Brain Neoplasms; Carcinoma, Renal Cell; Female; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Middle Aged; Mucin-1; Neoplasms, Second Primary; Stromal Cells; von Hippel-Lindau Disease

The authors report a case of cystic choroid plexus papilloma that originated in the posterior fossa. No connection with the ventricular system was found intraoperatively. Magnetic resonance (MR) and computerized tomography imaging did not furnish a diagnosis, but findings of pathological examinations were consistent with those of choroid plexus papilloma. The authors describe the different appearances of the tumor on MR images and discuss the differential diagnosis with other tumors of the posterior fossa.

Topics: Choroid Plexus Neoplasms; Cranial Fossa, Posterior; Cyst Fluid; Diagnosis, Differential; Hemangioblastoma; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Papilloma, Choroid Plexus; S100 Proteins; Tomography, X-Ray Computed