What's in a name? Intracranial peripheral primitive neuroectodermal tumors and CNS primitive neuroectodermal tumors are not the same.

BACKGROUND: Intracranial peripheral primitive neuroectodermal tumors (P-PNET) are extremely rare. They can be easily misdiagnosed as central nervous system primitive neuroectodermal tumors (CNS-PNET) or meningiomas. Little is known about the optimal treatment and prognosis of these tumors. PATIENTS AND METHODS: We evaluated the treatment and outcome of 17 patients with intracranial, nonmetastatic, genetically confirmed P-PNET. Three patients were treated at our institutions. Thirteen other cases providing sufficient treatment and follow-up information were extracted from the literature. RESULTS: The median age at diagnosis was 17 years. All patients underwent initial surgery. Complete resection was achieved in 9 of the 17 cases (53 %). Combined adjuvant treatment consisting of radiotherapy (focal, n = 10; craniospinal, n = 1) and chemotherapy was administered to 11 of the 17 patients (59 %). The median follow-up time was 1.4 years. In 8 of the 17 patients (47 %), the disease progressed; 4 of the 17 patients (24 %) died. The 2-year progression-free and overall survival rates were 64 % and 76 %, respectively. CONCLUSION: The differential diagnosis for intracranial, meningeal-based, small, round-cell tumors should include P-PNET. It is highly probable that complete resection has a positive impact on survival--as previously reported for extracranial P-PNET--but this cannot be shown by our data. Intensive adjuvant treatment consisting of radiotherapy and chemotherapy seems to be essential. A statistically grounded recommendation for the appropriate target volume and radiation dose is not yet possible. However, in most case reports of primary intracranial P-PNET published to date, patients were treated with focal irradiation. The optimal chemotherapy regimen has yet to be established, with both the Ewing tumor and CNS-PNET protocols being promising candidates for effective treatment.

Primary Ewing's sarcoma/primitive neuroectodermal tumor of the vagina in a 54-year-old woman: a case report.

BACKGROUND: Ewing's sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the genital tract of women is uncommon. Presentation in vagina is exceedingly rare. CASE: A 54-year-old Chinese woman presented with complaints of vaginal bleeding with fragmented bits occasionally. Physical examination revealed two nodules about 4 cm × 3 cm in the vagina. The immunohistochemical stains revealed a rare presentation of a primitive neuroectodermal tumor. The patient was treated with whole-pelvis external beam radiation, vaginal cylinder intracavitary brachytherapy, intracavitary afterloading radiotherapy and bilateral groin area radiotherapy. She died of clinical recurrence after 18 months of treatment. CONCLUSION: This is the oldest but virgin case, treated with radiation completely, of primitive neuroectodermal tumor located in the vagina reported in the literature.

Outcome of multidisciplinary treatment of peripheral primitive neuroectodermal tumor.

Peripheral primitive neuroectodermal tumors (PNETs) constitute very rare and aggressive malignancies. To date, there are no standard guidelines for management of peripheral PNETs due to the paucity of cases arising in various body sites. Therapeutic approach is derived from Ewing sarcoma family, which currently remains multimodal. Our study retrospectively analyzed 86 PNET patients from February 1, 1998 to February 1, 2018 at Peking Union Medical College Hospital with an additional 75 patients from review of literature. The clinicopathologic and treatment plans associated with survival was investigated. Surgery, chemotherapy, female sex, small tumor size, no lymph node metastasis, R0 surgical resection, (vincristine + doxorubicin + cyclophosphamide)/(isophosphamide + etoposide) regimen, and more than 10 cycles of chemotherapy were associated with improved overall survival in univariate analysis. Surgery, more than 10 cycles of chemotherapy, and small tumor size were independent prognostic factors for higher overall survival. Our data indicates that multimodal therapy is the mainstay therapeutic approach for peripheral PNET.

Multimodality treatment approach in management of primary peripheral primitive neuroectodermal tumor of the orbit.

Primitive neuroectodermal tumor is a small round cell malignancy which rarely involves the orbit. We report a case of a two-year old male child presenting as unilateral eccentric proptosis with extraconal and intraconal mass, diagnosed as primary peripheral primitive neuroectodermal tumor (pPPNET) on histopathology and immunohistochemistry. There is no defined consensus in the management of these tumors due to its rare presentation. We describe its distinguishing features with emphasis on multimodal and aggressive treatment approach which ensures appropriate management of these cases.

Ewing's sarcoma and primitive neuroectodermal tumour in adults: single-centre experience in The Netherlands.

BACKGROUND: Ewing's sarcoma and peripheral primitive neuroectodermal tumours (PNET) are rare tumours and closely related. They occur most often in children and adolescents. Few studies have been published on treatment outcome in adult patients. METHODS: We performed a retrospective analysis of patients aged >16 years who were primarily treated at our university hospital for Ewing's sarcoma or PNET. In general, treatment consisted of long-term multiagent chemotherapy, interrupted by individualised local treatment consisting of surgery and/or radiotherapy. We reviewed clinical features and outcomes to present our experience with Ewing's sarcoma and PNET in adults. RESULTS: From 1979 to 2002, 27 patients with Ewing's sarcoma (20) or PNET (7) were treated. There were 22 men and 5 women, with a median age of 25 years (range 17-49). Ten patients presented with metastases predominantly in lungs (4) or bones (6). Combination therapy consisted of chemotherapy (27), surgery (16) and radiotherapy (16). After a median follow-up of ten years, 14 patients have died (toxicity = 2, progressive disease = 12) and 13 patients are alive and free of disease. Five-year overall survival was 58%. All four patients with bone metastases died, while all five patients presenting with lung metastases are disease-free. CONCLUSION: The five-year overall survival of 58% in this small series on adult patients is in line with paediatric study outcomes. Patients with lung metastases may even be cured by multimodality therapy. We therefore strongly advocate referral of patients with this rare disease to a specialised oncology centre.

Primitive neuroectodermal tumour of the cervix: a rare diagnosis.

A 48-year-old woman presented with symptoms of lower abdominal pain and vaginal discharge for 6 months. Clinical examination and pelvic ultrasound scan suggested a diagnosis of infected Gartner's cyst, for which she underwent vaginal cystectomy. However, histopathology and immunohistochemistry revealed a diagnosis of primitive neuroectodermal tumour of the cervix. Further investigations revealed the stage to be FIGO IIIB, which was inoperable. She received neoadjuvant chemotherapy (vincristine, adriamycin, cyclophosphamide alternating with ifosfamide, cisplatin and etoposide, every 21 days), but the tumour did not respond to treatment and she was started on radiotherapy with definitive intent (55.8 Gray in 31 fractions over 6.2 weeks). A PET-CT performed 2 months after completion of radiotherapy showed complete response, and she is now receiving adjuvant chemotherapy.

Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group.

PURPOSE: To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. PATIENTS AND METHODS: Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. RESULTS: Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. CONCLUSION: Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.

L1-CAM knock-down radiosensitizes neuroblastoma IMR-32 cells by simultaneously decreasing MycN, but increasing PTEN protein expression.

Childhood neuroblastoma is one of the most malignant types of cancers leading to a high mortality rate. These cancerous cells can be highly metastatic and malignant giving rise to disease recurrence and poor prognosis. The proto-oncogene myelocytomatosis neuroblastoma (MycN) is known to be amplified in this type of cancer, thus, promoting high malignancy and resistance. The L1 cell adhesion molecule (L1-CAM) cleavage has been found upregulated in many types of malignant cancers. In the present study, we explored the interplay between L1-CAM, MycN and PTEN as well as the role played by PDGFR and VEGFR on tumorigenicity in neuroblastoma cells. We investigated the effect of L1-CAM knock-down (KD) and PDGFR/VEGFR inhibition with sunitinib malate (Sutent®) treatment on subsequent tumorsphere formation and cellular proliferation and migration in the MycN-amplified IMR-32 neuroblastoma cells. We further examined the effect of combined L1-CAM KD with Sutent treatment or radiotherapy on these cellular functions in our cells. Tumorsphere formation is one of the indicators of aggressiveness in malignant cancers, which was significantly inhibited in IMR-32 cells after L1-CAM KD or Sutent treatment, however, no synergistic effect was observed with dual treatments, rather L1-CAM KD alone showed a greater inhibition on tumorsphere formation compared to Sutent treatment alone. In addition, cellular proliferation and migration were significantly inhibited after L1-CAM KD in the IMR-32 cells with no synergistic effect observed on the rate of cell proliferation when combined with Sutent treatment. Again, L1-CAM KD alone exhibited greater inhibitory effect than Sutent treatment on cell proliferation. L1-CAM KD led to the simultaneous downregulation of MycN, but the upregulation of PTEN protein expression. Notably, radiotherapy (2 Gy) of the IMR-32 cells led to significant upregulation of both L1-CAM and MycN, which was abrogated with L1-CAM KD in our cells. In addition, L1-CAM KD radiosensitized the cells as exhibited by the synergistic effect on the reduction in cell proliferation compared to radiotherapy alone. Taken together, our data show the importance of L1-CAM interplay with MycN and PTEN on the MycN amplified neuroblastoma cell radioresistance, proliferation and motility.

Treatment of peripheral neuroepithelioma in children and young adults.

Seventeen patients with peripheral neuroepithelioma were treated with an intensive chemotherapy regimen of vincristine, Adriamycin (Adria Laboratories, Columbus, OH), and cyclophosphamide (VADRIAC) in combination with radiation therapy. Fifteen patients with stage III (seven) or stage IV (eight) at presentation were treated on a more intensive regimen including total body irradiation (TBI) (8 Gy). Two patients with stage I (one) or II (one) disease received a less intensive chemotherapy regimen of VADRIAC. Therapy was completed within 6 to 7 months in all patients. The disease arose in the chest wall in 12 patients, pelvis in three patients, and extremity in two patients. Sixteen of the 17 (94%) patients achieved a complete remission. With a median follow-up of 18 months, ten patients remain in complete remission with an actuarial survival of 68% and an actuarial relapse-free survival of 56% at 12 months. On the basis of our initial experience with this tumor, we believe that peripheral neuroepithelioma is a chemoresponsive and radioresponsive tumor.

Neoadjuvant chemotherapy for peripheral malignant neuroectodermal tumor of bone: recent experience at the istituto rizzoli.

PURPOSE: The results achieved in 44 patients with nonmetastatic peripheral neuroectodermal tumor (PNET) of bone treated with neoadjuvant chemotherapy are reported. PATIENTS AND METHODS: A six-drug regimen of chemotherapy (vincristine, doxorubicin, dactinomycin, cyclophosphamide, ifosfamide, and etoposide) was administered to all patients. Local treatment consisted of surgery in 20 patients, surgery followed by radiotherapy in 13, and radiotherapy only in 11. RESULTS: At a mean follow-up of 4.5 years (range, 2 to 7 years), 23 patients (52%) remain event-free, 20 have relapsed (45%), and one has died of chemotherapy-related toxicity. The 5-year event-free survival and overall survival were 54.2% and 62.7%, respectively. To assess the prognostic significance of neural differentiation in the family of Ewing's sarcoma, these results have been compared with the outcomes of 138 concomitant patients with typical Ewing's sarcoma (TES) who were treated according to the same protocol. Of these, 103 (75%) remained continuously event-free, 34 (24%) relapsed, and one died of chemotherapy-related toxicity. It follows that PNET patients treated with this chemotherapy regimen have a significantly worse prognosis than typical ES patients (5-year event-free survival, 54.2% v 70.6%, P <.012; 5-year overall survival, 62.7% v 78.3%, P <.002). CONCLUSION: The authors conclude that studies into new adjuvant therapy for Ewing's sarcoma modulated according to risk of relapse should also consider neural differentiation as a risk factor.

Ewing's sarcoma and peripheral primitive neuroectodermal tumor cells produce large quantities of bioactive tumor necrosis factor-alpha (TNF-alpha) after radiation exposure.

PURPOSE: In the present study, we examined human Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET) cell lines that are able to produce TNF-alpha as part of the response to irradiation. Radiation-induced tumor cell production of TNF-alpha may enhance irradiation efficacy and improve the effect of local tumor irradiation. On the other hand, radiation-induced tumor cell production of TNF-alpha may adversely affect the normal tissue. METHODS AND MATERIALS: Twelve different ES/pPNET cell lines were investigated in vitro and (after establishment as tumor xenografts in athymic nude mice) in vivo for their TNF-alpha mRNA expression (real-time quantitative reverse transcriptase polymerase chain reaction) and TNF-alpha protein production (in vitro: enhanced amplified sensitivity immunoassay; in vivo: immunohistochemistry) after exposure to different irradiation doses (2, 5, 10, 20, 30, or 40 Gy) and after different time intervals (1, 3, 6, 12, 24, 48, or 72 h after irradiation). The bioactivity of the TNF-alpha protein was evaluated in chromogenic cytotoxicity and neutralization assays. RESULTS: Nine out of 12 ES/pPNET cell lines express constitutively significant quantities of bioactive TNF-alpha in vitro. ES/pPNET cells originating from primary tumors secreted higher TNF-alpha levels than cells derived from metastatic lesions. In 5 of the 9 TNF-alpha-producing cell lines, TNF-alpha mRNA and protein levels were upregulated after irradiation exposure in a time- and dose-dependent manner. After establishment of the ES/pPNET cell lines in athymic nude mice, the radiation-induced TNF-alpha release could be demonstrated also in the xenograft tumors in vivo (analogous to the in vitro experiments). Using the same methods for quantitative analysis, it was determined that the TNF-alpha expression of the radiation-responsive tumor cells was up to 2000-fold higher compared to the maximal radiation-induced TNF-alpha release in normal lung tissue measured during the pneumonic phase. CONCLUSION: Certain ES/pPNET cell lines produce extremely large quantities of bioactive TNF-alpha after radiation exposure in a time- and dose-dependent manner. Radiation-induced TNF-alpha production of tumor cells may be of paramount importance in respect to not only tumor behavior, but also to potential damage to normal tissue and the clinical status of the host.

Definitive irradiation in multidisciplinary management of localized Ewing sarcoma family of tumors in pediatric patients: outcome and prognostic factors.

PURPOSE: To assess the effect of radiation dose on local tumor control of the Ewing sarcoma family of tumors in 79 patients with localized disease treated at a single institution. METHODS AND MATERIALS: Thirty-seven patients received vincristine, actinomycin D, cyclophosphamide, and doxorubicin, and 42 received vincristine, actinomycin D, and cyclophosphamide, with alternating cycles of ifosfamide and etoposide; all underwent definitive radiotherapy (median dose, 37.5 Gy) with either low-dose (<40 Gy) or standard dose (> or =40 Gy) radiation delivered according to the protocol. We calculated the cumulative incidence of local treatment failure, disease recurrence, and overall survival and analyzed the effect of known prognostic factors and radiation dose. RESULTS: The cumulative incidence of local treatment failure at 10 years was 30.4% and that of disease recurrence was 40%. The overall survival rate was 64.5%. Patient age > or =14 years and tumor size > or =8 cm were adverse prognostic factors for local treatment failure; patient age > or =14 years was also associated with worse survival. Although the radiation dose alone did not predict for local treatment failure, the cumulative incidence of local failure at 10 years was 19% when tumors <8 cm were treated with <40 Gy, and no patient treated with standard doses (> or =40 Gy) developed local recurrence (p = 0.084). CONCLUSION: Tumor size and patient age predict for local tumor control in patients with Ewing sarcoma family of tumors treated with systemic therapy and definitive radiotherapy. Patients treated with reduced-dose radiotherapy experienced unacceptably high rates of local recurrence.

Treatment of sarcomas of the chest wall using intensive combined modality therapy.

As part of two sequential protocols using intensive combined modality treatment in pediatric and adolescent sarcomas, 31 consecutive patients with primary chest wall tumors were treated between November 1977 and March 1986. This group included 13 patients with peripheral neuroepithelioma (Askin's tumor), 11 patients with Ewing's sarcoma, 3 patients with rhabdomyosarcoma, and 4 patients with undifferentiated sarcomas. Following complete work-up, 17 patients presented with localized disease and 14 patients presented with metastases. Patients received intensive combined modality treatment with combination chemotherapy (vincristine, cyclophosphamide, Adriamycin, +/- actinomycin-D and DTIC) and high-dose conventionally fractionated radiation therapy to the primary (55-60 Gy) and non-pulmonary metastases (45-50 Gy). Radiation techniques used for the primary chest wall tumor varied with the clinical presentation. Patients achieving a complete response received either low-dose fractionated TBI (1.5 Gy/0.15 Gy fx/5 weeks) or high-dose TBI (8 Gy/4 Gy fx/2 days) and an intensive cycle of chemotherapy followed by autologous bone marrow transplantation. Twenty-five of 31 patients were judged to have a complete response (including 1 patient with complete resection). With minimum follow-up of 6 months and median follow-up of 36 months from completion of treatment, 14 patients remain disease-free with 2 additional patients alive in second remission after relapse. Patients with localized disease at presentation have improved disease-free survival and overall survival compared to patients with metastases at presentation. All 17 localized patients achieved a CR and 11 are NED compared to 8 of 14 metastatic patients achieving a CR and only 3 are NED. There have been 5 loco-regional recurrences with 3 "in-field" failures and 2 failures in the regional pleura. There were no treatment-related deaths and no clinically significant cases of pneumonitis. To date, 2 patients have significant treatment related morbidity, including 1 patient with scoliosis requiring surgery and 1 patient with acute leukemia developing 42 months after the start of therapy (presently in remission). We conclude that this intensive combined modality therapy results in a high CR rate and good local control with acceptable morbidity. Patients with metastatic disease at presentation remain a therapeutic challenge.

Radiotherapy in Ewing's sarcoma and PNET of the chest wall: results of the trials CESS 81, CESS 86 and EICESS 92.

PURPOSE: Treatment results and the pattern of relapse were evaluated in the multimodal treatment of Ewing's sarcomas of the chest wall. METHODS AND MATERIALS: In a retrospective analysis, 114 patients with non-metastatic Ewing's sarcoma of the chest wall were evaluated. They were treated in the CESS 81, CESS 86, or EICESS 92 studies between January 1981 and December 1993. The treatment consisted of polychemotherapy (VACA, VAIA, or EVAIA) and local therapy, either surgery alone (14 patients), radiotherapy alone (28 patients) or a combination of both (71 patients). The median follow-up was 46.6 months (range 5-170). A relapse analysis for all patients with local or combined relapses was performed. RESULTS: Overall survival was 60% after 5 years, event-free survival was 50%. Thirty-seven patients had a systemic relapse (32.4%), 11 patients had a local relapse alone (9.6%), and 3 patients had a combined local and systemic relapse (2.6%). The risk to relapse locally after 5 years was 0% after surgery alone, 19% after radiation alone, and 19% after postoperative irradiation. None of the 8 patients with preoperative irradiation have failed locally so far. With the introduction of central radiotherapy planning in CESS 86, local control of irradiated patients improved. Ten of 14 patients with local failure could be evaluated in the relapse analysis: 3 patients had an in-field relapse, 4 patients had a marginal relapse, 2 patients had a relapse outside the radiation fields, and 1 patient failed with pleural dissemination. Six treatment deviations were observed. CONCLUSION: Local control was best after surgery alone in a positively selected group of patients. Local control after radiation or combined radiation and surgery was good. With diligent performance of radiotherapy, it will be possible to further improve the results in the radiotherapy group.

Sarcomas of the hand and foot: analysis of local control and functional result with combined modality therapy in extremity preservation.

PURPOSE: The records of 28 patients with sarcomas of the hand and foot treated at the National Cancer Institute (NCI) between 1977 and 1992 were reviewed to assess local control and functional results. METHODS AND MATERIALS: Histologic types included 15 cases of the Ewing's sarcoma family of tumors, 7 cases of alveolar rhabdomyosarcoma, and 6 cases of nonrhabdomyosarcoma soft tissue sarcomas. Median age of all patients was 18 years (range 4-61), with a median potential follow-up of 114 months following diagnosis. Surgery varied from incisional biopsies for Ewing's Sarcoma and rhabdomyosarcoma lesions to complete excision when possible for nonrhabdomyosarcoma soft tissue sarcoma lesions. Amputation was not primarily performed, except in two patients who underwent ray resections of hand lesions (patients 13 and 24). Radiotherapy generally consisted of 50 Gy/25 fractions (fx)/5 weeks for Ewing's Sarcoma, 54 Gy/30 fx/6 weeks for rhabdomyosarcoma, and 63 Gy/35 fx/7 weeks for nonrhabdomyosarcoma soft tissue sarcomas. Chemotherapy was administered on various NCI protocols. RESULTS: Actuarial local control for Ewing's Sarcoma was 84% at 5 and 10 years. All but one survivor are capable of hand/foot function for routine activities without orthotic requirements. Five of six patients (83%) who died of metastatic disease had functional distal extremities. Actuarial local control for rhabdomyosarcomas was 100%, with equivalent function. No patient developed a second malignancy in the treatment field. CONCLUSIONS: Although equivalent local control may be achieved in these lesions with either amputation or radiotherapy, a prudent management course would be to defer amputation for management of local recurrences. Many patients with these lesions fail in distant sites only and die without local failure. For these patients and for those who remain long-term survivors, we believe a functional hand and foot provides a better quality of life than a prosthesis.

Low CD4 lymphocyte count in a patient with P. carinii pneumonia after autologous bone marrow transplantation.

Authors report a case of P. carinii pneumonia in a child with 5% CD4 lymphocytes (absolute number 5/microliters) after autologous bone marrow transplantation followed by pulmonary irradiation. Serial evaluation of CD4 lymphocyte count or percentage or, at least, detection of significant and persistent lymphopenia could be useful for detecting a high risk of developing P. carinii pneumonia.

Esthesioneuroblastoma with intracranial extension.

The authors present five cases of olfactory neuroblastoma with intracranial extension operated on in the Department of Neurosurgery in collaboration with otorhinolaryngologists. This tumor is most frequently reported as growing inside the nasal cavities, and it can extend to the paranasal sinuses. Cases presenting initially as intracranial tumors have been infrequently reported. At present, histological diagnosis of this tumor is aided by the use of electron microscopy and immunocytochemistry. Total resection combined with radiation therapy remains the most satisfactory treatment.

Esthesioneuroblastoma: prognosis and management.

Forty-nine patients with esthesioneuroblastoma were treated at the Mayo Clinic between 1951 and 1990. Their clinical manifestations and treatment results were reviewed to identify possible prognostic factors. The 5-year survival rate for all patients was 69%. Tumor progression occurred in 25 patients (51%; no local control in 6 and local recurrence in 19). Metastasis was found in 15 patients (31%; regional in 10 and distant in 9). Nineteen patients died directly from metastatic or intracranial tumor extension. The pathological grade of the tumor was the most significant prognostic factor identified. The 5-year survival rate was 80% for the low-grade tumors and 40% for the high-grade tumors (P = 0.0001). Surgical treatment alone is effective for low-grade tumors if tumor-free margins can be obtained. Radiation is used for low-grade tumors when margins are close, for residual or recurrent disease, and for all high-grade cancers. The poor prognosis associated with high-grade tumors may also mandate the addition of chemotherapy. Recurrent tumor and regional metastasis should be treated aggressively because this approach has been shown to be worthwhile. A craniofacial resection is now the surgical procedure performed in all cases. Because recurrence can occur after 5 or even 10 years, long-term follow-up is mandatory.

Esthesioneuroblastoma.

A retrospective review of the clinical records of 31 patients with esthesioneuroblastoma is presented. A bimodal age distribution was noted. The tumor is extremely rare among blacks. Most patients presented with locally advanced disease. However, regional and distant metastases at the time of initial diagnosis are uncommon. Local recurrence at the primary site was very common, and this reflects either the conservative initial surgical treatment employed or the multicentric nature of the tumor. Cervical lymph node metastasis is present in less than 10 percent of patients at the time of diagnosis. Survival rates were better in patients with early stages of disease. From this study we conclude that the current management of these tumors should consist of a combination of radiation and surgery. Radical resection followed by postoperative radiotherapy appears to be the treatment combination of choice. The 5 year survival rate in our series was 52 percent.

Brain radiation necrosis following treatment of an esthesioneuroblastoma (olfactory neurocytoma).

Esthesioneuroblastoma is an uncommon malignant nasal tumor which may be difficult to diagnose. Once diagnosed, selection of treatment may be a dilemma. Some advocate preoperative radiation and surgery; others, surgery and postoperative radiation if needed. A case that developed brain necrosis from postoperative radiation is presented. It is felt that the possibility exists that the patient might still be living with tumor had irradiation not been given. This is a plea for the conservative approach to treatment. The author agrees with John S. Lewis that it is unwise to use all modalities at once as there is no definite evidence that any one method of treatment or a combination of surgery and irradiation will alter the prognosis. The paper stresses the brain hazards of irradiation.