Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022.

The 24th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Richmond, British Columbia, on 28-29 October 2022. The WCGCCC is an interactive multidisciplinary conference attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals such as dieticians, nurses and a genetic counsellor participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Colorectal Carcinoma: A Potential Area of Focus for Future Diagnostics.

Objective In this study, we aimed to explore the potential diagnostic utility of human epidermal growth factor receptor 2 (HER2) expression in colorectal carcinoma. We investigated the association of HER2 expression with the type and grade of the tumor along with the pattern, staining intensity, and the percentage of cells stained. Methods This was an observational study involving 50 cases of colorectal carcinoma that underwent immunohistochemistry to analyze the HER2 expression. Results The positive expression of HER2 was seen in 16 (32%) cases. The majority of the study population was between the fifth-seventh decades of life. The most commonly diagnosed tumor was conventional adenocarcinoma with grade II, cytoplasmic pattern, +2 positivity, and moderate intensity. The maximum positivity for HER2 was seen in tumors of the rectum in eight (16%) cases. Conclusion A substantial rate of HER2 overexpression paves the way for it to become a potential future target in cancer therapeutics.

Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in Endemic Area.

BACKGROUND: Typhoid fever remains a significant health problem in endemic countries like India. Various serological tests for the diagnosis of typhoid fever are available commercially. We assessed the usefulness of rapid test based on magnetic particle separation to detect Immunoglobulin against Salmonella typhi O9 lipopolysaccharide. AIM: Aim of this study was to compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of typhoid fever in an endemic country like India. MATERIALS AND METHODS: Serum samples collected from 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals residing in Amritsar were subjected to widal test, typhidot test and tubex TF test as per manufacturer's instructions. Data collected was assessed to find sensitivity and specificity of these tests in an endemic area. RESULTS: Significant widal test results were found positive in 68% of patients of typhoid fever and only 4% of non typhoid fever patients. Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid fever and normal healthy individuals respectively. Tubex TF showed higher sensitivity of 76% and specificity of 96-99% which was higher than typhidot and comparable to widal test. CONCLUSION: This was the first evaluation of rapid tubex TF test in northern India. In countries which can afford high cost of test, tubex TF should be recommended for the diagnosis in acute stage of the disease in clinical setting. However, there is urgent need for a highly specific and sensitive test for the diagnosis of typhoid fever in clinical settings in endemic areas.

Uranium-Toxicity and Uranium-Induced Osteosarcoma Using A New Regimen and Surgery : A First-Time Experience.

Uranium isotopes have always been problematic to mankind since many centuries. Different studies all over the world have been unable to reveal causal relationship between uranium and its toxic effects on kidneys, bone and lungs. In this case report, we present a rare association of uranium toxicity with renal dysfunction and possibility of induction of osteosarcoma by an unknown mechanism. The presentation of the 12-year-old patient was reduction in urine output along with joint pains, seemed like that of diabetes mellitus, as he was already on insulin. The patient later diagnosed to have uranium toxicity. This case is an instance of strong association between medicine and public health. With complete history, physical examination and required investigations, all common causes like NSAID toxicity, aminoglycoside toxicity and exacerbation of diabetes were ruled out. Uranium investigations were done lastly based on the toxicology report of drinking water (South African toxicologist, Caron Smith). In the management strategy, the new regimen CBMIDA, supported by studies in Europe, was used. However, to our surprise, joint symptoms tracked their way to a diagnosis of osteosarcoma, which was later operated upon by our orthopaedic surgery team. Histopathologically, it was found to be a chondroblastic type of osteosarcoma.

Cytological diagnosis of follicular carcinoma thyroid metastasis in pelvic muscles-a rare and unusual site.

Distant metastasis of thyroid neoplasm as an initial presentation is rarely encountered. The present case report describes a chance diagnosis of follicular carcinoma thyroid (FCT) metastasis in a 75-year-old female who was presented with symptoms related to pelvic mass. This is a rare site of reporting as only three cases have been reported previously at the first diagnosis. It is important to identify the presence of distant metastasis as it is the most important prognostic indicator (associated with 50% mortality). This is significant as this has a direct bearing upon its treatment and managing the patient. Hence more awareness is required by both diagnosticians and clinicians regarding this.

Subcutaneous dermatofibroma: a rare case report with review of literature.

A purely Sub-cutaneous benign fibrous histiocytoma (BFH; dermatofibroma) is rarely reported, as it is usually a dermally located mesenchymal tumour and in absence of supportive immunohistochemical (IHC) studies, it is often misdiagnosed. We are describing a case of a 19-year-old female who presented to the skin outpatient department with a painful swelling on the medial side of her thigh. Fine needle aspiration (FNA) revealed a sub-cutaneous spindle cell (mesenchymal) lesion which was corroborated on histopathology, with differentials of BFH and dermatofibrosarcoma protruberans (DFSP). BFH constitutes a diagnostic dilemma for both clinicians and pathologists, because the lesions share common clinical symptoms, radiological characteristics and histological features with many varied entities. For its subtyping and confirmation; immunohistochemical (IHC) studies were undertaken. In the present case, positivity of IHC markers, vimentin and smooth muscle actin emphatically proved that BFH arose exclusively from the subcutaneous region, with no dermal origin. Also, a negative CD34 immunostaining, along with low B-cell lymphoma 2 (Bcl-2) expression ruled out DFSP (both are strongly expressed in DFSP), MFH and other malignant mesenchymal lesions. Negative CD 68 staining ruled out giant cell lesions and their congeners. This case is worth reporting, as it not only describes a rare case presentation of BFH, but as it also highlights the importance of IHC, thus helping to comprehensively clinch the diagnosis by systematically ruling out other differentials.

Prominent Intracytoplasmic Crystals in Alveolar Soft Part Sarcoma (ASPS): An Aid in Cytological Diagnosis.

Alveolar soft part sarcoma (ASPS) is a rare neoplasm of unknown histogenesis with poor prognosis. Due to the epithelioid appearance of the neoplastic cells, ASPS may resemble many neoplastic conditions, such as metastatic epithelial cell tumours with clear cell change, metastatic renal cell carcinoma, granular cell tumour, epithelioid sarcoma, malignant melanoma and even paragangliomas. Presence of abundant, rod like crystals in the cytoplasm of tumour cells is an important finding characteristic of this tumour, which helps in differentiating it from the other entities. The case study highlights the importance of correlating cytological features that help in reaching the diagnosis such as the background, cell morphology and presence of characteristic rod shaped crystals as immunohistochemical studies are often non-conclusive. The case also is unique as it demonstrates presence of intra-cytoplamic crystals in such abundance.

Immunohistochemical (IHC) Analysis of Non-Hodgkin's Lymphoma (NHL) Spectrum According to WHO/REAL Classification: A Single Centre Experience from Punjab, India.

INTRODUCTION: The distribution of the major subtypes of non-Hodgkin's lymphoma (NHL) differs across geographic regions. This study, from the north Indian state of Punjab, has incorporated immunophenotypic findings while investigating the distribution of NHL subtypes based on World Health Organization (WHO)/ Revised European-American Classification of Lymphoid Neoplasms (REAL) system of classification. PATIENTS AND METHODS: Over all seventy seven cases of lymphoma over a period of one year (between April 2012 and April 2013) were diagnosed in the Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar (Punjab). Of these 30 cases (39%) were of Hodgkin's Lymphoma (HL) and 47 cases (61%) were of Non Hodgkins lymphoma NHL. Of the total of cases of lympho-proliferative disorders, the diagnosis of NHL was done by light microscopy alone. All the cases diagnosed provisionally as NHL were taken up for immunophenotyping with Immunohistochemical (IHC) studies. There was 100 % concordance between the light microscopy and IHC studies. The individual NHL cases were classified according to the WHO/REAL classification according to the positive or relevant negative immonophenotypic expression and tabulated to ascertain the morphological spectrum of NHL in this part of the country. RESULTS: B-cell lymphomas formed 89.3%, whereas T-cell lymphomas formed 10.7% of the NHLs. Diffuse Large B-Cell Lymphoma (DLBCL) was the most common subtype (46.8% of all NHLs). B-cell small lymphocytic lymphoma, Mantle-Cell Lymphoma (MCL), marginal zone B-cell lymphomas (including MALT lymphomas), Diffuse, mixed small cleaved cell and large-cell type and Follicular centre-cell lymphomas amounted to 17%, 12.8%, 2.1%, 2.1% and 4.3%, respectively. Among the T-cell lymphomas, T-cell lymphoblastic lymphoma, anaplastic large-cell lymphomas of T/null-cell type, and Angioimmunoblastic T-cell lymphoma (AITL) accounted for 6.4%, 2.1%, and 2.1% of all NHL cases, respectively. CONCLUSIONS: The distribution of NHL subtypes in India shows disparity with those from the rest of the world. Follicular Lymphoma (FL) and MCL are less common in India compared to Europe and the USA. Peripheral T-cell lymphomas and T/NK-cell lymphomas of nasal and nasal types, which are common in many other Asian countries, are also less prevalent. T-cell lymphoblastic lymphoma and anaplastic large T/null cell lymphoma are more prevalent in India.

Pleomorphic adenoma of external auditory canal.

Pleomorphic adenoma comprises about 80% of the benign salivary gland tumours and is characterised by a slow growth and a clinically benign course. This tumour is known to occur at various other anatomical locations apart from the major salivary glands. Case reports of this tumour arising from the nasal septum, tongue, turbinate, upper lip, lungs, trachea and lacrimal glands have been found in the literature. But case reports of pleomorphic adenoma from the external auditory canal have been extremely few.

The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation.

Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advanced-stage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy and radiation. Tissue microarrays were constructed using diagnostic biopsies available in 105 patients and stained with CD4, CD8, CD25, and forkhead/winged helix transcription factor 3 (FOXP3) antibodies. Both cell content and cell distribution were evaluated. For all antibodies, there were cases with a predominant intrafollicular or perifollicular localization of cells (follicular pattern) while others displayed a diffuse pattern. The median follow-up of living patients was 17.1 years. The International Prognostic Index score predicted overall survival (OS; P = .004) but not risk of transformation (RT). Cell content did not impact survival, while immunoarchitectural patterns of CD4/CD8 were significant for progression-free survival (PFS; P = .056), CD25 for both PFS and OS (P = .002 and P = .024, respectively), and FOXP3(+) predicted PFS, OS, and RT (P = .001, P < .001 and p = .002, respectively). A Cox multivariate model showed both International Prognostic Index score and FOXP3(+) pattern were independent predictors of OS (P = .008 and P < .001, respectively), while only FOXP3(+) pattern predicted RT (P = .004). We conclude that FOXP3(+) cell distribution significantly predicts survival and RT in FL.

Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma.

PURPOSE: To assess the incidence and predictive factors for development of transformed lymphoma in a population-based series of patients with follicular lymphoma (FL). PATIENTS AND METHODS: The Lymphoid Cancer Database was used to identify patients with FL diagnosed and treated in the province of British Columbia, Canada. Transformed lymphoma was defined as the development of aggressive non-Hodgkin's lymphoma (NHL) in patients with FL. Factors present at the time of initial diagnosis of indolent NHL and at transformation were analyzed for their impact on risk of transformation and subsequent outcome. RESULTS: Between 1986 and 2001, 600 patients with newly diagnosed FL met the inclusion criteria. With a median follow-up of 109 months (range, 10 to 244), 170 (28%) developed transformation, 107 (63%) based on biopsy confirmation. The annual risk of transformation was 3% continuously through 15 years. A multivariate analysis of clinical factors at diagnosis identified advanced stage as the only predictor of future transformation. The median post-transformation survival was 1.7 years. The 5-year survival was superior for patients with limited extent transformation compared with those with advanced cases (66% v 19%, P < .0001). Patients with transformation based on clinical versus histological criteria had an identical median survival of 1.8 years (P = .2). CONCLUSION: The annual risk of transformation of FL is 3% continuing without plateau beyond 15 years. Advanced stage at diagnosis is predictive of future transformation. Clinically diagnosed transformation has an equal impact on outcome as biopsy proven transformation.

Alemtuzumab in clinical practice: a British Columbia experience.

Limited information is available on alemtuzumab in the nonclinical trial setting. We evaluated its efficacy and safety in 42 consecutive unselected patients who received alemtuzumab monotherapy in British Columbia between October 2002 and August 2006. Information on patient demographics, baseline clinical characteristics, dose and schedule, clinical response, survival, and toxicities associated with alemtuzumab was collected retrospectively. Thirty-nine of 42 patients had chronic lymphocytic leukemia, two had mycosis fungoides, and one had T-cell post-transplant lymphoproliferative disorder. In contrast to previous reports, 42% were treated by community practitioners and 83% received alemtuzumab subcutaneously. The median time from diagnosis to alemtuzumab was 58 months. One of 42 patients (2%) achieved a complete response, 20 (48%) achieved a partial response, and 13 (31%) had stable disease. The post-alemtuzumab median overall survival was 15.1 months. Response to alemtuzumab correlated with an increased progression-free survival (11 vs. 3.6 months, p = 0.001) compared to that seen in non-responders. Significant adverse events included grade 3/4 neutropenia (76%), thrombocytopenia (45%), infections (60%) and death (12%). With careful monitoring, alemtuzumab can be safely administered in a wide variety of clinical settings, including community practice, and is associated with a high level of activity in situations with few available alternative treatment options.

CHOP-R therapy overcomes the adverse prognostic influence of BCL-2 expression in diffuse large B-cell lymphoma.

BCL-2 protein expression correlates with shorter survival in patients with diffuse large B cell lymphoma (DLBCL) who are treated with CHOP chemotherapy. We report a retrospective analysis of the prognostic significance of BCL-2 status in patients who received CHOP with the addition of rituximab (CHOP-R) for DLBCL. Patients over 15 years of age with de novo, HIV negative DLBCL, without CNS involvement, and known BCL-2 protein status were identified from the BCCA Lymphoid Cancer Database. BCL-2 tumour positivity was defined as over 50% of tumour cells with BCL-2 protein expression. 140 patients who received CHOP-R were analysed. The majority (59%) of patients were over 60 years of age. Disease stage distribution was limited (22%) and advanced (78%). BCL-2 protein expression was observed in 90 (64%) cases. IPI score was similar in both BCL-2 positive and negative cases. Median follow-up time for living patients is 40 months. BCL-2 status did not predict for either progression-free or overall survival. IPI score was predictive for progression-free survival but not overall survival. The addition of rituximab to CHOP chemotherapy negates the adverse prognostic influence of BCL-2 protein expression on progression free and overall survival in DLBCL.

Rapid infusion rituximab in combination with corticosteroid-containing chemotherapy or as maintenance therapy is well tolerated and can safely be delivered in the community setting.

The increasing usage of rituximab in the management of non-Hodgkin lymphoma (NHL) has created huge logistical challenges with respect to the delivery of this time- and labor-intensive drug. To address these challenges, we developed and tested the feasibility of a 90-minute infusion schedule for rituximab (20% of the dose administered in the first 30 minutes, remaining 80% administered over 60 minutes). A safety analysis performed in 150 patients receiving rituximab with corticosteroid-containing chemotherapy and 56 patients receiving rituximab as maintenance therapy demonstrated that this schedule was well tolerated, with no grade 3 or 4 infusion reactions observed. In addition, no increase in minor reactions was noted. More than 1200 patients have been treated with this rapid rituximab infusion schedule in the province of British Columbia (BC), demonstrating its safety in the community setting. The adoption of this 90-minute schedule as standard practice has had a positive impact on resource utilization.

The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, with patients exhibiting a wide range of outcomes. The addition of rituximab to CHOP chemotherapy (R-CHOP)has led to a marked improvement in survival and has called into question the significance of previously recognized prognostic markers. Since randomized controlled trials of R-CHOP in DLBCL have included select subgroups of patients, the utility of the International Prognostic Index (IPI) has not been reassessed. We performed a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of the IPI in the era of immunochemotherapy. The IPI remains predictive, but it identifies only 2 risk groups. Redistribution of the IPI factors into a revised IPI (R-IPI) provides a more clinically useful prediction of outcome. The R-IPI identifies 3 distinct prognostic groups with a very good (4-year progression-free survival [PFS] 94%, overall survival [OS] 94%), good (4-year PFS 80%, OS 79%), and poor (4-year PFS 53%, OS 55%) outcome, respectively (P < .001). The IPI (or R-IPI) no longer identifies a risk group with less than a 50% chance of survival. In the era of R-CHOP treatment, the R-IPI is a clinically useful prognostic index that may help guide treatment planning and interpretation of clinical trials.