Meningeal Ewing Sarcoma/Peripheral PNET: Clinicopathological, Immunohistochemical and FISH study of four cases.

Meningeal Ewing Sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) is a rare diagnostically challenging small round cell tumor in the CNS. This study investigates the clinical pathological features of four cases of this tumor from archives of 6 years in our hospital. Patients were within the median age of 21.5 years and male to female ratio was 1:1. The tumors distributed at the supra-tentorial location, posterior fossa and lumbar vertebral canal, usually presenting as the dura-sited nodule or having close connection with the meninges within the cranium or vertebral canal. Histopathologically, small round undifferentiated tumor cells with hypercellularities, scant cytoplasm and inconspicuous nucleoli were observed, although some components such as atypical larger vesicular nuclei, prominent nucleoli of tumor cells, necrotic foci and mesenchymal collagen proliferation forming the lobular structure, were also appreciated. Immunohistochemally, tumor cells displayed membranous positivity of CD99 (4/4), nuclear positivity of FLI-1 (4/4) and NKX2.2 (4/4), negativity of EMA, GFAP and synaptophysin expression. The histochemical PAS staining showed weak positivity in one case. Fluorescence in situ hybridization (FISH) test using EWSR1 (22q12) dual color break apart rearrangement probe showed positive results in two cases. Results suggest that using a panel of immunohistochemical markers, including NKX2.2, CD99, FLI-1, EMA, GFAP and synaptophysin, combined with the supplementary EWSR1 FISH test, helps to define the diagnosis of meningeal ES/pPNET of CNS.

Immunohistochemical detection of FLI-1 protein expression in Ewing Sarcoma/ peripheral primitive neuroectodermal tumour: A study of 50 cases.

OBJECTIVE: To determine friend leukaemia integration 1 transcription factor protein expression in cases of Ewing sarcoma. METHODS: This retrospective, descriptive study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, and comprised data of diagnosed cases of Ewing sarcoma related to the period from February 2013 to December 2014. Clinico-pathological features, including patient age, gender and site of biopsy were studied. Positivity of immunohistochemical markers such as cluster of differentiation 99(membranous staining) and Friend leukaemia integration 1 transcription factor (nuclear staining) were noted. SPSS17 was used for data analysis. RESULTS: Of the 50 Ewing sarcoma cases, 26(52%) related to women and 24(48%) to men. The overall mean age was 17+11.53 years (range: 3 to 42 years). Moreover, 30(60%) patients had presented with bone swelling or growth whereas 20(40%) had presented with soft tissue swelling. The site of presentation was upper extremities in 16(32%) patients, lower extremities in 14(28%), maxilla in 7(14%), chest wall in 6(12%), paraspinal region in 4(8%), scalp in 2(4%) and retroperitoneum in 1(2%). Membranous positivity for cluster of differentiation 99 was seen in 48(98%) cases. Nuclear positivity for Friend leukaemia integration 1 transcription factor was seen in 39(78%) cases. CONCLUSIONS: Friend leukaemia integration 1 transcription factor was found to be a useful marker in diagnosing Ewing sarcoma/peripheral primitive neuroectodermal tumour. However, its positivity was more dependable when it was used in combination with other markers such as cluster of differentiation 99.

[Small cell malignant tumors of bone: comparison between diagnosis using core needle biopsies and surgical specimens].

OBJECTIVE: To compare the pathologic diagnosis and immunohistochemistry of small cell malignant tumors (SCMT) of bone using both core needle biopsy and surgical specimen. METHODS: Seventy-seven cases of SCMT with core needle biopsies and surgical specimens available were respectively analyzed by histologic examination and immunohistochemical study, with literature review. RESULTS: The male-to-female ratio was 48:29. The age of the patients ranged from 6 to 73 years. The tumors studied included Ewing sarcoma/PNET (n = 38), myeloma (n = 23), lymphoma (n = 10), small cell osteosarcoma (n = 2), small cell carcinoma (n = 2) and mesenchymal chondrosarcoma (n = 2). The tumors involved limbs, axial skeleton and flat bones. Microscopically, the tumors shared similar histology, with small round cells and spindly cells arranged in diffuse sheets. The pathologic diagnosis by core needle biopsies correlated with that by surgical specimens in 84.4% (65/77) of the cases. CONCLUSIONS: SCMT represents a heterogeneous group of malignancy. Correlations with clinicoradiologic findings and application of ancillary investigations including immunohistochemistry and molecular study are important for definitive diagnosis. Pathologic diagnosis using core needle biopsies shows good results and provides useful information for surgical planning.

Primary pulmonary primitive neuroectodermal tumor (PNET): a clinicopathological and immunohistochemical study of six cases.

BACKGROUND: The clinicopathological and immunohistochemical features of six primary pulmonary primitive neuroectodermal tumors (PNETs) are reported. METHODS: The patients were four men and two women aged 22-56 years (mean = 32.3 years). The main presenting symptoms included chest pain, shortness of breath, and cough. The tumor size ranged from 4 to 9.6 cm. RESULTS: Macroscopically, the tumors were circumscribed, yellow-white in color, and of soft and friable consistency. Histologically, the lesions were composed of a monomorphic population of solidly packed round cells with a round-to-ovoid nucleus, fine chromatin, small nucleoli, and scanty pale cytoplasm. Immunohistochemically, the tumor cells were uniformly positive for CD99, neuron-specific enolase, and vimentin, and single cases focally expressed cytokeratin and S100. Fluorescence in situ hybridization analysis performed in two cases showed positive rearrangement for the EWSR1 gene at the 22q12 locus. Follow-up information available for four patients showed that three had died 24-54 months after diagnosis and one patient is alive 11 months after diagnosis. Two patients were lost to follow-up. CONCLUSION: Primary PNETs of the lung are rare tumors that need to be added to the differential diagnosis of primary pulmonary neoplasms composed of small cells. Awareness of this entity as a primary pulmonary neoplasm is required in order to avoid misdiagnosis and unsuitable treatment of patients.

Ewing sarcoma/primitive neuroectodermal tumor of the kidney: clinicopathologic analysis of 34 cases.

The present study describes the clinicopathologic analysis of 34 cases of Ewing sarcoma/primitive neuroectodermal tumor occurring in the kidney. The patients were 21 males and 13 females with an age range of 6 to 44 years. Clinically, patients presented with multiple symptoms including hematuria, pain, and/or lump in the abdomen. Nephrectomy was performed in most of the cases. Grossly, whole of the renal parenchyma was involved by a variegated tumor. Histologically, the tumor was composed of monomorphic, small, and round cells arranged in a variety of patterns. Rosettes, geographical areas of necrosis, and arborizing vascular pattern were the prominent histologic features. The nucleus was monomorphic and round. Anisonucleosis was also noted in some cases. The nucleus was mostly hyperchromatic. A mixture of hyperchromatic and powdery chromatin was noted in few cases. Immunohistochemically, MIC2 (CD99) was positive in 32 of 34 cases followed by neuron-specific enolase (9/12 cases), vimentin (8/14 cases), synaptophysin (1/8 cases), and S-100 protein (1/4 cases). Molecular analysis by reverse transcriptase-polymerase chain reaction that was carried out in 26 cases revealed presence of EWS-FLI-1 type 1 translocation in 12 cases, EWS-FLI-1 type 2 translocation in 10 cases, and both type 1 and type 2 EWS-FLI-1 translocation in 2 cases. Two cases did not demonstrate any translocation. Follow-up data were available for 17 of 34 cases. Local recurrence of the tumor was seen in 4 patients, and 10 patients were recorded to have distant metastasis in various organs, such as lung, bone, and lymph node, during the course of the disease.

[Primitive neuroectodermal tumor in female genital tract: a clinicopathologic study].

OBJECTIVE: To study the clinicopathologic features of primitive neuroectodermal tumor (PNET) in female genital tract. METHODS: Six cases of PNET arising in female genital tract were retrospectively reviewed. The clinicopathologic features, immunohistochemical findings and EWS gene translocation study results were analyzed. RESULTS: The age of patients ranged from 10 to 27 years (mean = 20 years). The sites of involvement included ovary (1 case), uterus (1 case), vulva (2 cases) and vagina (2 cases). The greatest diameter of the tumor ranged from 2 to 10 cm (mean = 5.4 cm). The tumor had nodular appearance and showed grayish-pink fleshy cut surface, accompanied by foci of hemorrhage and necrosis. Histologically, the tumor was composed of malignant small round cells with indistinct cell borders, hyperchromatic nuclei, dense chromatin, tiny nucleoli and scanty cytoplasm. The tumor cells were arranged in sheets or lobules. Homer-Wright rosettes were identified in 1 case. Immunohistochemical study showed that the tumor cells were positive for CD99, FLI-1 and CD56 (6/6). Focal expression of vimentin (5/6), NSE (5/6), nestin (4/6), synaptophysin (4/6), S-100 protein (2/6) and chromogranin A (1/6) was also demonstrated. EWS gene translocation was detected in 5 cases studied. Follow-up information was available in 2 patients (7 and 17 months of follow up, respectively). One of them died of tumor metastasis 17 months after diagnosis. The other patient was still alive. CONCLUSIONS: PNET arising in female genital tract is rare. It mainly involves ovary, uterus, vulva and vagina. Immunohistochemical study using a panel of antibodies and fluorescence in-situ hybridization play an important role in definitive diagnosis of this rare malignancy.

CD34 and microtubule-associated protein 2 expression in dysembryoplastic neuroepithelial tumours with an emphasis on dual expression in non-specific types.

AIMS: Three histological variants of dysembryoplastic neuroepithelial tumour (DNT) have been described, namely, simple, complex and non-specific. However, the concept of non-specific variants of DNT remains controversial, because they cannot be accurately distinguished by histological findings alone from ordinary gliomas. The aim was to characterize further the non-specific histological forms of DNT. METHODS AND RESULTS: Forty-one DNTs classified as three histological forms were investigated with CD34 and microtubule-associated protein 2 (MAP2) immunohistochemistry. CD34 immunoreactivity was more frequently observed in non-specific DNT types (16/18 cases; 88.9%) than in classic types (6/23 cases; 26.1%) (P < 0.001). Peritumoral CD34 expression of non-neoplastic cells was significantly associated with CD34-positive tumours (20/22 cases; 90.9%) than with CD34-negative tumours (3/19 cases; 15.8%) (P < 0.001). MAP2 positivity in oligodendroglia-like cells or glial elements was significantly different between classic types and non-specific types (P = 0.025). CD34 and MAP2 immunoreactivities were significantly more frequent in non-specific types (83.3%) than in simple (10%) and complex forms (30.8%) (P < 0.001). CONCLUSIONS: Non-specific DNTs are glioneuronal tumours that have a heterogeneous population of cells with more immature neuronal and glial phenotypes. Furthermore, with regard to practical implications, combined analysis of CD34 and MAP2 is useful in distinguishing DNTs from particularly diagnostically challenging mimics.

Giant extraosseous Ewing sarcoma of the lung in a young adolescent female--a case report.

Extraosseous Ewing sarcoma is a rare soft tissue tumour that is histologically indistinguishable from the bone Ewing sarcoma. The translocation involving chromosome 22 along with CD 99 expression is pathognomonic and is useful in differentiating from other small round cell tumours. Primary lung involvement by this malignant tumour is very uncommon and up to this date only ten cases have been reported. We report a further case in a 15 year-old-female who presented with a huge lung mass causing an opaque haemithorax.

[Expression of FLI-1 and analysis of prognostic factors in primitive neuroectodermal tumor].

OBJECTIVE: To observe the expression of FLI-1 in primitive neuroectodermal tumors (PNET), explore the value of immunohistochemical staining of FLI-1 in combination with other neural markers in diagnosis of PNET, and analyze the prognostic factors in PNET patients. METHODS: 35 cases of PNET, of which 33 cases with complete clinical data, were included in this study. Immmunohistochemistry (The En Vision method) was applied to detect the expression of FLI-1, CD99, Syn, NSE, S-100, NF, Vim in the tumor tissues. The clinicopathological data of 33 cases were analyzed by Cox regression. RESULTS: The positive expression rate of FLI-1 were 51.4% and that of CD99 was 88.6%. The sensitivity of FLI-1 combined with CD99 was up to 100%. The positive rates of Vim, Syn, NSE, s-100 and NF were 91.4%, 48.6%, 45.7%, 22.9% and 0, respectively. Cox regression analysis showed that the impact of primary location and treatment modality were of statistical significance (P < 0.05), but the age, sex, stage or size of tumors did not (P > 0.05). CONCLUSION: Immunohistochemical detection of FLI-1 and neural markers is a preferred method for clinical diagnosis of PNET. The main factors affecting the prognosis are the primary location of PNET and treatment modality.

Evaluating cellular impedance assays for detection of GPCR pleiotropic signaling and functional selectivity.

G-protein-coupled receptors can couple to different signal transduction pathways in different cell types (termed cell-specific signaling) and can activate different signaling pathways depending on the receptor conformation(s) stabilized by the activating ligand (functional selectivity). These concepts offer potential for developing pathway-specific drugs that increase efficacy and reduce side effects. Despite significant interest, functional selectivity has been difficult to exploit in drug discovery, in part due to the burden of multiple assays. Cellular impedance assays use an emerging technology that can qualitatively distinguish Gs, Gi/o, and Gq signaling in a single assay and is thereby suited for studying these pharmacological concepts. Cellular impedance confirmed cell-specific Gs and Gq coupling for the melanocortin-4 receptor and dual Gi and Gs signaling with the cannabinoid-1 (CB1) receptor. The balance of Gi versus Gs signaling depended on the cell line. In CB1-HEKs, Giand Gs-like responses combined to yield a novel impedance profile demonstrating the dynamic nature of these traces. Cellspecific signaling was observed with endogenous D1 receptor in U-2 cells and SK-N-MC cells, yet the pharmacological profile of partial and full agonists was similar in both cell lines. We conclude that the dynamic impedance profile encodes valuable relative signaling information and is sufficiently robust to help evaluate cell-specific signaling and functional selectivity.

Primary vulvar Ewing sarcoma/primitive neuroectodermal tumor: a report of 2 cases and review of the literature.

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) family of tumor is a very aggressive malignant round cell tumor characterized by translocations involving EWS-FLI1 genes. They are increasingly recognized in extraosseous sites as a result of improvements in diagnostic tools. In this paper, we report 2 additional cases arising in vulva of young adults who have been treated aggressively and have survived fore more than 7 and 4 years successively. Histologic examination showed small round (blue) cell morphology in both cases. The tumor cells contained glycogen and were positive for CD99 and vimentin and negative for keratins, lymphoid markers, S-100, synaptophysin, chromogranin, and desmin. Reverse transcriptase polymerase chain reaction analysis from paraffin-embedded tissue revealed EWS-FLI1 fusion product in 1 case. Collectively, 13 cases of vulvar ES/PNET have been reported in the literature. Only 8 cases have detailed follow-up information with an average follow-up data of 28 months. Ewing sarcoma/PNET should be considered in the differential diagnosis of any undifferentiated tumors involving the lower gynecologic tract and all axillary tests including molecular tests should be performed for correct diagnosis because prolonged survival is possible for this dreadful disease after complete surgical resection, followed by adjuvant therapy.

Estimation of diagnostic value of chosen markers of neural differentiation in neuroblastoma group of tumors and pPNETs.

Neuroblastoma and peripheral PNETs both are typical examples of wide group of small round blue cell tumors of childhood. Matured neuroblastoma show typical clinical presentation and easy to interpret microscopic picture. Unfortunately in everyday practice much commonly appeared less differentiated neuroblastomas with difficult to predict clinical behavior and impossible to diagnose in routine stain histologic view. Peripheral PNETs are found as morphologically similar entities to some neuroblastoma subtypes but they are treated as separate CD99 positive group of tumors with different biology and clinical behavior. The aim of our study was to estimate the usefulness of neural markers expression (Neuroblastoma Marker, neurospecyfic enolase and neurofilaments) in routine separation between neuroblastoma tumors and pPNETs and between neuroblastoma subtypes according to currently used classification of those entities. We investigated 63 tumor tissue samples and found differences in expression of investigated markers between both neuroblastoma subgroups and neuroblastoma group of tumors and pPNETs.

Intracranial peripheral-type primitive neuroectodermal tumor.

A 15-year-old man presented with headache. Magnetic resonance (MR) imaging revealed a large extraaxial tumor with cyst at the right frontotemporal region. The solid part of the tumor was homogeneously enhanced on T(1)-weighted MR imaging after injection of gadolinium. Digital subtraction angiography of the external carotid artery revealed sunburst appearance corresponding to the tumor, which was fed by the right middle meningeal artery. His headache worsened and computed tomography revealed enlargement of the tumor and intracystic hemorrhage, so emergent operation was performed. At surgery, the tumor strongly adhered to the dural membrane, and was obviously extraaxial. The tumor and cyst were gross totally removed. The attachment site at the dura mater was resected. Histological examination showed solid growth of small round cells with uniform round nuclei and minimal cytoplasm. Immunohistochemical staining showed the cells were positive for MIC-2 (CD99). The MIB-1 labeling index was 53%. The histological diagnosis was peripheral-type primitive neuroectodermal tumor (pPNET). Following surgery, radiation therapy and chemotherapy were given. Ewing's sarcoma and pPNET form a family of small round cell tumors arising in the bone or soft tissue. MIC-2 is a useful marker in the differential diagnosis. Good prognosis may be attained if complete surgical excision of intracranial pPNET is achieved.

Differential protooncogene expression characterizes histopathologically indistinguishable tumors of the peripheral nervous system.

We have found highly predictable patterns of protooncogene expression in cell lines and tumor tissue of neuroblastoma (NB), a tumor of the peripheral nervous system (PNS). These patterns make it possible to recognize two different genetically definable subgroups among histopathologically indistinguishable tumors. Additionally, we have identified a difference in neurotransmitter biosynthetic enzyme activity in these two subgroups of NB. The patterns of protooncogene expression and neurotransmitter biosynthetic enzymes suggests that these tumors arise in different cells of the PNS.

Immunohistochemistry of primary malignant neuroepithelial tumors of the kidney: a potential source of confusion? A study of 30 cases from the National Wilms Tumor Study Pathology Center.

Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET) is a rare primary tumor of the kidney with morphologic features similar to those of other primitive tumors. Previous studies have shown that these tumors frequently stain positively with immunostains against CD99 and FLI-1 and negatively with stains against WT-1, suggesting that these markers may be used for the distinction between Wilms tumor and pPNET. We present 30 cases of primary malignant neuroepithelial tumor with immunohistochemical profiles and reverse transcriptase polymerase chain reaction (RT-PCR) analysis and show that immunophenotypic overlap exists between Wilms tumor and pPNET. A subset of 30 neuroepithelial tumors from the National Wilms Tumor Study originally categorized as putative pPNETs of the kidney was stained with FLI-1, WT-1, and thyroid transcription factor-1. Bicolor fluorescence in situ hybridization studies were performed on 19 of the cases. Other data on these tumors were available from a previous study (Am J Surg Pathol 2001;25:133). Of 7 primary tumors that had the EWS/FLI-1 fusion transcript by RT-PCR, 6 exhibited strong immunopositivity for FLI-1. Nine that were negative by RT-PCR stained positively with the FLI-1 stain. Five fusion-negative cases stained with both FLI-1 and WT-1. Three fusion-negative cases were negative for FLI-1 but positive for WT-1. Five fusion-negative cases were negative for both FLI-1 and WT-1. Of the 30 cases, 29 were positive for CD99. Seven cases that were negative for the EWS-FLI-1 fusion by RT-PCR were positive by fluorescence in situ hybridization. All cases were negative for thyroid transcription factor-1. Reliance upon immunohistochemistry as the sole means of ancillary diagnosis in renal pPNET can lead to confusing results. We recommend molecular fusion studies for clarification of primitive renal tumors with unexpected immunophenotypic results.

Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS tumors but lack EWSR1 rearrangements. GFAP expression supports a morphologic impression of central PNET and is absent in Ewing sarcoma/peripheral PNET. Ewing sarcoma/peripheral PNETs lack morphologic features of CNS tumors.

p53-dependent p21 induction following gamma-irradiation without concomitant p53 induction in a human peripheral neuroepithelioma cell line.

We previously generated cell hybrids between a derivative of the E6-containing HeLa cell line and a p53 null peripheral neuroepithelioma (PNET) cell line. Although p53 protein from the hybrids was genotypically wild type, it did not demonstrate wild-type behavior. Therefore, in the present study, we introduced wild-type p53 into the PNET parent to investigate whether p53 retained wild-type function within this cell line. Although the p53 null PNET parent lacked detectable p21 protein, introduction of wild-type p53 resulted in a detectable expression of p21 protein in all clones tested, suggestive of wild-type p53 function. In addition, p53 expression was necessary for induction of p21 in response to irradiation, and, furthermore, we show this induction to occur at the transcriptional level. Although introduction of wild-type p53 seems to be responsible for p21 induction, the overall protein levels of p53 were not induced. The involvement of p53 in up-regulating p21 is further substantiated by the observation that p21 up-regulation was dependent on the introduction of the wild-type protein. Our results suggest that wild-type p53 is capable of up-regulating p21 in response to DNA damage in the absence of p53 induction.

Insulin-like growth factor I receptor-mediated circuit in Ewing's sarcoma/peripheral neuroectodermal tumor: a possible therapeutic target.

The disappointingly low survival rate observed in Ewing's sarcoma (ES)/peripheral neuroectodermal tumor (PNET) despite the adoption of aggressive multimodal treatments prompted us to study the existence of autocrine circuits to be used as innovative therapeutic targets. Of the several circuits analyzed, only the insulin-like growth factor receptor (IGF-IR)-mediated loop was found to be constantly present both in cell lines and clinical samples, suggesting a role for this autocrine circuit in the pathogenesis of ES/PNET. The in vitro inhibition of the IGF-IR-mediated circuit by the specific IGF-IR binding antibody alphaIR3 suppressed the growth of ES/PNET cells by decreasing the proliferative rate and increasing apoptosis. alphaIR3 also significantly inhibited the ability of ES/PNET cells to grow in soft agar and to migrate following a chemotactic stimulus. Inactivation of the IGF-IR signaling pathway may therefore be considered as an effective therapeutic modality for patients with ES/PNET.

Expression of the natural killer cell-associated antigens CD56 and CD57 in human neural and striated muscle cells and in their tumors.

The expression of the natural killer cell-associated antigens CD56 and CD57 which are known to show sequence homologies to the neural cell adhesion molecule N-CAM was examined immunohistochemically in normal and regenerative human neural and straited muscle cells and in their tumors using monoclonal antibodies Leu-19 and Leu-7. The pattern of expression of CD56 and CD57 in neural tissue was assessed in comparison with that of Mr 68,000 neurofilament. Dendritic interstitial cells were discriminated from neural cells by application of the pan leukocyte antigen CD53. In normal tissue, CD56 was expressed in thin nerve fibers, fine varicose and sensory nerve endings, cell membranes of ganglion cells, and fetal striated muscle cells. Thick nerve fibers, perikarya of ganglion cells, and adult striated muscle fibers were CD56 negative. In the normal state, CD57 was restricted to thick nerve fibers. Enhanced expression or reexpression of CD56 was found in regenerative neural cells which, in part, were also CD57 positive and in regenerative, CD57-negative striated muscle cells. In neural tumors, CD56 was detectable in 3 of 3 benign and 8 of 13 malignant schwannomas, 1 of 4 peripheral neuroepitheliomas, 4 of 4 ganglioneuromas, and 8 of 8 (ganglio-)neuroblastomas, whereas CD57 was restricted to one benign and one malignant schwannoma. Furthermore, CD56, but not CD57, could be found in 8 of 8 rhabdomyosarcomas. All in all, the pattern of expression of CD56 is comparable to that of N-CAM. CD57 exhibits a very restricted binding pattern which, in most instances, is complementary to that of CD56. The absence of CD56 in some neural tumors might reflect alterations in cell-cell interactions. Its reexpression in regenerative striated muscle cells and in rhabdomyosarcomas suggests a role of CD56 as an oncodevelopmental antigen.