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Objective: To determine the diagnostic ability of Beta-catenin in poorly differentiated colorectal carcinomas. Study Design: Cross-sectional study Place and Duration of Study: Department of Histopathology PNS Shifa Hospital, Karachi Pakistan from Jun 2019 to Jun 2020 Methodology: After ethical approval from the Institutional Review Board, 60 patients of both gender and all age group, diagnosed with a case of colorectal carcinoma on biopsy and resection specimens analyzed on histopathology on H & E staining at PNS SHIFA were included in the study. The resection specimens of CRC included those obtained from hemicolectomy, abdominoperineal resection and biopsies. Beta-catenin was interpreted using immunohistochemistry as cytoplasmic and nuclear staining with varying intensity. The scoring method was 0 as negative, 1+ as weakly positive, 2+ as moderate positive, and 3+ as strongly positive. Results: Among the 60 patients with resection specimens included from hemicolectomy, abdominoperineal resection and colorectal biopsies, strong nuclear positive results were observed in 30(50 %) patients, moderate nuclear positivity in 12 (20 %), weak nuclear positivity in 6(10 %) and positive cytoplasmic staining in 12(20 %) patients. Conclusion: Beta-catenin can be used successfully as a diagnostic utility in poorly differentiated colorectal carcinoma patients.

Objectives: To identify the role of immunohistochemistry in correctly identifying metastasis of bone disorders. Study Design: Cross-sectional study Place and Duration of Study: Department of Histopathology Pakistan Naval Ship, Shifa Hospital, Karachi Pakistan, from Jun 2019 to Jun 2020. Methodology: Patients aged 18-75 years, of either gender, already diagnosed case of the primary tumour, and now diagnosed with bone metastasis on biopsy were included. Various imaging techniques were used to locate the site of metastases. The histopathological reports of all the intra-operative specimens of bone metastases were reviewed. Results: The mean age of 60 patients was 59.5±28.8 years and mean weight was 67.4±13.5 kg. The period of presentation from diagnosis of the primary tumour was 34±15.4 months, and the period from onset of symptoms was 8.2±5.8 months. The most common site of the primary tumour was the breast in 18(30%) of patients, followed by the kidney in 14(23.3%) of patients. The most common site of metastasis was the femur in 30(50 %) of patients, followed by the spine in 15 patients. Conclusion: The most common site of primary tumour identified by immunohistochemistry was the breast, followed by the lungs. The femur was the most common site of metastasis, followed by the spine.

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.

Objective: To conduct a morphological evaluation quantitatively of two types of tumor-infiltrating lymphocyte populations, including those located in the stroma and intraepithelial cancer structures, in patients with colorectal cancer. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from Jan to Jul 2019. Methodology: Three levels of infiltration in the stroma by tumor infiltrating lymphocytes were determined. Level 1 was weak meaning (0-20% of stromal TILs), level 2 was moderate meaning (>20-50% of stromal TILs); and level 3 was strong meaning (50-90% of stromal TILs). TILs within tumor cells were divided into two groups. 0 meaning absent (no TILs present) and 1 meaning present (≥TILs in tumor cells) 1. Results: Out of 30 cases 22 were males and 8 females. Ages ranged between 25-83 with a mean of 57 years and a standard deviation of ± 16.4 years. All of the cases were diagnosed cases of adenocarcinoma. The levels of stromal tumor infiltrating lymphocytes was weak in 1 case, moderate in 18 cases and strong in 11 cases whereas intraepithelial lymphocytosis was seen in 22 cases. Conclusion: These results confirm that the infiltration of tumor infiltrating lymphocytes into the tumor in patients with colorectal carcinoma serves an important role in the invasion and progression of the disease, and should be considered in routine examinations.

Objective: To investigate the immunohistochemical expression of PD-1 and PD-L1 in breast cancer cases and its correlation with clinicopathological factors. Study Design: Cross sectional study. Place and Duration of Study: Histopathology department, Armed Forces Institute of Pathology Rawalpindi, form Jan to Jun 2019. Methodology: Sixty five cases of breast cancer were retrieved. Clinicopathological parameters like age, gender, tumor grade and receptor status were noted. Immunohistochemistry for PD-1 and PD-L1 was applied. The data was entered and statistical analysis was done using SPSS version 21. The associations between variables were found using the Fisher exact test. Results: Sixty five cases of breast cancer were investigated from tumour registry. The sample included female patients, having mean age of 50.86 ± 11.1 Years. Invasive mammary (ductal) carcinoma, NST was the most prevalent subtype 60 (92.3%) and most tumors were grade I/II 53(82%). PD-1 expression was seen in TIL’s 31 (48%) and PD-L1 expression was observed in tumour cells 30 (46%). Expression of PD-1/PD-L1 expression was more common in premenopausal age group and grade I/II tumors. Among molecular subtypes, PD-L1 expression was detected in 11 (52%) TNBC, 5 (71%) in HR-/HER2+ and 12 (32)% in HR + HER2 - and PD-1 expression was observed in 13 (62%) TNBC, 5 (71%) in HR-/HER2+ and 13 (35%) in HR+ HER2-. Conclusion: A large proportion of breast cancer cases show expression of PD-1 / PD-L1. Anti PD-1 and PD-L1 therapy may benefit these patients.

Objective: To evaluate interobserver variability in core breast biopsies of category B3 and B4 at a tertiary care centre Study Design: Retrospective, observational, cross-sectional study. Place and Duration of Study: Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from Mar 2017 to Jun 2018. Methodology: A total of thirty cases of histologically confirmed lesions of category B3 and B4 on core breast biopsies from March 2017 to June 2018 were retrieved from archive of Histopathology department, AFIP Rawalpindi. Patients’ age, histologic diagnosis and reporting B category were noted. The selected cases were anonymized and distributed among 3 pathologists for independent review. The participating pathologists were kept unaware of the findings given by fellow participants and previously agreed reference diagnoses. Study cases were reviewed by the participating pathologists. The results were analyzed and overall concordance rate, discordance rate, over interpretation rate and under interpretation rate were calculated. Results: A total of 30 (n=30) patients were enrolled of which 22 were assigned category B3 (73%) and 8 were assigned category B4 (27%) on initial microscopic evaluation (original opinion). The ages of the study patients ranged from 25 to 85 years. The average concordance rate of morphologic findings of study pathologists compared to the reference diagnosis was 63% (19/30). Among these the average concordance rate compared to reference diagnosis among category B3 lesions was 73% (16/22) and among category B4 lesions was 37.5% (3/8). The average rate of disagreement of morphologic findings of study pathologists compared with the reference diagnosis was 37% (11/30). Among these the average rate of disagreement compared to reference diagnosis among category B3 lesions 27% (6/22) and among category B4 lesions was 62.5% (5/8). The overall over inter-pretation rate was 44% and overall under interpretation rate was 56%. The overall rate of unanimous agreement of independent diagnoses among the three panel consultants was 50% (15/30). Among these 15 cases 12 were assigned category B3 and 3 were assigned category B4. The overall rate of disagreement of independent diag-noses among the three panel consultants was 50% (15/30). Conclusion: In our study the opinion was established by interpretation of a single slide. Average concordance rate among the participating pathologists’ findings and the previously agreed upon final diagnoses was 63% and disagreement was 37%, the rate of agreement being higher in the category B3 and lower in the category B4 lesions. However effect of these results on the therapy and prognosis of patients still needs to be evaluated

Objective: The purpose of this study was to evaluate the diagnostic utility of SATB2 in detecting CRC origin for patients presenting with metastatic carcinomas. Study Design: Cross sectional, comparative study. Place and Duration of Study: Study was conducted at department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from January 2019 to June 2019. Materials and Methods: Already diagnosed 68 cases of metastatic carcinoma of various origins with unknown primary were retrieved from tumour registry. Paraffin embedded blocks were taken and a panel of Immunohistochemistry was applied which includes CK7, CK20,CDX2 and SATB2. Positivity of SATB2 alone, and combination of SATB2 with CK 7,CK20 and CDX2 was evaluated. Results: Out of 68 metastatic adenocarcinoma cases 28(41%) had positive SATB2 expression and 38 (56%) were negative. All the positive SATB2 cases had 100 % (28/28) expression with CDX2, 93% (26/28) of the cases had expression with CK20 and 21% (6/28) of the cases showed expression of CK7. The sensitivity of SATB2 alone was 100% in metastatic colorectal carcinoma as compared to CK20 and CDX2. The sensitivity of SATB2 in combination with CDX2 (100%) and CK20 (93%)in comparison to the double combination of CK20 and CDX2(93 %). The sensitivity of SATB2 and CK20 combination was 93%, which was equal to CK20 and CDX2 combination. Conclusions: Our results show that SATB2 is a sensitive marker in the IHC panel for cases with suspected metastasis from colorectal region.

Objective: To evaluate immunohistochemical expression of EGFR in colorectal cancer (CRC). Study Design: Descriptive cross sectional study. Place and Duration of Study: Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from Mar 2017 to Aug 2017. Methodology: A total of 100 cases of histologically confirmed CRC were retrieved from archive of Histopathology department, AFIP Rawalpindi. Patients’ age, gender, histologic type and grade were noted. Immunohistochemistry for EGFR was applied and results were recorded. Data was analyzed using SPSS version 22. Descriptive statistics, frequencies and percentages were calculated. Results: A total of hundred (n=100) patients were enrolled. Mean age of the study patients was 54.3 ± 16.3 years. The group of patients consisted of 68 (68%) men and 32 (32%) women. The majority of primary tumours were located in the rectum 39, (39%), followed by ascending colon 16 (16%), rectosigmoid junction 14 (14%), cecum 13 (13%), sigmoid colon 9 (9%), transverse colon 5 (5%) and descending colon 4 (4%). Most frequent histologic type was adenocarcinoma 80 (80%), followed by mucinous adenocarcinoma 12, (12%) and signet ring cell carcinoma 8 (8%). Most tumours were moderately differentiated 47 (47%), followed by well differentiated 34 (34%) and poorly differentiated 19 (19%). EGFR expression was found in 39 cases (39%). Among adenocarcinoma 41% (n=33/80) were EGFR positive and among mucinous adenocarcinoma 50% (n=6/12) were EGFR positive. All signet ring cell carcinoma cases were EGFR negative. Among well differentiated CRCs 41% (n=14/34) were EGFR positive, among moderately differentiated 40% (n=19/47) were EGFR positive and among poorly differentiated 46% (n=6/13) were EGFR positive. Conclusion: A significant percentage of CRC expressed EGFR but no statistically significant correlation was seen between EGFR expression and clinicopathological variables. Estimation of EGFR expression status may help to select the patients with CRC for targeted therapy, which is likely to improve the response rates.

Objective: To determine expression of p16 mutant protein and ki67 in cutaneous and non-cutaneous melanoma. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from July 2017 to July 2018. Methodology: All cases of melanoma diagnosed by histopathological examination were included. P16 and ki67 antibodies for immunohistochemical studies were applied in all cases. Patient’s gender, age, tumor site and results of immunohistochemical (IHC) stains were noted. Results: A total number of 40 cases of melanoma were studied. It was more common in males 28 (70%) than females 12(30%). Mean age of presentation was 51.1 ± 1.17 years. Most of the patients i.e., 25 (62.5%), were in age group above 50 years, Cutaneous melanoma was the commonest type being 22 (55%), followed by ocular melanoma being 14 (35%) and mucosal melanoma 4 (10%). The immunohistochemical staining for p16 was positive in all cases (100%). Ki67 proliferative index was high in most cases 34 (85%). It was low in the rest of cases being 6 (15%). Conclusion: Melanoma was found more common in males in the age group above 50 years. Cutaneous melanoma was the most common type. There was strong correlation between p16 and ki67 expression. P16 was seen in all cases. High ki67 was seen in 85% of cases.

Objective: To evaluate expression of p53 and Ki67 proliferative index in triple negative breast carcinoma. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Histopathology, AFIP Rawalpindi, from Jan to Jul 2018. Methodology: Fifty-two cases of triple negative female breast carcinoma were included in this study regardless of age of patient, histological type and grade of the tumor. Tumors such as malignant tumors with positive immunohistochemical staining for ER, PR and Her 2 neu, stromal tumors, skin squamous cell carcinomas, lymphomas, poorly fixed specimens and specimens with scanty tumor tissue were excluded. Results: The mean age of patients was 53.28 ± 7.69 years (range 40-71 years). Most of the patients were in the age group 41–50 years 21 (40.4%) and 51-60 years 21 (40.4%), followed by age group more than 60 years 10 (9.2%). High Ki67 index was seen in 34 (65.4%) of cases. In the rest of the cases 18 (34.6%) the proliferative index was low. Out of the 52 cases of triple-negative breast cancer 44 cases (84.6%) showed nuclear positivity for P53, the rest of 8 cases (15.4%) were negative for p53. Conclusion: Most cases occurred in the 5th and 6th decades of life. The study showed strong correlation between p53 expression and high Ki67 proliferative index. This finding can help in the management of patients of TNBC and predicting the prognosis of the disease.

Objective: To determine the immunohistochemical (IHC) expression of transducer like enhancer of split 1 (TLE-1) in diagnosed cases of synovial sarcoma (SS). Study Design: Cross sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan, from Jan 2017 to Jun 2018. Methodology: In our study, 60 cases of SS diagnosed on hematoxylin & eosin (H&E) morphology, IHC expression of CD99 and epithelial membrane antigen (EMA) were retrieved from archive of Histopathology department AFIP Rawalpindi. Patient’s age, gender, tumor site and histologic type were noted. IHC for TLE-1 was applied and results were recorded. Data was analyzed using SPSS version 22. Results: A total of 60 cases were included in which 33 were males and 27 were females. The male to female ratio was 1.2:1. Mean age of the study patients was 36.6 ± 15 years. SS was found be more common in soft tissues of limbs/ extremities around tendons sheaths (76%); other sites being lungs, head & neck and retroperitoneum. Out of 60 cases of SS, 42 (70%) cases were monophasic, while 15 (25%) and 3 (5%) cases were biphasic and poorly differentiated SS, respectively. A total of 90% samples (n=54) showed immunoreactivity for TLE-1 (p=0.023) out of which 61% samples (n=33) had diffuse (2+) nuclear staining while 21 (39%) showed weak to moderate nuclear staining for TLE-1. However, 6 (10%) cases did not show nuclear staining for TLE-1. Conclusion: TLE-1 was found to be a novel marker which was extremely helpful in diagnosis of SS, especially in cases where diagnostic challenge arises when other spindle cell neoplasms are considered in the differential diagnosis and in laboratory set ups where advanced facilities of molecular testing by fluorescent in situ hybridization (FISH) is not available.

Objective: To evaluate ER and PR expression in epithelial ovarian cancers (EOC) and to determine its association with clinical stage. Study Design: Cross sectional study. Place and Duration of Study: Histopathology department, Armed Forces Institute of Pathology (AFIP) Rawalpindi, from Mar to Oct 2017. Material and Methods: A total of thirty three (n=33) histologically confirmed EOCs were analyzed. ER and PR expression status was assessed by immunohistochemistry using Allred scoring system and was compared with the clinical stage defined by The International Federation of Gynecology and Obstetrics (FIGO) staging system. Results: A total of thirty three (n=33) females were enrolled. Mean age of the study females was 50.8 ± 12.9 years. Most frequent histologic type was serous carcinoma (SC) 60.6% (n=20) followed by mucinous carcinoma (MC) 15.2% (n=5), endometrioid carcinoma (EC) 9.1% (n=3), clear cell carcinoma (CC) 9.1% (n=3), Brenner tumor (MBT) 3% (n=1) and seromucinous carcinoma (SMC) 3% (n=1). Most patients were in clinical stage I 61% (n=20) followed by stage II 24%, (n=8) and stage III 15% (n=5). Among SC, 90.0% (n=18/20) were ER and 65% (n=13/20) were PR-positive. All MC and CC were ER/PR negative. Two of the three ECs were ER and one was PR-positive. Higher percentage of stage I tumors exhibited ER 65% (n=13/20) and PR 45% (n=9/20) positive status (p>0.5). The correlation was very weak positive between clinical stages and both ER and PR scores (Allred) r=0.11 and 0.15 respectively p>0.05. Conclusion: Higher percentages of stage I tumors exhibited ER and PR positive status yet not statistically significant from stage II/III. Estimation of ER and PR receptor status may help to select the women with ovarian malignancy for hormonal therapy, which is more likely to improve the response rate.

Objective: To determine the frequency of immunohistochemically expression of Glypican-3 in hepatocellular carcinoma on liver biopsies. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from Jun 2015 to Jun 2016. Material and Methods: A total of 55 liver biopsies from the patients of hepatocellular carcinoma were included in the study. Age, gender, tumor grade and immunohistochemically expression of glypican-3 were noted. The data were analyzed by SPSS version 21. Mean and SD were calculated for numerical variables such as age. Percentages and frequencies were calculated for gender, tumor grade and immunohistochemically expression of glypican-3. The data collected for study were statistically analyzed using chi-square test. Results: Out of 55 patients of hepatocellular carcinoma, 44 (80%) were males and 11 (20%) were females. The age of the patients was between 41 and 80 years with an average age of 59.7 years and standard deviation of ± 8.8. Out of 55 cases, 32 cases (58.2%) were well differentiated, 18 cases (32.7%) were moderately differentiated and 5 cases (9.1%) were poorly differentiated. Forty-eight cases of hepatocellular carcinoma (87.3%) showed positivity for glypican-3 while 7 cases (12.7%) were negative. A significant statistical association was not seen among age, gender, tumor grade and glypican-3 expression, p-value being >0.05. Conclusion: The high expression of glypican-3 in hepatocellular carcinoma suggests its diagnostic utility and also its value in distinguishing hepatocellular carcinoma from other hepatic lesions. As antiglypican-3 therapy is currently under clinical evaluation, it might be useful as a therapeutic target in glypican-3 positive hepatocellular carcinoma cases.

Objective: To analyse the clinicopathological spectrum of synovial sarcoma cases presenting in our institution. Study Design: Descriptive case series. Place and Duration of study: Armed Forces Institute of Pathology (AFIP) Rawalpindi, from Jan 2010 to Jan 2015. Material and Methods: All cases of synovial sarcoma diagnosed on histopathological examination were recovered from the Armed Forces Institute of Pathology (AFIP) laboratory information management system.The inclusion criteria consisted of optimally processed Haematoxylin and Eosin stained slides. Positive immunohistochemistry for epithelial membrane antigen/cytokeratin and CD99. Both genders were included. Patients’ gender, age, tumour size, site, histological subtype, grade, microscopic margin status, depth and stage were noted. The data were analysed using SPSS Version 21. Frequencies and percentages were calculated for qualitative data and the standard deviation and mean for quantitative data. Results: Sixty-seven cases of synovial sarcoma (SS) were included in this study. The mean age of the patients was 35.1 years, with males at 55.2%. The most common site was the lower extremity 41.8%. The average size was 8.5 cm. The most common stage was pT2b (64.2%). Monophasic histological subtype was more common at 58.2%. Grade 2 tumours were 77.6%. Microscopic positive margins were 30.0%. Specimens that were fragmented or not oriented properly were 33.3%. Conclusion: The clinicopathological spectrum of synovial sarcoma in our institution is similar to that of other parts of the world. This study has highlighted that a significant proportion (33.3%) of resection specimens were fragmented or unmarked; therefore surgical margins could not be evaluated in these cases, increasing the chances of inadequate surgeries.

Post chemotherapy histiocyte-rich pseudotumour of spleen and lymph node are a rare occurrence and can be seen in patients after chemotherapy of haematological malignancies. We report the case of a two years old child, a diagnosed case of Acute Lymphoblastic Leukemia under going chemotherapy. He presented to the paediatric oncology department of Combined Military Hospital, Rawalpindi for follow up examination. Clinical examination and ultrasound abdomen revealed splenomegaly. Haematological investigations revealed worsening of blood counts. Splenectomy was planned in order to improve hypersplenism and to evaluate leukemic infiltration of spleen. Spleen and a perihilar lymph node were removed surgically and the specimens were sent to the histopathology department of Armed Forces Institute Pathology, Rawalpindi. Histologically, spleen and lymph node showed sinus dilatation and infiltration by numerous macrophages, which were positive for histiocytic immunohistochemical markers. On the basis of histopathological and immunohistochemical features, the diagnosis of post chemotherapy histiocyte-rich pseudotumour of spleen and lymph node was made. [ABSTRACT FROM AUTHOR]