Calcifying/ossifying synovial sarcoma: A clinicopathologic and molecular study of 5 cases.

Background: Synovial sarcoma (SS) is a soft tissue sarcoma with a generally aggressive behavior. Calcifying/ossifying SS is a rare variant associated with a favorable prognosis. Aim: The aim was to report clinicopathological features and molecular analysis of 5 cases of calcifying/ossifying SS. Materials and Methods: Record of 370 cases of SS reported in the section of Histopathology, of a tertiary care Hospital, between 2002 and 2011 were retrieved. Five cases exhibiting extensive calcification and ossification were identified. Immunohistochemistry was performed using Flex technique. Molecular analysis of these 5 cases was performed later at the collaborative Hospital abroad, by reverse transcription polymerase chain reaction. Results and Conclusions: The ages of the patients ranged from 13 to 44 years (mean age 27 years; female to male ratio 1.6:1). The duration of symptoms ranged from 5 months to 5 years. Histologically, 4 were monophasic, and 1 was biphasic. Three cases exhibited extensive calcification and two extensive ossification. Immunohistochemical stain (epithelial membrane antigen was positive in all 5 cases, CKAE1/AE3 (3/4), Bcl2 (4/4), S100 (4/4), CK7 (2/2), CD99 (1/3) and vimentin (2/2). Intact RNA was obtained from 3 cases, all of which were positive for the SYT/SSX fusion transcript. Follow-up was available in 4 cases and ranged from 19 months to 85 months (mean 50 months). Local recurrence was seen in 2 cases. In conclusions, we report clinicopathologic features of 5 cases of calcifying/ossifying SS. The duration of symptoms and mean age of patients is similar to the literature. A slight female predominance was seen in contrast to a male predominance described in the literature. The clinical course of our cases validates the favorable prognosis of this rare type of SS.

Time trends in the incidence of cancer cervix in Karachi South, 1995-2002.

INTRODUCTION: The objective of the study was to determine the trends of cancer cervix in Karachi South during an eight (1995-2002) year period. METHODOLOGY: Cancer cervix cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st December 2002 were analyzed. Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2 time periods, 1995-97 and 1998-2002. RESULTS: Cancer cervix ranked sixth in the 1995-97 period the age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.81 and 3.22. It reached the fifth ranking in the 1998-2002 period with an ASR and CIR of 7.5 and 4.0 per 100,000. Thus between 1995 and 2002, the incidence of cervical cancer registered an approximate 10% increase. The mean age of the cancer cases was 53.3 years (SD 11.6; 95% CI 50.58, 55.96; range 32-85 years) and 50.7 years (SD 11.7; 95% CI 48.8, 52.5; range 51 years) in period 1 and 2 respectively. The morphological components of squamous cell carcinoma and adenocarcinoma remained stable during this period, though a marginally higher component and increasing incidence of adenocarcinoma was observed throughout. A negligible down staging was observed in the 1998-2002 period. Localized malignancy was observed in 30.8% in period 2 as compared to 25.7% in period 1 and the component of carcinoma in situ increased from 0% percent in period 1 to 1.3% in the second period. Despite this two thirds of the cases still presented with a regional or distant spread of disease. CONCLUSION: Pakistan at present falls into a low risk cancer cervix region. The cause of concern is the steadily increasing incidence especially in the younger birth cohorts, the advanced disease at presentation; insignificant in-situ cancers and no preventive intervention or awareness practices in place.

Primary gastrointestinal malignancies in childhood and adolescence--an Asian perspective.

INTRODUCTION: Primary gastrointestinal (GI) malignancies are a rarity in childhood and adolescence, with limited information from Asian populations. This study was conducted with the objective of identifying the existence of malignant GI tumors in the young population of Pakistan and to determine high risk geographical areas of the country. METHODOLOGY: Pediatric and adolescence (<or=14 years; <or=19 years) gastrointestinal malignancies, ICD-10 categories C15-20 registered at the surgical pathology department of the Aga Khan University Hospital during 1st March 2004 to 30th April 2006 were included in the cross-sectional study. RESULTS: Sixty cases in <or=19 year age group were studied. The mean age was 16.2 years (SD+/-4.56). Carcinoma comprised 47 cases (78.3%; 32 boys and 15 girls.) and lymphoma 13 cases (21.7%; 12 boys and 1 girl). All cases presented as advanced malignancies. Categorization of carcinoma by site was colon (85.1%), stomach (6.4%) and esophagus (8.5%). Lymphoid malignancies were diffuse large B-cell lymphoma (30.8%), Burkitt lymphoma (46.1%) and Burkitt-like lymphoma (23.1%). The mean age at presentation was 11.1 years (SD+/- 4.6). CONCLUSION: This study has identified a substantial number of GI malignancies in the <or=19 year Pakistani population, involvement of esophagus, male predominance, preponderance of carcinoma versus lymphoma and a high signet ring cell and mucinous colo-rectal carcinoma. It has identified Baluchistan as a high risk region for esophageal cancer and diffuse large B-cell lymphoma and NWFP for Burkitt and Burkitt-like lymphoma. Most findings in the present study did not concur with published western data, indicating the need to study cancer in the Asian population.

Cancer profile of Larkana, Pakistan (2000-2002).

This present study was conducted with the objective of providing the cancer profile of Larkana, the fourth largest city of Sindh, Province. The study included two sets of patients. The first set included the incident cancer cases, residents of Larkana, who reached Karachi for diagnosis or treatment. The second set consisted of the incident cancer cases registered at the Aga Khan University (AKU) Pathology collection points at Larkana during 1st January 2000 to 31st December 2002. The age-standardized rates (ASR) for cancer (all sites) were 134.2/100,000 in males and 110.3/100,000 in females. The most common malignancies in males were lymphoma, oral cavity, prostate, liver, and urinary bladder. Cancers in females were breast, oral cavity, lymphoma, skin and thyroid. Tobacco-associated cancers accounted for approximately 35.0% of the tumors in males and 18.6% in females. The gender ratio was 1.5, the mean age of cancer all sites was 45.5 years (95% CI 34.6; 56.4) in males and 42.9 years (95% CI 33.6; 52.2) in females. This is the first attempt to determine the cancer incidence pattern of Larkana and should serve as a guideline for estimation of the cancer burden of Pakistan and the cancer control program of the country. The data must be interpreted with care, as they are largely pathology-based with approximately 15-30% population-wise under-registration. However, the chances of selective collection bias were minimized as the AKU pathology specimens were collected from 2 centers within the city, Each collection centre provided diagnostic service to several health centres giving wide population coverage, thus ensuring adequate sampling from the entire city.

Epidemiological review of head and neck cancers in Karachi.

Head and neck cancers, categories lip, oral cavity, pharynx and larynx are placed amongst the top ten malignancies globally. The cancers have a similar epidemiology, risk factors, morphology, and control measures. The geographical variations in incidence are indicative of the global differences in the prevalence of risk factors. The present study was conducted with the objective of reviewing descriptive epidemiological characteristics, incidence and time trends of head and neck cancers in Karachi (1995-2002). Head and neck cancers accounted for approximately one-fifth (21%) of the cancers in males and about one-tenth (11%) in females in the study period. The age standardized incidence rate (ASR) was 37.1/100,000 in males and 21.7/100,000 in females. In males, oral cavity and larynx were the commonly affected sites, followed by pharynx. In females, oral cavity was the preponderant site. The mean age of the patients was 53.0 years (95% CI 48.0; 58.0). A rising incidence was observed in both genders, more apparent in males. About 30% of oral cancer cases, 28.6% of the nasopharyngeal, 6.3% of the oropharyngeal, and 2.6% of laryngeal cancers occurred in patients 40 years and younger. The age specific incidence rates (ASIR) for oral cancer in males showed a gradual rise from 10 to 64+ years of age, for pharynx from 20 to 64+ and for larynx at 25+. The ASIR for oral cancer in females showed a gradual rise from 14 to 64+ years of age, for pharynx from 20 to 64+, a decade after the oral cancer rise and cancer larynx showed a rise at 25+, a decade and a half after the oral cancer rise. The peak incidence was at 64-69 years for all three cancer sites, in both genders. Pakistan falls into a high risk head and neck cancer geographical zone Presentation is late and treatment is not optimum. Recommendations, therefore for NCCP Pakistan, for short term benefits are selected community-based screening for the high risk population, early diagnosis, better treatment, rehabilitation and palliative care. These measures will improve survival and also contribute to a better quality of life. Primary prevention remains the only strategy for absolute cancer control.

Cancer profile of Hyderabad, Pakistan 1998-2002.

Hyderabad is the third largest city of Pakistan, the second largest city of Sindh Province and one of the oldest cities of the sub-continent. This administrative headquarter is located just east of the River Indus and is an important commercial and industrial center. Once a provincial capital, it is at a distance of approximately 200-km from Karachi. This present study was conducted with the objective of providing the cancer profile of Hyderabad, which has an urban population of 2,840,653 (52.2% M, 47.8% F) annual growth rate 1.13. The city is inhabited by all ethnicities of the country, however the predominant ethnicity is Sindhi, followed by Mohajirs (post-partition immigrants from India), and a lesser extent other ethnicities of Pakistan viz. Baluchs, Punjabis and Pathans. The study includes two sets of patients. First the incident cancer cases, residents of Hyderabad, who reached Karachi for diagnosis or treatment. Second the incident cancer cases registered at the Aga Khan University Pathology-based Cancer Registry (APCR) Pathology collection points at Hyderabad and subsequently registered at APCR, during 1st January 1998 to 31st December 2002. The pathology department of the AKU has 3 centers in Hyderabad, which provide diagnostic pathology especially oncopathology services to the city. The age-standardized rates (ASR) for cancer (all sites) 1998 to 2002 in Hyderabad were 91.6/100,000 in males and 96.0/100,000 in females. The most common malignancies (ASR per 100,000) in males were oral cavity (11.8), lymphoma (10.6), lung (8.0), urinary bladder (6.8), prostate (4.8), liver (4.4), pharynx (4.2), colo-rectum (3.6), larynx (3.2), and skin (3.2). The cancers in females (ASR per 100,000) were breast (22.4), oral cavity (11.5), gall bladder (4.8), esophagus (4.2), cervix (3.6), ovary (3.4), colo-rectum (3.4), lymphoma (3.4), uterus (3.4), and thyroid (2.4). Tobacco-associated cancers were responsible for approximately 40.0% of the tumors in males and 20.0% in females. Histological confirmation remained 96.3%, with 44.5% presenting in grade II or I, 55.5% presenting as stage III and IV. Information on grade and stage of malignancy was available in 70% and 50% of the cases respectively. Males comprised 53.1%, and females 46.9% of the cases. The mean age of cancer all sites, both genders was 45.2 years (95% CI 44.4; 45.9), males 45.4 years (95% CI 44.3; 46.5); females 44.9 years (95% CI 43.9; 45.9). Conclusions drawn from this database must be interpreted with care, as it may be identified as data from selected medical institutions. Chances of selective collection bias are minimized as the data of the AKU pathology is collected from multiple centers in the city of Hyderabad, dispersed at distances, which allows adequate sampling from the entire city. There is a slight preponderance of lymphomas in males which we feel is a true higher risk, yet it may indicate an over representation of easily accessible sites in pathology based-data. Nonetheless, this is the first attempt to determine the cancer incidence pattern of Hyderabad, and should serve as a guideline for estimation of the cancer burden and risk assessment statistics of Pakistan and the cancer control program of the country.

Increasing incidence of non-Hodgkin's lymphoma in Karachi, 1995-2002.

This first population-based study of non- Hodgkin lymphoma (NHL) from any region in Pakistan, provides an overview of the incidence pattern and time trends in Karachi and generates hypotheses for future experimental research. Epidemiological data for 429 incident (1(st) Jan 1995 to 31(st) Dec 2002), microscopically verified nodal and extra-nodal NHL cases, registered at the Karachi Cancer Registry (KCR) for Karachi South, were reviewed. The age standardized incidence rate (ASIR) was 5.3/100,000 in males (M) and 4.1/100,000 in females (F), in 1995. A gradual increase in the annual incidence was observed during the study period, with NHL incidence rate increasing in 2002 to 8.4/100,000 in men and 6.5/100,000 in women, almost double the 1995 rates. NHL affected all age groups in both genders and for each group the ASIR was higher among men than women, with an overall gender ratio of 1.9. The mean ages of the patients were 41.5 years (95% CI 39.1; 43.8) in males and 44.0 years (95% CI 40.8; 47.1) in females. The adult to childhood ratios were 8.6 (M) and 10.7 (F). B-cell NHL comprised 81.0% of NHL in males and 87.3% in females. One fourth of the NHL cases were extra-nodal, the largest group was of gastrointestinal origin (54.1% M, 38.5% F). The gastric component was 21% M and 25.6% F. Odds Ratios for sex, age-groups, ethnicity, religion, and subdivision by socio-economic categories were calculated by considering all malignancies, except lymphoproliferative disorders as controls. The odds ratio (OR) in men was 2.2 (95% CI 0.6; 3.0). Children and adolescents were at the highest risk of developing NHL, especially the 5-9 year olds, in both genders. A marginally higher risk was observed for the lower socioeconomic categories and for ethnicities belonging to Northern and North Western Pakistan (Punjabi, Pushtu and Baluch) residing in Karachi South. The incidence rates of NHL registered in Karachi South are likely to be a reflection of non-AIDS-associated NHL. Estimated HIV/AIDS incidence was too low during the study period in this population to have an impact on NHL incidence. The preponderance of low and intermediate grade lymphomas, paucity of central nervous system NHL and a higher childhood NHL component support this hypothesis. As yet unpublished reports, however, are raising the alarm on rising HIV positivity. NHL correlation with HIV/AIDS status and studies identifying risk factors of non- HIV/AIDS associated NHL (childhood viral infections, Hepatitis C virus, and Helicobacter pylori) are potential areas for future experimental and epidemiological research.

Rhabdomyosarcoma in Karachi 1998-2002.

The epidemiological features of rhabdomyosarcoma (RMS), an uncommon malignancy composed of cells with histopathologic features of striated muscle, were studied in Pakistan. Incident RMS cases recorded at the Karachi Cancer Registry during 1998 to 2004 were reviewed and to ensure maximum completeness of data, only those registered between 1998 and 2002 were considered for the present study. Two hundred and seventeen cases were reported to the Karachi Cancer Registry during this five-year period. One hundred and forty eight of the patients (60.4% males; 39.6% females) were residents of Karachi. The crude and standardized annual incidence rates/100,000 were 0.3 for males and 0.2 for females. The incidence was 0.5 in children below 15 years of age. The primary RMS sites in males were head and neck (28.1%), extremities (25.8%), genitourinary (GU) tract (17.9%), trunk (9.0%), orbit (7.9%), and retroperitoneum (3.4%). RMS occurred at other sites in 7.9% of the patients. Corresponding frequencies in females were head and neck (35.6%), extremities (16.9%), GU tract (16.9%), trunk (8.5%), orbit (8.5%) and other sites in 13.6%. Approximately 60% of the cases were childhood RMS and three fourths were below 21 years. The mean age of RMS cases all sites, males, was 18.5 years (95% CI 15.6; 21.4); for childhood RMS, 7.5 years (95% CI 6.0; 9.2); and for adult RMS 34.2 years (95% CI 28.3;40.2). In females, the corresponding figures were 18.2 (95% CI 13.7; 22.7); 6.6 (95% CI 5.0; 8.1) and 33.9 (95% CI 27.5; 40.5), respectively. One hundred cases were retraceable, and the mean survival time, RMS all sites and ages in both genders, was 1.5 years (95% CI 1.1; 1.9). The 5-year survival was 10%, and 3-year survival was 30% whereas 16.7% of the patients died within a year of diagnosis. The indicators of poor prognosis, a late presentation, rapid evolution, advanced disease, tumor burden (tumor size >5.cms) and regional lymph node involvement, are characteristic of RMS in Karachi. Recent advances in RMS multimodality treatment protocols have improved RMS prognosis in patients with limited disease. Pakistan should focus on early diagnosis and prompt treatment of malignancies. This requires health education for the general population to create awareness and training of health professionals at all levels to promote early diagnosis. An RMS group is required, which would monitor the treatment, recurrence, patient education and provide psychosocial support. Cytogenetic studies are advised for a better understanding of biologic differences in RMS cases in this population.

Retinoblastoma in Karachi, Pakistan.

The objective was to assess epidemiologic aspects of retinoblastoma development in Karachi, Pakistan. Incident cases, diagnosed clinically or microscopically and registered at Karachi Cancer Registry (KCR) during 1(st)January 1998 to 31(st) December 2002 were reabstracted, rechecked and reanalyzed for this purpose. One hundred and one cases of retinoblastoma were reported to KCR over the 5 years (1998-2002). Fifty-seven were residents of Karachi, 34 (59.6%) males and 23 (40.4%) females. The gender ratio (M:F) was 1.5. The mean age at diagnosis was 3.96 years (95% CI 2.92; 4.99) and 3.85 years (95% CI 2.72; 4.98) in males and females respectively. The annual crude incidence of retinoblastomas in Karachi was 4.0/100,000 and 2.4/100,000 in children under the age of 5 and 10 years respectively, the corresponding age standardized rates being 5.3/100,000 and 4.8/100,000. The age groups at risk of developing retinoblastoma, associated morbidity and possibility of almost 100% 5-year survival with available treatments, calls for ophthalmologic screening of all infants below 1 year, and high-risk children until the age of 7 years. In order to detect retinoblastoma, as early as possible, health education for parents and health providers, and improved training of ophthalmologists is essential. Genetic testing for siblings and children of retinoblastoma cases and identification of high-risk children would be helpful, but lacks financial feasibility in developing countries at present. Future health care planning should focus on capacity building for neonatal ophthalmologic screening, handling of parents'and children'emotional reactions and opportunities for education, occupational training and cosmetic rehabilitation for surviving retinoblastoma patients.

Epidemiology of ocular malignancies in Karachi.

The study was conducted with the objective of examining descriptive epidemiological characteristics of malignant ocular tumours in Karachi (1998-2002). The data for two hundred and forty two ocular malignancies registered at the Karachi Cancer Registry for Karachi Division during a 5-year period, from January 1(st) 1998 to December 31(st) 2002 were analysed. The age standardized incidence rate (ASIR) was 0.5/100,000 in males and 0.4/100,000 in females. The gender ratio (M:F) was 1.3. The mean age was 34.8 years (95% CI 30.1; 39.6) in males and 34.5 years (95% CI 28.0; 40.9) in females. A fourth of the malignancies were childhood tumours. The most common childhood malignancies were retinoblastomas and rhabdomyosarcomas, whereas the most common adult malignancies were conjunctival squamous cell carcinomas and melanomas. Approximately 97.0% of the tumours were histologically confirmed. The majority (62.5%) presented as low-grade (grade 1) lesions, and were localized to the eye (50%) at the time of diagnosis. The annual incidence rates remained stable during this period. The crucial importance of ocular malignancies is the high 5-year survival rates, associated disability following unilateral or bilateral enucleation and the implications as preventable components of Cancer Control Programs This article provides demographic statistics, which could be useful for the foundation, establishment and monitoring of a component of an effective cancer control program, the risk factors of ocular malignancies being well established. It is recommended that public health education to prevent ultraviolet light related ocular malignancies, information on preventative sun protection behavior, legislation for occupation related ocular cancers and genetic counseling for familial retinoblastoma should be essential primary components of all National Cancer Control Programs even in apparently low risk countries. In the long-term perspective, these efforts should further reduce the incidence - meanwhile stabilization of incidence rates could be achieved. Early detection and standardized treatment will reduce the associated morbidity and mortality.