Dr. R. K. Gadgil - An eminent Indian pathologist, pioneer in starting rural medical camps and a researcher who discovered an endemic focus of schistosomiasis in Maharashtra, India.

Dr. Ramchandra Krishnaji Gadgil (RKG) was a pioneer and an eminent researcher. Along with clinician colleagues, he started rural medical camps in 1952, in Maharashtra, India. Through his meticulous research, he discovered in the same year an endemic focus of schistosomiasis in the village, Gimvi, and in 1956, went on to establish a life cycle of the Schistosoma hematobium, involving a completely new intermediate Mollusk host "Ferrisia tenuis", a rather epoch making discovery in the realm of Mollusk intermediate host in relation to human schistosomiasis. His instructions and guidance to the Government Public Health department led eventually to eradication of the schistosomiasis focus in that village in 1969, thereby setting an example for pathologists to head out into the field, do clinical work and pursue with disciplined curiosity a new pathological finding in the laboratory. The fascinating story of his life, education and research is described in this paper.

Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee.

BACKGROUND: Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children's Cancer Group and Children's Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotype-phenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis). PROCEDURE: To distinguish prognostic subgroups in the genotype-phenotype discordant pNTs, two subgroups, "conventional" and "bull's eye," were identified based on the nuclear morphology. The "conventional" tumors (35 cases) included: Neuroblastoma, poorly differentiated subtype (NB-PD, 26 cases) with "salt-and-pepper" nuclei; neuroblastoma, differentiating subtype (4 cases); ganglioneuroblastoma, intermixed (3 cases); and ganglioneuroma, maturing subtype (2 cases). The "bull's eye" tumors included NB-PD with prominent nucleoli (16 cases). Clinicopathologic characteristics of these two subgroups were analyzed. N-myc protein expression was tested immunohistochemically on available tumors. RESULTS: No significant difference was found between these two subgroups in the distribution of prognostic factors such as age at diagnosis, clinical stage, histopathology category/subtype, mitosis-karyorrhexis index, ploidy, 1p LOH, and unbalanced 11q LOH. However, prognosis of the patients with "conventional" tumors (5-year EFS 85.7 ± 12.2%; OS 89.3 ± 10.3%) was significantly better than those with "bull's eye" tumors (EFS 31.3 ± 13.0%; OS 42.9 ± 16.2%; P = 0.0010 and 0.0008, respectively). Immunohistochemically all (11/11) tested "conventional" tumors were negative, and 10/11 tested "bull's eye" tumors were positive for N-myc protein expression. CONCLUSIONS: Based on the presence or absence of prominent nucleoli (the putative site of RNA synthesis/accumulation leading to N-myc protein expression), two prognostic subgroups, "conventional" with a better prognosis and "bull's eye" with a poor prognosis, were distinguished among the genotype-phenotype discordant pNTs.

Revision of the International Neuroblastoma Pathology Classification: confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular.

BACKGROUND: Ganglioneuroblastoma, nodular (GNBn) comprises one of the categories of peripheral neuroblastic tumors. All tumors in this category, according to the original International Neuroblastoma Pathology Classification, are classified into an unfavorable histology group. Subsequently, it has been reported that GNBn can be divided into two prognostic subsets, a favorable subset (FS) and an unfavorable subset (US). METHODS: Histology slides from 70 patients who were enrolled in Children's Cancer Group studies 3881 and 3891 and who had a diagnosis of GNBn were reviewed jointly by the members of International Neuroblastoma Pathology Committee (INPC): 1) to confirm the diagnosis of GNBn, 2) to identify the FS and US by applying the same age-linked criteria that were used to distinguish the favorable histology group and unfavorable histology group in conventional neuroblastoma tumors from the neuroblastomatous component of GNBn tumors, and 3) to verify the significant prognostic difference between these two subsets. The patients had been used in a previous study, and survival data for the patients were updated since the time of their last report. RESULTS: The review clarified and illustrated morphologic characteristics of classical GNBn and it variants. The diagnosis of GNBn was confirmed in 67 of 70 patients. There were 22 patients with GNBn in the FS and 45 patients with GNBn in the US. The estimated survival differences between the FS and US patients with GNBn were statistically significant (8-year event free survival rate: 86.1% vs. 32.2%; P = 0.0003; overall survival rate: 90.5% vs. 33.2%; P = 0.0003). CONCLUSIONS: This study confirmed the recently defined prognostic subsets of GNBn. The INPC proposes to modify the International Neuroblastoma Pathology Classification by distinguishing the FS and the US among patients with GNBn tumors.

Risk factors for pediatric human immunodeficiency virus-related malignancy.

CONTEXT: Although cancers occur with increased frequency in children with human immunodeficiency virus (HIV) infection, the specific clinical, immunological, and viral risk factors for malignancy have not been identified. OBJECTIVE: To identify risk factors for malignancy among HIV-infected children. DESIGN, SETTING, AND PATIENTS: A multicenter case-control study of children with HIV at 26 institutions participating in the Pediatric Oncology Group. Forty-three case patients with a new malignancy and 74 control patients without a malignancy were matched based on the duration of their infection. Patients were enrolled between January 1992 and July 1998. MAIN OUTCOME MEASURES: Clinical and laboratory factors assessed as putative risk factors included demographic characteristics, HIV characteristics, prior antiretroviral treatment, and CD4 cell count. Coviral infections with Epstein-Barr virus (EBV), cytomegalovirus, and human herpesvirus 6 were assessed by semiquantitative polymerase chain reaction assays and serological testing. RESULTS: Case malignancy diagnoses included 28 non-Hodgkin lymphoma, 4 B-cell acute lymphoblastic leukemia, 1 Hodgkin disease, 8 leiomyosarcoma, 1 hepatoblastoma, and 1 schwannoma. Epstein-Barr virus viral load of more than 50 viral genome copies per 105 peripheral blood mononuclear cells was strongly associated with cancer risk but only for children with CD4 cell counts of at least 200/ microL (odds ratio [OR], 11.33; 95% confidence interval [CI], 2.09-65.66, P<.001). High EBV viral load was not associated with cancer for children with CD4 cell counts of less than 200/ microL (OR, 1.12; 95% CI, 0.13-9.62; P =.99). Zidovudine antiretroviral therapy did not confer a significant protective effect for either the high (OR, 0.81; 95% CI, 0.22-3.09; P =.77) or the low CD4 cell count groups (OR, 0.27; 95% CI, 0.04-1.46; P =.16). The route of HIV infection was not associated with increased cancer risk. CONCLUSIONS: Route of infection, demographic characteristics, and zidovudine use were not associated with the development of malignancy in HIV-infected children. High viral burden with EBV was associated with the development of malignancy in HIV-infected children although the effect was modified by CD4 cell count. The pathogenesis of HIV-related pediatric malignancies remains unclear and other contributing risk factors can be elucidated only through further study.

Soft tissue perineuriomas in children: report of three cases and review of the literature [corrected].

Perineuriomas (PN) are uncommon, slowly growing, usually benign tumors composed of well-differentiated perineural cells. Two variants are recognized: intraneural perineuriomas and soft tissue perineurioma, which includes a sclerosing subset of tumors. They are usually reported in the adult population. We present three cases of soft tissue perineuriomas in children. One was located in the deep soft tissue of the retroperitoneum in a 14-year-old girl, the second one in the left thumb of a 14-year-old boy, and the third one in the index finger of a 16-year-old boy. This report, which describes the clinicopathologic, immunohistochemical, and ultrastructural features of these tumors, should alert pathologists to the occurrence of perineuriomas in children. A review of the English language literature on perineuriomas in children is also included.

Proliferative and neoplastic disorders in children with acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is a multisystem disease and, besides infections, various proliferative and neoplastic disorders are seen in cytology, biopsy, and autopsy specimens from infected children. These lesions can be classified into four types: systemic lymphoproliferation, smooth muscle tumors, Kaposi sarcoma (KS), and human papilloma (HPV)-related genital lesions. In addition, isolated cases of multiple miscellaneous tumors have been reported. Proliferative and neoplastic disorders are categorized as lesions of undetermined pathogenesis; however, there are certain factors that are suggested to be related to their pathogenesis. The symptoms related to them may be atypical or difficult to appreciate, and proliferative and neoplastic disorders may clinically mimic an opportunistic infection. The type and site of proliferative and neoplastic disorder also tends to be atypical as compared with those seen in non HIV-infected children. This is a brief but detailed review of these disorders in children with AIDS.

Morphologic features of neuroblastoma (Schwannian stroma-poor tumors) in clinically favorable and unfavorable groups.

BACKGROUND: After the establishment of the International Neuroblastoma Pathology Classification system, the authors studied retrospectively the prognostic impact of morphologic features in a series of two clinically distinct subsets of patients with peripheral neuroblastic tumors (NTs), i.e., tumors in the neuroblastoma category. METHODS: Forty-seven NTs categorized into either clinically favorable or unfavorable subgroups were selected randomly from 100 NTs for a histologic review that included the evaluation of 14 morphologic characteristics. The review was performed individually followed by a group review. The correlations of the prognostic significance of the individual morphologic features and the correlations among them were determined by use of odds ratios (ORs) with corresponding 95% confidence intervals (95%CIs). The inter-rater agreement was determined by using the Cohen kappa coefficient. RESULTS: Ten of 14 morphologic features, including nuclear size, cellularity, prominent nucleoli in undifferentiated or poorly differentiated neuroblasts, and the number of mitotic and karyorrhectic cells (MKI), showed a significant correlation with the clinical groups (ORs between 36.9 and 10.5 and P values between < 0.001 and 0.002). In addition to the patient's age at diagnosis (OR, 7.4; 95%CI, 1.9-28.9; P = 0.002), 8 of 14 features also provided prognostic information (ORs between 35.1 and 7.9 and P values between < 0.001 and 0.039). CONCLUSIONS: This study again confirmed the prognostic impact of the criteria used in the Shimada system and revealed that some other morphologic features, such as prominent nucleoli in undifferentiated and poorly differentiated neuroblasts, identify unfavorable tumor biology, partly independent from the patient's age at diagnosis. However, the prognostic impact of these features needs to be confirmed by analysis of a large series of neuroblastic tumors.