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In this report, the novel and site-specific radioiodination of biomolecules by using aryl diamine and alkyl aldehyde condensation reaction in the presence of a Cu 2+ catalyst under ambient conditions was reported. 125 I-labeled alkyl aldehyde was synthesized using a tin precursor with a high radiochemical yield (72 ± 6%, n = 5) and radiochemical purity (>99%). The utility of the radioiodinated precursor was demonstrated through aryl diamine-installed c[RGDfK(C)] peptide and human serum albumin (HSA). Radioiodinated c[RGDfK(C)] peptide and HSA protein were synthesized with high radiochemical yields and purity. 125 I-HSA protein showed excellent in vivo stability and negligible thyroid uptake as compared with directly radioiodinated HSA by using the tyrosine group. Excellent reaction kinetics and the in vitro and in vivo stabilities of 125 I-labeled alkyl aldehyde have suggested the usefulness of the strategy for the radioiodination of bioactive molecules., Competing Interests: The authors declare no competing financial interest.

Background: Metastatic tumors to bone constitute the majority of bone malignancies. The site of metastasis to bone and the prognosis depend chiefly on the primary tumor. Despite all the advances in diagnostic techniques, identifying the primary tumor has not improved significantly., Methods: A total of 576 cases (Lebanon; n = 306, Pakistan; n = 270) presenting with microscopic evidence of metastasis to bone were reviewed between 1996 and 2016. Clinical and radiologic data were recorded., Results: Out of 20 types of primary tumors, unknown primary (38.2%), followed by breast (23.8%), lung (10.4%) and thyroid (4.9%) tumors were the most commonly presenting with bone metastasis. The primary source of the tumor showed significant correlation with the site of metastasis, time lag to metastasis and radiologic presentation (p < 0.001). Interestingly, a significant variation was noted between the 2 observed populations., Conclusion: The patterns of pathologically confirmed metastasis to skeletal sites in Near East population showed a special distribution, and variation was even observed between the 2 studied centers. Understanding the biologic variations of the primary tumors in our population may further explain the variation in patterns of metastasis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels-Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give 125 I-labeled product ([ 125 I]1) with high radiochemical yield (65±8%) and radiochemical purity (>99%). For radiolabeling application of [ 125 I]1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrates were reacted with [ 125 I]1 under mild condition to provide the radiolabeled products [ 125 I]6 and [ 125 I]8, respectively, with excellent radiochemical yields. The biodistribution study of [ 125 I]8 in normal ICR mice showed significantly lower thyroid uptake values than that of 125 I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore [ 125 I]8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that [ 125 I]1 will be used as a valuable prosthetic group for radiolabeling of biomolecules., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: There is growing evidence that there are differences in histological and genetic characteristics along with clinical behavior between right- and left-sided colon carcinomas. We have compared various parameters of the two types and assessed associations of the results with prognosis in patients in Pakistan., Materials and Methods: We reviewed 200 cases from our institutional database; 100 cases of right-sided and 100 cases of left-sided colon cancer. Parameters including age, gender, TNM stage, histological features and clinical outcome were analyzed., Results: The patients with right-sided colon cancer were significantly older as compared to their counterparts with left-sided cancer. They presented with a lumbar mass rather than symptoms of obstruction and perforation as seen in left-sided colon cancers, and the histology showed higher percentage of poorly differentiated tumors with advanced pT stage. Moreover, Crohn's-like reactions, intra tumoral lymphocyte responses and other poor prognostic factors like lymph vascular invasion and perineural invasion were more common in right-sided cancers., Conclusions: We found that right- and left-sided colon cancers are different from each other in terms of clinical presentation, histology and clinical behavior. Right-sided colon cancers are more aggressive and are associated with poorer clinical outcome as compared to left sided colon cancers in our population.

Objective: To evaluate human epidermal growth factor receptor 2 (HER2/neu) interobserver variability between specially trained and untrained general histopathologists., Methods: The retrospective study cases of invasive breast carcinoma received at Shifa International Hospital, Islamabad, from June 2010 to December 2011, for assessment of HER2/neu status by immunohistochemistry which were retrieved from the files and, 30 consecutive cases each of score 0, 1+, 2+ and 3+ were selected for a total of 120 cases. Two groups of two histopathologists each examined the cases blindly. One group had attended a short course in Germany, while the other group comprised two qualified histopathologists who had not had any special training. Each histopathologist reported the cases independently according to standard guidelines. Kappa statistics were applied., Results: The trained group of histopathologists showed agreement in 113 (94%) cases. Kappa value was calculated to be 0.96 which means 'perfect agreement. In contrast the untrained group showed agreement in 83 (69%) cases with a kappa value of 0.59 which means 'moderate agreement., Conclusion: Interobserver variability in immunohistochemical scoring of HER-2/neu in breast carcinoma is high among untrained general histopathologists. This may adversely affect the selection of patients with cancers who could benefit from Herceptin therapy.

Objective: To study the immunohistochemical pattern of CD 117, glial fibrillary acidic protein (GFAP), smooth muscle actin (SMA) and CD 43 in pleomorphic adenoma (PA), adenoid cystic carcinoma (AdCC) and polymorphous low grade adenocarcinoma (PLGA) of minor salivary glands., Materials and Methods: Twenty cases of PA, 20 cases of AdCC and 10 cases of PLGA were retrieved from record files along with their paraffin blocks at Armed Forces Institute of Pathology, Pakistan. New histological diagnosis was made on freshly prepared H&E sections followed by application and analysis of immunostains., Results: The mean age of the patients was 44 ± 15 (mean SD) (range; 17-86) years. There were 26 male and 24 female patients with a male to female ratio of 1.08:1. Fourteen cases of PA, 14 cases of AdCC and 6 cases of PLGA were positive for CD117. In case of GFAP, only 9 cases of AdCC and 3 cases of PLGA were positive; however, 16 cases of PA were also positive. Twelve cases of AdCC and 7 cases of PA were positive for SMA and half of the PLGA cases were also reactive. Nonetheless, the least expression was seen in case of CD 43, where only five cases of AdCC were positive. Six cases of PA and three cases of PLGA were also positive., Conclusion: Our results suggest that the use of GFAP, SMA, CD 117 and CD 43 as an adjunct to histological examination is not helpful in differentiating PA, AdCC and PLGA from one another.

Objective: To evaluate the diagnostic utility of endoscopic ultrasound guided fine needle aspiration cytology in the diagnosis of mediastinal and abdominal lesions., Methods: Endoscopic ultrasound guided aspiration cytology was carried out on a total of 155 cases during the study period. The lesions were categorized according to the site of needle biopsy. Clinical impression and provisional diagnoses were compared with the final cytological diagnoses and the percentage of inadequate/non diagnostic smears was calculated., Results: Out of 155 cases, 18 cases (11.5%) were reported as inadequate while a definite diagnosis was given in the remaining cases (88.5%). The mean patient age was 49 +/- 14.0 years. There were 105 (68%) males and 50 (32%) females. The most common site biopsied was mediastinal lymph nodes followed by pancreas. The most frequent diagnosis was adenocarcinoma mostly of pancreas followed by chronic granulomatous inflammation of mediastinal and abdominal lymph nodes. The average number of passes made was 3. The size of the lesions ranged from 0.6 cm to 25 cm with mean size of 3 cm as measured by endoscopic ultrasound probe., Conclusion: Endoscopic ultrasound guided aspiration cytology is a useful procedure in the evaluation of deep seated lesions of gastrointestinal tract (GIT), abdominal cavity and mediastinum.

Objective: To study the frequency and distribution of non-cutaneous malignant melanoma in Northern Pakistan using a cross-sectional descriptive design at the Armed Forces Institute of Pathology Rawalpindi, from 1987-2008., Materials and Methods: A total of 234 cases of malignant melanoma reported from 1987-2008 were retrieved from the AFIP tumour registry and analysed for age, gender and site using computer software SPSS 12., Results: Of a total of 58,680 malignant cases reported at AFIP from 1987-2008, only 234 (0.4%) were of malignant melanoma, 142 in males and 92 in females. The age range was 10-97 years, with a mean of 53 ± 16. Only 69 (29.5%) were cutaneous and 165 (70.5%) were non-cutaneous in origin: there were 62 (37.4%) cases from anorectal region, 39 (23.4%)were from eye ball and 17 (10.2%) in the nasopharynx, 13 cases (7.8%) from oral mucosa and 11 (6.6%) from the vagina., Conclusion: Malignant melanoma is markedly less cutaneous in Pakistan as compared to the western world, often being found in the anorectal region followed by the eye, nasopharynx, and oral mucosa in descending order.

Objective: To determine the HER-2/neu status by chromogenic in situ hybridization (CISH) on tissue specimens with a borderline (2+) immunohistochemistry (IHC) score in carcinoma breast by a descriptive, cross-sectional study in the Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jun 2008 to Dec 2009., Methods: Tissue block specimens from 50 consecutive patients having HER-2/neu score of borderline (2+) on IHC assay were tested for HER-2/neu gene amplification by CISH. Mean and standard deviation were calculated for quantitative variables like age and HER-2/neu gene copy signal/clusters by using SPSS version 14. Frequencies and percentages were also calculated for qualitative variables like type of carcinoma and results of HER-2/neu by CISH (amplified/nonamplified)., Results: HER-2/neu gene amplification by CISH was found in 10 (20%) out of 50 patients with borderline (2+) IHC score. All CISH amplified cases belonged to invasive ductal carcinoma type. No significant correlation was noted between type of carcinoma and HER-2/neu gene amplification., Conclusion: Chromogenic in situ hybridization (CISH) is a practical, cost-effective and reliable method for analysis of HER-2/neu borderline (2+) cases which may be candidates for Herceptin therapy.

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.

Background: Not all patients with histologically mild chronic Hepatitis C progress to cirrhosis. Many patients being treated on the basis of raised ALT and positive PCR alone may not be actually requiring it., Methods: All adult patients suffering from chronic Hepatitis C, qualifying for combination interferon ribavirin therapy, under went liver biopsies. Tissue samples were sent to Armed Forces Institute of Pathology (AFIP) Rawalpindi for histopathology. Reporting was done according to modified Ishaq score., Results: Total number of patients was 147. Out of these, 75 (51%) were female and 72 (49%) were male. Mean age of females and males were 35.1 +/- 8.12 and 36.31 +/- 8.56 year respectively. Out of these, 19 (12.9%) were stage zero, 61 (41.5%) at stage 1, and 31 (21.1%) at stage 2 of modified fibrotic Ishaq score. In all, 111 (75.5%) of the patients were < or = 2 of modified Ishaq fibrotic score in either sex or 80 (54.4%) < or = 1 of modified Ishaq fibrotic stage. The necroinflammatory score has been divided into minimal (0-3), mild (4-8), moderate (9-13), and severe (14-18). About the same number of our patients (74%) had minimal to mild inflammation., Conclusion: Since the majority of the patients have fibrotic score less than 3, so it will be cost effective to individualise their treatment on liver histpathology. Patients with low fibrotic score and minimal to mild inflammation may not be treated, but only monitored with serial ALT and liver biopsy every 4-5 years. Treatment may be started if there is increase in fibrosis on surveillance biopsy. However, there is a need to conduct prospective studies in similar group of patients to evaluate the natural course of disease in untreated patients.

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: The study was undertaken to document and highlight the shortcomings of histopathology reporting of breast carcinoma in Pakistan so that improvements can be recommended and a standardized protocol devised., Methods: This was a descriptive cross sectional study and was conducted at Histopathology Department, Armed Forces Institute of Pathology, Rawalpindi from 1st January 2008 to 31st October 2008. Fifty consecutive breast carcinoma reports received for review from different laboratories were analyzed for documentation of patients age, sex, type of procedure/specimen, specimen size, tumour size, invasive tumour type, invasive tumour grade, comment on excision margins, extent of lymph node involvement, insitu component, lymphovascular invasion, necrosis, skin involvement and tabular format. Frequencies and percentages were calculated for presence of these above mentioned variables in different reports, keeping in mind the possible information that could be obtained from a particular sample., Results: It was found that the variable least mentioned in the reports was in situ component commented upon in only 23.2% of reports. Necrosis was mentioned in 35% of reports. Tabular format was found in 36% of reports only., Conclusion: Marked deficiencies are seen in histopathology reports for breast carcinoma due to the lack of any standardized reporting system. Separate checklist formats for trucut biopsies, lumpectomies and mastectomies should be introduced to ensure uniform reporting.

Objective: To compare the histological prognostic markers in breast carcinoma over three decades in Northern Pakistani population and analyse for any change in trends in terms of prognostic markers., Methods: 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., Results: Total 822 cases of breast cancer were diagnosed with 541 (64.9%) cases of mastectomy. The mean age was 48 +/- 12 years with a mean tumour size of 4.6 +/- 2 cm. Atumour size of >5 cm 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 <5 cm 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., Conclusion: 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.

Objective: The objective of the study was to determine the frequency of bcl-2 gene rearrangement in B-cell Non-Hodgkin's lymphoma (NHL) and identify different breakpoints of bcl-2 gene., Methods: Thirty cases of B-cell lymphoma (including 8 cases of follicular lymphoma, 19 cases of diffuse large B-cell lymphoma and 3 cases of T-cell rich B-cell lymphoma) were included in the study. Good quality of DNA was extracted in 4 cases from formalin fixed paraffin embedded tissue and in 26 cases from fine needle aspirate. The polymerase chain reaction was done for major break point region (mbr), minor cluster region (mcr) and intermediate cluster region (icr) of the bcl-2 gene., Results: The bcl-2 gene rearrangement was identified in 23.3% of B-cell lymphoma, 50% of follicular lymphoma, 15% of diffuse large B-cell lymphoma and no bcl-2 rearrangement was identified in any of the T-cell rich B-cell lymphomas. Further analysis showed the icr breakpoint in 16.7% of B-cell lymphoma, 37.5% of follicular lymphoma and 10.5% of diffuse large B-cell lymphoma. Involvement of the mbr breakpoint was found in 6.7% of B-cell lymphoma, 12.5% of follicular lymphoma, and 5.3% of diffuse large B-cell lymphoma. Involvement of the mcr breakpoint was not seen in any of the cases., Conclusion: The bcl-2 gene rearrangement is quite frequent in follicular lymphoma, followed by diffuse large B-cell lymphoma. The commonest breakpoint in present series is icr followed by mbr. This indicates that primers for bcl-2 gene must include icr primer, whenever the bcl-2 gene is being evaluated for B-cell NHL in this part of the world and this might reduce the variability of frequency of bcl-2 gene rearrangement within and between different regions.

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.

Objective: To study routine histological as well as immunohistochemical prognostic markers including ER, PR, p-53 and Her-2/neu in male breast carcinoma and compare the above parameters with breast carcinoma in female patients of the same population. Association of the immunohistochemical markers with histological prognostic markers was also studied., Methods: Cross-sectional descriptive study was carried out from January 2004 to May 2007 at AFIP, Rawalpindi on 55 cases of male breast carcinoma. Assessment of tumour size on gross examination followed by microscopic evaluation of tumour grade and lymph node metastasis was done. Immunohistochemistry was performed for ER, PR, Her-2/neu and p-53., Results: The male breast cancer patients had a mean age at diagnosis of 57 years with a mean tumour size of 4.25cm, constituting 4.7% of malignancies in men. Infiltrating ductal carcinoma was the predominant subtype with 47 (87.3%) cases. Majority of the tumours were grade II (64.2%) followed by grade III (32.1%). Out of 28 cases with axillary clearance; lymph node metastasis was present in 20 (71%) cases. ER and PR expression was seen in 81% and 79.3% cases respectively while Her-2/neu expression was seen in 24.5%. p-53 was expressed in 14 (26.4%) patients. No association of immunohistochemical markers was seen with lymph node and tumour grade., Conclusion: Male breast cancer has a higher incidence and occurs in a decade younger than the Western population with a larger tumour size and higher number of patients with lymph node metastasis. Men have a higher ER, PR expression as compared to female breast cancer patients without any association with histological prognostic markers. Her-2/neu and p-53 expression in males is comparable to the West but their prognostic role in terms of survival and treatment strategies needs to be ascertained by follow up studies.

Objective: The study was carried out to document the occurrence of early onset breast cancer in our population and to assess prognostic variables., Methods: Records of a total of 1,644 female patients diagnosed with breast carcinoma during the last four years (Jan 2005 - Dec 2008) at the Histopathology Department, Armed Forces Institute of Pathology (AFIP) were retrieved from the AFIP tumour registry. All cases of breast carcinoma diagnosed in young females, 30 years of age or less, were selected and assessed for the type of specimen, tumour type, size and grade, presence or absence of lymph node metastasis, number of lymph nodes recovered and number of lymph nodes involved. Data were entered into SPSS version 11 to calculate mean, median, mode and standard deviation for quantitative variables and frequencies and percentages for qualitative variables., Results: The mean age was 28+/-2.7 years and the mean tumour size was 3.7+/-2.9 cm. Most frequent age group was 26-30 years (78.6%). The most common histological tumour type was invasive ductal carcinoma (88.7%), followed by invasive lobular carcinoma (5.4%). Seven out of 168 (4.2%) tumours were less than 2 cm in size, 69(41.1%) were between 2-5 cm and 39 (23.2%) were greater than 5 cm. Grade 2 (57.1%), followed by grade 3 (29.8%) were the most frequent. Out of 68 cases in which lymph nodes were included, lymph node metastasis was seen in 55(80.8%)., Conclusion: Breast cancer is much commoner in young women in Pakistan as compared to the rest of the world. It is important to keep this in mind when evaluating even very young females with breast lumps.

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.

Objective: To determine the spectrum of malignant lymphomas in our set up, according to the WHO classification., Methods: All the cases diagnosed as malignant lymphoma, during the year 2005, were retrieved from the institution based tumour registry record and classified according to WHO criteria depending on the immunohistochemical results of a panel of lymphoma markers., Results: The male to female ratio was 2.5:1 for almost all types of malignant lymphomas. The age range was 3 to 80 years. The frequency of Hodgkin's lymphoma, Burkitt's lymphoma and lymphoblastic lymphoma were higher amongst the children, whereas follicular lymphomas, mantle cell lymphoma and CLL/SLL were more frequently reported in 5th, 6th and 7th decades. Of the total cases 62% were nodal and 38% extranodal (majority in the GI tract). Non Hodgkin's lymphoma was more (73%) frequent than Hodgkin's disease. Mixed cellularity and nodular sclerosis were the main histological variants of Hodgkin's disease., Conclusions: Immunohistochemistry is not very frequently used in our set up and also at very few other centres. Therefore, its application should be encouraged to raise the quality of data on lymphoid neoplasms and contribute to their control.

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 determine the pattern of testicular malignant tumours in northern Pakistan., Methods: The study included all malignant testicular tumours, diagnosed from January 2001 to June 2006. All histologically diagnosed malignant tumours of testis were retrieved from the case files. Basic epidemiological data regarding each case was collected from the request forms. The data was then analysed for the site of involvement, age distribution and histological types of tumours., Results: During the study period a total of 107 patients had testicular malignancies, constituting 0.74% of all malignant tumours and 1.24% of all male malignancies diagnosed during this period. Peak incidence was in 30-40 years age group and a second peak was observed in the above 60 age group. Germ cell tumours (67%) were the most frequent histological type followed by non Hodgkin lymphoma; the latter particularly was responsible for the peak in the older age groups. Statistical analysis showed that there was no significant increase registration of testicular tumours as compared to our previous analysis., Conclusion: The study points out that the incidence of testicular cancer is low in our set up as in other Asian countries. The histological pattern is predictable except that the testicular non Hodgkin lymphoma is more contrary, to reported elsewhere and probably responsible for the second peak observed in the present series.

Objective: To provide information regarding frequency of malignant tumours through data retrieved from pathology based tumour registry of AFIP, Rawalpindi, Pakistan., Methods: All malignant tumours recorded with the AFIP tumour registry over a period of 10 years (1992-2001) were analysed in terms of age group, gender and type of tumour with relation to site. A comparison with the previously published material from same setting, national and international studies were also done., Results: The total malignant tumours in the 10 years period were 21,168. Out of these, 12584 (59.5%) were seen in male patients while 8584 (40.5%) were in females. Total malignant tumours in pediatric age group were 927 (4.4%). The common malignant tumours in males in order of decreasing frequency were, those of prostate, skin, lymph node, leukaemia, urinary bladder, colorectum, bone, lung, stomach and liver. In females, breast carcinoma was on top followed by skin, leukaemia, ovary, coloretum, lymph node, bone, liver, cervix and gall bladder. In females, contrary to the Western studies and India, ovarian tumours were more frequent than cervical cancers. Comparison of this analysis with our previous analysis, national and international studies showed some interesting features., Conclusion: It was found that in males, tumours of the prostate were the most frequent as compared to the previous study, which showed lymphomas and leukemias to be the most common. On the other hand in females, tumours of the breast remained to be consistently most frequent.

Objective: To determine the pattern of childhood cancer in northern Pakistan., Design: A descriptive study., Place and Duration: January 1992 to December 2001 at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan., Materials and Methods: All histologically diagnosed malignant childhood tumours registered with the tumour registry of our institute were retrieved from the case files. Basic epidemiological data regarding each case were collected from the request forms and analysed for the site of involvement, age distribution and histological types of tumour., Results: During the ten year study period a total of 922 childhood malignancies, constituting 4.3% of all malignant tumours, were seen. Haematological malignancies (lymphomas and leukaemias) were the commonest, accounting for 50.4% in males and 37.7% in females. The haematological malignancies were followed by tumours of bone (6.3%), CNS (6.3%), and eye (4.84%) in males and soft tissue tumours as 5th common in females. Skin, renal and colorectal tumours were also in the ten commonest in both sexes and so were ovarian tumours in females., Conclusions: Lymphomas and leukaemias are the main bulk of childhood cancer. Malignant tumours were twice more common in males than females in this series.

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.

Carcinoma of the male breast, histologically identical to that seen in females, is a rare malignant epithelial tumour. We retrospectively studied 141 cases of male breast carcinoma diagnosed during a ten year period (1992-2001). These tumours comprised 0.7% of all cancers, 1.1% of all malignancies in males and 5.9% of all breast carcinomas in both genders. A male to female ratio of 1:16 was observed. The peak incidence was in the age group between 50-60 years and majority of the patients were below 60 years. Most of the patients presented with a painless lump and infiltrating ductal carcinoma was the main histological type. While compared with our previous similar analysis, a highly significant increase (p< 0.0001) was found for total numbers of breast carcinoma in both sexes and total number of malignancies in males.

Objectives: To determine the pattern of gastrointestinal (GI) malignancies in northern Pakistan., Design: A retrospective pathology based tumour registry data analysis., Place and Duration: January 1992 to December 2001 at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan., Materials and Methods: All histologically diagnosed malignant tumours of GI tract registered with the tumour registry were retrieved from the case files. Basic epidemiological data regarding each case was collected from the request forms and then analysed for the site of involvement, age distribution and histological types of tumours., Results: During the study period a total of 2279 patients had GI tract malignancies, constituting 10.8% of all malignant tumours diagnosed in this period. Males were more frequently affected than females (M:F ratio 2.3:1). Peak incidence was in the 50-60 year age group. Colorectal tumours were most frequent (44.6%), followed by stomach (24%), esophagus (22.6%), anal (4.6%) and small intestinal (3.7%) malignancies. Ten cases of malignant tumours of the appendix, 6 in females and 4 in males were also found. The histological pattern was predictable. Statistical analysis showed that there was significant increase (P<0.01) in registration of stomach, anorectal and small intestinal tumours over the period studied,whereas esophagus and colorectal tumours remained the same., Conclusion: Colorectal tumours are more frequent in our material as compared to other developing countries. Peak incidence is in slightly younger age group and cases in <20 years age group are also more frequent as compared to Western studies.

Objective: To determine the cause of sudden cardiac death and observe the morphological changes in the heart after death., Methods: A cross sectional survey of 66 cases was carried out at Armed Forces Institute of Pathology (AFIP) Rawalpindi from 1992 to 1994. A detailed autopsy including external and internal postmortem examination was done. Representative sections were taken for histopathological examination and some viscera were sent to Chemical Examiner at Lahore for chemical analysis., Results: All the cases were male with age range from 21 to 58 years. These cases died within 60 minutes with or without onset of symptoms. Fifty two cases revealed mild to severe atherosclerosis. Coronary occlusion with thrombosis was seen in 37 cases whereas 9 cases showed critical narrowing without evidence of thrombosis. Five showed both symmetric and asymmetric hypertrophy. Changes in conduction system of the heart were seen in 4 individuals. Myocarditis was noted in 2 cases only. The cause of death could not be determined in 3 cases., Conclusion: Majority of the cases died of coronary atherosclerosis whereas 17% cases revealed hypertrophic cardiomyopathy, changes in conduction system and myocarditis and 4% cases were undetermined. A detailed and thorough postmortem examination is mandatory to ascertain the cause of sudden cardiac death.

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.