Central nervous system neurocytoma and neuroblastoma in adults-report of eight cases

Summary The clinical features, pathologic findings and treatment courses of eight adults with central nervous system small-cell neuronal tumors were reviewed. Five patients had central neurocytomas, two patients central nervous system neuroblastomas, and one patient a neurocytoma-like spinal cord tumor. The neurocytomas were intraventricular, moderately cellular tumors with bland nuclei and perinuclear halos. Patients with neurocytoma were treated with surgery, radiation therapy, and/or chemotherapy, and have followed favorable clinical courses. The neuroblastomas were intraparenchymal, hypercellular tumors with necrosis and frequent mitoses. Patients with neuroblastomas were treated with surgery, radiation therapy and chemotherapy, with some clinical response, but overall poor survival. One of the two patients developed extracranial metastasis. The spinal cord tumor had histologic features of neurocytoma, and responded well to biopsy and radiation therapy. The cases are compared with the varieties of small-celled neuronal tumors described in the literature, and pathologic, histogenetic and treatment implications are discussed. This paper was presented in part at the United States and Canadian Academy of Pathology meeting, Boston, MA, March 7, 1990     

Neurocytomas: long-term experience of a single institution

There is a lack of studies reporting on outcomes of control and treatment toxicities for neurocytomas. A 25-year retrospective review of a tertiary center's experience with neurocytomas was completed to report on these outcomes. All cerebral neurocytoma cases (19 patients; median age, 31 years; range, 18-62 years; 18 intraventricular and 1 extraventricular) treated between 1984 and 2009 were analyzed, including central pathology and radiology reviews. Median follow-up was 104.5 months (range, 0.75-261.7 months). Primary treatment was surgery alone (n = 18 patients), followed by surgery and adjuvant radiotherapy (n = 1). The crude local control rate after surgery was 68% for all cases (cerebral neurocytomas) and 74% for central neurocytomas. Salvage therapies included further surgery (n = 4), radiation (n = 3), and chemotherapy (n = 1). Ten-year Kaplan-Meier overall and relapse-free survival rates were 82% and 62% and 81% and 57%, respectively, for all cases and for central neurocytomas only. The median overall survival and relapse-free survival were 104.5 and 79.3 months, respectively, for all cases and for central neurocytomas. Ten patients had grade 3/4 toxicity, and 1 patient had a grade 5 perioperative hemorrhage that resulted in death 23 days after surgery. Late grade 3/4 toxicities occurred in 9 patients. Three patients had permanent grade 2 motor or cognitive deficits. We provide the first report outlining toxicities and survival outcomes in a series of 19 patients. Our experience suggests that initial surgery provides durable local control rates in two-thirds of patients, with low risk for significant permanent deficits. Salvage therapy with surgery and/or radiation provides durable local control in tumors that recur after surgery.     

Olfactory Neuroblastomas: Survival Rate and Prognostic Factor

Olfactory neuroblastomas are known to be rare and clinically malignant tumors. The authors analyzed the clinical features, long-term treatment outcomes, and prognostic factors related to 21 cases of olfactory neuroblastomas, treated between January 1979 and October 2000, retrospectively reviewed with medical records and radiologic findings. The mean follow-up period was 28.7 months (range 4–178). The extent of tumor was classified according to the UCLA staging system. Statistical analysis for survival was done using the Kaplan–Meier method and the log-rank test. The mean age was 27 years (13–62), the peak incidence occurred in the second decade (8/21, 38%), and the male to female ratio was 13 : 8. According to the UCLA staging system, there were 3 cases of T1, 5 of T2, 6 of T3, and 7 of T4. The 5-year survival rate was 21.3% and the average survival time was 28.9 months. The group (n = 14) undergoing radical surgical resection as the primary modality, registered a higher survival rate than the radiation and chemotherapy group (n = 7), with 2-year survival rates being 76.2% vs. 14.3%, respectively (p = 0.0274). The early stage (T1, T2) groups exhibited a better survival rate than the advanced (T3, T4) groups with 5-year survival rates being 38.1% vs. 9.1%, respectively (p = 0.0336). The mean recurrence free time was 7.8 months (range 1–25). From these findings we could conclude that tumor detection in the early stage, radical surgical resection as the primary treatment modality, and regular follow-up with radiologic evaluation for recurrence or metastasis, represent important factors for an improved outcome.     

儿童纵隔神经母细胞瘤临床特征分析

  目的  探讨纵隔神经母细胞瘤临床特征。  方法  收集2008年3月至2012年9月中国医科大学附属第四医院儿科收治的神经母细胞瘤110例, 其中26例肿瘤位于纵隔, 其他部位84例。将纵隔神经母细胞瘤的临床表现、肿瘤标志物、生物学预后因素与其他部位对比。  结果  纵隔组平均年龄25.5个月, 与其他部位组相近。初诊时纵膈组88.5%有症状, 高于其他部位组60.7%（P < 0.05）; 早期病例（Ⅰ、Ⅱ期）34.6%, 高于其他部位组8.3%（P < 0.05）; 血清NSE>100 ng/L者达21.4%, 低于其他部位组86.1%（P < 0.001）。纵隔组N-myc基因拷贝数均 < 10, 其他部位组N-myc基因拷贝数>10者为23.1%（P < 0.05）。纵隔组4年总生存率为80.0%, 其中局限性肿瘤（Ⅰ、Ⅱ、Ⅲ期）达100%, 分别高于其他部位组44.0%、82.0%。  结论  多数纵隔神经母细胞瘤表现出临床分期早（Ⅰ、Ⅱ期）和良好的生物学预后因素, 这些特征可能与纵隔神经母细胞瘤良好的预后相关。      

Electrochemotherapy of cholangiocellular carcinoma at hepatic hilum: A feasibility study

Aim

We evaluated feasibility, safety and efficacy of Electrochemotherapy (ECT) in a prospective series of patients with unresectable Perihilar-Cholangiocarcinoma (PHCCA).

Central neurocytoma. A clinico-pathologic study of five cases.

Five cases of central neurocytomas are described. The tumors occurred in relatively young patients (range 14 to 43 years; mean age, 27) with no predilection for sex. All the lesions were located in the anterior portion of the lateral ventricles or in the third ventricle, involving the septum pellicidum or the fornix. Histologically, they were composed of uniform cells with round nuclei and clear cytoplasm resembling oligodendrogliomas or, to a lesser extent, ependymomas. In 4 tumors, protein cell nuclear antigen immunostaining showed a low cell proliferation rate. All cases were positive for neuron-specific enolase. Four of the 5 cases were strongly immunoreactive for synaptophysin. The immunohistochemical data were consistent with neuronal differentiation. Resection was subtotal in 4 cases and total in one. Postoperative radiotherapy was given in only one case. The follow-up revealed a good prognosis: 4 patients were alive and had a long survival (from 2 to 8 years). Only one patient died after 14 months for causes unrelated to the neoplasm. The authors emphasize the importance of immunohistochemistry to recognize this benign intraventricular tumor.     

Central neurocytoma: histologic atypia, proliferation potential, and clinical outcome

BACKGROUND: Although central neurocytomas are considered benign, recent reports suggest that some patients with histologic atypia and/or elevated proliferation potential may have a poor outcome. METHODS: A retrospective review identified 15 cases of central neurocytoma. Clinical follow-up was available for 14 patients. Each tumor was evaluated for the presence of atypical histologic features, including cellular pleomorphism, endothelial proliferation, and necrosis. The proliferation potential was assessed by MIB-1 immunohistochemistry. The correlation among histology, MIB-1 labeling index (MIB-1 LI), and clinical outcome was evaluated. RESULTS: Histologic atypia was identified in 3 tumors (20%). The MIB-1 LI ranged from 0.1% to 6.0%, and 5 cases (33%) had an MIB-1 LI >2%. The correlation between histologic atypia and MIB-1 LI was poor, with only 1 tumor having both atypia and MIB-1 LI >2%. Clinical follow-up ranged from 13 to 255 months postoperatively (mean, 68 months). Although most patients were alive and well at last follow-up, three developed symptomatic recurrence and one died as a result of increased tumor growth. The tumors from all 4 patients with a poor outcome had MIB-1 LI >2%, but only 1 had histologic atypia. CONCLUSIONS: The proliferation potential of central neurocytoma is a useful predictor of clinical outcome, whereas histologic atypia alone is not prognostically significant. It would be appropriate to recognize a subgroup of central neurocytomas with elevated proliferation potential as WHO Grade 2 lesions. The terms "atypical" and "anaplastic" are not appropriate to describe these lesions, as they imply a certain histologic appearance. The most accurate designation would be "proliferating neurocytoma."     

Disseminated neuroblastomas under 1 year of age: cell biology and prognosis

Tumor specimens of 203 infants with neuroblastomas of different clinical stages — registered in successive multicenter clinical trials of the German Society of Pediatric Oncology — could be examined for N-myc amplification, chromosome 1-ploidy and — structure, CD₄₄ std. expression (in tumor tissue, and also in patients sera).Eightyseven (= 43%) of these infants had a non-localized, disseminated neuroblastoma, mainly involving sympathetic nerve tissue, lymphnodes, liver, skin, bone marrow and bones (46 patients were classified into the 4_s group, 41 patients in the true 4 group).If the clinical classification between stage 4 and stage 4_swas neglected, then 17 of these infants (= 20%) had N-myc amplification (4—64 copies) with 16 already dead. Seven of 9 examined patients with true stage 4 had chromosome 1p aberrations (with N-myc amplification in 5), and among the dead there were 2 with CD₄₄ negative expression.In another series, serum CD₄₄ std. was measured by ELISA, and the highest (significantly different) Kruskal-Wallis mean rank values (147.8) were found in infants (n = 6) with stage 4_s compared to the low mean-rank-value of 71.9 in patients with stage 4 (n = 65). Stage 1—3 patients (n = 42) had values of 99.8—88.6.Thus, infants with disseminated neuroblastomas, showing non-diploidy, normal chromosome 1p structure, non-N-myc amplification and high CD₄₄ std. expression in tumor tissue, and also high CD₄₄ std. values in serum, will have the highest chance of survival due to tumor-non-progression.On the other hand, N-myc amplification in the tumor cells was found to be characteristic for stage 4_s neuroblastoma patients with tumor progression (n=6). Therefore, 4_s neuroblastoma-patients with N-myc amplified tumors should be aggressively treated like true stage 4 tumor patients!     

Computed tomography attenuation predicts the growth of pure ground-glass nodules

Objectives

Cases of lung cancer with pure ground-glass nodules (GGNs) have been detected with increasing frequency since the advent of computed tomography (CT), and growth is sometimes noted during follow-up. The objective of this study was to evaluate the potential predictive factors for pure GGN growth.

Materials and methods

We retrospectively examined 124 cases involving pure GGNs. Patients were monitored for >2 years using high-resolution CT. After a median follow-up period of 57.0 months, GGNs showed growth in 64 of the 124 cases. We compared the patient characteristics and tumor properties of cases with and without growth. The predictive value of the mean CT attenuation for GGN growth was evaluated using receiver operating characteristic curve analysis.

Results

Univariate analysis revealed significant differences between mean CT attenuation values in patients with and without growth (−602.9 ± 90.7 Hounsfield units [HU] vs −705.7 ± 77.7 HU, P < 0.0001). The final incidence of growth was estimated to be significantly higher for lesions with a mean CT attenuation value of ≥−670 HU (n = 62; 93.2%) than for lesions with values of <−670 HU (n = 62; 31.6%; P < 0.0001). The sensitivity and specificity for predicting tumor growth using this cutoff value were 78.1% and 80.0%, respectively (area under the curve, 0.81).

Conclusion

The mean CT attenuation value could be useful in predicting the growth of GGNs.     

Nested Stromal Epithelial Tumor of the Liver—Liver Transplantation and Follow-Up

Background

The nested stromal epithelial tumor (NSET) of the liver is a rare tumor entity which is being reported in young girls.

Case Report

In our 16-year-old female patient, we have performed a liver transplantation (LTX) for a non-metastasizing non-resectable liver tumor. The patient was tumor free in the follow-up. At 28 months postoperatively, we detected lung metastases in the F18-FDG-PET/CT. The patient died 37 months after LTX from progressive pulmonary metastases.

Conclusion

LTX should not have been generally recommended for NSET. Further statements about the value of LTX for NSET will be possible only after evaluation of the course of the disease in a larger number of transplanted patients.     

Sequential CT Findings in Patients With Non–small-cell Lung Cancer Receiving Nivolumab

Background

Nivolumab is a novel immunotherapy that was recently approved for treatment of advanced non–small-cell lung cancer (NSCLC). Patients treated with checkpoint inhibitors may show variable computed tomography (CT) features on follow-up imaging, and it is unclear how reliable conventional response criteria are to determine patient management and outcomes. We report the spectrum of sequential CT findings in patients with advanced stage lung cancer who received nivolumab in an effort to better inform appropriate imaging strategies.

A decrease in the size of ground glass nodules may indicate the optimal timing for curative surgery

Objectives

Although ground glass nodules (GGNs) are generally considered to grow slowly to a large size, their natural progression remains unclear, and a decrease in tumor size has been reported in a few previous studies. The study aimed to retrospectively review the radiologic and pathological characteristics of resected ground glass nodules (GGNs) followed with chest computed tomography (CT) for at least a year before surgery to clarify the natural progression of GGNs.

Patients and methods

The chest CT cans and clinical charts of 32 GGNs in 31 patients who underwent pulmonary resection between January 2006 and March 2013 were retrospectively reviewed. The definitions of pure GGNs and part-solid nodules were based on the tumor shadow disappearance rate. The tumor size was measured twice, and the mean size was used for evaluation.

Results

The mean GGN size before surgery was 15.2 mm, and the median follow-up period before surgery was 21 months. In the follow-up period, 15 (58%) of 26 pure GGNs at the initial CT remained pure GGNs at the last CT. However, a solid component appeared in the remaining 11 tumors (42%) of the 26 initial pure GGNs. Furthermore, 1 GGN of the 15 GGNs that remained pure and 10 of the 11 GGNs with solid component also showed a size decrease. In addition, 6 part-solid nodules were observed at the initial CT. Of these, 3 showed a decrease in size during follow-up. Overall, 47% of the GGNs showed a size reduction on follow-up chest CT.

Conclusions

A size reduction was observed in nearly half of the GGNs and suggested the progression to an invasive adenocarcinoma. When a mild collapse of the GGNs is observed, a careful follow-up is necessary to identify a solid component. Tumor size decreases may represent the optimal timing of pulmonary resection for curative treatment.     

Two cases of atypical central neurocytomas

Central neurocytomas (CNs) are usually considered benign; however, some subsets of these tumors with histologic atypia and elevated proliferation potential have been reported to have a poor outcome. It has been proposed that those CNs exhibiting a MIB-1 labeling index (LI) greater than 2% and/or vascular proliferation be defined as atypical central neurocytoma (ACN). Two cases of ACN are reported here. Case 1 was a 13-year-old male who complained of headache. An MRI showed an enhancement of the tumor in the third ventricle and left lateral ventricle. The tumor was completely removed transcortically by a left frontotemporal craniotomy. The tumor showed anaplastic features, including microvascular proliferation, mitosis, and necrosis. The MIB-1 LI was 7.8%. The patient received 50 Gy of focal irradiation. After 16 months of follow-up, no recurrence was observed. Case 2 was a 17-year-old female who presented with headache. An MRI showed an enhancement of the tumor in the right lateral ventricle. To preserve the internal cerebral vein, the tumor was partially removed by the transcingulate approach after a bifrontal craniotomy. Histologically, the tumor displayed the typical features of a CN. The MIB-1 LI was 7.0%. Complete remission was achieved through 50 Gy of focal irradiation. After 15 months of follow-up, there was no recurrence. The differences in the histopathological findings in these two cases indicate the presence of a variety of histopathological features among ACNs.     

Central,Extraventricular and Atypical Neurocytomas: a Clinicopathologic Study of 35 Cases from Pakistan Plus a Detailed Review of the Published Literature

Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. Aim: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. Materials and Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. Results: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer- Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.     

Isolated cardiac peripheral primitive neuroectodermal tumor: A case report

Background: Peripheral primitive neuroectodermal tumor isolated in the heart, presenting as a primary cardiac tumor is considered as extremely rare.

Methods: We present a 53-year-old Chinese female with a cardiac tumor which was discovered by CT.

Results: A hypo-intense tumorous mass was shown extending from the left ventricle by Cardiac CT, and fused FDG positron emission tomography demonstrated no other abnormal FDG active lesions in the body. We performed a total resection surgery of the tumor subsequently and the patient recovered well and discharged from hospital 6 d after surgery.

Conclusion: The pathological diagnosis was primary cardiac peripheral primitive neuroectodermal tumor. No tumor recurrence was shown by echocardiography during the 24 months follow-up visits.     

Rapid shrinkage of remnant central neurocytoma after gamma knife radiosurgery: a case report

Central neurocytomas are typically benign tumors that have high local control rates after gross total resection. Radiotherapy for residual or recurrent central neurocytomas is controversial.We report a 30-year-old male with a central neurocytoma in the lateral ventricle. The tumor was subtotally resected through a transcallosal approach, and subsequently treated with gamma knife radiosurgery. The tumor had shrunken markedly by 2 months after radiosurgery and remained unchanged during the one year follow-up period.Gamma knife radiosurgery may be an option for effective treatment of patients with residual or recurrent central neurocytomas.     

Gastrointestinal stromal tumors as an incidental finding in patients with a presumptive diagnosis of ovarian cancer

Objective

To report the clinical presentation and oncologic outcomes of a series of patients who presented with an abdominal or pelvic mass and were diagnosed with a gastrointestinal stromal tumor (GIST).

Methods

Data were obtained on all patients who presented with an abdominal or pelvic mass between September 2007 and June 2010 and who were ultimately diagnosed with a GIST. The patients'' medical records were reviewed. A literature review was also conducted.

Results

Six patients were identified who met the inclusion criteria. All six patients had a tumor in the intestinal tract arising from the small bowel. The mean tumor size was 12 cm (range, 6 to 22 cm). A complete resection was achieved in five of the six patients. There were no intraoperative complications; one patient had a postoperative complication. Two patients were treated with imatinib after surgery. The mean follow-up time was 32 months (range, 0.3 to 40 months). At the last follow-up, five of the six patients were without any evidence of disease. One patient died of an unrelated hepatic encephalopathy. The incidence in our institution is 3%.

Conclusion

GISTs are uncommon; however, they should be considered in the differential diagnosis of patients presenting with an abdominal or pelvic mass.     

N-myc genomic content and DNA ploidy in stage IVS neuroblastoma

DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required.     

Transformation of Hodgkin''s disease to high-grade B-cell lymphoma: remission after Rituximab monotherapy.

Purpose:We demonstrate the usefulness of immunotherapy with theCD20 antibody Rituximab in a case of transformation of Hodgkins disease(HD) to high-grade non-Hodgkins lymphoma (NHL). Case report:A 45-year-old women suffering from lymphocytepredominant HD of paragranuloma type (stage IVb) since 1995 showed mediastinalrelapse despite of 6 cycles of chemotherapy following the COPP/ABVD-protocolin 1998. Again complete remission could be achieved after escalated BEA-COPPII therapy in May 1998. Six months later chest radiograph and CT depictedpulmonary nodules. The non-typical resection of the lung revealed pulmonaryinvolvement of a high-grade T-cell rich large B-cell lymphoma with 100%of the tumoral cells CD20 positive. Since the symptoms occurred shortly afterthe BEA-COPP-escalated protocol chemotherapy resistance had to be assumed.Because of this problems and supported by the refusal of a high-dosechemotherapy with stem-cell transplantation by the patient we decided toperform a mono-immunotherapy with the monoclonal CD20 antibody Rituximab.Today, 14 months later, the patient is still in complete remission includingthe absence of B symptoms. Conclusions:Immunotherapy against CD20 positive cells in casesof sequential HD and NHL seems to be an effective therapy in chemotherapyresistant cases because of the suspected clonally relation of bothdiseases.     

儿童多发性神经母细胞瘤7 例临床分析*

目的:总结儿童多发性神经母细胞瘤（neurobl astoma ,NB）的临床特征及生物学行为,以期对这类肿瘤的治疗及预后判断提供依据。方法:回顾性分析天津医科大学肿瘤医院儿童肿瘤科1995年1 月至2015年12月收治的7 例多发性NB患儿的临床资料并对其随访。结果:共收治360 例NB患儿,其中多发NB仅7 例（1.9%）。 患儿平均年龄（19.4 ± 11.9）个月;原发部位胸腹多发3 例,双肾上腺多发4 例;临床分期4S 期4 例（57.1%）,3 期2 例（28.6%）,4 期1 例（14.3%）。 7 例共15个原发灶:14个手术完整切除;组织学预后良好型（favorable histology ,FH）12个（85.7%）,组织学预后不良型（unfavorable histology,UH）2 个（14.3%）;13个（92.9%）MYCN 基因无扩增。随访满3 年的5 例患儿,3 年总生存率（overall survivalrate ,OS）为100% 。结论:多发性NB极其罕见,具有初次诊断年龄较低、以4S 期为主、手术易完整切除的临床特征,肿瘤细胞分化较成熟、FH居多、少见MYCN 基因扩增等生物学行为。该病多数预后较好,应避免过度治疗。