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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.

Background The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC). Methods A quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS). Results Database searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others. Conclusion Nevertheless, the study has provided significant insights into CC stage progression for further investigation.

Aims: A sub-population of cells named cancer stem cells (CSCs) that initiate and promote tumour growth have been demonstrated to exist in several malignancies including colon carcinoma. The objective of our pilot study was to isolate CD133+CD26+CD44+ CSCs from patient colon tumours, culture spheres or organoids and observe their proliferation in primary cultures. Parallel cultures of non-cancer controls from colon normal lining and nonadenomatous polyps were set up. Methods: Magnetic activated cell sorting was used to isolate CD133+CD26+CD44+ cell populations followed by primary cell culturing under stem cell culture conditions. Number, cells/organoid and daughter generations of organoids were calculated using phase contrast microscope. Trypan blue exclusion method was used to test the viability of the cells. Results: Both colon tumour and colon non-adenomatous polyp formed floating organoids in suspension; however non-adenomatous polyp cultures did not show self-renewal properties for more than 1 passage. Normal colon singlecell suspension did not create organoids. Metastatic colon tumours rapidly produce cancer cell organoids in less than 24 hours in larger numbers compared to non-metastatic colon tumours (1-3 weeks). Metastatic colon tumour organoids have the ability for proliferation for upto five daughter generations in primary culture compared to three generations for those grown from non-metastatic tumours. Conclusions: This in vitro CSC organoid model will help study colon cancer biology, in particular providing a valuable source of primary cell-derived tissue for studying personalized molecular profiling using ‘omics strategies to direct therapeutic intervention.

Idiopathic Retroperitoneal fibrosis is a rare clinical condition recently identified as an autoimmune process related to Immunoglobulin G4 (IgG4) deposition. Herein we report a case of a 46 year old male presenting with 4 months history of backache, fever, flank pain and leg swelling for 2 weeks. Investigations revealed acute kidney injury diagnosed as a result of bilateral ureteric obstruction. This was later confirmed to be retroperitoneal fibrosis on CT scan and biopsy. Histopathology was consistent with IgG4 related disease. Treatment with immunosuppressive agents showed reduction in the fibrosis and normalization of the kidney functions. We discuss the IgG4 related retroperitoneal fibrosis in detail along with its varied presentations.