Pleomorphic Xanthoastrocytoma; Clinicopathological spectrum of An Intriguing neoplasm.

BACKGROUND & OBJECTIVE: Pleomorphic xanthoastrocytoma (PXA) is a rare primary WHO Grade II astrocytic tumor comprising of < 1% of all astrocytomas. It is generally benign and slow growing however disease progression and malignant transformation with anaplastic features have been infrequently reported. Our objective was to assess clinicopathological characteristics of this rare tumor at our center. METHODS: A retrospective study was conducted at Aga Khan University Hospital from January 1992 till January 2016. Data was entered on a proforma including patient demographics, clinical features, tumor location, histological features and follow-up, where available. RESULTS: Forty Seven cases of PXA were retrieved during the study period. The mean age was 23.8 years (SD=15.1) and median age was 19 years. The most frequent symptom was head ache (n=31). Male were more frequently affected (n=26). The commonest location was temporal lobe. On microscopic examination, tumors were pleomorphic without mitoses or necrosis, however two cases showed increased mitotic activity, and one case revealed associated gliosarcoma. Follow-up of only 29 cases was available for a period ranging between 2 and 184 months (85 months +/- 56 months). Outcome was good in 27 patients with the last follow up showing no radiographic or clinical evidence of tumor recurrence. CONCLUSIONS: PXA is an infrequent tumor in our population also, with less than 50 cases identified in two decades study period. Due to its rarity and its bizarre histomorphology, it should be diagnosed correctly, as it has got better prognosis than other astrocytic tumors.

Nigella sativa Oil Reduces Extrapyramidal Symptoms (EPS)-Like Behavior in Haloperidol-Treated Rats.

The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1 mg/kg) on NS (0.2 ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls. Immunohistochemical analysis indicates that NS reduced astrogliosis in caudate and accumbens nuclei. These results suggest that NS may consider as an adjunct to antipsychotics to reduce the EPS-like side effect.

Olfactory neuroblastoma: A clinicopathological experience of a rare entity from Pakistan.

OBJECTIVES: To present the clinicopathological experience of Olfactory Neuroblastoma (ONB) with emphasis on histopathological and immunohistochemical features. METHODS: A descriptive cross-sectional study was done on 36 cases of ONB, selected by non-probability purposive sampling. Theses cases of ONB were retrieved and reviewed from surgical pathology database of Aga Khan University Hospital reported between January 1993 and March 2015. RESULTS: Tumor size and age of presentation was wide in range without any distinct bimodal distribution. Nasal cavity was most common site along with involvement of paranasal sinuses. More than 50% cases had Kadish stage A. Microscopically, most cases were Grade-1 and majority showed partial or complete lobular architecture. Neurofibrillary matrix was observed in 2/3(rd) of cases. Among immunohistochemical markers, Neuron Specific Enolase was most frequently expressed. Unusual positive expression of Cytokeratin AE1/AE3 and Cytokeratin CAM5.2 was also seen focally in few cases. CONCLUSION: The ONB has great variability of histological and clinical presentation, and immunohistochemical markers are useful to differentiate from more common small round blue cell tumours of nasal cavity.

Cystic Neutrophilic Granulomatous Mastitis.

Granulomatous lobular mastitis (GLM) is an infrequent inflammatory breast disease, which can simulate malignancy on the basis of clinical and imaging features. It is typically found in parous or lactating women. The differential diagnosis of granulomatous mastitis includes infections caused by bacterial, fungal or mycobacterial agents, and autoimmune disorders like rheumatoid arthritis, sarcoidosis, giant cell vasculitis, and granulomatosis with polyangiitis. Cystic neutrophilic granulomatous mastitis (CNGM) is a sporadic sub-type of GLM that can be linked with infection with Gram-positive bacilli, specifically, Corynebacterium. It is characterised by lipogranulomas that comprise of "cystic" spaces lined by neutrophils which may contain Gram-positive rod-shaped bacteria. The majority of cases of GLM are still "idiopathic" as this pattern of inflammation still remains a mystery. We herein report three cases of CNGM and review the relevant literature. Key Words: Granulomatous mastitis, Corynebacterium, Gram-positive rods, Inflammatory breast disease, Cystic neutrophilic granulomatous mastitis.

Cytological features of a complete hydatidiform mole in a cervicovaginal smear: A case report.

Exfoliated trophoblastic cells can be seen in a cervicovaginal smear in cases of normal pregnancy or gestational trophoblastic disease (GTD) and can mimic high-grade squamous intraepithelial lesion (HSIL) or malignancy. Although they appear highly anaplastic, cytological features such as high nuclear to cytoplasmic ratio, irregular nuclear contours and scanty basophilic cytoplasm admixed with cytologically benign squamoid and endocervical cells can aid in differentiating them from malignant cells. We present a case of a 37-year-old woman with abnormal uterine bleeding for 3-months. There was no history of recent pregnancy or previous GTD. Her cervicovaginal smear showed a hypercellular smear exhibiting cytologically benign superficial and intermediate squamous cells along with clusters of benign endocervical cells with interspersed mononucleate cells. These mononucleate cells were large, with a hyperchromatic, pleomorphic nuclei, and scant basophilic cytoplasm. Cytological features were suggestive of trophoblastic cells and workup for pregnancy and GTD was advised. Her laboratory investigations showed markedly raised levels of ß human chorionic gonadotropins (ß-HCG) and ultrasound showed a uterine mass with snowstorm appearance. A uterine evacuation was performed after which histopathological examination showed microscopic features consistent with a complete hydatidiform mole. The rare presence of trophoblastic cells in a cervicovaginal smear can easily be confused with malignant cells and can be misleading to the pathologist. Trophoblastic cells should always be kept in mind when evaluating a cytology smear of a young patient irrespective of gestational status.

Patho-epidemiology of breast cancer in Karachi '1995-1997'.

OBJECTIVE: Provide an overview of the demographics and pathology of breast cancer in the female population of Karachi South during a 3 year period, 1995-1997. METHODS: Epidemiological data for 709 incident breast cancer cases, ICD-10 category C50 registered at Karachi Cancer Registry during 1st January 1995 to 31st December 1997 were reviewed. RESULTS: Breast cancer accounted for approximately one-third of the cancers in females. The age standardized incidence rate (ASR) world per 100,000 was 53.8, the crude incidence rate was 30.9. In KS 60% of the newly diagnosed breast cancers were observed in women below 50 years. The age-specific curves showed a gradual increase in risk from the third up till the seventh decade, followed by an actual/apparent decrease in risk. The socio-economic distribution was 24.9% in category I the financially deprived class, 38.9% in category II the middle class and 35.9% in category III, the affluent class. Microscopic confirmation of malignancies was 99%. Invasive breast cancers predominated with 99.4%, with in-situ cancers contributing to 0.6% of the malignancies. The morphology of cancers was tilted towards duct cell carcinoma (DCC), pure DCC (92%), combinations of DCC /Paget's disease (0.6%) and lobular carcinoma (0.4%). Approximately 45% of duct cell carcinoma were seen in the premenopausal age group (<45 years). All bilateral breast cancers were duct cell carcinoma with a family history of first degree relative with breast cancer. The majority of the cases presented as moderately differentiated or grade 2 lesions (59.0%). Approximately 56% cancers had spread to the regional lymph nodes and 8.3% to a distant site at the time of diagnosis. A family history of first degree relative with breast cancer was present in 3% and second degree relatives in 7% of the cases. Odds ratio (OR) for 680 breast cancer cases with complete demographic information was calculated with 675 gender matched controls. A slightly higher risk was observed in non-Muslims and migrant ethnicities: two to three fold elevation in the Indian migrants (Gujrati speaking Mohajirs OR 3.86 (95% CI 2.51; 5.92) Urdu speaking Mohajirs OR 2.85 (95% CI 2.05; 3.96), Memon Mohajirs OR 2.21 (95% CI 1.48; 3.29) and Afghan migrants [OR 2.99 (95% CI 11.20; 7.44)]. The risk was also high in the females of Punjabi ethnicity settled in KS [OR 2.73 (95% CI 1.87; 3.99)]. The risk seems much less for the ethnicities belonging to North Western Pakistan i.e. Pathans [OR 1.684 (95% CI 0.89; 3.17)] and Baluchs [OR 0.90 (95% CI 0.58; 1.39)]. A marginally higher risk was observed in the higher socio-economic categories. The risk of developing breast cancer increased gradually for each age category from illiterate [OR 1.2 (95% CI 0.94; 1.55)] to college graduates [OR 13.12 (95% CI 7.31; 23.73)]. CONCLUSIONS: The incidence of breast cancer in Karachi South (KS) for the period 1995-1997 was the third highest in Asia. The hallmarks were a high reproductive age malignancy involving a higher socio-economic class, an invasive duct cell carcinoma diagnosed at an advanced stage, in younger more educated females and a low in-situ malignancy. More studies are required to obtain a deeper insight into this breast cancer epidemic in Karachi. Implementation of breast cancer screening with stress on public health education is today a major responsibility of the government.

Patho-epidemiology of Cancer Cervix in Karachi South.

INTRODUCTION: The present study was conducted with the objective of examining descriptive epidemiological and pathological characteristics of cancer cervix in Karachi South, an all urban district population of Karachi, Pakistan. METHODOLOGY: A total of 74 cases of cancer cervix, ICD-10 (International Classification of Diseases 10th Revision) category C53 were registered at the Karachi Cancer Registry, for Karachi South, during a 3 year period, 1st January, 1995 to 31st December 1997. RESULTS: The age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.81 (5.2, 8.43) and 3.22 (2.49 to 3.96). Cancer cervix accounted for approximately 3.6% of all cancers in females and was the sixth malignancy in hierarchy. The mean age of the cancer cases was 53.27 years [standard deviation (SD) 11.6; 95% confidence interval (CI) 50.58, 55.96; range (R) 32-85 years)]. The distribution by religion was Muslims (90.5%), Christians (8.1%) and Hindus (1.4%). There were no cases reported in Parsees. The frequency distribution by ethnicity was Urdu speaking Mohajirs (20.3%), Punjabis (17.6%), Gujrati speaking Mohajirs (4.1%), memon Mohajirs (8.1%), Sindhis (10.8%), Baluchs (8.1%), Pathans (5.4%) and Afghan migrants (2.7%). The ethnicity was not known in approximately a fourth (23.0%) of the cases. The socio-economic distribution was 27.0% financially deprived class, 24.4% lower middle class and 48.7% upper middle and affluent classes. The majority of the women were married (86.5%); a smaller number were unmarried (2.7%) or widows (10.8%). The age-specific curves showed a gradual increase in risk from the fourth up till the seventh decade, followed by an actual apparent decrease in risk after 64 years of age. The peak incidence was observed in the 60-64 year age group. The morphological categorization was squamous cell carcinoma (86.5%), adenocarcinoma (10.9%) and adenosquamous carcinoma (2.6%). The majority of cases presented with moderately differentiated or grade 2 lesions (45.9%). There were no in-situ cases. Approximately half the cancers (58.1%) had spread regionally and 8.1% to a distant site at the time of diagnosis. Odds ratios (OR) were calculated for socioeconomic residential categories, religion, ethnicity, age groups and education. The OR for socioeconomic residential categories ranged between 0.69 and 2.9 with a marginally higher risk in the lower [OR 2.09 (95% CI .97; 4.49)] and lower middle class [OR 2.08 (95%CI 0.95; 4.58)]. Hindus [OR 1.2 (95% CI 0.18; 2.2)] had a slightly higher risk then the Muslims [OR 0.14 (95% CI 0.17; 1.2)]. A higher risk was also observed for Christians [OR 7.76 (95% CI 1.74; 34.5)]. CONCLUSION: The incidence of cervical cancer in Karachi South (1995-97) reflects a low risk population with a late presentation and a high stage disease at presentation. It is suggested that cervical screening if implemented should focus on once a life time methodology involving 36-45 year old women. This should be combined with HPV vaccination for the young and public health education for all. A regular cervical screening program would require mobilization of considerable financial, structural and human resources along with training for personnel. This may burden the already stretched health resources of a developing country.

Thymoma : a clinicopathologic association of world health organization histologic subtype and invasive behaviour.

OBJECTIVE: To re-classify thymic epithelial neoplasms reported at Aga Khan University Hospital during the past seven years according to the revised WHO classification, to assess the ease of application and determine association between WHO histological subtype and invasive behaviour. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The study was carried out in the section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, from January 2000 to October 2006. MATERIAL AND METHODS: All cases of thymic epithelial neoplasms reported in the past seven years were retrieved using SNOMED coding system. Small biopsies where the tissue was insufficient for definite classification were not included. All cases were reviewed and reclassified according to WHO classification into types A, AB, B1, B2 and B3. Capsular invasion as well as extension into neighboring structures such as perithymic fat, pleura, pericardium, lung etc. was noted on morphology. RESULTS: A total of 62 cases were diagnosed as Thymic Epithelial Tumors (TET). Out of these, there were 5 type A (6 %), 17 type AB (21%), 7 type B1 (8.6%), 26 type B2 (32%) and 7 type B3 (8.6%) thymomas. Age range was from 22-78 years with a median age of 46 years. Male to female ratio was 6:1. History of associated myasthenia gravis was present in 21% of cases. A significant association was observed between WHO histologic subtype and invasive behaviour where types A, AB and B1 have lesser number of invasive cases as compared to non-invasive, whereas in types B2 and B3, more cases have shown invasion as compared to non-invasive cases (c2 = 14.093, df =1, p-value < 0.001 ). CONCLUSION: The WHO classification is simple and easy to apply and has significant association with aggressive behavior. To some extent, it reflects the clinical behaviour of thymomas along with stage and status of resection. However, morphologically benign looking thymomas can behave aggressively. Hence, tumour stage, extent of resection and histology should be combined to predict the clinical behaviour of thymomas.

Clear cell carcinoma of ovary with associated mucinous cystadenoma and endometriosis.

A 45 year old woman presented with right sided ovarian mass with multiple omental deposits and liver metastases. The right ovary was enlarged and showed a partly cystic partly solid cut surface. Histological picture showed clear cell carcinoma with areas of mucinous cystadenoma and endometriosis. Clear cell carcinoma is known to be associated with endometriosis. To the best of author's knowledge, it's association with mucinous cystadenoma has been described only once in the literature, where clear cell carcinoma was shown to be associated with mucinous cystadenoma without any evidence of endometriosis.

Atypical Teratoid/ Rhabdoid Tumor of Brain: a Clinicopathologic Study of Eleven Patients and Review of Literature

Background: Atypical teratoid/ rhabdoid tumor (AT/RT) is a rare aggressive embryonal central nervous system (CNS) tumor of infancy and early childhood. Majority of the cases arise in the posterior fossa, and remaining in the cerebrum. Aims: To analyze the clinicopathologic features of AT/RT on a cohort of cases. Materials and methods: All reported cases of AT/RT at the Department of Pathology and Laboratory Medicine, Aga Khan University Hospital (AKUH) from 2007 to 2016 were reviewed for clinical and pathological features. Immunohistochemical stain for INI-1 was performed in all 11 cases. Follow up was obtained. Results: A total of 11 cases were identified. Seven patients were males and 4 were females. The ages ranged from 1 month to 48 months (mean 26.6 months). Six tumors were located in the cerebrum and 3 in the posterior fossa. Exact Location was not known in 2 cases. Histologically, rhabdoid cells were present in sheets in variable proportions in five cases, Medulloblastoma and PNET like areas were seen in 2 cases each. Immunohistochemical stains EMA (10/10), vimentin (7/7), CKAE1/AE3 (8/9), and CD99 (3/4), GFAP (6/10), ASMA (3/4) and synaptophysin (3/4) were positive in varying proportions while desmin was negative in all 6 cases in which it was performed. All 11 tumors lacked immunoreactivity for INI-1 protein. Four patients died of disease with a follow up ranging from 5 to 24 months. Conclusions: AT/RT is a rare highly aggressive embryonal tumor of CNS. A male predominance was noted in our series. We report the first and largest series from Pakistan.

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.

Patho-epidemiology of lung cancer in Karachi (1995-2002).

The objective of the study was to provide an overview of the demographics of lung cancer, the number one cancer killer of men in Karachi South (1995-2002). Lung cancer cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st December 2004 were analyzed. To allow for maximum data completion, cases recorded from 1st January 1995 to 31st December 2002 were included for final analysis. Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2 time periods, 1995-1997 and 1998-2002. Odds ratio for sex, age-groups, ethnicity, religion, and residence by socio-economic categories were calculated by considering all malignancies (except tobacco-associated malignancies) for each group, registered at KCR for the same period as controls. Cancer of the lung ranked the most frequent malignancy in men in Karachi in the entire 1995-2002 period, though it did not feature amongst the first 10 malignancies in the females. In the 1995-1997 period, the ASR per 100,000 population for cancer of the lung was 21.4 and 2.9 in males (M) and females (F) respectively. The mean age of the patients was 60.4 years (95% CI, 59.1-61.7) M and 53.7 years (95% CI 48.9-58.5) F. In the 1998-2002 period the incidence rate increased to 25.5 per 100,000 (M) and 4.2 per 100,000 (F). Thus between 1995 and 2002, the incidence of lung cancer registered a 19% increase in men and almost 100% in women. The component of adenocarcinoma in females remained stable during 8 years, but increased 55% in males. Histologic confirmation was 80%; majority of cancer cases presented as grade 3 and grade 4 lesions (62.3%), and were discovered at advanced stages (stage III 35.7%; stage IV 55.8%). The odds ratio (OR) in men was 4.5 (95% CI 3.7; 5.4). The risk of developing lung cancer increased with age, the highest risk being observed in the 65+ age group. A marginally higher risk was observed in the higher socio-economic categories for men and in the lower socio-economic categories for women. A higher risk was also observed for men who were residing along the coastal belt, and for ethnicities belonging to Southern Pakistan (Sindhi and Mohajir) residing in Karachi South. In conclusion, Pakistan at present falls into a low risk lung cancer region in females and a moderate risk region for males and the highest registered increase between 1995 and 2002 was observed in the older age groups (65+). It is however a cause of concern that the overall lung cancer incidence rates continue to rise. The age specific rates though stable in the younger age groups (35-49 years), are at present equivalent to contemporary rates in high- risk countries. These rates correspond with the trends of smoking prevalence in the younger age groups in the last 2 decades. Published studies have given alerts to increase in the smoking habits of the present day youngsters and with an expanding population the country can expect a substantial increase in lung cancer. This threat can only be averted by implementation of stringent anti-tobacco rules and health education; prohibition of smoking in educational institutions at all levels and a ban on the sale of cigarettes to minors.

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.

Desmoplastic small round cell tumor.

Desmoplastic small round cell tumour (DSRCT) is a unique, highly aggressive neoplasm that chiefly affects adolescent male and young adults and most frequently presents as a large abdominal mass with widespread peritoneal involvement at the time of diagnosis. Histologically, it is composed of nests of small, undifferentiated round or oval hyperchromatic cells embedded in abundant desmoplastic stroma. Co-expression of epithelial, mesenchymal, and neural antigens in the same cell provides evidence of origin from a primitive pluripotent stem cell with multiphenotypic differentiation. A multidisciplinary treatment including high-dose chemotherapy, aggressive debulking surgery, radiation and myeloablative chemotherapy with stem cell rescue might be the proper approach to treat this rare malignancy and may improve progression-free survival.

Frequency and characteristics of breast lymphomas presenting to a tertiary care hospital, Pakistan.

OBJECTIVE: To assess the relative frequency of (primary and secondary) mammary lymphomas presenting to a tertiary care hospital, Pakistan and its categorization according to WHO classification of lymphoid neoplasms. METHODS: All NHLs (nodal and extra nodal) diagnosed in the section of histopathology during 1992-2004 were retrieved and reviewed. All patients (n=30) diagnosed with lymphomatous involvement of the breast were selected. Distinction between primary and secondary breast lymphomas was not made owing to lack of availability of clinical information. RESULTS: A total of 5637 breast malignancies were diagnosed in our department during the study period of 10 years and the total number of NHLs (Nodal and extra Nodal) was 2632. Thirty (n=30) patients accounting for 1.13% were diagnosed to have lymphomatous involvement of the breast. The Female to Male ratio was 13.5:1; age range was 12-92 years with a median age of 43 years (Mean age 46.5 years and Standard deviation of age was 16.88 years). The sites of the lesions were the right breast in 11 cases (37.93%), left breast in 9 cases (31.03%) and both breasts in 2 cases (6.89%), while the location of 8 masses (27.58%) was unknown. Immunohistochemical studies were negative for cytokeratins (MNF and Cam 5.2) in all cases. All cases of DLBCL expressed B cell lineage antigens and were positive for LCA and Pan B (CD20 and 79a). CONCLUSION: We concluded that breast lymphomas represent 1.13% of all NHL and 0.5% of all breast malignancies in this study. The most frequent morphologic type was diffuse large B-cell lymphoma. As patients with primary breast lymphoma have a better prognosis than those with carcinoma of the breast or patients with extranodal lymphomas, a multidisciplinary approach including surgery, radiotherapy, and chemotherapy when needed would result in a more favourable outcome.

Significance of immunohistochemistry in accurate characterization of malignant tumors.

BACKGROUND: To determine in a large series of surgical biopsies the role and significance of immunohistochemistry in the adequate and accurate characterization of malignant tumors. METHODS: A retrospective study of 20,000 consecutive surgical biopsies reported in the Section of Histopathology, AKU in 2003. Data was obtained by retrieving the filed surgical biopsy reports in the section. RESULTS AND CONCLUSIONS: Out of the 20,000 biopsies, 6534 (32.67%) were neoplastic. 4726 neoplasms (72.33%) were malignant, and 1808 (27.67%) were benign. Immunohistochemistry was performed on 29.49% of malignant tumors, and 4.97% of benign tumors. Immunos were performed on only 2.82% of routine squamous cell carcinomas and adenocarcinomas of various organs, and in only 1.9% of infiltrating breast carcinomas, the commonest malignant tumors in females. In contrast, immunos were performed on 97.12% of non-Hodgkin's lymphomas, 97.94% of Hodgkin's lymphomas, 98.09% of malignant spindle cell neoplasms, 87.96% of small round blue cell tumors of childhood, 87.30% of neuroendocrine neoplasms, and 84.37% cases of malignant melanomas. In addition, immunos were performed on all cases of malignant undifferentiated neoplasms and were able to resolve the issue in over 89% of such cases. Immunos were also performed on 54.74% of metastatic tumors. Lymph nodes were the commonest organs on which immunos were performed i.e. 96.50% of lymph node tumors, followed by CNS and renal neoplasms with 33.01% and 25.92% respectively.

Central, Extraventricular and Atypical Neurocytomas: a Clinicopathologic Study of 35 Cases from Pakistan Plus a Detailed Review of the Published Literature.

BACKGROUND: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. AIM: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. MATERIALS AND METHODS: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. RESULTS: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer- Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.

Commonest Cancers in Pakistan - Findings and Histopathological Perspective from a Premier Surgical Pathology Center in Pakistan.

CONTEXT: There are no recent authoritative data about incidence and prevalence of various types of cancers in Pakistan. AIM: To determine the frequency of malignant tumors seen in our practice and provide a foundation for building a comprehensive cancer care strategy. MATERIALS AND METHODS: 10,000 successive cases of solid malignant tumors reported in 2014 were included. All cases had formalin fixed, paraffin embedded specimens available and diagnosis was based on histological examination of H and E stained slides plus ancillary studies at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi. The latest WHO classifications were used along with the latest CAP protocols for reporting and the most updated TNM staging. RESULTS: There were 9,492 (94.9%) primary tumors while 508 (5.1%) were metastatic. Some 5,153 (51.5%) were diagnosed in females and 4,847 (48.5%) in males. The commonest malignant tumors in females were breast (32%), esophagus (7%), lymphomas (6.8%), oral cavity (6.7%) and ovary (4.8%), while in males they were oral cavity (13.9%), lymphomas (12.8%), colorectum (7.9%), stomach (6.9%) and esophagus (6.6%). Malignant tumors were most common in the 5th, 6th and 7th decades. About 8% were seen under 20 years of age. CONCLUSIONS: Oral cavity and gastrointestinal cancers continue to be extremely common in both genders. Breast and esophageal cancers are prevalent in females. Lung and prostate cancer are less common than in the west. Ovarian cancer was very common but cervix cancer was less so.

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.