Pediatric and adolescent chronic myeloid leukemia: A follow-up study in Western India.

Background: Chronic myeloid leukemia (CML) is relatively rare in pediatric and adolescent age groups. The purpose of this study was to evaluate the clinical, hematopathological, and biochemical parameters of CML in pediatric and adolescent age groups, along with an assessment of the treatment response with first-line tyrosine kinase inhibitors (TKI) and its correlation with the prognostic scoring systems of adults. Materials and Methods: A retrospective study of 44 Breakpoint Cluster Region-Abelson leukemia virus (BCR-ABL1)-positive pediatric and adolescent CML cases registered at our hospital was done. The clinical and laboratory parameters were evaluated using hospital software. The treatment response was monitored and scoring was performed using mathematical calculations. Results: The mean age was 11.6 (±4.7) years. The median hemoglobin was 8.4 g/dL and 63.6% of the cases showed white blood cell (WBC) counts >250,000/µL. The average follow-up was 21 months. A total of 97.7 and 78.1% cases achieved complete hematological response (CHR) and molecular response, respectively, during the treatment course. The maximum number of patients had low Sokal and European treatment and Outcomes Study (EUTOS) scores. Seventy-five per cent of the cases achieved CHR at 3 months, while 73.6 and 78.6% CML-Chronic phase (CP) cases with low Sokal and EUTOS scores achieved CHR at 3 months, respectively. Conclusion: This study revealed that the CML cases in pediatric and adolescent age groups are normally present with higher WBC counts at the time of diagnosis. The association of the prognostic scoring system with treatment response was statistically insignificant. However, a larger cohort study is needed to determine the treatment response of TKI in children and adolescent CML and its correlation with the prognostic scoring systems.

Nonhomologous end joining repair pathway molecules as predictive biomarkers for patients with oral squamous cell carcinoma.

PURPOSE: Nonhomologous end-joining (NHEJ) is critical for the repair of either pathologic double-strand breaks (DSBs) and/or for the repair of physiologic DSBs created during radiotherapy to kill the tumor cell. Therefore, patients with higher expression of NHEJ repair proteins might develop resistance to ionizing radiation, allowing the disease to recur. As cancer of the oral cavity is a serious health problem globally, the present study aimed to examine the expression of Ku70/80, X-ray repair cross-complementing protein 4 (XRCC4) and DNA ligase IV-core molecules of the NHEJ pathway in patients with oral cancer. MATERIALS AND METHODS: Protein expression of Ku70/80, XRCC4, and DNA ligase IV were studied by Immunohistochemistry and mRNA expression of Ku70 and Ku80 were studied using reverse transcription polymerase chain reaction. Data were analyzed statistically using SPSS. RESULTS: A univariate survival analysis revealed an association of Ku70 mRNA with shorter overall survival (OS). While protein expression of XRCC4 showed an association with reduced relapse-free survival and shorter OS. Multivariate survival analysis demonstrated that XRCC4 and DNA ligase IV are independent prognosticators for predicting adverse disease outcomes. CONCLUSION: Strong expression of repair proteins - XRCC4 and DNA ligase IV is associated with unfavorable disease outcome in patients with oral squamous cell carcinoma.

Transcriptome profiling and pathway analysis in squamous cell carcinoma of buccal mucosa.

BACKGROUND: High recurrence and poor overall survival in buccal mucosa squamous cell carcinoma (BMSCC) are not well addressed due to lack of efficient prognostic biomarkers and targeted therapies. To uncover gene candidates for the same, transcriptome profiling has been examined in BMSCC, which is not explored yet. METHODS: We compared 9 BMSCC and 2 normal oral FFPE tissues using Agilent SurePrint G3 Human gene expression v3 microarray chips. The obtained RNA signatures were interrogated in the cancer genome atlas (TCGA) dataset for alteration values and survival data. RESULTS: We found total 237 protein coding RNAs and 85 long non-coding RNAs (lncRNAs) which displayed significant differential expression with criteria of at-least 2 fold change and Benjamini Hochberg FDR < .05. In protein coding RNAs, RUNX3 and EMX2 showed utmost degree of up-regulation and down-regulation, respectively. Likewise, among lncRNAs, ARGFXP2 and lnc-SYCP3-2 displayed highest degree of up-regulation and down-regulation, respectively. Besides, an analysis of the RNA list in TCGA dataset spotted deregulation of 21 genes in both, our cohort and TCGA cohort. Among which, MRTO4 and EIF3J genes, and LINC00310, a lncRNA showed greatest expression alterations. Strikingly, at RNA expression level, up-regulation of two genes, EIF3J and SDCBP, was significantly associated with disease free survival and poor overall survival, respectively. CONCLUSION: Our data documented significant findings to enhance understanding of the disease biology. The proposed RNA candidates (RUNX3, EMX2, MRTO4, EIF3J, SDCBP and LINC00310) may serve as putative therapeutic targets and potential biomarkers for BMSCC diagnosis and prognosis.

The value of cytology in diagnosis of serous effusions in malignant lymphomas: An experience of a tertiary care center.

BACKGROUND: Malignant lymphomas (ML) are often complicated by serous effusions. The present study is an attempt to cytologically assess a large series of serous effusions associated with ML, identify the immunoreactivity of cells and to evaluate the role of various ancillary methods in confirming and subtyping these cases. METHODS: A cross-sectional study of 4612 serous effusions was undertaken at the Department of Cytology, Gujarat Cancer and Research Institute by retrieving data from the year 2015 to 2017. Total 169 cases of ML, clinically suspicious, were included. All cerebrospinal fluids, serous effusions involved by myeloid neoplasms, and cases of primary effusion lymphomas were excluded from our study. Pap stained smears of all these serous effusions were examined. Ancillary methods such as immunohistochemistry were used to further subtype the positive cases using the WHO classification of hematopoietic and lymphoid neoplasms (2016). RESULTS: Out of total 169 clinically suspicious cases, 109 cases were cytologically positive for ML which included 73 (66.9%) pleural effusions, 34 (31.1%) ascitic fluids, and 2 (1.8%) pericardial effusions. T-lymphoblastic lymphoma (36.9%) and Burkitt's lymphoma (38.2%) were the most common ML involving the pleural and ascitic fluids respectively. Non-Hodgkin's lymphoma (NHL) more frequently involved the serous cavities than Hodgkin's lymphoma. (P value <.0001). Among the NHL, T-cell lymphomas more commonly lead to serous effusions than B-cell lymphomas (P value <.0048). CONCLUSION: Cytological examination of serous effusions is an accurate, prompt, affordable technique having diagnostic and therapeutic implications. With the help of ancillary methods, we can identify the phenotype of cells, classify as well as confirm our diagnosis.

Metastasis of soft tissue sarcomas in lymph node: A cytomorphological study.

BACKGROUND: Soft-tissue sarcoma (STS) rarely metastasizes to lymph node compared to carcinoma. Fine-needle aspiration cytology (FNAC) carries a pivotal role in diagnosis of metastatic tumor to lymph node. This study highlights the role of FNAC in diagnosis of STS metastasis to lymph node. METHOD: A retrospective study over a period by 4 years carried out. FNAC of enlarged lymph node was performed in patients with STS. Cytology smears were examined in conjunction with clinical details. Histopathology and Immunohistochemistry (IHC) were correlated in synchronous cases. RESULTS: Out of 326 patients, 21 with STS had enlarged lymph nodes, of which 19 cases showed involvement (5.8%). Sixteen cases were metachronous and 3 cases showed synchronous involvement. Fifteen cases had regional lymph nodes while 4 cases had distal lymph node involvement. Head and neck and lower extremities were the most common primary sites of STS. Rhabdomyosarcoma was the most common sarcoma metastasing to the lymph nodes followed by synovial sarcoma, malignant peripheral nerve sheath tumor, and clear cell sarcoma. Other rare tumors included leiomyosarcoma, epitheloid sarcoma, liposarcoma, malignant fibrous histiocytoma, and Ewing's sarcoma/peripheral neuroectodermal tumor. We had a case of dermatofibrosarcoma protuberance (DFSP) of scalp with cervical lymph node metastasis. Very unusual about this case was its rare primary site and the rarer lymph node metastasis. CONCLUSION: FNAC plays an important role in the diagnosis of lymph node metastasis in cases of STS.

Plasmacytoma rectum extending to para-rectal region.

Solitary plasmacytoma most commonly presents in bone (80%), while extramedullary plasmacytoma (EMP) is an uncommon (20%) entity that most commonly involves nasopharynx or upper respiratory tract. Involvement of the gastrointestinal tract occurs in approximated 10% of EMP cases, in that also solitary EMP of the rectum is an exceedingly rare entity. Here we are presenting a case of 55-year-old male patient who was diagnosed to have EMP of rectum in September 2012 who was initially operated in which de-bulking surgery with abdominoperineal resection was done with large residual lesion postoperatively. Then patient was treated with postoperative radiotherapy (RT) with conventional portals 40 Gy in 20 fractions with complete response at 3 months. Patient was followed-up until now (1 year and 2 months post-RT), without any symptom or recurrence.

Solid pseudopapillary tumor of pancreas in a male child: a diagnosis by fine needle aspiration cytology.

Solid pseudopapillary tumor (SPT) is an uncommon pancreatic neoplasm with low malignant potential. It occurs predominantly in young women. It is very rare in males and nonrelated pediatrics. In children, SPT commonly present as abdominal mass and pain. A 10-year-old male presented with progressively growing palpable tumor in upper abdomen. SPT of pancreas is diagnosed on preoperative fine needle aspiration cytology. This was subsequently confirmed by histopathology and immunohistochemistry. Due to rarity, SPT is not the first option to rule out, especially in children. Preoperative cytological diagnosis of SPT helps in management of this surgically curable neoplasm with good prognosis.

Prognostic significance of molecular markers in oral squamous cell carcinoma: a multivariate analysis.

BACKGROUND: Multiple marker accumulation impacts tumor progression and biologic phenotypes affect clinical outcome of patients with head and neck cancer. Hence, this study investigated a battery of molecular markers that may help to reflect biologic aggressiveness and predict prognosis. METHODS: Epidermal growth factor receptor (EGFR), Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67, and Bcl-2 were localized immunohistochemically in 135 oral squamous cell carcinoma patients to assess prognostic value. RESULTS: In univariate analysis of total patients, p53, Stat3, and p16 predicted both relapse-free survival (RFS) and overall survival (OS). In Cox multivariate analysis, after adjusting for tumor size, nodal status, and lymphatic permeation, p53 was independently associated with RFS and OS, and p16 with RFS only. In only early-stage patients, in univariate analysis, nuclear Stat3 was significant for RFS and OS. CONCLUSION: Immunostaining of p53, p16, and Stat3 might serve as potential adjuncts in pathologic evaluation of oral tumors to predict risk of relapse.

Dietary risk factors for hypopharyngeal cancer in India.

OBJECTIVE: The Indian subcontinent has among the highest rates of hypopharyngeal cancer worldwide. The purpose of this study was to examine the associations between the Indian diet and hypopharyngeal cancer. METHODS: We used data from a hospital-based case-control study of 513 incident hypopharyngeal cancers and 718 controls from four centers in India. Dietary information was assessed using a 67-item semi-quantitative food frequency questionnaire. Intakes of related foods were combined across food groups and were categorized by quartile. We used unconditional logistic regression modeling, stratified by ever tobacco use, to analyze the association between food intakes and hypopharyngeal cancer. RESULTS: Among persons who had ever smoked or chewed tobacco, protective associations were seen at the highest quartiles of total fruit intake (OR = 0.37, 0.20-0.69), curds (OR = 0.35, 0.17-0.69), and leafy green (OR = 0.25, 95% CI 0.13-0.51), root (OR = 0.22, 95% CI 0.11-0.43), and cruciferous vegetable intakes (OR = 0.41, 0.20-0.84). Results were similar, although not as robust, among persons who had never smoked or chewed tobacco. An increased risk of disease was seen among tobacco users who drank milk daily (OR = 1.84, 1.14-2.98). CONCLUSIONS: Dietary factors might contribute to the high risk of hypopharyngeal cancer observed in India.

Indoor air pollution from solid fuels and risk of hypopharyngeal/laryngeal and lung cancers: a multicentric case-control study from India.

BACKGROUND: A recent monograph by the International Agency for Research on Cancer (IARC) has identified indoor air pollution from coal usage as a known human carcinogen, while that from biomass as a probable human carcinogen. Although as much as 74% of the Indian population relies on solid fuels for cooking, very little information is available on cancer risk associated with these fuels in India. METHODS: Using data from a multicentric case-control study of 799 lung and 1062 hypopharyngeal/laryngeal cancer cases, and 718 controls, we investigated indoor air pollution from various solid fuels as risk factors for these cancers in India. RESULTS: Compared with never users, individuals who always used coal had an increased risk of lung cancer [odds ratio (OR) 3.76, 95% confidence interval (CI) 1.64-8.63]. Long duration of coal usage (>50 years) was a risk factor for hypopharyngeal (OR 3.47, CI 0.95-12.69) and laryngeal (OR 3.65, CI 1.11-11.93) cancers. An increased risk of hypopharyngeal cancer was observed among lifelong users of wood (OR 1.62, CI 1.14-2.32), however this was less apparent among never-smokers. Increasing level of smokiness inside the home was associated with an increasing risk of hypopharyngeal and lung cancer (P(trend) < 0.05). CONCLUSION: This study showed differential risks associated with indoor air pollution from wood and coal burning, and provides novel evidence on cancer risks associated with solid fuel usage in India. Our findings suggest that reducing indoor air pollution from solid fuels may contribute to prevention of these cancers in India, in addition to tobacco and alcohol control programs.

Study of grading of urothelial carcinoma in transurethral resection of urinary bladder tumor specimens.

This study is conducted to evaluate prognostic significance of recently introduced WHO (World Health Organization) 1999 grading system for urothelial carcinoma on transurethral resection of urinary bladder tumor (TURBT) specimens reported during the period from 1996 to 2000. Progression free survival estimates were obtained by Kaplan-Meier method on SPSS software with log rank test application. Among 70 cases, progression occurred in 38 patients from which grade I were 3, grade II were 11 and grade III were 24. The mean period from diagnosis to progression was 76.8, 19.2 and 3.5 months for grade I, II, III respectively. The progression free survival rates at one year were 100% for grade I, 42% for grade II and 5% for grade III. (Log rank test: p < 0.001). WHO 1999 grading system can classify urothelial carcinomas into prognostically different groups, which is statistically significant.

Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: a multicentric case-control study from India.

Hypopharyngeal and laryngeal cancers are among the most common cancers in India. In addition to smoking, tobacco chewing may be a major risk factor for some of these cancers in India. Using data from a multicentric case-control study conducted in India that included 513 hypopharyngeal cancer cases, 511 laryngeal cancer cases and 718 controls, we investigated smoking and chewing tobacco products as risk factors for these cancers. Bidi smoking was a stronger risk factor compared to cigarette smoking for cancer of the hypopharynx (OR(bidi) 6.80 vs. OR(cig) 3.82) and supraglottis (OR(bidi) 7.53 vs. OR(cig) 2.14), while the effect of the 2 products was similar for cancer of the glottis (OR(bidi) 5.32 vs. OR(cig) 5.74). Among never-smokers, tobacco chewing was a risk factor for hypopharyngeal cancer, but not for laryngeal cancer. In particular, the risk of hypopharyngeal cancer increased with the use of Khaini (OR 2.02, CI 0.81-5.05), Mawa (OR 3.17, CI 1.06-9.53), Pan (OR 3.34, CI 1.68-6.61), Zarda (OR 3.58, CI 1.20-10.68) and Gutkha (OR 4.59, CI 1.21-17.49). A strong dose-response relationship was observed between chewing frequency and the risk of hypopharyngeal cancer (p(trend) < 0.001). An effect of alcohol on cancer of the hypopharynx and supraglottis was observed only among daily drinkers (OR 2.22, CI 1.11-4.45 and OR 3.76, CI 1.25-11.30, respectively). In summary, this study shows that chewing tobacco products commercially available in India are risk factors for hypopharyngeal cancer, and that the potency of Bidi smoking may be higher than that of cigarette smoking for hypopharyngeal and laryngeal cancers.

Primary chondrosarcoma of lung: case report and review of literature.

A case of primary chondrosarcoma of the left lung in 50 year-old man is presented. The tumor was diagnosed as primary chondrosarcoma of the lung after exclusion of any primary lesion elsewhere. Histologically, tumor consisted of predominantly chondromatous lesion. Immunohistochemistry showed that tumor cells positive for S-100 protein and vimentin, and negative for epithelial markers. On the basis of clinical, histological and immunohistochemical studies, the tumor was diagnosed as a primary chondrosarcoma of the lung.

Cytological grading of breast neoplasia and its correlation with histological grading.

Cytological grading of breast cancer is not well established despite histological grading having gained a strong foothold. In our study we have analyzed 50 cases of breast carcinoma which included invasive ductal carcinoma, invasive lobular carcinoma, mucinous carcinoma, stromal sarcoma, apocrine carcinoma, papillary carcinoma. Papanicolaou smears were graded according to established Hunt's, Simplified Black and Modified Black grading systems. They were then compared with the Scarff Bloom Richardson grading system. Simplified Black grading system has been recommended for cytological grading of breast neoplasia because of its lucidity and its reproducibility. Cytological grading of breast neoplasia is important for neo adjuvant chemotherapy and also for predicting the prognosis of the patient on FNAC alone. Incorporation of other parameters like apoptosis and bcl-2 is also recommended.