Profile of Childhood Cancers From Hospital-Based Cancer Registries in India, 2012-19.

OBJECTIVE: To describe the clinical pattern of childhood and adolescent cancers across India using hospital-based data in the National Cancer Registry Program. METHODS: Records of 60720 cancer cases in the 0-19 year age group for the period 2012-2019 from 96 hospital-based cancer registries were reviewed. Childhood cancers were classified based on the International Classification of Childhood Cancer (ICCC). Descriptive analysis was used to examine the distribution of cancer by five-year age groups, sex and ICCC diagnostic groups and subgroups. Data were analysed using IBM SPSS software and visualised using R software. RESULTS: 3.2% and 4.6% of all cancer cases in India were among children in the 0-14 year and 0-19 year age groups respectively. The male-to-female ratio for all cancers was 1.72 for 0-14 years and 1.73 for 0-19 years. The four leading groups of cancers among 0-14 year olds were leukemia (40%), lymphoma (12%), central nervous system tumor (11%) and bone cancer (8%). The four leading cancers among the 0-19 year age group were leukemia (36%), lymphoma (12%), bone (11%) and central nervous system tumor (10%). CONCLUSION: Cancers in the 0-14 and 0-19 age groups accounted for a considerable proportion of all cancers with significant male preponderance. Such information helps to fine-tune research and planning strategies.

18F-FDG PET/CT in Lymphomatoid Papulosis Mimicking Primary Cutaneous Anaplastic Large Cell Lymphoma.

Lymphomatoid papulosis is a benign self-healing condition, presenting as papulonodular skin eruptions and mimicking malignant cutaneous lymphomas histopathologically. F-FDG PET/CT findings in this benign condition have not been described in detail in the literature. We present a case of lymphomatoid papulosis mimicking primary cutaneous anaplastic large cell lymphoma histopathologically and demonstrating intensely FDG-avid cutaneous lesions on F-FDG PET/CT, which disappear spontaneously in the follow-up scan.

Adamantinoma-Like Ewing's Family Tumor of the Sino Nasal Region: A Case Report and a Brief Review of Literature.

Ewing's sarcoma family of tumors (EFTs) are malignant mesenchymal tumors with a predilection for bone and soft tissue. They are characterized by their monomorphic small blue round cell morphology. However rare morphologic variants of EFTs can also show overt epithelial differentiation in the form of squamoid differentiation along with strong cytokeratin expression. This particular subset of EFTs are known as adamantinoma-like EFTs which can be difficult to differentiate from epithelial head and neck malignancies. Here we report a case of sinonasal adamantinoma-like EFT in an 18-year-old male patient. The lesion differed from a typical EFT by means of overt squamoid differentiation which showed a basaloid appearance with peripheral palisading. The immunohistochemistry was positive for pan-cytokeratin, p40, p63, ERG, FLI1, and CK5/6. It was negative for actin, desmin, and WT-1. Initial diagnosis of a basaloid squamous cell carcinoma was made. Further molecular studies were also done due to the complex presentation of the tumor. EWSR testing with break-apart analysis confirmed EWSR1 and FLI1 rearrangements. Further confirmation was done with RT-PCR. The case was found to be positive for EWS-FLI-1 translocation. The revised immunohistochemistry panel showed CD99, ERG, FLI1, and synaptophysin positivity. The lesion was reclassified as an adamantinoma-like ES. Our case reinforces the fact that a subset of EFTs can show histomorphologic and immunohistochemical features of aberrant epithelial differentiation. These cases are difficult to differentiate from usual epithelial malignancies which occur in this region. This diagnostic pitfall can be avoided by the inclusion of CD99 and/or FLI1 in the immunohistochemical assessment of any round cell malignancy at any anatomic location. A strong and diffuse CD99 positivity should prompt molecular testing for the presence of EWSR1 gene rearrangements.

Atypical Presentation of T-Cell Large Granular Lymphocytic Leukemia Mimicking Pleural Malignancy on 18F-FDG PET/CT.

T-cell large granular lymphocytic leukemia is a rare form of leukemia, caused by clonal proliferation of cytotoxic T-cells, characterized by modest lymphocytosis and cytopenias of other lineage with hepatosplenomegaly and relatively rare lymph nodal involvement. Involvement of other organs is extremely rare. It is predominantly an indolent disease and most of patients remain asymptomatic for a long period. We present a rare case of aggressive form (CD56 positive) of large granular lymphocytic leukemia with atypical presentations mimicking pleural malignancy on F-FDG PET/CT.

A phase 3, randomized, double-blind study of single-dose fosaprepitant for prevention of cisplatin-induced nausea and vomiting: results of an Indian population subanalysis.

CONTEXT: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian patients. AIMS: This post hoc study assessed the efficacy and safety of fosaprepitant compared with aprepitant for prevention of CINV in the Indian population. A subgroup analysis was performed from data collected in a phase 3 study of intravenous (IV) fosaprepitant or oral aprepitant, plus the 5-HT 3 antagonist ondansetron and the corticosteroid dexamethasone, in cisplatin-naοve patients with solid malignancies. MATERIALS AND METHODS: Patients scheduled to receive cisplatin (≥70 mg/m 2 ) were administered a single IV dose of fosaprepitant dimeglumine (150 mg) on day 1 or a 3-day dosing regimen of oral aprepitant (day 1:125 mg, days 2 and 3:80 mg) with standard doses of ondansetron and dexamethasone. Patients recorded nausea and/or vomiting episodes and their use of rescue medication and were monitored for adverse events (AEs) and tolerability. STATISTICAL ANALYSIS USED: Differences in response rates between fosaprepitant and aprepitant were calculated using the Miettinen and Nurminen method. RESULTS: In the Indian subpopulation (n = 372), efficacy was similar for patients in both the fosaprepitant or aprepitant groups; complete response in the overall, acute, and delayed phases and no vomiting in all phases were approximately 4 percentage points higher in the fosaprepitant group compared with the aprepitant group. Fosaprepitant was generally well-tolerated; common AEs were similar to oral aprepitant. CONCLUSIONS: IV fosaprepitant is as safe and effective as oral aprepitant in the Indian subpopulation and offers an alternative to the oral formulation.

Safety and efficacy of an indigenous recombinant interferon-alpha-2b in patients with chronic myelogenous leukaemia: results of a multicentre trial from India.

BACKGROUND: Compared to hydroxyurea, treatment with interferon-alpha (IFN-alpha) is known to prolong survival in patients with chronic phase of chronic myelogenous leukaemia (CML) and was considered as first-line therapy till recently. We conducted a multicentre trial using an indigenous recombinant IFN-alpha-2b to evaluate its efficacy and toxicity in chronic phase CML. METHODS: Between September 2000 and August 2001, patients with chronic phase CML were recruited within 8 weeks of diagnosis at 7 centres in India. The study was approved by the Ethics Committee of each participating Institute and Informed, written consent was obtained from all patients. All patients were given the study drug in a dose of 5 million units daily subcutaneously. Response and survival analyses were done with intent-to-treat analysis. RESULTS: One hundred and fourteen patients (75 men and 39 women) were included in the study. Their ages ranged from 18 to 62 years (median 37 years). Fifty-seven per cent of patients had a haematological response; complete response in 31.6% and partial response in 25.4%. The median time to achieve complete haematological response was 6 months (range 3-12 months). Cytogenetic response was seen in 39.4% of patients; complete in 1.8%, partial in 28% and minimal in 9.6%. The median time to achieve partial and complete cytogenetic response was 6 and 12 months, respectively. Nineteen patients had progression (blast crisis n=15, accelerated phase n=4) while on treatment. Two patients refused further treatment after the initial 4 weeks due to IFN-a toxicity, mainly bone pains and fever. The major toxic effects of treatment were fever (78%), fatigue (25.4%) and myalgia (52%). No patient died of toxicity. Currently, 95 patients are alive, 91 in the chronic phase and 4 in the accelerated phase. Four patients were lost to follow up and all 15 patients with blast crisis died of progressive disease at a median Interval of 6.5 months (range 1-15 months). The Kaplan-Meier probability of survival at 36 months was 76%. CONCLUSION: This study confirms the efficacy of the indigenous recombinant IFN-alpha-2b in chronic phase CML. The drug has a toxicity profile similar to that of other preparations.

Increased expression of interleukin-1 beta is associated with persistence of the disease and invasion in complete hydatidiform moles (CHM).

Complete hydatidiform moles (CHM), a post-conceptual pathologic condition of the placenta, have a high prevalence rate (12/1,000 deliveries) in Kerala, India. This study addresses the expression of IL-1 alpha and beta by immunohistochemistry in relation to persistence and invasion of the disease. Mild to moderate expression of IL-1 alpha in the villous cytotrophoblasts, syncytiotrophoblasts and decidua of the first trimester in the normal placenta and all gestational ages in the molar placenta were observed. IL-1 beta expression was observed in the extravillous trophoblasts, syncytiotrophoblasts and decidua in both the normal and molar placentae and also in the villous cytotrophoblasts and the stromal Haufbaur cells in molar placentae. Strong expression of IL-1 beta in the placenta suggests its involvement in placental physiology supporting earlier reports. Higher expression of IL-1 beta correlated well with the invasive and persistent nature of the tumour and holds potential as a marker of persistence and invasion in CHM.

Spontaneous rectovaginal fistula and repair using bulbocavernosus muscle flap.

Spontaneous fistula between anorectum and vagina is extremely uncommon. Successful repair depends on etiology, location and the expertise of the surgeon. We report two cases of spontaneous stercoral perforation resulting in rectovaginal fistula (RVF). Both occurred in bedridden patients with fecal impaction. One patient was successfully repaired with a bulbocavernosus (BC) flap interposition. Flap interposition prevents vaginal stenosis in repair of multiple RVF.

Primary osteosarcoma of metatarsal bone.

Primary osteosarcomas of the short tubular bones of hands and feet are rare. We describe a 46-year-old woman with osteosarcoma of the left metatarsal bone with pulmonary metastases. This is the first reported case of osteosarcoma at this site.

Primary granulocytic sarcoma of the ovary.

Granulocytic sarcomas are rare extramedullary tumors of malignant myeloid precursor cells. Exceedingly rare in childhood, it commonly involves skin, lymph nodes, bone, and the spine. Ovarian involvement is rare. It can arise de novo, precede the development of acute nonlymphocytic leukemia, or be the sole manifestation of relapse. We describe a 26-year-old woman with granulocytic sarcoma of the ovary without any hematologic disorder.

Chronic systemic (hepatosplenic) candidiasis in a patient with granulocytic sarcoma.

Chronic systemic (hepatosplenic) candidiasis (CSC) is a syndrome of invasive candidiasis characterized by fever without localizing signs or symptoms. It occurs predominantly in patients with acute leukemia, after prolonged severe neutropenia. We report a young woman who underwent extensive chemotherapy for granulocytic sarcoma of the ovary; CSC then developed in this patient. She was successfully treated with fluconazole and liposomal amphotericin B. Clinical presentation, diagnostic problems, and the current successful treatment with fluconazole and liposomal amphotericin B are discussed.

A multivariate analysis of prognostic indicators in complete hydatidiform moles (CHM).

OBJECTIVE: To analyse prognostic factors in complete hydatidiform moles using multiple logistic regression analysis. METHODS: Evaluation of host and tumour related parameters including (a) gestational age, patient age, parity, molar phenotype, grade of proliferation of the tumour and cytological atypia, (b) expression of beta-HCG, EGF, EGFR, TGF-alpha, TGF-beta, IL1-alpha, IL1-beta by immunohistochemistry, (c) serial monitoring of serum beta-HCG levels by ELISA, and (d) lectin binding using jack fruit lectin histochemistry as indices for persisting trophoblastic disease (PTD). RESULTS: Serum beta-HCG levels at 4 weeks, cellular atypia, lectin binding, expression of TGF-alpha and IL1-beta showed highly significant correlation with persistence of the tumour (P<0.001). The sensitivity and specificity at 4 weeks in combination with cytological atypia to identify spontaneously regressing lesions was 100% and those requiring chemotherapeutic intervention was 80%. CONCLUSION: The concentration of serum beta-HCG 4 weeks post evacuation(<300 mIU/ml) combined with cytological abnormalities could identify nearly 100% of the spontaneously regressing lesions (low risk) and 80% of those needing chemotherapeutic intervention (high risk), thereby suggesting that patients who have a serum beta-HCG at 4 weeks of evacuation <300 mIU/ml with no cytological atypia of the trophoblasts need only be followed up at long intervals, while those having a serum beta-HCG at 4 weeks of evacuation >300 mIU/ml accompanied with cytological atypia of the trophoblasts should be closely followed up.

Granulocyte macrophage--colony stimulating factor (GM-CSF) as adjunct in induction therapy of acute myeloid leukemia.

Use of growth factors (G-CSF/GM-CSF) as adjunct in induction therapy of AML is controversial. Possible stimulation of leukemia cell clones has been the major cause of concern. We treated 50 cases of AML with GM-CSF as an adjunct during induction therapy. 35 patients (70%) achieved complete remission out of which 13 patients relapsed at a median relapse period of 15 months. Average duration of neutropenia was 10.5 days. (15 days in the control) Febrile episodes were fewer and antibiotic support was required for an average period of only 7.6 days (16.9 days in the control). The benefits including the economic analysis of the role of GM-CSF in this setting is discussed.

Ocular metastasis of choriocarcinoma.

Metastatic tumours of the eye commonly occur from primaries of the breast or lung. The prognosis is poor and the mean life expectancy is 6.5 months from diagnosis. Although metastatic tumours of the eye are not a rarity, ocular metastasis from choriocarcinoma has not been reported previously. We report a case of gestational choriocarcinoma with ocular metastasis.

Primary choriocarcinoma of the ovary. Report of two cases.

Primary choriocarcinoma of the ovary (PCO) is rare. This can be gestational (GCO) or nongestational (NGCO) in origin. It is difficult to differentiate between CGO and NGCO. NGCO carries a worse prognosis than GCO. We present two cases of metastatic GCO who were treated successfully with combination chemotherapy and are alive and disease free at the time of reporting.

Renal metastasis from squamous cell carcinoma of the lung.

Symptomatic renal metastases from primary malignancy elsewhere in the body is an uncommon feature in disseminated cancer. Postmortem diagnosis is more frequent. A case is reported here of a patient with renal metastasis from lung carcinoma who presented with haematuria.

Radiotherapy in the treatment of solitary plasmacytoma.

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.

Primary malignant germ cell tumours of the mediastinum--results of multimodality treatment.

Primary malignant mediastinal germ cell tumours are rare and considered to have poorer prognosis compared with those arising from gonads. Eighteen patients with primary mediastinal germ cell tumour were treated over an 1-year period; 9 had seminoma and 9 non-seminoma. Eight patients, 4 each with seminoma and non-seminoma underwent initial tumour excision and the rest had biopsy only. All patients received cisplatin-based chemotherapy. All patients with seminoma received consolidation radiotherapy to mediastinum. Three patients with non-seminoma received radiotherapy following partial response. All 9 patients with seminoma achieved complete response at the end of chemotherapy. Two patients with NSGCT had complete response to chemotherapy, 5 partial response and 2 no response. Two patients who underwent resection of the residual tumour mass are surviving free of disease. Addition of radiotherapy or second-line chemotherapy did not bring about any added response in partial and non-responders. Nine out of 9 patients with seminoma and 4/9 with non-seminoma are surviving disease-free at a median follow-up of 48 months (range 16 153 months). Mediastinal seminoma has excellent prognosis with cisplatin combination chemotherapy, whereas non-seminoma carries poor prognosis, and aggressive chemotherapy with resection of residual masses may improve the outcome. The role of additional radiotherapy and initial tumour debulking needs further evaluation.

Clinical implications of cytogenetic classification in adult acute lymphoblastic leukaemia patients.

Cytogenetic analysis performed on pretreated unstimulated, bone marrow/peripheral blood samples of 46 adult patients with acute lymphoblastic leukaemia (ALL) showed sufficient metaphases in 39 patients and insufficient metaphases in 7 patients. G-banded karyotype analysis of these 39 patients revealed non-random clonal chromosome abnormalities in 31 patients and apparently normal karyotypes in 8 patients. Numerical abnormalities involving chromosome trisomies and structural abnormalities involving different types of chromosomal translocations and deletions were encountered in varying percentages. These patients were grouped into various cytogenetic subsets on the basis of their karyotype pattern and followed-up to evaluate their prognosis. Patients with apparently normal karyotypes showed good prognosis and those with 6q- showed intermediate prognosis. But all other patients with hyperdiploid, pseudodiploid and hypodiploid karyotypes were associated with poor prognosis. Cytogenetic classification of ALL patients is thus of clinical importance, as it helps the early identification of clinically important prognostic groups.

Nonrandom karyotype abnormalities in 36 multiple myeloma patients.

G-banded analysis performed on pretreated bone marrow samples of 36 multiple myeloma patients allowed the identification of clonal chromosome abnormalities. Abnormalities consisting of trisomies, monosomies, translocations, deletions, and marker chromosomes apparently followed a nonrandom pattern. The chromosomes involved in the production of abnormal karyotypes were numbers 1,2,3,11,12,14,17, and 18. Even though no specific chromosome pattern has been identified, the involvement of chromosomes 1, 3, and 14 was found to be more frequent. Many of the chromosomes and chromosomal breakpoints involved in these abnormalities correspond to the location of identified oncogenes or tumor suppressor genes. Hence, it is presumed that these chromosome abnormalities may be playing an important role in the genesis of multiple myeloma by altering the structure or function of oncogenes or tumor suppressor genes.