bromochloroacetic-acid and Peripheral-Nervous-System-Neoplasms

The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1-3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5-S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.

Topics: Adolescent; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Diagnosis, Differential; Diagnostic Errors; Female; Fibroadenoma; Humans; Keratins; Male; Melanins; Melanoma-Specific Antigens; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurilemmoma; Peripheral Nervous System Neoplasms; Pigmentation Disorders; Prognosis; S100 Proteins; Sacrococcygeal Region; Sarcoma, Clear Cell; Spinal Nerve Roots; Syndrome; Vimentin

Paragangliomas are rare neuroendocrine tumors originating from neural crest-derived paraganglion cells. Primary cauda equina paraganglioma (CEP) pose both diagnostic and surgical challenges. We report 12 cases of CEP to characterize the diagnostic and operative approach to these rare tumors. 12 cases with primary CEP were studied; 5 patients were male (41.7%) and 7 were female (56.3%). The median age was 44 years (range: 15-64 years). The most common symptom was lower back pain of variable duration. Radiologically, the lesions were intradural and extramedullary with well-defined margins, and ranged from 1 to 4.5 cm. in diameter (mean: 1.65 cm). 9 tumors were composed of sheets and nests of cells with a neuroendocrine pattern and intense vascularity and displayed a characteristic Zellballen pattern. Interestingly, CAM 5.2 was diffusely or focally positive with a dot-like or membrane pattern in 8/11 cases (72.7%). Similarly, CK was diffusely or focally positive with membrane and cytoplasmic staining or with a dot-like pattern in 7/11 (63.6%) and 2/11 cases (18.2%). None of the cases showed deletion of SDHB nor expression of GATA3. CEP can display aberrant keratin positivity, and this should be considered in the differential diagnosis of these lesions. This finding also raises the possibility that CEP may be an entirely different entity than non-spinal paragangliomas.

Topics: Adult; Cauda Equina; Female; Humans; Keratins; Male; Neuroendocrine Tumors; Paraganglioma; Peripheral Nervous System Neoplasms

Topics: Gait Disorders, Neurologic; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Peripheral Nervous System Neoplasms; Peroneal Nerve; Sarcoma

Topics: Cauda Equina; Humans; Keratins; Magnetic Resonance Imaging; Middle Aged; Nerve Tissue Proteins; Papilloma, Choroid Plexus; Peripheral Nervous System Neoplasms

The paper discusses morphologic and immunohistochemical characteristics of sclerosing perineurioma. Generally, it is well circumscribed and consists of tiny spindle-shaped plump epitheloid cells embedded in collagenous hyalinized matrix. Immunohistochemically, it was represented by EMA+, S-100, AE1/AE3, CAM 5.2, smooth muscle actin and desmin. Being benign, tumor was identified by differential diagnosis using fibroma of tendon sheath, sclerosing one, glomal tumor, giant cell tumor and sclerosing epitheloid cell sarcoma.

Topics: Adult; Antiporters; Biomarkers; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; S100 Proteins; Sclerosis

Schwannomas have been variably observed to be glial fibrillary acid protein (GFAP) and occasionally keratin positive, with antibodies reacting with multiple keratins (pankeratins, keratin cocktail (CK), but specific keratin polypeptides (K) have not been examined for in schwannoma. Since we observed CK positivity in retroperitoneal schwannomas, we wanted to study a large group of retroperitoneal and peripheral schwannomas with GFAP, CK and Ks to explore the frequency and biologic background of this finding. We immunohistochemically evaluated a large number of retroperitoneal (n=115) and peripheral schwannomas (n=22) for GFAP, 16 individual K and AE1/AE3 keratin cocktail. The great majority (104/115, 90%) of retroperitoneal schwannomas were positive for GFAP, and 72/104 (69%) cases were positive for AE1/AE3, often extensively. Both markers highlighted the cellular Antoni A areas, particularly adjacent to the capsule, myxoid or degenerative areas, and perivascularly. Most cases 87/104 (84%) stained for both AE1/AE3 and GFAP at least focally. No tumors stained for keratins that were GFAP negative. None of the immunostains for individual K showed positivity comparable to that obtained with AE1/AE3 CK. However, 62% were focally positive for high molecular weight K1 and 8/61 (13%) for K7. None of the retroperitoneal schwannomas were positive for other keratins including K2, 4, 5, 8, 9, 10 and K14-20. Peripheral schwannomas showed GFAP-positivity in only three of 22 cases (14%), and all were negative for keratins, both cocktail and individual K. We conclude that crossreactivity of AE1/AE3 with other intermediate filament proteins, such as GFAP, as previously observed in brain and glioma tissue, probably accounts for the extensive keratin-positivity seen in some retroperitoneal schwannomas. However, focal expression of K1 and K7 cannot be ruled out. Keratin-positive schwannomas should not be confused with other keratin-positive tumors, such as sarcomatoid carcinoma, mesothelioma, and synovial sarcoma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neurilemmoma; Peripheral Nervous System Neoplasms; Retroperitoneal Neoplasms

The authors present a case of pseudoglandular schwannoma with immunohistochemical findings consistent with epithelial metaplasia. Pseudoglandular schwannoma is a rare morphological variant of benign schwannoma characterized by the presence of glandlike structures lined with Schwann cells. To the best of the authors' knowledge, this is only the fifth case of pseudoglandular schwannoma reported in the literature. Clinical, imaging, and pathological findings are described. The pathological findings were consistent with a pseudoglandular schwannoma composed of typical Schwann cells arranged in an Antoni B pattern, with numerous large pseudocystic spaces. Serial immunohistochemical studies of tissue sections revealed that the cells lining the pseudoglandular spaces were not only diffusely reactive for S100 protein, but also demonstrated focal positivity for epithelial membrane antigen and cytokeratins AE and AE3. The particular immunohistochemical features of incompletely differentiated Schwann cells in the present case give support to the metaplastic theory of the origin of glandlike structures in benign peripheral nerve sheath tumors.

Topics: Adult; Cauda Equina; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Neurilemmoma; Peripheral Nervous System Neoplasms; S100 Proteins; Schwann Cells

Topics: Back Pain; Biomarkers, Tumor; Cauda Equina; Chromogranins; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Middle Aged; Pain, Intractable; Paraganglioma; Peripheral Nervous System Neoplasms; S100 Proteins; Spinal Cord; Synaptophysin; Vimentin

Topics: Carcinoid Tumor; Cauda Equina; Diagnosis, Differential; Humans; Keratins; Paraganglioma; Peripheral Nervous System Neoplasms; Sacrum

Although benign epithelioid peripheral nerve sheath tumors have been described, they are rare, and benign epithelioid schwannomas have not yet been established as a specific histologic variant. We present four cases of tumors which we believe would meet criteria to be classified as benign epithelioid schwannomas. Biopsy specimens obtained from four different patients were examined with routine and immunohistochemical staining. All the tumors were well-circumscribed lesions that were surrounded by a capsule containing EMA-positive cells. The cellular component was composed of epithelioid cells, in which there was a lack of mitotic activity. Immunohistochemical studies showed the tumor cells were S-100 protein and Leu 7 positive and HMB-45 negative. In addition, type IV collagen encircled individual cells within the tumor, indicating a continuous basal lamina. We report a group of cutaneous epithelioid schwannomas. Although the presence of such tumors is not unexpected, this diagnosis may not be initially considered because of this rare cytologic feature.

Topics: Adult; Antigens, Neoplasm; Collagen; Female; Humans; Immunohistochemistry; Keratins; Male; Melanoma-Specific Antigens; Mucin-1; Neoplasm Proteins; Nerve Sheath Neoplasms; Neurilemmoma; Peripheral Nervous System Neoplasms; S100 Proteins; Schwann Cells; Skin Neoplasms; Vimentin

Synovial sarcoma is a relatively common sarcoma in adults, which in its classic bimorphic form infrequently poses a diagnostic problem. Monomorphic spindled variants, as well as the less common poorly differentiated variants, may be confused with other soft-tissue sarcomas; the poorly differentiated variant (PDSS), in particular, may be histologically indistinguishable from other small, blue, round cell tumors, including primitive neuroectodermal tumors (PNETs). Detection of the synovial sarcoma-associated t(X;18) by either cytogenetic or molecular genetic approaches may be necessary to confirm the diagnosis of synovial sarcoma in difficult cases. We evaluated 10 cases of PDSS from eight patients using a panel of antibodies (including those to intermediate filament proteins, nerve-sheath associated markers, and neuronal and neuroectodermal associated markers) in order to better establish the immunophenotype of this tumor and to help distinguish it from the tumors with which it may be confused, particularly PNETs and high-grade malignant peripheral nerve sheath tumors (MPNSTs). Our results showed PDSS to have significant immunophenotypic overlap with both PNETs and MPNSTs. In most instances these three entities may be differentiated by a panel of antibodies that should include those to both low and high molecular weight cytokeratins, epithelial membrane antigen, type IV collagen, CD99, CD56, and S-100 protein. Our results also suggest that synovial sarcoma may be a tumor showing combined neuroectodermal and nerve sheath differentiation--perhaps because of translocation-associated expression of specific proteins--rather than a carcinosarcoma of soft tissues or a tumor of specialized arthrogenous mesenchyme.

Topics: 12E7 Antigen; Adolescent; Adult; Antigens, CD; Biomarkers, Tumor; Cell Adhesion Molecules; Child; Collagen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Middle Aged; Mucin-1; Nerve Sheath Neoplasms; Neuroectodermal Tumors, Primitive; Neurofilament Proteins; Peripheral Nervous System Neoplasms; Sarcoma, Synovial

To examine whether adrenal phaeochromocytomas and extra-adrenal paragangliomas are immunoreactive for commercially available and routinely used cytokeratin antibodies.. 18 extra-adrenal paragangliomas and seven adrenal phaeochromocytomas were stained with CAM 5.2, AE1/3, and 34 beta E12 following microwave antigen retrieval of formalin fixed tissue.. A single case from the cauda equina was positive for both CAM 5.2 and AE1/3. In addition, two other cases--an intravagal and an orbital paraganglioma--also showed strong immunopositivity with CAM 5.2 and AE1/3. All phaeochromocytomas were negative with all epithelial markers.. Cauda equina paragangliomas are known to stain with cytokeratins; however, occasional paragangliomas from other sites may also be immunoreactive with cytokeratins. If the results of immunohistochemistry are not interpreted in the clinical and morphological context, the failure to recognise that extra-adrenal paragangliomas may on occasion react with anticytokeratin antibodies may lead to their being confused with metastatic carcinomas.

Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Carotid Body Tumor; Cauda Equina; Child; Cranial Nerve Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Microwaves; Middle Aged; Orbital Neoplasms; Para-Aortic Bodies; Paraganglioma, Extra-Adrenal; Peripheral Nervous System Neoplasms; Pheochromocytoma; Staining and Labeling; Vagus Nerve

Topics: Cell Differentiation; Epithelioid Cells; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms

We describe a case of synovial sarcoma occurring in a 36 year-old woman, 8 years after radiation therapy for Hodgkin's disease. The tumor showed histological, immunohistochemical, ultrastructural, and molecular features diagnostic of synovial sarcoma. To our knowledge, this is the first report of a fully documented case of radiation associated synovial sarcoma.

Topics: Adult; Biomarkers, Tumor; Female; Hodgkin Disease; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Mucin-1; Neoplasms, Radiation-Induced; Peripheral Nervous System Neoplasms; Sarcoma, Synovial; Translocation, Genetic

We report the findings of 19 cases of a previously undescribed spindle cell tumor of soft tissues that resembles a low-grade fibromyxoid sarcoma but contains distinctive rosettelike structures. The tumors occurred principally as a painless, slowly growing, deeply situated mass of the proximal extremities in young to middle-aged adults (age range 14-65 years; mean 38). Although grossly circumscribed, the tumors had infiltrative borders microscopically and were composed of bland spindled cells situated in a hyalinized to myxoid stroma. The most characteristic feature of the tumor was scattered large rosettelike structures that often merged with serpinginous areas of dense hyalinization. The rosettes consisted of a central collagen core surrounded by a rim of rounded cells morphologically and immunophenotypically different from the cells of the spindled stroma. These cells expressed a number of antigens, including S-100 protein, neuron-specific enolase, and leu 22, in contrast to the stroma, which usually lacked these antigens. Of the 12 patients with available follow-up information, one patient treated with simple excision clinically developed local recurrence of the tumor 20 months after initial biopsy. No other recurrences were reported during the limited follow-up period, and no patient developed metastatic disease. However, the favorable prognosis of the patients in our series to date may relate to the limited follow-up period (approximately 3 years), as well as initial treatment by wide excision in nearly half of the patients. We regard the hyalinizing spindle cell tumor with giant rosettes as a distinctive type of low-grade fibroblastic tumor that with time may prove to behave similar to a low-grade fibromyxoid sarcoma and, hence, to represent an unusual variant thereof.

Topics: Actins; Adolescent; Adult; Aged; Antigens, CD; Desmin; Diagnosis, Differential; Female; Fibroma; Fibrosarcoma; Humans; Keratins; Male; Middle Aged; Neurilemmoma; Peripheral Nervous System Neoplasms; Retrospective Studies; S100 Proteins; Soft Tissue Neoplasms; Vimentin

A primary malignant peripheral nerve sheath tumor (MPNST) of the pleura that clinically mimicked a malignant mesothelioma in a 57-year-old man is described. Histologically, the tumor had features similar to those described in cases of the so-called epithelioid MPNST. A unique finding in this case was the demonstration of keratin expression in the epithelioid component of the tumor, as well as the presence of rhabdomyoblasts. This is the first example of an MPNST with heterologous elements arising in the pleura. Immunohistochemical and ultrastructural studies were important in differentiating this tumor from other malignancies with sarcomatoid and epithelioid features involving the pleura.

Topics: Actin Cytoskeleton; Biomarkers, Tumor; Cell Differentiation; Diagnosis, Differential; Fatal Outcome; Glycogen; Humans; Keratins; Male; Mesothelioma; Middle Aged; Neoplasm Recurrence, Local; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Pleural Neoplasms; Rhabdomyosarcoma

We describe two histologically unusual cases of ependymoma of the filum terminale. Both tumors occurred in 14-year-old boys. An intradural encapsulated mass attached to the filum terminale was demonstrated radiologically in both cases and totally resected at surgery. In case 1 the neoplasm was uniformly composed of pleomorphic giant cells and was without perivascular pseudorosettes or myxopapillary changes. Case 2 was a myxopapillary ependymoma with multiple foci of pleomorphic giant cells. Neither tumor had prominent mitotic activity, necrosis, or endothelial proliferation. Both tumors were immunopositive for cytokeratin and glial fibrillary acidic protein. Ultrastructural features included basal laminae, interdigitating cell processes, microvilli, cilia, intercellular junctions, and cytoplasmic intermediate filaments. Cytogenetic analysis in case 1 showed a hypodiploid karyotype with monosomy of chromosomes 1, 10, 14, 16, 20, and 22. We interpret both tumors as most consistent with a variant of ependymoma. Because of the unique gigantocellular light microscopic appearance of the entire tumor in case 1, we propose classifying this tumor as a new morphologic subtype: giant cell ependymoma of the filum terminale. The combination of gigantocellular and myxopapillary features in case 2 supports a histogenetic relationship between giant cell ependymoma and myxopapillary ependymoma.

Topics: Adolescent; Cauda Equina; Ependymoma; Giant Cells; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunohistochemistry; Keratins; Male; Peripheral Nervous System Neoplasms

Topics: Adult; Cauda Equina; Female; Humans; Immunoenzyme Techniques; Immunophenotyping; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Paraganglioma; Peripheral Nervous System Neoplasms

Forty-two cases of peripheral neuroepithelioma (PN) retrieved from the files of the National Cancer Institute (Bethesda, MD) and the Pathology Department of Padua University, Italy, were reviewed. No sex predilection was observed (25M/17F) and ages ranged from 7 to 54 yr (median 22 yr). Roughly a third of the tumors were thoracopulmonary ("Askin tumor"), a third were axial, and a third were in extremities. A lobular pattern with rosettes or pseudo-rosettes characterized PN. Seventeen cases showed a strong diastase-sensitive PAS positivity. Transitional areas with an Ewing's-like appearance and, in one case, transition to malignant nerve sheath tumor have been documented. The presence of neuron specific enolase (NSE), S-100 protein, HNK-1, neurofilaments, vimentin, keratin (AE1-AE3), beta 2-microglobulin, chromogranin A, and synaptophysin was investigated using the avidin-biotin technique. Immunocytochemically, NSE (95% of cases), beta 2-microglobulin (77.5%), synaptophysin (73.3%), and S-100 protein (67.5%) were the most consistently positive markers. Ultrastructurally, PN is characterized by a primitive appearance, although it was routinely possible to recognize neural features such as primitive neuritic extensions and dense core granules, either in the cytoplasm or in the cellular processes. In our experience, a light microscopic picture of a primitive round cell tumor with a lobular pattern, and particularly with rosettes when present, with NSE and beta 2-microglobulin positivity by immunocytochemistry, ideally with positive synaptophysin, along with supportive electron microscopy, is required for the diagnosis of PN. Conversely, no one feature alone is generally sufficient for diagnosis, but does allow distinction from extraosseous Ewing's, which (like osseous Ewing's) lacks features of neural differentiation.

Topics: Adolescent; Adult; beta 2-Microglobulin; Child; Child, Preschool; Chromogranin A; Chromogranins; Cytoskeleton; Desmin; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neuroectodermal Tumors, Primitive, Peripheral; Peripheral Nervous System Neoplasms; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

The presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone-fixed frozen sections. Results revealed that keratins 8 and 18 were present in a high number of tumors: 9 of 9 synovial sarcomas, 5 of 7 leiomyosarcomas, 5 of 5 malignant schwannomas, and 1 of 4 undifferentiated spindle cell sarcomas. In addition to keratins 8 and 18, the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19. Also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution, but desmoplakin was absent in other spindle cell sarcomas. Furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas. In contrast, keratins 7, 13, and 19 were practically absent in leiomyosarcomas, malignant schwannomas, and undifferentiated spindle cell sarcomas. The widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells, previously described in cultured transformed fibroblasts. The presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas.

Topics: Cytoskeletal Proteins; Desmoplakins; Desmosomes; Humans; Keratins; Leiomyosarcoma; Neurilemmoma; Peptides; Peripheral Nervous System Neoplasms; Sarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms

The purely epithelioid malignant peripheral nerve sheath tumor (PNST) is a rare form of PNT possibly first described by McCormack et al. in 1954. This tumor type is distinguishable from the glandular PNT and PNT with differentiated neuroepithelium (medulloepithelioma and neuroepithelioma) and differs from the ordinary epithelioid PNT because of the absence of a spindle cell component typical of malignant PNSTs. The two examples of purely epithelioid malignant PNT we describe arose in the popliteal fossa from the sciatic and tibial nerves of men with no definite evidence of von Recklinghausen's neurofibromatosis. Both tumors were partly mucinous, and so closely mimicked carcinoma and a few non-neurogenic myxoid sarcomas histologically that their final classification depended upon proof of a neural origin.

Topics: Adult; Antibodies, Monoclonal; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Myelin Sheath; Peripheral Nervous System Neoplasms; S100 Proteins