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Objective: To evaluate the NKX3.1 expression by immunohistochemistry in normal testicular parenchyma and in Sertoli cell tumours and Sertoli Leydig cell tumours of the testes and ovary. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore Pakistan, from 20102021. Methodology: We used immunohistochemistry to evaluate the positivity and loss of nuclear expression of NKX3.1 in the Sertoli cell tumour (11 cases), Sertoli Leydig cell tumour (31 cases) and in normal testicular parenchyma (7 cases). Results: In our study, there were 49 cases. All the cases of benign testicular parenchyma expressed positivity with nuclear staining of NKX 3.1 in Sertoli cells. Two out of 11 Sertoli cell tumours expressed positivity with nuclear positivity of NKX 3.1 in Sertoli cell component (18.18%) and 9 of the cases showed loss of staining of NKX 3.1 (81.8%). All Sertoli Leydig cell tumours showed loss of staining of NKX 3.1. Conclusion: Nuclear expression of NKX 3.1 is seen in Sertoli cells of normal testicular parenchyma. This staining is lost in Sertoli cell tumours and Sertoli Leydig cell tumours. [ABSTRACT FROM AUTHOR]

Objective: To calculate tumour budding pT2 colorectal carcinomas and study its association with other prognostic indicators. Study Design: Cross-sectional study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research centre, from 2018-2019. Methodology: Hematoxylin and eosin-stained slides of 50 Patients using 4-5 microns' thick sections were prepared using Leica Peloris for processing, Leica ST 5020 for staining and Leica CV 5030 for cover slipping. An Olympus cx31 microscope was used to assess tumour budding. The "Hotspot method" (as proposed by ITBCC) was used. Results: 26 (52%) slides showed low tumour budding (BD1), 8 (16%) showed intermediate tumour budding (BD2), and 16 (32%) showed high tumour budding (BD3). one patient out of 26 had positive nodal status in the low tumour budding category (3.8%). However, at the initial diagnosis, this number was significantly higher in the intermediate (50%) and high tumour budding (37.5%) categories. The mean survival in patients with low tumour budding was 22.615 months, which was significantly higher than 12.250 months and 13.188 months for intermediate and high tumour budding, respectively, with overall mean survival of 17.94 (±5) months. The overall survival rate in our study was 92.30% (24/26 patients), 25% (2/8 patients) and 12.5% (2/16 patients) for BD1, BD2 and BD3 patients, respectively (p=0.001). Conclusion: Our study supports the inclusion of tumour budding in colorectal tumour checklists because of its association with survival and lymph node metastases. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of chemotherapeutic response on resection specimens and to assess their effect on prognosis. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Peshawar Pakistan, from Jan 2010 to Mar 2018. Methodology: This study included 42 cases of Ewing sarcoma diagnosed, treated and followed at our institute. Various diagnostic parameters were noted and were assessed for their impact on two-year overall survival, development of distant metastasis, recurrence and cancer-related death. Results: This study included 28 males and 14 females. The majority involved long bones followed by the axial skeleton and soft tissue. Nine cases (9) were confirmed by molecular testing. On the post-neoadjuvant chemotherapy resection specimens, 45% cases had Huvos grade I necrosis, 17% had grade-II, 12% had grade-III and 26% cases had Huvos grade-IV necrosis. Increasing Huvos grade was associated with improved disease-free survival (21%, 43% and 69% for grades-I, II and III/IV respectively). The site and size did not significantly affect the development of recurrence, development of metastasis, or twoyear survival (p>0.05). Conclusion: Meticulous assessment of post neoadjuvant resection specimens for necrosis provides helpful information about the prognostic outcome. Increasing grade of tumour necrosis was associated with increasing disease-free survival. The response to chemotherapy in our study population was worse than Western data, which may be linked to a variety of factors. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of four immunohistochemical stains in the categorization of hepatoblastoma. Study Design: Retrospective longitudinal study. Place and Duration of Study: Histopathology Department, Shaukat Khanum Memorial Cancer Hospital, Peshawar Pakistan, from 2016 to 2018. Methodology: We retrospectively reviewed 50 cases of hepatoblastoma from 2016-2018, from our hospital database and studied the pattern of four immunohistochemical stains (Beta-catenin, Glutamine synthetase, Heppar 1 and Cyclin D1) in various subtypes. Results: Ten out of fifty cases were mixed epithelial and mesenchymal hepatoblastomas, and forty were pure epithelial. In the pure epithelial category, the fetal subtype showed Heppar 1 and Cyclin D1 positivity in twenty-eight cases, while Glutamine synthetase and Beta-catenin were positive in all the thirty cases. One case of embryonal subtype displayed negativity for Heppar 1; the rest of the immunohistochemical stains were positive. Ten tumours exhibiting mixed epithelial and mesenchymal morphology showed positivity for all the four immunohistochemical stains in the epithelial component. However, Heppar 1 and cyclin D1 were negative in the mesenchymal component in all the ten cases. Five cases (50%) showed Glutamine synthetase and Beta-catenin positivity in the mesenchymal component. Conclusion: All the four immunohistochemical stains, especially Beta-catenin and Glutamine synthetase, were efficient diagnostic tool, especially for tumours with complex or vague morphological features. [ABSTRACT FROM AUTHOR]

Objective: To assess the patterns of myoinvasion of endometrial endometrioid adenocarcinoma, their frequencies in our hospital and to correlate these patterns with survival. Study Design: Retrospective observational study. Place and Duration of Study: Department of Pathology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, from Aug 2019 to Apr 2020. Methodology: All cases of endometrial endometrioid adenocarcinoma between 2015 and 2017 were retrieved from the archives, independently reviewed by two researchers, all key reporting parameters recorded in addition to the pattern of myoinvasion as per their operational definitions described by Cole and Quick. The follow-up of 3-5 years was obtained from archives and through telephonic contact for outside hospital patients. Disease free survival and relapse-associated mortality were represented through Kaplan-Meier curves. Results: Eighty cases of myoinvasive endometrial endometrioid adenocarcinoma were reviewed. We found that infiltrating irregular gland pattern was the most frequent in all the age groups. Thirty-five (43.75%) cases showed this type of invasion, followed by broad front pattern 23 (28.75%), Microcystic Elongated and Fragmented (MELF) pattern 15 (18.75%) and adenomyotic pattern 6 (7.5%). One case showed a combination of the last two patterns, whereas adenoma malignum pattern was not seen. Follow-up of these patients showed 8 (10%) patients with relapse related mortality including 5 (62.5%) infiltrating irregular glands, 2 (25%) adenomyosis-like and 1 (12.5%) broad front pattern of myoinvasion. Seventy-two (90%) patients had recurrence free survival. Conclusion: Frequency of infiltrating irregular pattern of myoinvasion in endometrial endometrioid adenocarcinoma is high and associated with recurrence related mortality. Recognition of these patterns is important as their impact on overall management and prognosis is, however, unknown, and further studies are required to determine the importance of these patterns. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence ERG fusion positive adenocarcinoma and its correlation with gleason grade and gleason group. Study Design: Cross-sectional study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital & Research Centre (SKMCH & RC), Lahore Pakistan, from Jan 2018 to Jan 2019. Methodology: A total of 100 cases of prostatic adenocarcinoma were retrieved and ERG immunohistochemical stain was applied on all these cases. ERG expression, extent of staining, percentage of tumor cells positive for ERG, pattern of staining was recorded. We found out relationship of ERG expression and gleason grade/gleason group. Results: ERG expression was seen in 62/100 (62%) cases. Mean patient age of ERG positive prostatic adenocarcinoma patients was 69.68 years. In GG1 (14.5%) 9 cases exhibited ERG positivity. In GG2-3, 41.93% cases and in GG4-5, 43.54% cases showed ERG expression. Conclusion: To conclude, age of presentation of ERG positive adenocarcinoma was high. ERG expression was seen in 62% of our cases which was much higher than reported in other Asian countries. In our study we found a significant correlation between ERG expression and high gleason grade group. [ABSTRACT FROM AUTHOR]

Objective: To assess the sensitivity and specificity of DOG 1 in the diagnosis of chondroblastomas. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from Jun 2015 to Jul 2017. Methodology: Total fifty-two patients were included in this study using simple random sampling technique including 19 chondroblastomas, 21 giant cell tumors and 12 chondromyxoid fibromas. DOG 1 antibody was applied on all the cases. Results: DOG 1 was positive in 100% of cases of chondroblastomas. However, intensity and proportion of staining pattern was variable among them. Fifteen (78%) cases showed diffuse moderate to strong expression while 4 (22%) cases showed focal weak expression. Only 2 (10%) cases of giant cell tumors and 4 (33%) cases of chondromyxoid fibromas expressed focal weak expression for DOG 1. Conclusion: This study confirms 100% expression of DOG 1 in cases of chondroblastomas but intensity and proportion of staining pattern was variable. Therefore DOG 1 may prove to be a useful immunohistochemical marker for diagnosis of chondroblastomas in the future in difficult cases in correlation with histological and radiological features. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of Ki67 as a surrogate marker for Mitotic Karyorrhectic Index (MKI) in Neuroblastoma. Study Design: Cross-sectional study. Place and Duration of Study: This was a retrospective study conducted at Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. 41 cases of neuroblastoma from 2010 to 2014 were retrieved. Methodology: Forty one cases of neuroblastoma were evaluated. Clinical and morphological features like age, gender and subtype of tumor were quantified. For each case, Mitotic Karyorrhectic Index was calculated and categorized as low, intermediate and high. This was followed by immunostaining for Ki67 on each case. Using linear regression model an equation was derived to calculate ki67 from Mitotic Karyorrhectic Index. The equation was as follows: Mitotic Karyorrhectic Index = (Ki67 x 0.115) ± 1.355. Using this equation, the cut-off values for low, intermediate and high Ki67 were <5.60%, 5.60% - 23.0% and >23.0% respectively. Results: Twenty four cases had low Mitotic Karyorrhectic Index and in 18/24 cases, Ki67 was also low. There were 5 cases with intermediate Mitotic Karyorrhectic Index with two cases showing correspondingly intermediate Ki67 index. There were 12 cases with high Mitotic Karyorrhectic Index and 10/12 cases showed a high Ki67 index as well. Conclusion: Ki67 is a useful technique and may be used as an adjunct to Mitotic Karyorrhectic Index for better evaluation of cases. [ABSTRACT FROM AUTHOR]

Objective: To stratify diffuse gliomas into subtypes including diffuse astrocytomas, oligodendrogliomas and glioblastomas based on recent molecular updates and assess their frequencies in our local subpopulation. Study Design: Cross-sectional study. Place and Duration of Study: Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from Jun 2015 to Jul 2017 Methodology: Two hundred and fourteen (n=214) cases of adult diffuse gliomas were evaluated. Clinical and morphological features like age, gender and type of tumor were quantified. Molecular studies including IDH 1 by antibody and PCR, ATRX by antibody and 1p/19q co-deletion by FISH were tested. Gliomas were subcategorised based on WHO 2016 guidelines. Results: Mean age of presentation was 39 years. Overall n=146/214 (68.2%) of the cases were completely classifiable including Diffuse Astrocytomas, Oligodendrogliomas and Glioblastomas. Out of the glioblastomas (n=81), 67/81(n=82.7%) were IDH Wild type and 14/81 (17.3%) were IDH Mutant. Conclusion: In this study, glioblastomas are the most frequent gliomas as categorized by current WHO molecular guidelines followed by diffuse astrocytomas. Oligodendrogliomas are the least common. [ABSTRACT FROM AUTHOR]

Objective: To assess the expression of GATA-3 among epithelial tumors of four organs including invasive mammary carcinoma, prostatic adenocarcinoma, colorectal carcinoma and high grade serous carcinoma of ovary. Study Design: Case series study. Place and Duration of Study: The study was performed at Shaukat Khanum Memorial Cancer Hospital and Research Center, from Jul 2017 to Dec 2017. Methodology: Twenty cases of each of these tumors were collected and stained with ready to use GATA-3 immunohistochemical stain (Cell marque (L50-823) mouse monoclonal antibody) using BOND III Leica automated immunostainer. The expression of the antibody was assessed by two histopathologists. Diffuse nuclear staining in more than 30% of tumor cells was considered as positive. Results: All the breast carcinomas showed diffuse strong positivity in tumor cells, while all the cases of prostatic adenocarcinoma showed negative staining. Aberrant and focal staining was observed in a few cases of high grade serous and colorectal carcinomas. Three cases of high grade serous carcinoma showed weak nuclear staining in 10% of cells. Only one case of colorectal carcinoma showed weak nuclear blush in 10 to 20% of tumor cells. Conclusion: GATA-3 was found a sensitive and specific marker for mammary carcinomas. It is a useful diagnostic tool and should be included in a panel of immunohistochemical markers when working on a metastatic tumor of unknown origin. [ABSTRACT FROM AUTHOR]

Objective: To differentiate ovarian clear cell carcinoma and serous carcinoma by expression of Napsin A positivity. Study Design: Cross-sectional & descriptive study. Place and Duration of Study: The study was conducted in Shaukat Khannam Memorial cancer hospital from 2016 to 2017. Material and Methods: A total of n=59 cases of previously diagnosed cases of clear cell carcinoma and high grade serous carcinoma were selected for this study. The slides were reviewed by an expert panel. Napsin A (MRQ-60) Ventana monoclonal antibody was applied to all the cases. Weak to strong membranous staining in more 5% tumor cells was considered positive. Results: Mean age of patients in the study was 46.25 ± 11.1 years. There were n=33 (55.9%) cases of serous carcinoma, n=23 (38.9%) cases of clear cell carcinoma and n=3 (5.08%) cases had biphasic morphology. CK7 was applied and showed positive expression in all the cases. Napsin A was found positive in all the cases of clear cell carcinoma as compared to only n=1 (3%) high grade serous carcinomas and none of the mixed tumors. The relationship was considered significant with a p-value of <0.05. Conclusion: Expression of Napsin A showed a significant difference in high grade serous carcinoma and clear cell carcinoma. Therefore, Napsin A was found a sensitive and specific marker for the diagnosis of ovarian clear cell carcinoma and can reliably differentiated it from high grade serous carcinoma. Current research recommends a study with large sample size to insight the expression of Napsin A and other immunohistochemical stains. [ABSTRACT FROM AUTHOR]

Objective: To assess of the pathologic response of patients of osteosarcoma, after neoadjuvant chemotherapy. Study Design: Descriptive study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore from Jan 2016 to Aug 2016. Material and Methods: A total of 60 cases of osteosarcoma found suitable by inclusion criteria were included in this study. Demographic details such as name, sex and age were collected. All specimens were grossed and staged according to CAP guidelines. Tumor response was assessed by two pathologists and graded as good and poor response. Results: Sixty percent (n=36) of patients were between 7-18 years of age while 40% (n=24) of patients were between 19-45 years of age. Mean age was 17.65 years. A total of 58.33% (n=35) of patients were males and 41.67% (n=25) of patients were females. Thirty percent (n=18) of the patients had good response, while 70% (n=42) of patients had poor response to chemotherapy. Conclusion: We concluded that the assessment of pathologic response of osteosarcoma after neoadjuvant chemotherapy in terms of good response and poor response is a useful tool for the pathologist and the oncologist. It gives us useful information regarding patient's response to neoadjuvant chemo radiotherapy that also helps in determining the further management and overall survival rate of the patient. [ABSTRACT FROM AUTHOR]

Objective: To assess the frequency of loss of expression of succinate dehydrogenase-B (SDH-B) in gastrointestinal stromal tumors (GISTS) of our population through immunohistochemistry. Study Design: Descriptive study. Place and Duration of Study: Department of Pathology, Shaukat Khanum Hospital & Research Centre, Lahore for a duration of 6 months, Apr 2015 to Sep 2015. Patients and Methods: A total of 63 diagnosed cases of GISTS suitable by inclusion criteria were included in the study. The blocks of already diagnosed cases was reviewed by 2 pathologists and after confirmation SDH-B immunohistochemical stain was applied with normal tissue as its control. Lack of staining in tumor was interpreted as "Loss of expression". Results: Mean age of our population was n=44.83 ± 17.76 years. The most common tumor site was small intestine n=23 (63.5%) cases, followed by stomach, n=15 cases. CD117 was positive in all the tumors. Only n=3 tumors were found to be SDH-B deficient. All of these tumors involved the stomach and had a median age of 20 years. All of these tumors had an epithelioid morphology. Conclusion: Immunohistochemistry was found reliable and cost-effective method for detecting mutation in SDH gene. Based on findings of this study it is recommended that all gastric GISTs below the age of 30 years with epithelioid morphology should be tested for SDH deficiency. [ABSTRACT FROM AUTHOR]

Objective: To study the morphological and immunohistochemical features of solid pseudopapillary tumor of pancreas. Study Design: Retrospective study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre from Jun 2016 to Mar 2017. Material and Methods: Sixty-four patients (n=64) including 61 females and 3 males with pathological diagnosis of solid pseudopapillary tumor were selected from archives of Shaukat Khanum Memorial Cancer Hospital and Research Center for the period of 2000-2017. For the sample selected, their morphological features and immunohistochemical profile were reviewed and analyzed. The morphological features are considered as gold standard for the diagnosis. Results: The mean age was 33 years (range 8-50 years). Immunohistochemical stains were performed on formalin fixed paraffin embedded section of 55 cases. Pancytokeratin was performed on 8 cases, out of which only 2 cases showed positivity. CD10 was performed on 14 cases, out of which only 12 cases showed positivity. Neuron specific enolase (NSE), CD56, vimentin, progesterone receptor (PR) and ß catenin were performed on 8,5,3,13 and 16 cases respectively and showed positivity in majority of cases. Neuroendocrine markers (chromogranin and synaptophysin) were performed on 25 and 6 cases, from which it showed weak positivity in 3 cases. CD99 was performed on 19 cases and showed characteristic dot like staining. Conclusion: Among the immunohistochemical stains, CD99 had a specific dot like staining pattern and was used as a first line marker in diagnosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: to determine unusual morphological features and a panel of immunohistochemical markers to diagnose Xp11 translocation carcinoma. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital, Lahore Pakistan, from Jun 2015 to Feb 2020. Methodoldogy: We analyzed clinicopathological features, and evaulated intensity and extent of TFE 3 immunoreactivity of 18 cases with suggested diagnosis of xp11 translocation associated renal cell carcinoma from 2015-2020. Results: Different morphological pattern includes papillary (8/18, 44%), nested (2/18, 11.1%), alveolar (3/18, 16.7%), nested and papillary (3/18, 16.7%), solid and nested (1/18, 5.6%), cystic and nested (1/18, 5.6%). Four cases show papillary architecture with a linear array of nuclei away from the basement membrane, a pattern seen in SFPQTFE3 renal cell carcinoma and NONOTFE3 renal cell carcinoma. Strong nuclear TFE3 expression was seen in 9/18 (50%) cases. Cathepsin k expression was seen in 6/11 (54%) cases, Ck7 was focal weak positive in 4/12 (25%) cases, PAX8 was positive in 8/8 (100%) cases, and CA IX was focal weak positive in 1/5 (20%) case. According to follow-up data, disease progression was seen in only one case with the lowstage disease. No death was reported due to renal cell carcinoma to date of follow-up. Conclusion: We have suggested that young patient age, unusual morphological features and an immunohistochemical panel may help reach the diagnosis in countries with limited resources. [ABSTRACT FROM AUTHOR]

Objective: To correlate the scoring system using histopathologic parameters; worst pattern of invasion (WPOI), lymphocytic host response (LHR) and peri-neural invasion (PNI), with disease recurrence, overall survival and cervical lymph node metastasis in OSCC patients. Study Design: Cross sectional. Place and Duration of Study: Department of Histopathology, Shaukat Khanam Memorial Cancer and Research Hospital, Lahore in collaboration with Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi. Study completed in 2 years. Material and Methods: A "Risk Scoring system" was applied to 50 cases of OSCC with 2 years follow-up data, based on histopathologic parameters WPOI, LHR and PNI. The cases were divided into High risk and Non-High risk categories according to the specified parameters and then correlated with disease recurrence, overall survival and cervical lymph node metastasis. Results: There were 7 low risk, 17 intermediate risk and 26 high risk cases. No correlation was seen between the risk groups and disease recurrence, overall survival or cervical lymph node metastasis. However, when assessing the individual parameters, significant correlation was observed between PNI with disease recurrence (p = 0.03), and between WPOI and overall survival (p = 0.02) and cervical lymph node metastasis (p = 0.005). Conclusion: The individual parameters, peri-neural invasion and worst pattern of invasion are observed to be significant prognostic indicators in OSCC patients. A study with a larger number of cases is required to truly assess the value of the scoring system in Pakistani patients. [ABSTRACT FROM AUTHOR]

The article offers a review of and the histogical types of oral sqamous cell carcinoma. Topics covered include the oldest known tumor found in East Africa, the epidemiology the disease and causes of oral sqamous cell carcinoma including tobacco smoking, smokeless tobacco and radiation and ultraviolet light. The variants of oral sqamous cell carcinoma are also mentioned.