Enlarged and Prominent Nucleoli May Be Indicative of MYCN Amplification
|
|
- Hugh Harold Cook
- 6 years ago
- Views:
Transcription
1 174 Enlarged and Prominent Nucleoli May Be Indicative of MYCN Amplification A Study of Neuroblastoma (Schwannian Stroma Poor), Undifferentiated/Poorly Differentiated Subtype with High Mitosis-Karyorrhexis Index Chie Kobayashi, M.D. 1 Hector L. Monforte-Munoz, M.D. 1 Robert B. Gerbing, M.A. 2 Daniel O. Stram, Ph.D. 3 Katherine K. Matthay, M.D. 4 John N. Lukens, M.D. 5 Robert C. Seeger, M.D. 6 Hiroyuki Shimada, M.D., Ph.D. 1 1 Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles/Keck School of Medicine, University of Southern California, Los Angeles, California. 2 Operations Office, Children s Oncology Group, Arcadia, California. 3 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. 4 Department of Pediatrics, University of California San Francisco School of Medicine, San Francisco, California. 5 Division of Pediatric Hematology/Oncology, Vanderbilt Children s Hospital, Nashville, Tennessee. 6 Division of Hematology/Oncology, Childrens Hospital Los Angeles/Keck School of Medicine, University of Southern California, Los Angeles, California. Supported in part by Grant CA from the Division of Cancer Treatment, National Cancer Institute. The authors thank Dr. Inge M. Ambros (Children s Cancer Research Institute, St. Anna Kinderspital, Vienna, Austria) for her generous support and encouragement throughout the course of the current study. The authors also thank Mrs. Judy Kelly for her assistance with article preparation. Address for reprints: Hiroyuki Shimada, M.D., Ph.D., Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, 4650 Sunset Blvd., M.S. #43, Los Angeles, CA 90027; Fax: (323) ; hshimada@chla.usc.edu Received May 20, 2004; revision received September 1, 2004; accepted September 7, BACKGROUND. According to the International Neuroblastoma Pathology Classification, neuroblastomas exhibiting MYCN amplification (A-MYCN) have unique histologic features namely, undifferentiated/poorly differentiated subtype with a high mitosis-karyorrhexis index (U/PD-H). Nonetheless, certain tumors possessing these histologic characteristics contain a nonamplified MYCN gene (NA-MYCN). METHODS. The clinical characteristics of patients from the Children s Cancer Group (CCG) 3881 and 3891 studies who had neuroblastoma, U/PD-H, exhibiting A-MYCN (n 68) or NA-MYCN (n 33) were investigated. The histologic and cytologic features of tumors (A-MYCN, n 62; NA-MYCN, n 28) filed at the Pathology Reference Laboratory, Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, were reviewed, and nucleolar areas in undifferentiated neuroblastic cells were evaluated using image analysis methods. RESULTS. All 68 patients whose tumors exhibited A-MYCN had disease that was in an advanced clinical stage (Stage III or IV); 89.7% of these patients were diagnosed between ages 0.5 and 3.5 years, and 67 of the 68 had been treated with the high-risk protocol in the CCG-3891 study. Children whose tumors exhibited NA-MYCN were evenly distributed across all age groups; 30 of these 33 children had advanced-stage disease, and 26 had been treated with a high-risk protocol. The prognosis associated with A-MYCN (event free survival [EFS], 15.7%; overall survival [OS], 22.2%) was significantly poorer than the prognosis associated with NA-MYCN (EFS, 56.1%; OS, 69.3%). The lone histologic/cytologic difference between tumors exhibiting A-MYCN and tumors exhibiting NA-MYCN involved nucleolar appearance. Neuroblastic cells in tumors exhibiting A-MYCN were characterized by the presence of 1 or more large, prominent nucleoli, and the mean nucleolar area was significantly greater in the 18 tumors exhibiting A-MYCN that were assessed (7.63 m 2 ) than in the 16 tumors exhibiting NA-MYCN that were assessed (5.53 m 2 ; P 0.004). CONCLUSIONS. Neuroblastomas, U/PD-H, were found to vary in terms of molecular background and clinical behavior. The results of the current study indicate that nucleolar enlargement in neuroblastic cells may be a sign of MYCN amplification. Cancer 2005;103: American Cancer Society. KEYWORDS: neuroblastoma, International Neuroblastoma Pathology Classification, MYCN status, histology, cytology, nucleoli, morphometry, clinical characteristics, prognosis. Peripheral neuroblastic tumors (pnts [neuroblastomas, ganglioneuroblastomas, and ganglioneuromas]) make up a unique group of pediatric solid tumors. These tumors, which are derived from primordial neural crest cells, can be found in the adrenal medulla or in structures anatomically related to the sympathetic nervous system. In the past, pnts have been characterized as enigmatic neoplasms, due to their unpredict American Cancer Society DOI /cncr Published online 17 November 2004 in Wiley InterScience (
2 Large Nucleoli in MYCN-Amplified NB/Kobayashi et al. 175 able clinical behavior; possible clinical courses include involution, spontaneous regression, maturation, and aggressive progression. 1 In 1984, Shimada et al. 2 proposed an age-linked histologic classification system for pnts that included the following four categories: neuroblastoma; ganglioneuroblastoma, intermixed; ganglioneuroma; and ganglioneuroblastoma, nodular. Those investigators also described the possible clinical courses associated with tumors (especially neuroblastomas) possessing a given set of morphologic features. In 1999, the Shimada system was adopted as the International Neuroblastoma Pathology Classification, with neuroblastomas being separated into age-linked prognostic categories on the basis of grade of neuroblastic differentiation (undifferentiated, poorly differentiated, or differentiating) and mitosis-karyorrhexis index (MKI; low, 100 per 5000 cells; intermediate, per 5000 cells; or high, 200 per 5000 cells). 3,4 These categories repeatedly proved to be significantly predictive of clinical outcome for patients with neuroblastoma. 5 MYCN gene amplification is known to be strongly predictive of poor clinical outcome for patients with pnts. 6,7 In addition, biologically and prognostically significant associations between histopathologic characteristics and MYCN status have been documented in pnts. 8 MYCN amplification, with the subsequent overexpression of MYCN protein, is considered to be a powerful driving force with regard to the prevention of neuroblastic differentiation and the up-regulation of mitotic and karyorrhectic activity. 9 In the Children s Cancer Group (CCG) 3881 and 3891 studies, 93.9% of all MYCN-amplified neuroblastomas (108 of 115) exhibited no neuroblastic differentiation, and 86.1% had either a high (71 of 115 [61.7%]) or intermediate MKI (28 of 115 [24.3%]). Thus, an MYCN-amplified tumor can most commonly be described as a neuroblastoma (Schwannian stroma poor) of undifferentiated or poorly differentiated subtype with high MKI (NBL, U/PD-H). 8 Despite these findings, some pnts without MYCN amplification also exhibit no neuroblastic differentiation and increased MKI. In the current study, we compared the clinical and morphologic characteristics of MYCN-amplified and MYCN-nonamplified tumors that were originally classified as NBL, U/PD-H, by the central pathologic review boards for the CCG-3881 and CCG-3891 studies. MATERIALS AND METHODS A total of 911 patients with pnts were enrolled in the CCG-3881 and CCG-3891 studies between August 1, 1991, and August 1, The CCG-3881 study was designed for patients in the low-risk and intermediaterisk categories; low-risk patients received surgery alone, 10 whereas intermediate-risk patients received surgery plus a moderate dose of chemotherapy. 11,12 In contrast, the CCG-3891 protocol, which was designed for high-risk patients, consisted of intensive chemotherapy with or without autologus bone marrow transplantation. 13 Appropriate informed consent procedures were followed, with consent being obtained from patients parents or guardians. Between these two studies, a total of 628 tumors were histopathologically evaluated and tested for MYCN status. Three-hundred thirty-nine tumors were found to have favorable histology (FH) and nonamplified MYCN (NA-MYCN), 8 were found to have FH and amplified MYCN (A-MYCN), 172 were found to have unfavorable histology (UH) and NA-MYCN, and 109 were found to have UH and A-MYCN. 14 Central histopathologic evaluation was performed at the Pathology Reference Laboratory, Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles (Los Angeles, CA), using the International Neuroblastoma Pathology Classification. Between 1989 and 1993, MYCN status was assessed via Southern blot analysis of gene copy numbers. Since 1993, immunoperoxidase staining has been used to detect MYCN protein expression, and semiquantitative polymerase chain reaction analysis has been used to evaluate MYCN gene copy numbers. MYCN was considered to be amplified if more than 10 copies of the gene were detected. 6,7 MYCN testing was performed at the CCG Neuroblastoma Reference Laboratory, Childrens Hospital Los Angeles. Of the cases that were evaluated, 101 were classified as NBL, U/PD-H, including 6 cases of undifferentiated subtype (NA-MYCN, n 2; A-MYCN, n 4) and 95 cases of poorly differentiated subtype (NA-MYCN, n 31; A-MYCN, n 64). In accordance with the International Neuroblastoma Pathology Classification, all cases of NBL, U/PD-H, were placed in the UH group, regardless of the patient s age at diagnosis. Clinical Information For the 101 patients with NBL, U/PD-H, clinical characteristics, including age, clinical stage, 15 and protocol assignment, were compared between the A-MYCN group (n 68) and the NA-MYCN group (n 33). Event-free survival (EFS) and overall survival (OS) from the time of study entry were analyzed using the Kaplan Meier method. 16 The log-rank test was used to compare EFS and OS between the A-MYCN group and the NA-MYCN group; these survival comparisons were performed for all 101 patients with NBL, U/PD-H, and
3 176 CANCER January 1, 2005 / Volume 103 / Number 1 TABLE I System for Assessment of Histologic/Cytologic Features of Neuroblastoma, Undifferentiated/Poorly Differentiated Subtype with High MKI Morphologic feature Cellularity a High Intermediate Low Amount of neuropil Amount of cytoplasm Cellular pleomorphism Nucleolar appearance Definition 2000 cells per hpf cells per hpf 1000 cells per hpf Not detectable Barely detectable Easily detectable (occupying 50% of tumor tissue area) Abundant (occupying 50% of tumor tissue area) Not detectable Barely detectable Easily detectable Ample cytoplasm (diameter 2 times larger than nuclear diameter) Absent Focally present (25% of tumor tissue area) Present (25 50% of tumor tissue area) Diffusely present (50% of tumor tissue area) Barely detectable Easily detectable but not prominent Small but prominent Large and prominent MKI: mitosis-karyorrhexis index; hpf: high-power field. a Assessed using a BH-2 microscope (Olympus, Melville, NY) equipped with a superwide head (objective, 40; eyepiece, 10). also for the subset of 93 patients with NBL, U/PD-H, who were enrolled in the CCG-3891 (high-risk) study. Histologic/Cytologic Review Pathology slides from 90 of the 101 tumors examined had been filed at the Pathology Reference Laboratory and were available for review in the current study (range, 1 21 slides per tumor; mean, 4.8 slides per tumor). These 90 tumors included 62 from the A- MYCN group and 28 from the NA-MYCN group. The histologic and cytologic features investigated in the current study (by C.K., H.L.M.-M., and H.S.) included cellularity, amount of neuropil, amount of cytoplasm, degree of cellular pleomorphism, and nucleolar appearance (Table 1). Image Analysis for the Evaluation of Nucleolar Area Morphometric analyses of the nucleoli of neuroblastic cells in tumors from the A-MYCN group and the NA- MYCN group were performed. First, 16 tumors from the NA-MYCN group were selected for analysis (patient age range, years; Stage III, n 4; Stage IV, n 12), and then 18 age- and stage-matched tumors (patient age range, years; Stage III, n 3; Stage IV, n 15) were selected from the A-MYCN group. Representative high-resolution digital photomicrographs of each tumor were obtained using a DP-11 digital camera mounted on a BH-2 microscope (Olympus, Melville, NY) with a 100 oil immersion lens. Images were corrected for canvas size, color contrast, and brightness using Photoshop 6.0 software (Adobe, San Jose, CA), and corrected images subsequently were uploaded onto the BIOQUANT Image Analysis System (Nova Prime MST; BIO- QUANT, Nashville, TN). Calibration was performed using an objective micrometer (Olympus) and the same 100 oil immersion objective lens that was used for photomicrography. For each tumor sample, morphometric analysis was performed using topography and area arrays, with nucleolar perimeter being manually delineated in 50 cells containing visible nucleoli. When multiple nucleoli were present in a single nucleus, an additive mode function was used to ensure that the reported value represented the nucleolar area per cell. The results of all array measurements were downloaded onto an Excel spreadsheet (Microsoft, Redmond, WA); average and median nucleolar areas, along with standard deviations, were calculated using the built-in formula functions. After these calculations were performed, the t test was used to compare the NA-MYCN group and the A-MYCN group with respect to average nucleolar area. RESULTS Clinical Characteristics The median age at diagnosis of NBL, U/PD-H, was 1.78 years (range, years). The distribution of ages at diagnosis peaked between 1 and 1.5 years for patients in the A-MYCN group, with most patients in this group (61 of 68 [89.7%]) having been diagnosed between ages 0.5 and 3.5 years (Fig. 1). In contrast, patients in the NA-MYCN group were evenly distributed with respect to age at diagnosis, with patients as old as age years being found in this group. All patients in the A-MYCN group had advanced-stage disease (Stage III, n 12; Stage IV, n 56). The vast majority of patients in the NA-MYCN group (30 of 33 [90.9%]) also had advanced-stage disease (Stage III, n 9; Stage IV, n 21), although 3 patients in this group had Stage II tumors. Sixty-seven patients in the A-MYCN group (age 1 year with Stage III disease, n 11; age 1 year with Stage IV disease, n 10; age 1 year with Stage IV disease, n 46) and 26 patients in the NA-MYCN group (age 1 year, n 26; Stage III disease, n 7; Stage IV disease, n 19) received the CCG-3891 (high-
4 Large Nucleoli in MYCN-Amplified NB/Kobayashi et al. 177 FIGURE 1. Distribution of ages at diagnosis for patients with neuroblastoma (Schwannian stroma poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index. MYCN-amplified cases, n 68; MYCNnonamplified cases, n 33. risk) protocol, whereas 1 patient in the A-MYCN group (age 1 year with Stage III disease) and 7 patients in the NA-MYCN group (age 1 year, n 7; Stage II disease, n 3; Stage III disease, n 2; Stage IV disease, n 2) received the CCG-3881 (low-/intermediate-risk) protocol. The expected 10-year EFS (15.7%) and OS rates (22.2%) for patients in the A-MYCN group were significantly lower than the corresponding rates (56.1% and 69.3%, respectively) for patients in the NA-MYCN group (P and P , respectively). When only patients who received the CCG protocol were considered, significant differences between the A-MYCN group and the NA-MYCN group in terms of EFS (14.2% vs. 52.9%; P ) and OS (20.8% vs. 61.3%; P ) remained (Fig. 2). Histologic/Cytologic Features Table 2 summarizes the histologic features of the 62 tumors in the A-MYCN group and the 28 tumors in the NA-MYCN group. There were no statistical differences between the A-MYCN group and the NA-MYCN group in terms of cellularity, amount of neuropil, amount of cytoplasm, or extent of cellular pleomorphism. Nucleoli were prominent (large or small) in the majority of tumors in both groups (NA-MYCN, 71.4%; A-MYCN, 88.7%); however, 1 or more large, prominent nucleoli were detected in more than half of all tumors in the A-MYCN group (33 of 62 [53.2%]), compared with only 14.3% of all tumors in the NA-MYCN group (4 of 28; P ) (Fig. 3). It was noted that nucleolar enlargement, if present in a given tumor, was evident in every microscopic field corresponding to that tumor. Nonetheless, the proportion of cells containing prominent nucleoli varied from tumor to tumor; in some cases, almost all FIGURE 2. Prognosis for high-risk patients with neuroblastoma (Schwannian stroma poor), undifferentiated/poorly differentiated subtype with high mitosiskaryorrhexis index, who received the Children s Cancer Group 3891 treatment protocol. (A) Event-free survival (P 0.006). (B) Overall survival (P ). NA-MYCN: nonamplified MYCN (n 26); A-MYCN: amplified MYCN (n 67). tumor cells contained prominent nucleoli, whereas other tumors were composed of a combination of tumor cells with and without prominent nucleoli. This variability may be attributable in part to poor sample preservation and/or fixation. Morphometric analysis (Fig. 4) revealed that nucleolar area was significantly larger in the A-MYCN group than in the NA-MYCN group. The mean nucleolar area for tumors in the A-MYCN group was 7.63 m 2, compared with 5.53 m 2 in the NA-MYCN group (P 0.004). DISCUSSION pnts represent one of the best models for investigating correlations between genotypic (i.e., molecular) properties and phenotypic (i.e., morphologic) manifestations. In the current study, we analyzed a group of neuroblastomas that had unique histologic features namely, poor or no differentiation and a high MKI. All tumors examined had UH according to the International Neuroblastoma Pathology Classification, and more than two-thirds of these tumors exhibited MYCN amplification. Thus, most of the patients included in the current study received the high-risk protocol in our previous clinical trial (CCG-3891). Our findings indicate that MYCN status (amplified or nonamplified) was significantly associated with age at diagnosis and clinical outcome. In addition, histologic/cytologic examination revealed that in tumors exhibiting MYCN amplification, the nuclear appearance of neuroblastic cells was characterized by the presence of one or more large, prominent nucleoli. NBL, U/PD-H, exhibiting MYCN amplification ac-
5 178 CANCER January 1, 2005 / Volume 103 / Number 1 TABLE II Morphologic Characteristics of Neuroblastoma, Undifferentiated/Poorly Differentiated Subtype with High MKI Characteristic A-MYCN No. of cases (%) NA-MYCN Cellularity High 54 (87.1) 22 (78.6) Intermediate 7 (11.3) 6 (21.4) Low 1 (1.6) 0 (0) Amount of neuropil 4 (6.5) 2 (7.1) 6 (9.7) 1 (3.6) 49 (79.0) 22 (78.6) 3 (4.8) 3 (10.7) 0 (0) 0 (0) Amount of cytoplasm 8 (12.9) 3 (10.7) 35 (56.5) 13 (46.4) 19 (30.6) 12 (42.9) 0 (0) 0 (0) Pleomorphism 46 (74.2) 20 (71.4) 10 (16.1) 4 (14.3) 3 (4.8) 3 (10.7) 3 (4.8) 1 (3.6) Nucleolar appearance 0 (0) 1 (3.6) 7 (11.3) 7 (25.0) 22 (35.5) 16 (57.1) 33 (53.2) 4 (14.3) Total 62 (100) 28 (100) MKI: mitosis-karyorrhexis index; A-MYCN: amplified MYCN; NA-MYCN: nonamplified MYCN. counted for 10.8% of all pnts in the CCG-3881 and CCG-3891 studies (68 of 628) and appeared to develop in patients with a relatively uniform set of clinical characteristics. Such tumors tended to be diagnosed in advanced clinical stages, with the distribution of patient ages at diagnosis showing a single peak between 0.5 and 1.5 years. Despite the use of an intensive treatment strategy, NBL, U/PD-H, with MYCN amplification was found to carry a poor prognosis. NBL, U/PD-H, without MYCN amplification was relatively rare, accounting for 5.3% of all pnts in the CCG-3881 and CCG-3891 studies (33 of 628). These tumors also were typically diagnosed in advanced clinical stages; however, unlike their counterparts in the A-MYCN group, tumors in the NA-MYCN group were diagnosed with comparable frequency across a range of ages, from infancy to later in childhood. Furthermore, among patients receiving intensive treatment, these tumors were associated with significantly higher survival rates compared with tumors that exhibited MYCN amplification. In the current report, we have confirmed the presence of a significant association between nucleolar enlargement and MYCN amplification in NBL, U/PD-H. Two other reports have documented an association between prominent nucleoli and poor clinical outcome in patients with neuroblastoma. 17,18 Nonetheless, to our knowledge, the current report is the first to clearly demonstrate a significant correlation between MYCN amplification and nucleolar enlargement in undifferentiated neuroblasts. Similar nucleolar enlargement has been observed in differentiating neuroblasts and ganglion cells in tumors that typically do not exhibit MYCN amplification. It should be noted that either single or multiple enlarged nucleoli were found in undifferentiated neuroblasts from tumors exhibiting MYCN amplification and that such nucleolar enlargement was never accompanied by cytoplasmic differentiation. In contrast, the prominent nucleoli found in differentiating neuroblasts and ganglion cells typically are single and situated in eccentrically located vesicular nuclei, and nucleolar enlargement normally is accompanied by cytoplasmic enlargement (cytoplasmic diameter 2 times the nuclear diameter) in this setting. In 1991, Matsumoto et al. 19 reported the presence of large, prominent nucleoli in proliferating cells from seven small cell lung carcinoma cell lines, with these cells exhibiting rapid growth, elevated S-phase fraction, and elevated c-myc or N-myc oncogene expression. In addition, using AgNOR staining (i.e., silver staining of proteins associated with nuclear organizing regions), both Pession et al. 20 (in seven neuroblastoma cell lines) and Derenzini et al. 21 (in xenograft models of seven colon carcinoma cell lines and three neuroblastoma cell lines) found that increased nucleolar area was significantly correlated with shorter tumor cell doubling time. Pession and colleagues also reported that the mean AgNOR-stained area in MYCNamplified neuroblastomas (n 9) was not significantly different from the corresponding area in MYCN-nonamplified neuroblastomas (n 39). Nonetheless, the current study, in which morphometric analysis was used to directly measure nucleolar area in hematoxylin and eosin stained sections, clearly demonstrated that the mean nucleolar area in neuroblastic cells was significantly larger in the A-MYCN group than in the NA-MYCN group. As has been reported in tissue culture cells 22,23 and mouse Sertoli cells, 23 the presence of large, prominent nucleoli in tumors in the A-MYCN group may be attributable to the nuclear localization and/or accumulation of the MYC transcript. Recent advances in clinical, translational, and basic research clearly suggest that the identification of molecular targets will be critical in the development of
6 Large Nucleoli in MYCN-Amplified NB/Kobayashi et al. 179 FIGURE 3. Typical nuclear features in neuroblastoma (Schwannian stroma poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index. (A) Large, prominent nucleoli (arrows) in neuroblastic cells from an MYCN-amplified tumor. (B) Prominent but small nucleoli (arrows) in neuroblastic cells from an MYCN-nonamplified tumor. Original magnification therapeutic strategies for the management of patients with pnts. In the current study, tumors histologically classified as NBL, U/PD-H, according to the International Neuroblastoma Pathology Classification were found to vary in terms of molecular background and clinical behavior. NBL, U/PD-H, exhibiting MYCN amplification appeared to constitute a uniform group of tumors that carried a poor prognosis, and these tumors were characterized by the frequent presence of one or more large, prominent nucleoli in undifferentiated neuroblastic cells. In contrast, the molecular properties of tumors in the NA-MYCN group have not yet been investigated. In conclusion, we believe that the data presented in the current genotypic, phenotypic, and clinical analysis of neuroblastomas will facilitate further collaboration among those investigating this highly complex disease. FIGURE 4. Mean nucleolar area as determined by image analysis in neuroblastoma (Schwannian stroma poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index. Each circle represents the average of 50 nucleolar areas from a given tumor. Horizontal bars represent group averages (P 0.004). A-MYCN: amplified MYCN (n 18); NA-MYCN: nonamplified MYCN (n 16). REFERENCES 1. Brodeur GM, Maris JM. Neuroblastoma. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology (4th edition). Philadelphia: Lippincott Williams & Wilkins, 2002: Shimada H, Chatten J, Newton WA, et al. Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst. 1984;73: Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B. Terminology and morphologic criteria of neuroblastic tumors. Recommendations by the International Neuroblastoma Pathology Committee. Cancer. 1999;86: Shimada H, Umehara S, Monobe Y, et al. International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors. A report from the Children s Cancer Group. Cancer. 2001;92: Shimada H, Ambros IM, Dehner LP, et al. The International Neuroblastoma Pathology Classification (the Shimada system). Cancer. 1999;86: Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM. Amplification of N-myc in untreated human neuroblastoma correlates with advanced disease stage. Science. 1984;224: Seeger RC, Brodeur GM, Sather H, et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985;313:
7 180 CANCER January 1, 2005 / Volume 103 / Number 1 8. Shimada H, Stram DO, Chatten J, et al. Identification of subsets of neuroblastoma by combined histopathologic and N-myc analysis. J Natl Cancer Inst. 1995;19: Schwab M. MYCN amplification in neuroblastoma. In: Brodeur GM, Sawada T, Tsuchida Y, Voute PA, editors. Neuroblastoma. Amsterdam: Elsevier, 2000: Perez CA, Matthay KK, Atkinson JB, et al. Biologic variables in the outcome of Stage I and II neuroblastoma treated with surgery as primary therapy: a Children s Cancer Group Study. J Clin Oncol. 2000;18: Matthay KK, Perez CA, Seeger RC, et al. Successful treatment of Stage III neuroblastoma based on prospective biological staging: a Children s Cancer Group study. J Clin Oncol. 1998;16: Schmidt ML, Lukens JN, Seeger RC, et al. Biologic factors determined prognosis in infants with Stage IV neuroblastoma: a prospective Children s Cancer Group study. J Clin Oncol. 2000;18: Matthay KK, Villablanca JG, Seeger RC, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med. 1999;341: Goto S, Umehara S, Gerbing RB, et al. Histopathology (International Neuroblastoma Pathology Classification) and MYCN status in patients with peripheral neuroblastic tumors. A report from the Children s Cancer Group. Cancer. 2001;92: Evans AE, D Angio GJ, Randolph J. A proposed staging for children with neuroblastoma. Cancer. 1971;27: Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53: Ambros IM, Hata J, Joshi VV, et al. Morphologic features of neuroblastoma (Schwannian atroma-poor tumors) in clinically favorable and unfavorable groups. Cancer. 2002;94: Tornoczky T, Kalman E, Kajtar P, et al. Large cell neuroblastoma a distinct phenotype of neuroblastoma with aggressive clinical behavior. Cancer. 2004;100: Matsumoto T, Terasaki T, Mukai K, et al. Relation between nucleolar size and growth characteristics in small cell lung cancer cell lines. Jpn J Cancer Res. 1991;82: Pession A, Trere D, Perri P, et al. N-myc amplification and cell proliferation rate in human neuroblastoma. J Pathol. 1997;183: Derenzini M, Trere D, Pession A, Govoni M, Sirri V, Chieco P. Nucleolar size indicates the rapidity of cell proliferation in cancer tissues. J Pathol. 2000;191: Arabi A, Rustum C, Hallberg E, Wright AP. Accumulation of c-myc and proteasome at the nucleoli of cells containing elevated c-myc protein levels. J Cell Sci. 2003;116: Bond VC, Wold B. Nucleolar localization of myc transcripts. Mol Cell Biol. 1993;13:
Histopathology Defines Prognostic Subsets of Ganglioneuroblastoma, Nodular
1150 Histopathology Defines Prognostic Subsets of Ganglioneuroblastoma, Nodular A Report from the Children s Cancer Group Shunsuke Umehara, M.D. 1 Atsuko Nakagawa, M.D. 1 Katherine K. Matthay, M.D. 2 John
More informationHistopathology (International Neuroblastoma Pathology Classification) and MYCN Status in Patients with Peripheral Neuroblastic Tumors
2699 Histopathology (International Neuroblastoma Pathology Classification) and MYCN Status in Patients with Peripheral Neuroblastic Tumors A Report from the Children s Cancer Group Shoko Goto, M.D. 1 Shunsuke
More informationganglioneuroma (GN; Schwannian stroma-dominant); Takeda et al. Journal of Medical Case Reports (2018) 12:119 https://doi.org/ /s
Takeda et al. Journal of Medical Case Reports (2018) 12:119 https://doi.org/10.1186/s13256-018-1640-0 CASE REPORT Open Access Usefulness of fluorodeoxyglucose positron emission tomography/computed tomography
More informationRecommendations for Reporting of Tumors of the Adrenal Cortex and Medulla
A J C P / REPORTING OF TUMORS OF THE ADRENAL CORTEX AND MEDULLA Recommendations for Reporting of Tumors of the Adrenal Cortex and Medulla Association of Directors of Anatomic and Surgical Pathology" Key
More informationPublished Ahead of Print on October 3, 2011 as /JCO J Clin Oncol by American Society of Clinical Oncology INTRODUCTION
Published Ahead of Print on October 3, 11 as 10.10/JCO.11.35.9570 The latest version is at http://jco.ascopubs.org/cgi/doi/10.10/jco.11.35.9570 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T
More informationSurgical Outcomes of Patients with Neuroblastoma in a Tertiary Centre in Hong Kong: A 12-year Experience
HK J Paediatr (new series) 2009;14:186-193 Surgical Outcomes of Patients with Neuroblastoma in a Tertiary Centre in Hong Kong: A 12-year Experience IHY CHAN, KKY WONG, GCF CHAN, PKH TAM Abstract Key words
More informationJ Clin Oncol 29: by American Society of Clinical Oncology INTRODUCTION
VOLUME 29 NUMBER 33 NOVEMBER 11 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Prognostic Value of the Stage 4S Metastatic Pattern and Tumor Biology in Patients With Metastatic Neuroblastoma
More informationStandards and datasets for reporting cancers. Dataset for peripheral neuroblastic tumours histopathology reports
Standards and datasets for reporting cancers Dataset for peripheral neuroblastic tumours histopathology reports December 2010 Coordinator: Dr Catherine Cullinane, Leeds Teaching Hospitals Trust Unique
More informationChromosome 1p and 11q Deletions and Outcome in Neuroblastoma
original article Chromosome 1p and 11q Deletions and Outcome in Neuroblastoma Edward F. Attiyeh, M.D., Wendy B. London, Ph.D., Yael P. Mossé, M.D., Qun Wang, M.D., Ph.D., Cynthia Winter, B.A., Deepa Khazi,
More informationJ Clin Oncol 30: by American Society of Clinical Oncology INTRODUCTION
VOLUME 30 NUMBER 15 MAY 20 2012 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Douglas R. Strother, University of Calgary and Alberta Children s Hospital, Calgary, Alberta; Paul Thorner, Hospital
More informationProtocol applies to the examination of specimens from patients with neuroblastoma and related neuroblastic tumors.
Neuroblastoma Protocol applies to the examination of specimens from patients with neuroblastoma and related neuroblastic tumors. Procedures Cytology (No Accompanying Checklist) Incisional Biopsy (Needle
More informationMorphologic Alteration of Metastatic Neuroblastic Tumor in Bone Marrow after Chemotherapy
The Korean Journal of Pathology 2013; 47: 433-442 ORIGINAL ARTICLE Morphologic Alteration of Metastatic Neuroblastic Tumor in Bone Marrow after Chemotherapy Go Eun Bae Yeon-Lim Suh Ki Woong Sung 1 Jung-Sun
More informationPresence of Differentiating Neuroblasts in Bone Marrow is a Favorable Prognostic Factor for Bone Marrow Metastatic Neuroblastoma at Diagnosis
Original Article Diagnostic Hematology Ann Lab Med 2013;33:89-96 ISSN 2234-3806 eissn 2234-3814 Presence of Differentiating Neuroblasts in Bone Marrow is a Favorable Prognostic Factor for Bone Marrow Metastatic
More informationNature Genetics: doi: /ng Supplementary Figure 1. Phenotypic characterization of MES- and ADRN-type cells.
Supplementary Figure 1 Phenotypic characterization of MES- and ADRN-type cells. (a) Bright-field images showing cellular morphology of MES-type (691-MES, 700-MES, 717-MES) and ADRN-type (691-ADRN, 700-
More informationAssociation of microrna 21 With Biological Features and Prognosis of Neuroblastoma
Special Report Association of microrna 21 With Biological Features and Prognosis of Neuroblastoma Yaodong Zhou, MD, and Bo Sheng, MD Background: The aim of this study was to assess the differences in microrna
More informationProtocol for the Examination of Specimens from Patients with Neuroblastoma
Protocol for the Examination of Specimens from Patients with Neuroblastoma Protocol applies to neuroblastoma and related neuroblastic tumors. No AJCC/UICC TNM Staging System The International Neuroblastoma
More informationORIGINAL ARTICLE CLINICOPATHOLOGICAL ANALYSIS AND CLASSIFICATION OF NEUROBLASTIC TUMOURS - EXPERIENCE OF PAEDIATRIC HOSPITAL
CLINICOPATHOLOGICAL ANALYSIS AND CLASSIFICATION OF NEUROBLASTIC TUMOURS - EXPERIENCE OF PAEDIATRIC HOSPITAL M. Ramani 1, Kazi Wajid Husain 2, O. H. Radhika Krishna 3, Ramesh Reddy 4, P.Sreenivasa Reddy
More informationDepartment of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland; 2
& 2005 USCAP, Inc All rights reserved 0893-3952/05 $30.00 www.modernpathology.org Chromogenic in situ hybridization-detected hotspot MYCN amplification associates with Ki-67 expression and inversely with
More informationNeuroblastoma. Elizabeth Roberts. Data Coordinator CIBMTR Data Managers Mentor. Tandem Meeting February 18
Neuroblastoma Elizabeth Roberts Data Coordinator CIBMTR Data Managers Mentor Tandem Meeting February 18 Objectives Know what neuroblastoma is, how it is diagnosed, and how it is treated Complete form 2026:
More informationRecommendations for Modification of Terminology of Neuroblastic Tumors and Prognostic Significance of Shimada Classification
2183 Recommendations for Modification of Terminology of Neuroblastic Tumors and Prognostic Significance of Shimada Classification A Clinicopathologic Study of 2 13 Cases From the Pediatric Oncology Group
More informationOncologist. The. Neuro-Oncology. Case Report: An Unusual Case of Adrenal Neuroblastoma in Pregnancy
The Oncologist Neuro-Oncology Case Report: An Unusual Case of Adrenal Neuroblastoma in Pregnancy MARWAN M. REFAAT, a SHEREENE Z. IDRISS, b LAWRENCE S. BLASZKOWSKY a,c a Department of Medicine, b Department
More informationThe Role of ploidy in neuroblastoma. Michael D. Hogarty, MD Division of Oncology Children s Hospital of Philadelphia
The Role of ploidy in neuroblastoma Reprinted from NB Journal Summer Issue 2003 Children s Neuroblastoma Cancer Foundation Michael D. Hogarty, MD Division of Oncology Children s Hospital of Philadelphia
More informationUSCAP 2012: Companion Meeting of the AAOOP. Update on lacrimal gland neoplasms: Molecular pathology of interest
USCAP 2012: Companion Meeting of the AAOOP Vancouver BC, Canada, March 17, 2012 Update on lacrimal gland neoplasms: Molecular pathology of interest Valerie A. White MD, MHSc, FRCPC Department of Pathology
More informationThe Harvard community has made this article openly available. Please share how this access benefits you. Your story matters
MYC-family protein overexpression and prominent nucleolar formation represent prognostic indicators and potential therapeutic targets for aggressive high-mki neuroblastomas: a report from the children
More informationPulmonary Metastases at Diagnosis of Neuroblastoma in Pediatric Patients: CT Findings and Prognosis
amidele F. Kammen 1,2 Katherine K. Matthay 3 Preeyacha Pacharn 1,4 Robert Gerbing 5 Robert C. rasch 1,3 Charles. Gooding 1,3 Received June 30, 2000; accepted after revision ugust 28, 2000. Supported by
More informationGray Zones and Double Hits Distinguishing True Burkitt Lymphoma from Other High-Grade B-NHLs Burkitt Lymphoma Burkitt-Like Lymphoma DLBCL Patrick Tres
Gray Zones and Double Hits Distinguishing True Burkitt Lymphoma from Other High-Grade B-NHLs Burkitt Lymphoma Burkitt-Like Lymphoma DLBCL Patrick Treseler, MD, PhD University of California San Francisco
More informationOutcome after Reduced Chemotherapy for Intermediate-Risk Neuroblastoma
original article Outcome after Reduced Chemotherapy for Intermediate-Risk Neuroblastoma David L. Baker, M.D., Mary L. Schmidt, M.D., Susan L. Cohn, M.D., John M. Maris, M.D., Wendy B. London, Ph.D., Allen
More informationProtocol for the Examination of Specimens From Patients With Neuroblastoma*
Protocol for the Examination of Specimens From Patients With Neuroblastoma* Version: Neuroblastoma 3.1.0.3 Protocol Posting Date: August 2016 This protocol is NOT required for accreditation purposes *This
More informationPredicting clinical outcomes in neuroblastoma with genomic data integration
Predicting clinical outcomes in neuroblastoma with genomic data integration Ilyes Baali, 1 Alp Emre Acar 1, Tunde Aderinwale 2, Saber HafezQorani 3, Hilal Kazan 4 1 Department of Electric-Electronics Engineering,
More informationNeuroblastoma: experience from National University Health System, Singapore ( )
Singapore Med J 2012; 53(1) : 19 Neuroblastoma: experience from National University Health System, Singapore (1987 2008) Tan C 1, BA, Sabai SM 2, MBBS, Tin AS 3, MBBS, MMed, Quah TC 4, MBBS, MMed, Aung
More informationMass Histology Service
Mass Histology Service A complete anatomical pathology laboratory www.masshistology.com Telephone: (877) 286-6004 Report on Pathology A Time Course Study of the Local Effects of Intramuscular XXXXXXX Injection
More informationRESEARCH ARTICLE NEUROBLASTOMA;VARIABLE SYMPTOMS OF A NEUROGENIC TUMOR; A REPORT FROM IRAN
RESEARCH ARTICLE NEUROBLASTOMA;VARIABLE SYMPTOMS OF A NEUROGENIC TUMOR; A REPORT FROM IRAN M. T. Arzanian MD, H. Esfahani MD. Assistant professor, pediatric Hematologist and Oncologist, Mofid s Children
More informationNEUROBLASTOMA IS the most common extracranial
Correlation of Early Metastatic Response by 123 I-Metaiodobenzylguanidine Scintigraphy With Overall Response and Event-Free Survival in Stage IV Neuroblastoma By Katherine K. Matthay, Veronique Edeline,
More informationCase 3. Ann T. Moriarty,MD
Case 3 Ann T. Moriarty,MD Case 3 59 year old male with asymptomatic cervical lymphadenopathy. These images are from a fine needle biopsy of a left cervical lymph node. Image 1 Papanicolaou Stained smear,100x.
More informationRaman spectroscopic investigation of frozen and deparaffinized tissue sections of pediatric tumors: neuroblastoma and ganglioneuroma
Research article Received: 6 January 2012 Revised: 1 July 2012 Accepted: 26 October 2012 Published online in Wiley Online Library: 21 November 2012 (wileyonlinelibrary.com) DOI 10.1002/jrs.4223 Raman spectroscopic
More informationThe Adrenal Glands. I. Normal adrenal gland A. Gross & microscopic B. Hormone synthesis, regulation & measurement. II.
The Adrenal Glands Thomas Jacobs, M.D. Diane Hamele-Bena, M.D. I. Normal adrenal gland A. Gross & microscopic B. Hormone synthesis, regulation & measurement II. Hypoadrenalism III. Hyperadrenalism; Adrenal
More informationNEUROBLASTOMA is a childhood cancer that
Vol. 334 No. 4 ALLELIC LOSS OF CHROMOSOME 1p AND PROGNOSIS IN NEUROBLASTOMA 22 ALLELIC LOSS OF CHROMOSOME 1p AS A PREDICTOR OF UNFAVORABLE OUTCOME IN PATIENTS WITH NEUROBLASTOMA HUIB CARON, M.D., PH.D.,
More informationCorrelation between expression and significance of δ-catenin, CD31, and VEGF of non-small cell lung cancer
Correlation between expression and significance of δ-catenin, CD31, and VEGF of non-small cell lung cancer X.L. Liu 1, L.D. Liu 2, S.G. Zhang 1, S.D. Dai 3, W.Y. Li 1 and L. Zhang 1 1 Thoracic Surgery,
More informationClinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma
ORIGINAL ARTICLE Oncology & Hematology http://dx.doi.org/1.3346/jkms.15.3.8.162 J Korean Med Sci 15; 3: 162-167 Clinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma
More informationCytological grading of breast carcinoma with histological correlation
Journal of BUON 10: 251-256, 2005 2005 Zerbinis Medical Publications. Printed in Greece ORIGINAL ARTICLE Cytological grading of breast carcinoma with histological correlation M. Jovicić-Milentijević 1,
More informationDiplomate of the American Board of Pathology in Anatomic and Clinical Pathology
A 33-year-old male with a left lower leg mass. Contributed by Shaoxiong Chen, MD, PhD Assistant Professor Indiana University School of Medicine/ IU Health Partners Department of Pathology and Laboratory
More informationJ of Evolution of Med and Dent Sci/ eissn , pissn / Vol. 3/ Issue 19/May 12, 2014 Page 5307
PROGNOSTIC SIGNIFICANCE OF PROLIFERATIVE ACTIVITY (KI67 EXPRESSION) IN OSTEOSARCOMA IN CHILDREN Moumita Paul 1, Arnab Karmakar 2, Uttara Chatterjee 3, Uttam Kumar Saha 4, Koushik Saha 5, Nanda Dulal Chatterjee
More informationremoval and cut into slices (approximately 2 mm wax, sectioned at 4,tm, stained by Harris's and mounted in balsam.
J Clin Pathol 198;35:954-958 Study of nuclear diameters in non-hodgkin's lymphomas J CROCKER, EL JONES, RC CURRAN From the Department ofpathology, The Medical School, University ofbirmingham, Edgbaston,
More informationG3.02 The malignant potential of the neoplasm should be recorded. CG3.02a
G3.02 The malignant potential of the neoplasm should be recorded. CG3.02a Conventional adrenocortical neoplasm. Each of the below parameters is scored 0 when absent and 1 when present. 3 or more of these
More informationCINtec PLUS Cytology. Interpretation training
CINtec PLUS Cytology Interpretation training Objectives After reviewing this learning module, you will have a basic understanding of how to interpret CINtec PLUS Cytology, including: The mechanism of action
More informationNon-Hodgkin lymphomas (NHLs) Hodgkin lymphoma )HL)
Non-Hodgkin lymphomas (NHLs) Hodgkin lymphoma )HL) Lymphoid Neoplasms: 1- non-hodgkin lymphomas (NHLs) 2- Hodgkin lymphoma 3- plasma cell neoplasms Non-Hodgkin lymphomas (NHLs) Acute Lymphoblastic Leukemia/Lymphoma
More informationPathological Classification of Hepatocellular Carcinoma
3 rd APASL Single Topic Conference: HCC in 3D Pathological Classification of Hepatocellular Carcinoma Glenda Lyn Y. Pua, M.D. HCC Primary liver cancer is the 2 nd most common cancer in Asia HCC is the
More informationCurrent update on diagnosis and management of neuroblastoma
Leading Article Current update on diagnosis and management of neuroblastoma Julius Scott 1 Sri Lanka Journal of Child Health, 2016; 45(4): 241-246 DOI: http://dx.doi.org/10.4038/sljch.v45i4.8182 (Key words:
More informationProceedings of the 36th World Small Animal Veterinary Congress WSAVA
www.ivis.org Proceedings of the 36th World Small Animal Veterinary Congress WSAVA Oct. 14-17, 2011 Jeju, Korea Next Congress: Reprinted in IVIS with the permission of WSAVA http://www.ivis.org 14(Fri)
More informationNeuroendocrine Lung Tumors Myers
Diagnosis and Classification of Neuroendocrine Lung Tumors Jeffrey L. Myers, M.D. A. James French Professor Director, Anatomic Pathology & MLabs University of Michigan, Ann Arbor, MI myerjeff@umich.edu
More informationKobe University Repository : Kernel
Title Author(s) Citation Kobe University Repository : Kernel Issue date 1997-01-24 Resource Type Resource Version DOI URL Argyrophilic Nucleolar Organizer Regions (AgNOR) in Colorectal Cancer Patients
More informationPrognostic Significance of Gene Expression Profiles of Metastatic Neuroblastomas Lacking MYCN Gene Amplification
Prognostic Significance of Gene Expression Profiles of Metastatic Neuroblastomas Lacking MYCN Gene Amplification Shahab Asgharzadeh, Roger Pique-Regi, Richard Sposto, Hong Wang, Yujun Yang, Hiroyuki Shimada,
More informationInternational Society of Gynecological Pathologists Symposium 2007
International Society of Gynecological Pathologists Symposium 2007 Anais Malpica, M.D. Department of Pathology The University of Texas M.D. Anderson Cancer Center Grading of Ovarian Cancer Histologic grade
More informationACCME/Disclosures. Cribriform Lesions of the Prostate. Case
Cribriform Lesions of the Prostate Ming Zhou, MD, PhD Departments of Pathology and Urology New York University Langone Medical Center New York, NY Ming.Zhou@NYUMC.ORG ACCME/Disclosures The USCAP requires
More informationCANCER. Clinical Validation of Breast Cancer Predictive Markers
Clinical Validation of Breast Cancer Predictive Markers David Hicks, MD Loralee McMahon, MS, HTL(ASCP) CANCER The human body is composed of billions of highly regulated cells Cancer cells no longer respond
More informationUniversity Journal of Pre and Para Clinical Sciences
ISSN 2455 2879 Volume 2 Issue 1 2016 Metaplastic carcinoma breast a rare case report Abstract : Metaplastic carcinoma of the breast is a rare malignancy with two distinct cell lines described as a breast
More informationCase year old female presented with asymmetric enlargement of the left lobe of the thyroid
Case 4 22 year old female presented with asymmetric enlargement of the left lobe of the thyroid gland. No information available relative to a prior fine needle aspiration biopsy. A left lobectomy was performed.
More informationCase 4 Diagnosis 2/21/2011 TGB
Case 4 22 year old female presented with asymmetric enlargement of the left lobe of the thyroid gland. No information available relative to a prior fine needle aspiration biopsy. A left lobectomy was performed.
More informationPediatric Oncology. Vlad Radulescu, MD
Pediatric Oncology Vlad Radulescu, MD Objectives Review the epidemiology of childhood cancer Discuss the presenting signs and symptoms, general treatment principles and overall prognosis of the most common
More informationNeuroblastoma Originating from Extra-abdominal Sites: Association with Favorable Clinical and Biological Features
J Korean Med Sci 2009; 24: 461-7 ISSN 1011-8934 DOI: 10.3346/jkms.2009.24.3.461 Copyright The Korean Academy of Medical Sciences Neuroblastoma Originating from Sites: Association with Favorable Clinical
More informationPresacral Neuroblastoma Joseph Junewick, MD FACR
Presacral Neuroblastoma Joseph Junewick, MD FACR 01/12/2010 History 16 month old male with irritability. Diagnosis Presacral Neuroblastoma Additional Clinical Initial US to evaluate for intussusception
More informationnumber Done by Corrected by Doctor Maha Shomaf
number 16 Done by Waseem Abo-Obeida Corrected by Zeina Assaf Doctor Maha Shomaf MALIGNANT NEOPLASMS The four fundamental features by which benign and malignant tumors can be distinguished are: 1- differentiation
More informationBONE MARROW involvement by neuroblastoma is
Quantitative Tumor Cell Content of Bone Marrow and Blood as a Predictor of Outcome in Stage IV Neuroblastoma: A Children s Cancer Group Study By Robert C. Seeger, C. Patrick Reynolds, Richard Gallego,
More informationXXV Congreso de la Sociedad Española de Anatomía Patológica y División Española de la International Academy of Pathology
XXV Congreso de la Sociedad Española de Anatomía Patológica y División Española de la International Academy of Pathology NUEVOS FENOTIPOS DEL CÁNCER DE MAMA: NUEVOS PROBLEMAS PARA EL PATÓLOGO? Tienen actualmente
More informationNuclear morphometric study of Non- Hodgkin's Lymphoma (NHL)
Original Research Article Nuclear morphometric study of Non- Hodgkin's Lymphoma (NHL) Sridhar Reddy Erugula 1, P. Sujatha 2, Ayesha Sameera 3, B. Suresh Reddy 4, Jesudass Govada 5, G. Sudhakar 6, Kandukuri
More informationPROCARBAZINE, lomustine, and vincristine (PCV) is
RAPID PUBLICATION Procarbazine, Lomustine, and Vincristine () Chemotherapy for Anaplastic Astrocytoma: A Retrospective Review of Radiation Therapy Oncology Group Protocols Comparing Survival With Carmustine
More informationAdult onset of ganglioneuroblastoma of the adrenal gland: case report and review of the literature
Bolzacchini et al. Surgical Case Reports (2015)1:79 DOI 10.1186/s40792-015-0062-0 CASE REPORT Adult onset of ganglioneuroblastoma of the adrenal gland: case report and review of the literature Elena Bolzacchini
More informationCNS pathology Third year medical students. Dr Heyam Awad 2018 Lecture 12: CNS tumours 2/3
CNS pathology Third year medical students Dr Heyam Awad 2018 Lecture 12: CNS tumours 2/3 Pilocytic astrocytoma Relatively benign ( WHO grade 1) Occurs in children and young adults Mostly: in the cerebellum
More informationDIAGNOSTIC SLIDE SEMINAR: PART 1 RENAL TUMOUR BIOPSY CASES
DIAGNOSTIC SLIDE SEMINAR: PART 1 RENAL TUMOUR BIOPSY CASES Dr. Andrew J. Evans MD, PhD, FACP, FRCPC Consultant in Genitourinary Pathology University Health Network, Toronto, ON Case 1 43 year-old female,
More informationThe New England Journal of Medicine
The New England Journal of Medicine Copyright, 1999, by the Massachusetts Medical Society VOLUME 31 O CTOBER 1, 1999 NUMBER 16 TREATMENT OF HIGH-RISK NEUROBLASTOMA WITH INTENSIVE CHEMOTHERAPY, RADIOTHERAPY,
More informationGlioblastoma Multiforme
Glioblastoma Multiforme Highly malignant, invasive, difficult-to-treat primary brain tumor" " Frequency: 9,000 cases/year (peak age, 55 65 years)" " Recurrence: rapid growth; size may double every 10 days"
More informationNeuroendocrine neoplasms of the lung
Neuroendocrine neoplasms of the lung M Papotti, L Righi, & M Volante University of Turin at San Luigi Hospital TORINO NETs OF THE LUNG Menu - Spectrum of NE lung tumors - CARCINOID TUMORS - SCLC /LCNEC
More informationSmall cell neuroendocrine carcinoma icd 10
Small cell neuroendocrine carcinoma icd 10 1-10-2017 Free, official coding info for 2018 ICD - 10 -CM C34.90 - includes detailed rules, notes, synonyms, ICD -9- crosswalks, DRG. In most series, LCLC's
More informationALAEZI CM 1 *, ADISA JO 2, OKOROCHI EC 3 and OKECHI OO 4
Global Journal of Scientific Researches Available online at gjsr.blue-ap.org 2014 GJSR Journal. Vol. 2(2), pp. 51-55, 28 February, 2014 E-ISSN: 2311-732X METHYL GREEN PYRONIN: A PROGRESSIVE NUCLEAR STAIN
More informationSIGNIFICANCE OF SILVER STAINING OF NULCEAR ORGANIZER REGIONS IN FINE NEEDLE ASPIRATION SMEARS OF BREAST LESIONS
ORIGINAL ARTICLE SIGNIFICANCE OF SILVER STAINING OF NULCEAR ORGANIZER REGIONS IN FINE NEEDLE ASPIRATION SMEARS OF BREAST LESIONS Dimple H Darad 1, Aditi D Dholakia 2, Savitri Chauhan 1 1 Associate professor;
More informationDr. Issraa Ali Hussein
CLINICAL 09888888;rCYTOLOGY Dr. Issraa Ali Hussein objectives Define diagnostic cytology (clinical cytology). Explain the differences between histopathology and cytopathology. Recognize the methods for
More informationCitation Acta medica Nagasakiensia. 1994, 39
NAOSITE: Nagasaki University's Ac Title Significance of AgNORs Ratio as a P Author(s) Hatano, Kazuhiko Citation Acta medica Nagasakiensia. 1994, 39 Issue Date 1994-10-25 URL http://hdl.handle.net/10069/15998
More informationCorporate Medical Policy
Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for Solid Tumors of File Name: Origination: Last CAP Review: Next CAP Review: Last Review: hematopoietic_stem-cell_transplantation_for_solid_tumors_childhood
More informationPeritoneal Involvement in Stage II Colon Cancer
Anatomic Pathology / PERITONEAL INVOLVEMENT IN STAGE II COLON CANCER Peritoneal Involvement in Stage II Colon Cancer A.M. Lennon, MB, MRCPI, H.E. Mulcahy, MD, MRCPI, J.M.P. Hyland, MCh, FRCS, FRCSI, C.
More informationFrom the Archives of the AFIP
AFIP ARCHIVES 911 CME FEATURE See accompanying test at http:// www.rsna.org /education /rg_cme.html LEARNING OBJECTIVES FOR TEST 6 After reading this article and taking the test, the reader will be able
More informationAn ImageJ Based Semi-Automated Morphometric Assessment of Nuclei in Oncopathology
Original Article DOI: 10.17354/ijss/2015/475 An ImageJ Based Semi-Automated Morphometric Assessment of Nuclei in Oncopathology Vijayashree Raghavan 1, K Ramesh Rao 2 1 Professor and Head, Department of
More information(From The Rockefeller Institute) Materials and Methods. Observations with the Electron Microscope
ELECTRON MICROSCOPE STUDY OF THE DEVELOPMENT OF THE PAPILLOMA VIRUS IN THE SKIN OF THE RABBIT* BY ROBERT S. STONE,~ M.D., RICHARD E. SHOPE, M.D., DAN H. MOORE, P,~.D. (From The Rockefeller Institute) PLATES
More informationNUCLEAR MORPHOMETRY IN RELATION TO METASTASES IN CANINE SPONTANEOUS CUTANEOUS SQUAMOUS CELL CARCINOMAS
Trakia Journal of Sciences, Vol. 8, No. 1, pp 74-78, 2010 Copyright 2009 Trakia University Available online at: http://www.uni-sz.bg ISSN 1313-7050 (print) ISSN 1313-3551 (online) Original Contribution
More informationBasaloid Carcinoma of the Lung: A Really Dismal Histologic Variant?
Carcinoma of the Lung: A Really Dismal Histologic Variant? Dae Joon Kim, MD, Kil Dong Kim, MD, Dong Hwan Shin, MD, Jae Y Ro, MD, and Kyung Young Chung, MD Departments of Thoracic and Cardiovascular Surgery,
More informationMorphometric Analysis of the Human Trigeminal Nerve
Okajimas Folia Anat. Jpn., 78(2-3): 49-54, August. 2001 Morphometric Analysis of the Human Trigeminal Nerve By Hiromitsu EZURE, Noboru GOTO, Naoko NONAKA, Jun GOTO and Hiroaki TANI Department of Anatomy,
More informationNEUROBLASTOMA IS a common solid tumor of
Circulating Neuroblastoma Cells Detected by Reverse Transcriptase Polymerase Chain Reaction for Tyrosine Hydroxylase mrna Are an Independent Poor Prognostic Indicator in Stage 4 Neuroblastoma in Children
More informationUniversity of Zurich. Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice and Pitfalls. Zurich Open Repository and Archive
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2009 Histology and Immunophenotype of Invasive Lobular Breast Cancer. Daily Practice
More information3/24/2017. Disclosure of Relevant Financial Relationships. Mixed Epithelial Endometrial Carcinoma. ISGyP Endometrial Cancer Project
Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position to influence or control the content of CME disclose any relevant financial relationship
More informationApplication of Artificial Neural Network-Based Survival Analysis on Two Breast Cancer Datasets
Application of Artificial Neural Network-Based Survival Analysis on Two Breast Cancer Datasets Chih-Lin Chi a, W. Nick Street b, William H. Wolberg c a Health Informatics Program, University of Iowa b
More informationLUNG CANCER PATHOLOGY: UPDATE ON NEUROENDOCRINE LUNG TUMORS
LUNG CANCER PATHOLOGY: UPDATE ON NEUROENDOCRINE LUNG TUMORS William D. Travis, M.D. Attending Thoracic Pathologist Memorial Sloan Kettering Cancer Center New York, NY PULMONARY NE TUMORS CLASSIFICATION
More informationMorphometric Characterization of Small Cell Lymphocytic Lymphoma
ARS Medica Tomitana - 2014; 4(79): 179-183 10.1515/arsm-2015-0002 Chisoi Anca 1, Aşchie Mariana 2, Poinăreanu I. 2 Morphometric Characterization of Small Cell Lymphocytic Lymphoma 1 Spitalul Clinic Judetean
More informationTrichofolliculoma of the Guinea Pig 1,2
Trichofolliculoma of the Guinea Pig 1,2 Raymond D. Ediger, Garrett S. Dill, Jr., and Robert M. Kovatch, Aerobiology and Evaluation Laboratories and Medical Sciences Laboratories, Fort Detrick, Frederick,
More informationCase Report A Rare Cutaneous Adnexal Tumor: Malignant Proliferating Trichilemmal Tumor
Case Reports in Medicine Volume 2015, Article ID 742920, 4 pages http://dx.doi.org/10.1155/2015/742920 Case Report A Rare Cutaneous Adnexal Tumor: Malignant Proliferating Trichilemmal Tumor Omer Alici,
More informationDifferential cell counts in the histiocytic variant of lymphocytic predominance subtype of Hodgkin's
Journal of Clinical Pathology, 1978, 31, 1234-1238 Differential cell counts in the histiocytic variant of lymphocytic predominance subtype of Hodgkin's disease FIONA I. SUTHERLAND, J. B. MAcGILLIVRAY,
More informationInvasive breast cancer: stratification of histological grade by gene-based assays: a still relevant example from an older data set
Histopathology 14, 65, 429 433. DOI: 1.1111/his.12423 SHORT REPORT Invasive breast cancer: stratification of histological grade by gene-based assays: a still relevant example from an older data set Leslie
More informationPost Neoadjuvant therapy: issues in interpretation
Post Neoadjuvant therapy: issues in interpretation Disclosure: Overview D Prognostic features in assessment of post treatment specimens: Tumor size Cellularity Grade Receptors LN Neoadjuvant chemotherapy:
More informationORIGINAL ARTICLE A HISTOMORPHOLOGICAL STUDY OF PAEDIATRIC ADRENAL TUMOURS
A HISTOMORPHOLOGICAL STUDY OF PAEDIATRIC ADRENAL TUMOURS M.Ramani 1, O.H.Radhika Krishna 2, K.Geetha 3, K.Ramesh Reddy 4, P.Sreenivas Reddy 5,Chandu Revathi 6, Ibraheem Javeed 7, Puja Deshmukh 8. 1. Professor,
More informationNeoplasia 2018 Lecture 2. Dr Heyam Awad MD, FRCPath
Neoplasia 2018 Lecture 2 Dr Heyam Awad MD, FRCPath ILOS 1. List the differences between benign and malignant tumors. 2. Recognize the histological features of malignancy. 3. Define dysplasia and understand
More informationProgress in treatment and risk stratification of neuroblastoma: Impact on future clinical and basic research.
Progress in treatment and risk stratification of neuroblastoma: Impact on future clinical and basic research. Øra, Ingrid; Eggert, Angelika Published in: Seminars in Cancer Biology DOI:.1/j.semcancer..0.00
More information