[en] Objective: To determine concordance and discordance between radiological and pathological findings of palpable breast lesions. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Oct 2018 to Mar 2019. Methodology: Imaging and histopathologic reports of a total of 170 female patients with breast lumps were analyzed. Concordance and discordance rates were estimated by comparing histopathology and imaging findings. All the reports were divided into four categories. Malignant concordant lesions showed malignant features and benign concordant lesions showed benign features on both imaging and histopathology. Malignant discordant lesions were those lesions, which were reported benign on imaging but proved to be malignant on histopathology and benign discordant lesions were those showing malignant features on imaging but turned out to be benign on histopathology. Results: Overall concordance was observed in 138 (81.2%) cases with a discordance rate of 18.8% (15.3% benign discordant and 3.5% malignant discordant). All malignant discordant cases (n=6, 3.5%) were reported as Breast Imaging Reporting and Data System category III on imaging and all came out to be invasive ductal carcinoma on histopathology. All benign discordant cases (n=26, 15.3%) were reported as Breast Imaging Reporting and Data System category IV on imaging. Conclusion: A higher discordance rate between imaging and histopathologic findings was observed in the present study as compared to what cited in the literature. Discordant cases should be followed by repeat biopsy for confirmation of diagnosis. (author)

[en] Objective: To determine the grades of gastrointestinal neuroendocrine tumours using World Health Organization criteria and Phosphohistone H3 mitotic index and to determine the concordance between the two methods. Study Design: Cross-sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Mar to Oct 2019. Methodology: Forty-two (n=42) patients of either gender between the ages of 18-70 years were enrolled. All the enrolled patients were diagnosed with primary gastrointestinal neuroendocrine tumours and underwent either surgical or endoscopic resection. Tumour grades were determined using World Health Organization criteria and Phosphohistone H3mitotic index. The results obtained with both methods were compared, and the concordance rate was calculated. Results: When mitotic counts were determined through PHH3, MI resulted in a change of grade of 12 (28.6%) tumours, which were graded by the current WHO system. 11 (26.2%) were changed from grade II to grade I and 1 (2.4%) from grade I to grade I1. The agreement (concordance rate) between the two systems was moderate and statistically significant (71.4%, n=30/42, κ= 0.51, p= 0.001) Conclusion: In the present study, we observed a moderate agreement between the Ki-67 labelling index and the PPH3 mitotic index, and both correlate well with the mitotic counts. The PPH3 mitotic index demonstrated a better correlation with mitotic counts when compared with Ki-67 LI. Hence, the inference can be drawn that the mitotic index with Phosphohistone H3 is associated more closely with mitosis in gastrointestinal neuroendocrine tumours. (author)

[en] To evaluate performance of thin layer agar (TLA) 7H11 method for detection of ofloxacin (OFX) and kanamycin (KM) resistance in smear positive clinical specimens of patients with tuberculosis comparing the results with gold standard MGIT 960 system. Study Design: Cross-sectional validation study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from April to September 2017. Methodology: Acid fast bacilli (AFB) smear positive specimens submitted at the study place, were inoculated on TLA 7H11 agar. Growth was examined along with susceptibility of OFX and KM and compared with gold standard MGIT 960 system. Results: One hundred and sixty specimens were evaluated. Sensitivity and specificity of TLA for OFX was found to be 100% and 99.3%, respectively; and PPV and NPV was found to be 90.9% and 100%, respectively. Overall diagnostic accuracy was 99.38%. Sensitivity and specificity of TLA for KM was found to be 80% and 100%, respectively. PPV and NPV was found to be 100% and 99.36%, respectively. Overall diagnostic accuracy was 99.38%. Conclusion: Thin layer agar is reliable, easy to perform and cost effective technique not only for rapid detection of MTB but also for drug susceptibility (DST) of second line anti TB agents. It is a suitable alternative to culture on LJ medium and can also be alternative to MGIT 960 system in resource-poor settings. (author)

[en] Objective: To identify effect of pre-analytical variables on serum thyroid stimulating hormone. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP) Rawalpindi, Department of Chemical Pathology & Endocrinology, from Mar 2018 to Aug 2018. Methodology: Hundred subjects with ages ranging from 18 to 34 years, irrespective of gender, were randomly selected for this study. Five milliliters venous blood sample was collected from each subject in a serum separator and divided into two aliquots. First aliquot was centrifuged and analyzed immediately for TSH, while second aliquot was stored for 24 hours and was then analyzed. TSH was measured by third generation assay using chemiluminescence technique on ADVIA Centaur® XP. Serum TSH levels were also analyzed twice daily; in the morning (0800 to 0900 hours) and afternoon (1400 to 1600 hours). Data was analyzed using SPSS version 24. Frequency and percentages were calculated for qualitative variables like gender and pre-analytical variables. Test of significance Mann-Whitney U-test was applied and p-value <0.05 was taken as significant. Results: Mean age of subjects was 23 ± 3.4 years. Change in circadian rhythm was observed in 17 (28%) males and 14 (36%) females. Statistically significant association was found between morning and evening TSH levels, while no change was observed in TSH level by early and late centrifugation of samples. Conclusion: TSH levels vary significantly between blood samples collected at different timings of the day from the same person. TSH is resistant to degradation, immunologically stable, and reasonably insensitive to potential problems associated with routine specimen handling, when measured by immunoassay technique. Therefore, it is helpful in large epidemiological studies and small size laboratory, which require long transportation time and storage. (author)

[en] To determine age-related association of Her-2/neu expression with histological and immunohistochemical prognostic markers in female breast carcinoma. Study Design: Cross sectional, observational study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2004 to December 2007. Methodology: Patients of primary operable female breast carcinoma were categorised as < 40 years (pre-menopausal), 41-50 years (peri-menopausal) and > 50 years (post-menopausal) age groups. Histological type, tumour size, tumour grade and lymph node status were determined while estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu expression were evaluated immunohistochemically. Association of Her-2/neu with histological and immunohistochemical prognostic markers was determined in pre-menopausal, peri-menopausal and post- menopausal age groups using the x2 test for uni- and multivariate analysis. Results: Out of the 722 patients, 230 (31.9%) were in pre-menopuasal, 221 (30.6%) in peri-menopausal and 271 (37.5%) in post-menopausal age group. Infiltrating ductal carcinoma was the pre-dominant subtype in all the age groups. Mean tumour size was 4.3 +- 2.3 cm (range 0.4-17 cm) and lymph node metastasis was seen in 310 (70.8%) cases. Her-2/neu showed association with ER in the all the age groups while PR only showed association in the peri-menopausal and postmenopausal women. Her-2/neu showed no association with tumour size, tumor grade and lymph node metastases in pre-menopausal and peri-menopausal women while it showed positive association with tumour size and lymph node metastasis in the post-menopausal women (p < 0.05). Conclusion: Majority (62%) patients were under 50 years as against the Western epidemiology. Association of Her-2/neu with ER, PR, tumour size and lymph node metastasis was age related as pre-menopausal, peri-menopausal and postmenopausal had variable expression of these prognostic markers with therapeutic and prognostic implications. (author)

[en] To compare the histological prognostic markers in breast carcinoma over three decades in Northern Pakistani population and analyze for any change in trends in terms of prognostic markers. Cross-sectional descriptive study was carried out from January 2004 to December 2006 at AFIP, Rawalpindi on 822 cases of female breast carcinoma. Assessment of tumour size on gross examination followed by microscopic evaluation of tumour type, tumour grade, lymph node metastasis and skin involvement was done. The results of the present data were compared with studies of Wahid et al (January 1994 to December 1997) and Malik et al (January 1984 to December 1986) from the same institute. Total 822 cases of breast cancer were diagnosed with 541(64.9%) cases of mastectomy. The mean age was 48+-12years with a mean tumour size of 4.6+-2 cm. A tumour size of >5cm was seen in 30.6% cases and only 18.8% cases had a size <2 cm. Infiltrating ductal carcinoma was the commonest subtype in 674 (81%) cases with histological grade II in 533(64%) cases. Lymph node metastasis was present in 74.6% cases and skin involvement in 36% cases. The comparison of the results of the present study with those over the past two decades in Pakistan show that the mean age at diagnosis remains around 48 years. There is statistically significant increase in the tumours of <5cm at presentation and a higher frequency of tumours with dermal invasion. No significant change is seen in frequency of lymph node metastasis at operation and tumour grade. The comparison of results of other studies done over the past three decades in the region are not very encouraging. The age of presentation remains younger as compared to the West. A positive note is seen in terms of a decreasing tumour size but lack of DCIS cases in our material underlines the need of mammography and launching of effective screening programmes at the national level. Early detection of cases will help in treatment and subsequently improve prognosis in these patients as advocated by the West (JPMA 59:835; 2009).(author)

[en] To estimate blood lead levels (BLL) by atomic absorbance spectrometry in small scale local battery workers in Pakistan. Study Design: Comparative cross sectional study. Place and Duration of Study: Department of Chemical Pathology & Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2017 to Apr 2018. Methodology: We measured blood lead levels of 100 male workers from local battery dealing workshops (minimum exposure of 10 years) on atomic absorption spectrometry and compared with that of 100 healthy nonexposed controls living at least 30 km away from the industrial area. Independent sample t-test and chi-square were used to test the significance mean difference and association, respectively. Results: Blood lead levels in exposed and unexposed group were 38.31 ± 3.78 and 1.84 ± 0.085 µg/L respectively. 22 (22%) workers had blood lead levels >100 µg/L and 78 (78%) had <100 µg/L which were statistically significant. In group with high BLL, 5 (22.7%) had exposure of up to 10 years while 17 (77.3%) had more than 10 years showing significant association with duration of exposure. Health problems included infertility 5 (5%), hypertension 10 (10%), gastric problems 11 (11%), confusion and headache 18 (18%), with no significant association with lead levels (p=0.306). Conclusion: Workers involved in various processes of battery handling in local shops have elevated blood lead levels and subsequent health issues, thus necessitating improvement in health awareness in both industrial and small scale employees. (author)

[en] Objective: To determine the frequency of change in diagnosis and level of errors in cases referred to Armed Forces Institute of Pathology for second opinion and their impact on modifications of treatment and prognosis. Study Design: Cross sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, form Mar to Oct 2017. Methodology: All the cases referred for review diagnosis were tested by applying panel of immunohistochemical markers and special stains on formalin fixed paraffin embedded tissue sections as decided on morphology. Level of errors were defined as level I error: minor discrepancy with no impact on management, level II: minor discrepancy with impact on management, level III: main category remains same but there was change/confirmation of specific diagnostic entity with an impact on management and level IV: gross changes in diagnosis with significant impact on management. Level IV was further subdivided into IV a: benign misdiagnosed as malignant, IV b: malignant misdiagnosed as benign and IV c: changes in tumor subtype. Results: A total of 100 cases, where review diagnosis was changed were included. Minor discrepancies (level I and level II) were observed in only 7% cases with little or no impact on the management. Most frequent discrepancy observed as level III in 75% cases. Major discrepancy (level IV errors) was noted in 18% cases. Conclusion: There were high discrepancy rates between previous diagnosis and review diagnosis. The higher use of extended panels of immunohistochemistry markers were the most likely explanations. (author)

[en] A 3-year child is discussed who presented with dyskinesia, large head size, developmental delay, and recurrent infections necessitating multiple hospital admissions. The diagnosis was not made at initial presentation or even after multiple hospital admissions. An organic acidemia was suspected, based on raised ammonia and lactate levels and metabolic acidosis and the diagnosis of glutaric aciduria Type 1 was established by finding markedly elevated levels of glutaric acid and its specific metabolites on urine organic acids analysis by gas chromatography-mass spectrometry, in the setting of specific clinical features. Further supporting evidence was provided by CT scan brain showing subdural hygroma along left cerebral hemisphere causing gyral flattening and widening of sylvian fissure. (author)

[en] To compare immunohistochemical estrogen receptor expression on formalin-fixed, paraffin-embedded breast carcinoma tissue sections by using regular, extended microwave heating and pressure cooker technique for heat induced antigen retrieval. The study was conducted on 40 cases of breast carcinoma diagnosed on histopathology and selected by convenience sampling. One section each of the tumour was separately subjected to regular microwave heating (10 minutes), extended microwave heating (20 minutes) and pressure cooker (heating for 2 minutes after reaching full pressure). A nuclear staining of > 10% cells with moderate intensity was considered positive and frequency of ER expression by each technique was compared statistically. Sensitivity and specificity of the techniques was determined using pressure cooker technique as the gold standard for this study. Out of 40 cases, ER expression in 24 (60%) cases was seen by microwave regular heating (MRH) and in 30 (75%) cases by microwave extending heating (MEH) technique. Pressure cooker (PC) technique for antigen retrieval demonstrated 34 (85%) cases with ER expression. Out of 16 which were negative by MRH technique, 6 became positive by MEH while 10 became positive by PC. Statistically significant difference in ER expression by PC and MEH technique was seen in comparison to MRH with a p-value of < 0.05. Moreover, 4 cases which were negative by MEH technique turned positive for ER expression by PC. MRH and MEH had 100% specificity but sensitivity was 70.6% and 88.2% respectively taking PC technique as gold standard with diagnostic accuracy of MEH as 90% and MRH as 75%. Pressure cooker antigen retrieval technique is a better method than microwave heating. The increase in duration of heating improves the percentage of positive cells as well as intensity of ER immuno-staining which entitles breast cancer patient to benefit from ER positive treatment protocols which have better prognosis. (author)