Primitive neuroectodermal tumor of the kidney.

We report a 21-year-old man with a primitive neuroectodermal tumor (PNET) of the kidney that was difficult to distinguish from other small round cell tumors, e.g., small cell carcinoma, malignant lymphoma, and Wilms' tumor. Pathologically, a primitive rosette-like pattern was shown by H&E staining; expression of MIC-2 was indicated by an immunohistochemical test; rather primitive organelles were observed by an ultrastructural method; and translocation of chromosome 22 was confirmed by FISH. We therefore diagnosed the current case as PNET. The patient had undergone a right radical nephrectomy more than 1.5 years earlier. After neither metastases nor recurrences for 0.5 year, imaging examinations revealed masses in his liver. He received chemotherapy and underwent surgery again, but the masses were not composed of viable tumor cells. PNET of the kidney is extremely rare; fewer than 30 cases have been reported in the English literature, and there are few data on the expression of p53, ki67, and bcl2. We investigated the relationships between these markers in the current case using immunohistochemical tests and observed strong expression of p53, Ki-67, and bcl-2. Such results generally indicate poor prognosis, and the patient eventually had some masses in his liver, but no viable tumor cells were found. The prognostic significance of these various markers in PNET of the kidney still remains unclear, but p53, ki-67, and bcl-2 might not be so important as indicators of prognosis in the kidneys as they are in other organs. Further studies are needed to investigate this, and we hope that the patient recovers completely.

Ependymoblastomatous exencephaly: a unique fetal malformation.

Exencephaly/anencephaly is a rare neural tube defect occurring early in embryogenesis. We report a 14-week-old fetus with exencephaly in whom central nervous system tissue was developed and preserved. There were 2 symmetrical structures grossly resembling cerebral hemispheres, which on histologic and ultrastructural study, consisted of a combination of ependymoblastomatous rosettes and canals and primitive neural tissue. The brainstem and spinal cord were partially normally formed, although descending tracts were not apparent. No cerebellar tissue was found. The eyes were formed. This appears to represent a rare example of exencephaly not covered by skin, which did not undergo necrosis and early transformation into a residual area cerebrovasculosa, characteristic of anencephaly. It may be appropriate to regard this as a unique neural tube closure defect that might be termed "ependymoblastomatous exencephaly."

Unique cellular features of peripheral primitive neuroectodermal tumor: ultrastructural evidence of its unique cytodifferentiation.

We present a case of primitive neuroectodermal tumor (PNET) showing a unique differentiation phenotype based on ultrastructural observation. Rapidly growing tumor involving the retroperitoneum of a 68-year-old woman was characterized by histological findings including proliferation of diffuse poorly differentiated small round cells with scattered rosette formation similar to Homer-Wright type and by the ultrastructure demonstrating cytoplasmic neurosecretary granules and short cytoplasmic cilial structures. These cells revealed immunoreactivity only with neuron-specific enolase (NSE). We also observed a chromosomal translocation, t (11; 22) (q24; q12), which is an identical recurrent alteration found in the neoplastic cells in the spectrum of PNETs. These findings may support the explanation that tumor cells observed in our case shared phenotypes of both neuronal and ependymal cell lineages and give a unique insight suggesting the possible histogenesis of PNETs.

Primitive neuroectodermal tumor of the kidney. Report of a case initially diagnosed by fine needle aspiration cytology.

BACKGROUND: Primitive neuroectodermal tumor (PNET) is a malignant small round cell tumor that exhibits neuroepithelial differentiation, most often presenting as a bone or soft tissue mass in the trunk or axial skeleton in adolescents and young adults. Isolated cases of PNET have been observed at visceral sites, such as the ovary, testis, uterus, bladder and pancreas. We present a case of PNET in the kidney initially diagnosed by fine needle aspiration (FNA). CASE: A 21-year-old woman presented with microhematuria. Urine cytology was negative for malignant cells. Physical examination was without abnormal findings. Computerized tomography revealed a partially cystic tumor in the left kidney. FNA showed monotonous-appearing small round tumor cells with occasional rosette formation. The differential diagnoses include other primitive small round cell tumors. The tumor cells were immunoreactive for neuron specific enolase and O13 (CD99). A cytologic diagnosis of PNET was suggested and subsequently confirmed on histopathology. CONCLUSION: To our knowledge, this is the first description of PNET of the kidney initially diagnosed by FNA. This nerve tumor must be included in the differential diagnosis of small cell malignant tumors of the kidney and adjacent organs.

Atypical neuronal-glial tumors of cerebral hemispheres in adults with PNET-like component: clinicopathological features of 5 cases.

We investigated 5 cases with brain tumors composed ofneuronal and astrocytic differentiated tumor cells occurring in the cerebral hemispheres of adults. Patients ranged from 33 - 69 years of age, 3 females and 2 males. Radiologically, contrast enhancement was demonstrated in these tumors. All tumors were surgically resected following radiotherapy and chemotherapy. Four patients have been free of recurrence for 2-5 years. One recurred 15 years after the operation. Histologically, tumor cells were mainly composed of round or oval nucleate cells with scant cytoplasm and compactly arranged with neurocytic features. Immunohistochemically, some tumor cells were immunoreactive for synaptophysin, neurofilament, beta-tubulin, chromogranin A, GFAP and vimentin. There were little immunoreactive cells for myelin basic protein and epithelial membrane antigen. Ultrastructurally, tumor cells were variably differentiated as follows: undifferentiated cells having prominent nuclei and scanty cytoplasm with inconspicuous organelles; neuronal cells consisting of neurosecretory granules or vesicles and abortive synapses, and astrocytic cells with cytoplasmic intermediate filaments. The Ki-67 labeling index ranged from 4.5 - 9.8%. Allelic loss of chromosome Ip occurred in 2 cases (50%) and allelic loss of chromosome 19q occurred in 2 cases (50%) of 4 informative cases. These tumors were characterized as neuronal and astrocytic differentiated tumors with primitive PNET-like component. However, there was little oligodendrocytic or ependymal differentiation in these tumors.

Immunohistochemical and ultrastructural investigation of neural differentiation in Ewing sarcoma/PNET of bone and soft tissues.

The authors evaluated the role of immunohistochemistry and electron microscopy in defining neural differentiation in 28 cases of Ewing sarcoma/PNET. The panel of primary antibodies used included vimentin, MIC-2, NSE, S-100 protein, leu7, neurofilaments, GFAP, and chromogranin A. Cases were considered undifferentiated when neural markers were absent, poorly differentiated if one neural marker was present, and well differentiated if two or more markers were observed. Cases were also evaluated for the presence of cytoplasmic processes, microtubules, and neurosecretory granules as ultrastructural features of neural differentiation: the tumor was classified as well differentiated if two of these features were present; and poorly differentiated if one was evident; all other cases were considered undifferentiated. According to immunohistochemistry, 10 cases (35.7%) were undifferentiated, 12 cases (42.9%) were poorly differentiated, and 6 (21.4%) were well differentiated. According to the ultrastructural analysis, 10 tumors were undifferentiated (35.7%), 14 poorly differentiated (50%), and 4 well differentiated (14.3%). The overall concordance between the two techniques was low (35.7%), and both modalities were concordant in classifying only 1 well-differentiated, 5 poorly differentiated, and 4 undifferentiated tumors. In conclusion, the authors suggest that investigations devoted to test the prognostic significance of neural differentiation in these neoplasms should employ both immunohistochemistry and electron microscopy, separately and in combination, to assess what is the most effective choice for predicting the clinical course.

Cerebral primitive neuroectodermal tumor in an adult male. A case report.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) are very rare. Malignant tumors of the cerebrum in young individuals are composed predominantly of undifferentiated cells, with moderate differentiation along either neuronal or glial lines. To our knowledge, cerebral PNETs in adults are extraordinarily rare and have been reported in only 11 cases, with little cytologic documentation in the literature. The cytopathologic, immunohistochemical and ultrastructural features of cerebral PNET arising in an adult male are presented. CASE: A cystic tumor, on computed tomography and magnetic resonance imaging, arose from the left frontal lobe in a 39-year-old man and contained histopathologic features of PNET. Specimens obtained from surgery revealed the presence of an undifferentiated type of PNET with moderate neuronal and glial differentiation and mild characteristic findings of peripheral PNET. The cytologic and histologic specimens showed evidence of a scattered pattern of blastic and undifferentiated tumor cells and a neural arrangement with Homer-Wright-like rosettes. Immunohistochemically, the tumor cells were glial fibrillary acidic protein, neuron-specific enolase, synaptophysin and CD-99 positive and epithelial membrane antigen, S-100 protein and vimentin negative. Ultrastructurally, neither microtubular structures nor intermediate filaments, except neurosecretory granules, were found in the tumor cells. CONCLUSION: Both immunohistochemical and ultrastructural studies on cytologic and histologic slides were important for the diagnosis of PNET because of establishing not only undifferentiated tumor cells but also neural and glial differentiation.

EWS/ETS fusion genes induce epithelial and neuroectodermal differentiation in NIH 3T3 fibroblasts.

Ewing's sarcoma is the least differentiated member of the peripheral primitive neuroectodermal (pPNET) tumor family. Chromosomal translocations involving the EWS gene and five different Ets family transcription factor genes create fusion genes encoding aberrant transcription factors and are implicated in the vast majority of Ewing's sarcoma cases. Here, NIH 3T3 fibroblasts were infected with control (tk-neo or RAS) and two different EWS/ETS-expressing retroviruses. In vitro studies of established polyclonal lines expressing the two EWS/ETS genes, either EWS/FLI1 or EWS/ETV1, showed induction of cytokeratin 15 gene expression. Both fusion genes also caused characteristic gross morphologic, histologic, and ultrastructural changes in NIH 3T3 cells when transformed cell lines were injected into CB-17-scid mice. Native NIH 3T3 cells with a spindled cell morphology were converted to polygonal cells with high nucleo-cytoplasmic ratios that continued to express abundant cytokeratin. Extracellular collagen deposition was abolished, rough endoplasmic reticulum was markedly diminished, and rudimentary cell-cell attachments appeared. Most strikingly, neurosecretory-type dense core granules like those seen in pPNET were now evident. This murine model, created in mesenchyme-derived NIH 3T3 cells, demonstrated new characteristics of both neuroectodermal and epithelial differentiation and resembled small round cell tumors microscopically.

Ovarian small cell tumors: an electron microscopic review.

Small cell tumors of the ovary are uncommon but represent an important group to recognize in the differential diagnosis of primary and metastatic ovarian neoplasms. In some cases the correct diagnosis cannot be confidently made on the basis of clinical setting, routine light microscopy, and immunohistochemistry, and electron microscopy may be supportive or definitive in establishing cell type. The cell type is often important in choosing optimal therapy and in predicting prognosis. The authors performed electron microscopy on a moderate number of ovarian small cell tumors and here describe and illustrate the diagnostic features of representative examples of various types. The ultrastructural features of the metastatic tumors, such as embryonal rhabdomyosarcoma, neuroblastoma, and melanoma, are identical to those of their respective primary tumors, are well known, and usually pose no problem in diagnosis. On the other hand, the ultrastructural features of some primary ovarian small cell tumors may present a more difficult differential diagnosis, because they have features that are subtle and/or in common. Exemplary of tumors in this category are diffuse adult granulosa cell tumor, endometrial stromal sarcoma, and small cell carcinomas of the hypercalcemic and pulmonary (oat cell) types. Distinguishing among them may be difficult but is possible, and electron microscopy may be a valuable supplement to the diagnostic information obtained from the clinical presentation, light microscopy, immunohistochemistry and, in some tumors, cytometric analysis of these neoplasms.

Primary endocervical extraosseous Ewing's sarcoma/PNET.

A 36-year-old woman presented with intermenstrual spotting and was found to have a cystic mass involving the uterine cervix on a pelvic ultrasound examination. A necrotic and hemorrhagic tumor was excised by hysterectomy and processed for light and electron microscopic investigation and molecular analysis. Microscopic examination revealed a small round cell tumor that immunohistochemical studies (including staining for the highly restricted surface antigen p30/32MIC2) and ultrastructural studies indicated was an extraosseous Ewing's sarcoma (EES)/primitive neuroectodermal tumor (PNET). This diagnosis was established by detection of EWS/ERG fusion transcript through reverse transcription polymerase chain reaction (RT-PCR) with nested primers. Full body computed tomography failed to detect any extrauterine tumor, and the patient is clinically free of disease 18 months after hysterectomy. This case represents the first report of a primary EES/PNET arising in the uterine cervix.

An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript.

We report an intra-abdominal round cell tumor in a young man which exhibited the light and electron microscopic appearance of a peripheral primitive neuroectodermal tumor (PNET), in addition to the clinical and topographic characteristics, desmoplasia and a complex immunophenotypic profile of the intra-abdominal desmoplastic round cell tumor (DSRCT). Reverse transcription polymerase chain reaction revealed a EWS/FLI-1 fusion transcript as in PNET/Ewing's sarcoma, instead of the EWS/WT1 transcript of DSRCT. The tumor was also strongly positive for the mic2 protein. This is a unique case of a hybrid tumor arising in the peritoneal cavity of a young male. The existence of such a hybrid tumor in this location suggests that DSRCT and PNET may be related and possibly share a common histogenesis.

Unique intracerebral tumor with divergent differentiation in a patient presenting as NF2: report of a case with features of astrocytoma, ependymoma, and PNET.

Patients with neurofibromatosis 2 (NF2) are predisposed to a variety of neoplastic and dysplastic lesions, including schwannomas, neurofibromas, meningiomas, astrocytomas, and ependymomas, as well as entities such as meningioangiomatosis, schwannosis, and hamartomas. This study reports a unique intracerebral frontotemporal tumor in a 6-year-old boy with presumed NF2, on the basis of bilateral cerebellopontine tumors consistent with acoustic neuromas. The intracerebral tumor revealed a variety of histological patterns, including foci of primitive neuroectodermal tumor (PNET), low-grade astrocytoma and ependymoma, as well as neuroepithelial rests with immature ganglion cells and hamartomatous areas. The MIB-1 labeling index ranged from 63% in the foci of PNET to 4-7% in other foci. The PNET component revealed immunopositivity for synaptophysin and neurofilament and showed cells with delicate intercellular junctions, profiles of rough endoplasmic reticulum, mitochondria, and dense core granules, and cell processes with microtubules and neurofilaments. The glial and ependymal components showed bundles of glial filaments and prominent cell junctions, cilia, and microvilli. The hamartomatous component also included aggregates of cells with hyaline eosinophilic cytoplasm. By EM these cells contained abundant amorphous flocculent material. This constellation of pathologic findings, especially the finding of PNET, is unique and not previously reported in the setting of NF2.

Primitive neuroectodermal tumor of the myocardium: a case report, review of the literature, immunohistochemical, and ultrastructural study.

We report the case of a primitive neuroectodermal tumor (PNET) arising in the heart of a 63-year-old man. The neuroectodermal nature of this tumor was confirmed by the immunohistochemical positivity for O13 (CD99) (the P30/32MIC2 gene product) neuron specific enolase (monoclonal and polyclonal), synaptophysin and vimentin. Other markers, such as actin, desmin, myoglobin, chromogranin, keratin, and leukocyte common antigen were negative. The diagnosis was made on an endomyocardial biopsy and was confirmed in sections from the myocardial tumor found within the heart excised during cardiac transplant. Primitive neuroectodermal tumors have been reported in a variety of sites, most commonly in the extremities. No case has ever been reported within the myocardium, although one has been reported in the pericardium. In addition to morphological similarities, PNET and extraskeletal Ewing's sarcoma have been shown to possess the same chromosomal translocation, t11;22, and the same cell surface antigen, P 30/32. Separation of this case from extraskeletal Ewing's sarcoma was possible because of the absence of PAS positivity, as well as the immunohistochemical positivity for at least two neural markers, as extraskeletal Ewing's sarcoma is only positive for neuron specific enolase.

Contribution of transmission electron microscopy to fine-needle aspiration biopsy diagnosis: comparison of cytology and combined cytology and transmission electron microscopy with final histological diagnosis.

This report evaluates 74 fine-needle aspiration biopsies processed for transmission electron microscopy with subsequent surgical procedure. The specificity of diagnosis obtained by cytology alone was compared to that obtained by cytology and electro microscopy, using histologic diagnosis as the gold standard. When cytology gave a diagnosis of malignancy but could not give tumor category or type, electron microscopy could correctly give both. When cytology could give tumor category but not type, electron microscopy correctly identified type in the majority of cases. When cytology gave tumor category and type, electron microscopy confirmed the diagnosis. Transmission electron microscopy is very helpful when the cytopathologist can diagnose malignancy but cannot give tumor category and/or type. When the cytopathologist is specific in his/her diagnosis, TEM is not as helpful.

Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone.

Small round cell tumors (SRCTs) of the bone make up a family of primary bone sarcomas with morphologically, biologically, and clinically specific features. Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties such as atypical ES, large cell ES, and ES with neuroectodermal differentiation (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of the bone) have been identified recently. Histology and electron microscopy together with the variable expression of several epitopes (as shown by immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for characterizing the group within the context of neuroectodermal-derived neoplasms. A number of other ES-like tumors with small round cells, mimicking those previously described, have been characterized; Askin's tumor of the thoracopulmonary region will be considered as an ES similar to those already described, but within a particularly anatomic location. On the other hand, the presence of an endothelial appearance within a poorly differentiated neoplasm may be present in some ES-like SRCTs (atypical ES with endothelial features). The differential diagnosis with other sarcomas defined by small round to spindle cell contours might prove difficult. Particular attention must be paid to small cell osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of bone" is considered in this study because it is a very rare neoplasm differing from the formerly discussed types; its pluripotentiality provides this tumor a blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's lymphoma is an unusual presentation when primary to the bone, previous to any other anatomic location. Several subtypes have been considered within a histology that encompasses that seen in lymph nodes.