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Objective:  To evaluate the frequency of intraductal component (IDC-P) in prostatic adenocarcinoma and its effect on the final grade using the ISUP and GUPS grading system., Study Design:  Descriptive study. Place and Duration of the Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, between June 2021 and June 2022., Methodology: The study included 250 cases of prostatic adenocarcinoma. The presence of the intraductal carcinoma prostate (IDC-P) was confirmed by patchy or complete staining of the basal cell layer by p63 immunohistochemical stain. Cases with IDC-P were then graded using two different methods, first using the grading criteria based on the ISUP recommendations and then by the grading criteria based on the GUPS recommendations., Results: Two hundred and fifty cases showed invasive prostatic carcinoma ranging from Gleason grade group 2-5. IDC-P was identified in 5 of the 250 biopsies (2%). The final Gleason grade remained unchanged in these cases, when they were graded using the ISUP and GUPS recommendations., Conclusion:  Although the present results are based on a relatively small sample size, IDC-P was not frequently present in biopsies of patients with adenocarcinoma in the studied population. Grading IDC-P in invasive prostate cancer led to only a minor change in grade group assignment of prostate cancer biopsies., Key Words:  Prostatic adenocarcinoma, Intraductal carcinoma, IDC-P, ISUP, GUPS, Gleason Grade group.

Objective: To ascertain the effectiveness of IHC markers of vascular origin like CD31, CD34, FLI1 and ERG in vascular soft tissue sarcomas including angiosarcomas, Kaposi sarcomas, epithelioid hemangioendothelioma and a non-vascular soft tissue sarcoma (Epithelioid sarcoma)., Study Design: Descriptive study., Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from 2011 to 2017., Methodology: Diagnosed cases of angiosarcomas (n=48), epithelioid hemangioendothelioma (n=9), Kaposi sarcoma (n=9) and epithelioid sarcoma (n=20) were selected. Immunohistochemical staining as performed on formalin fixed paraffin embedded sections. The sections were stained for the following markers: CD34 (VENTANA clone Q Bend 10), CD31 (Leica clone 1 A 10), FLI1 (CELL MARQUE clone MRQ-1) and ERG (CELL MARQUE clone EP111)., Results: A complete panel of CD34, CD31 and ERG was applied on 8/48 cases of angiosarcomas with triple positivity in 6 cases. Eight cases showed positivity for only CD31 and ERG and 2 cases showed positivity for only ERG. A complete panel of CD34, CD31 and ERG was applied on 3/9 cases of epithelioid hemangioendothelioma with positivity for all markers in 2 cases. Combined positivity for ERG and CD34 was seen in 2 cases and on 4 cases only CD31 immunohistochemical was solely applied with 100% positivity. FLI1 was not applied on any case. Among 9 cases of Kaposi sarcoma, ERG, CD34 and CD31 in combination were applied on only 1 case with triple positivity. Remaining cases show positivity for either CD34, CD31 or FLI1. Majority of cases of epithelioid sarcomas were diagnosed on the basis of cytokeratin and CD34 positivity with loss of INI1. The other vascular markers showed negativity in all cases., Conclusion: Among these four markers, ERG immunohistochemical stain is highly effective for endothelial differentiation due to its specific nuclear staining pattern in normal blood vessel endothelial cells (internal control) as well as neoplastic cells of vascular tumors and lack of background staining.

Objective: To determine sensitivity and specificity of paraffin-based immunohistochemistry in the evaluation of glomerular diseases in renal biopsies using immunofluorescence as gold standard., Study Design: Cross-sectional analytical study., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from August 2008 to August 2009., Methodology: Seventy renal biopsy specimens fulfilling the inclusion criteria for light microscopy and immunofluorescence during the study period were evaluated. Antibodies to immunoglobulins (IgG, IgA, and IgM) and components of complement system (C3) were applied on 70 formalin-fixed paraffin-embedded renal biopsy specimens previously classified by means of light microscopy and immunofluorescence (IF). Staining for these antibodies was recorded as positive and negative for immunohistochemistry (IHC) and IF in paired proportions presuming IF as gold standard test. The sensitivity, specificity, positive predicitive value and negative predicitive value of individual antibody were calculated., Results: Of 70 patients, mean age was 33 ± 18 years ranging from 2 to 80 years. Forty five (64%) were males and 25 (36%) were females. The sensitivity, specificity and predictive values of individual antibodies to IgG, IgA, IgM and C3 were very low and generally in the range of 40 - 60%., Conclusion: The sensitivity, specificity and predictive values of immunohistochemistry on formalin-fixed paraffin-embedded renal biopsy specimens were very low and therefore, not suitable for evaluation of renal biopsies in current circumstances.

Objective: 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 immnuohistochemical 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-menopausal, 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.

Objective: 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., Study Design: Quasi experimental study., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from August 2006 to July 2007., Methodology: 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., Results: 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%., Conclusion: 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.

Objective: To determine steroid hormone receptor expression and their association with histological prognostic markers and biological profile in female breast carcinoma in Northern Pakistan., Study Design: Cross sectional, observational., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2004 to December 2007., Methodology: Female patients belonging to Northern Pakistan with primary operable breast carcinoma were included in the study. Patient's age, microscopic tumour size, tumour grade, lymph node status and biological profile for Her-2/neu status were evaluated. Immunohistochemical expression for ER and PR was determined individually and conjointly for ER+PR+ and ER-PR- while their association with above prognostic markers was determined using the c2 test for univariate analysis., Results: Out of the 726 cases, there were 657 (90.4%) cases of infiltrating ductal carcinoma with mean age of 48+/-12 years and mean tumour size of 4.2+/-2.3 cm. Tumour was grade-II in 65% and lymph node metastases in 71.5% cases with Her-2/neu+ in 28.1%. ER and PR expression was 74.6% and 68.3% respectively. Conjoint expression of ER+PR+ was 456 (62.8%), ER-PR- in 21.2%, ER+PR- in 86 (11.8%) and ER-PR+ in 30 (4.1%) cases. Individually, ER and PR showed positive association with age, lymph node metastasis, tumour grade and inverse association with Her-2/neu. Conjoint expression of ER+PR+ (62.8%) and ER-PR-(21.2%) showed positive association with age, tumour grade, lymph node metastasis and inverse association with Her-2/neu (p < 0.05)., Conclusion: Hormone receptor expression of ER and PR expression is comparable to the West with ER and PR showing inverse association with Her-2/neu and positive association with age, tumour grade and lymph node metastases.

Objective: To determine the morphological profile and association of HER-2/neu expression with histological prognostic markers and hormonal receptor expression in female breast carcinoma in Northern Pakistan., Study Design: Cross-sectional, observational study., Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2004 to May 2007., Methodology: A total of 535 patients of primary operable female breast carcinoma with hormonal profile and biological status were included in the study. Patient's age, microscopic tumour size, tumour grade, lymph node status, Estrogen Receptor (ER), Progesterone Receptor (PR) and joint ER/PR status were evaluated and their association was determined with HER-2/neu expression using the x2 test for univariate analysis., Results: Out of 535 cases, there were 481 (89.9%) cases of infiltrating ductal carcinoma with mean age of 48 years and mean tumour size of 4.4 cm. Tumour grade II was seen in 68% cases and lymph node metastases were present in 65% cases. HER-2/neu expression was seen in 31% cases, while ER and PR expression was seen in 72.3% and 62.6% respectively. ER and PR showed inverse association with HER-2/neu while positive association was seen with lymph node metastases (p < 0.05). No association was seen between tumour size and tumour grade. Joint ER and PR expression also showed a higher number (73.5%) of HER-2/neu negative cases., Conclusion: HER-2/neu, ER and PR expression is comparable to the West with inverse association with ER and PR and positive association with lymph node metastases. Since HER-2/neu expression is variable in carcinomas with different tumour characteristics, it is not possible to predict hormone receptor expression in all the cases.

Synovial sarcoma is a mesenchymal spindle cell tumour, which is unrelated to synovium and shows variable epithelial differentiation. Typically, synovial sarcoma arises in the soft tissues of the extremities but cases in the head and neck region are less common and oral cavity involvement is extremely rare. A 17-year-old girl presented with a gradually increasing swelling on the right cheek for 2 years, which on biopsy, revealed a biphasic tumour comprising fascicles of spindle shaped cells with gland formation by epithelial cells and scattered masts cells. Histological diagnosis of biphasic synovial sarcoma was confirmed on immunohistochemistry by strong positivity for EMA, S-100 and CD-99 in both epithelial as well as spindle cell areas.

Ossifying fibromyxoid tumor is a rare tumor of mesenchymal origin with varied presentation at different sites including head and neck. Clinically these are slow growing lesions and patients have a variable age at presentation. A 14 years old girl presented with a slowly enlarging gingival swelling, which on radiological examination showed increased rarefaction in the mandible with a provisional diagnosis of an inflammatory lesion. Microscopically, the tumor had spindle to oval shaped cells in a fibromyxoid background with a peripheral shell of lamellar bone. Histological diagnosis of ossifying fibromyxoid tumor was made after immunohistochemical stains for vimentin and S-100 protein. Recurrence, metastasis and histologically increased mitotic count are indicative of atypical or malignant ossifying fibromyxoid tumors.

Objective: To compare audited results with original reports in cases of breast carcinoma, as a part of quality assurance programme., Design: A descriptive study., Place and Duration of Study: January 2001 to December 2001 at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan., Materials and Methods: Slides and original reports of 191 cases of breast carcinoma diagnosed by different consultants in the department were retrieved from the case files. The cases were re-examined for histological type, nuclear grade, tumour grade, lymphovascular invasion and tumour necrosis without knowledge of the previous report. The new independent observations were recorded and differences from original reports were analysed. Chi-square test was used for statistical analysis., Results: There was no discrepancy about malignant nature of all the 191 lesions. However, 39 cases (20.4%) showed some differences of grade, lymphovascular invasion and necrosis, from their original reports. Omission of most of the parameters (n=45) was due to lack of tabulated reporting. The differences of results of lymphovascular invasion and necrosis were not statistically significant (p-values = 0.90 each), but differences of nuclear and tumour grade were statistically significant (p-value <0.001 and <0.01)., Conclusion: There was no discrepancy in the reports such as histological types or the presence of tumours. Tabulated form of reporting has less chance of omission of important parameters.

Objective: To determine the frequency of microalbuminuria (MA) and its associated medical risk factors in type II diabetic patients., Place and Duration of Study: This cross-sectional analytical study was conducted during Ist half of 2003 at Combined Military Hospital, Lahore. Non-probability purposive sampling was employed., Materials and Methods: Study population included 150 type II diabetic patients (70 women, 80 men) attending outpatient department of the hospital. Patients having clinical albuminuria and with other causes of proteinuria were excluded., Results: Women and men were of comparable ages. Women (26.4 kg/m2) had higher body mass index (BMI) than men (24.3 kg/m2). The frequency of MA was 46.7%, higher in males (50.6%) than females (41.5%). Fasting plasma glucose and HbA1c levels were significantly higher in patients with MA compared to those with normoalbuminuria (p <0.001). The microalbuminuric patients had significantly decreased HDL-c levels compared to normoalbuminuric subjects (p < 0.001). However, no relation of MA with age, gender, known duration of diabetes, BMI, history of smoking, hypertension and serum: total cholesterol, LDL - c, triglyceride, urea and creatinine was found., Conclusion: There is a strong association of poor glycaemic control and decreased HDL-c levels with the presence of microalbuminuria.

Objective: To find out Gleason grades, scores and to see the correlation of these morphological features with tumour markers in prostatic carcinoma., Design: A descriptive study., Place and Duration of Study: The study was conducted at the Departments of Histopathology and Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi, over a period of one year., Materials and Methods: Fifty cases of prostatic carcinoma were studied. Gleason grades and score of tumour were determined by doing haematoxylin and eosin (HE) staining. Pre-operative serum prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) assays were carried out in these cases., Results: The patients seen were between 50-102 years of age with an average of 70.9 years. There were 49 cases of adenocarcinoma and 01 case of mixed adeno and transitional cell carcinoma of prostate. Twenty-eight (56%) patients had Gleason score of 5-7. Twenty-nine (58%) patients were having serum PSA levels between 10.0 ng/ml and 50.0 ng/ml. Thirteen (26%) cases showed PSA assays >50 ng/ml. The sensitivity of PSA test was 84 % in these cases. Thirty-five (70%) patients were having PAP values >3.7 U/l (sensitivity 70 %)., Conclusion: The Gleason grading system is a specific morphological predictor. The serum PSA showed better sensitivity and specificity with Gleason grades and scores as compared to serum PAP. The serum PAP levels showed better correlation with morphological features as compared to serum PSA.