Publications by authors named "Rani Kanthan"

68 Publications

Recovery of borderline oxacillin-resistant (BORSP) from bone and soft tissue of a rheumatoid arthritis patient with severe osteoporosis: transmission from the family dog.

J Chemother 2021 Feb 1:1-6. Epub 2021 Feb 1.

University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

We report a case of borderline oxacillin-resistant (BORSP) in a rheumatoid arthritis patient with severe osteoporosis. The organism is also resistant to erythromycin and clindamycin. We also present clear evidence on transmission from the family dog.
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http://dx.doi.org/10.1080/1120009X.2021.1879581DOI Listing
February 2021

Mixed epithelial endocrine neoplasms of the colon and rectum - An evolution over time: A systematic review.

World J Gastroenterol 2020 Sep;26(34):5181-5206

Division of General Surgery, University of Saskatchewan, Saskatoon S7N 0W8, SK, Canada.

Background: Mixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.

Aim: To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases.

Methods: A comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms ["mixed tumors colon" OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis.

Results: In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified proposal for a new, simple, clinically relevant, non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms (MEENs).

Conclusion: MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high, intermediate or low grade malignant potential. This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.
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http://dx.doi.org/10.3748/wjg.v26.i34.5181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495040PMC
September 2020

Bacteremia with in a 4 month old pediatric oncology patient.

J Chemother 2020 Sep 15;32(5):260-262. Epub 2020 Jun 15.

University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

colonizes and is a pathogen of dogs and is being increasingly recognized from specimens from humans with various infections. We describe a case of bacteremia in a 4 month old pediatric oncology patient with clear evidence of transmission from the family pet.
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http://dx.doi.org/10.1080/1120009X.2020.1773627DOI Listing
September 2020

Multiple colonic and ileal perforations due to unsuspected intestinal amoebiasis-Case report and review.

Pathol Res Pract 2020 Jan 19;216(1):152608. Epub 2019 Aug 19.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0W8, Canada.

Amoebiasis, caused by the intestinal protozoan Entamoeba histolytica, though a relatively common parasitic disease in the tropical and subtropical regions, is uncommon in the developed countries. In these countries, as amoebic colitis shares similar clinical symptoms and endoscopic features with inflammatory bowel disease (IBD), these cases can be easily unrecognized and misdiagnosed. In this case report, we discuss the case of an adult patient with invasive intestinal amoebiasis, who was initially managed as Crohn's disease on corticosteroid treatment and subsequently rapidly deteriorated and developed multiple perforations in the colon and ileum. Despite total colectomy followed by resection of the small bowel, he died of multiple organ failure and sepsis within two months of his initial clinical presentation of diarrhea with abdominal pain. The learning point of this case is that invasive intestinal amoebiasis should be considered as a differential diagnosis at the first clinical adult presentation of IBD-like symptoms despite suggestive endoscopic findings of Crohn's like ulcers. Regardless of negative endoscopic biopsies, due to the low sensitivity of microscopic examination, serology test for antibody and molecular test for Entamoeba DNA are recommended for accurate detection and identification of Entamoeba species, especially in the high risk populations with recent travel to endemic zones and for patients with immunosuppression and comorbidities such as diabetes mellitus, tuberculosis, alcoholism, HIV/AIDS and in pregnant women. Amoebiasis should be completely ruled out prior to corticosteroid administration, to avoid severe complications such as fulminant intestinal amoebiasis which is associated with an inherently high mortality.
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http://dx.doi.org/10.1016/j.prp.2019.152608DOI Listing
January 2020

Forensic, investigative and diagnostic microbiology: similar technologies but different priorities.

Future Microbiol 2019 05 31;14:553-558. Epub 2019 May 31.

University of Saskatchewan, Saskatoon, SK, S7N 0W8, Canada.

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http://dx.doi.org/10.2217/fmb-2019-0088DOI Listing
May 2019

Extrapelvic Metastases in Endometrial Stromal Sarcomas: A Clinicopathological Review With Immunohistochemical and Molecular Characterization.

Int J Surg Pathol 2019 Apr 20;27(2):208-215. Epub 2018 Aug 20.

1 University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Endometrial stromal sarcoma is a rare uterine tumor associated with favorable outcomes despite its ability to recur and metastasize to distant sites. Most recurrences are local, being limited to the abdomen/pelvis, but distant metastases can occur. Metastatic endometrial stromal sarcoma can occur many months to years after the original diagnosis or may present prior to the primary, potentially creating a diagnostic challenge. We report a bi-institutional review of 10 cases of endometrial stromal sarcoma with extrapelvic metastases without a prior history of endometriosis. The histologic, immunophenotypic, and molecular characteristics of these tumors are analyzed in the context of a relevant literature review.
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http://dx.doi.org/10.1177/1066896918794278DOI Listing
April 2019

Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer.

J Pathol Clin Res 2018 10 23;4(4):241-249. Epub 2018 Aug 23.

Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.

Breast cancer can occur in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT-qPCR in matched MBC and FBC samples as well as in tumour-associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan-Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender-specific STC2 gene expression showed a 5.6-fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease-free survival (DFS; Log-rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log-rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.
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http://dx.doi.org/10.1002/cjp2.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174618PMC
October 2018

Hepatic endometrial stromal sarcoma.

Pathol Res Pract 2018 Oct 17;214(10):1726-1731. Epub 2018 May 17.

Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Canada. Electronic address:

Endometrial stromal sarcomas are rare tumors that may recur or metastasize many years after their initial presentation. Though most recurrences are within the pelvis, distant metastases can occur, and are most common to the lungs. Metastases to the liver are extremely rare. Herein we report two cases of endometrial stromal sarcoma with metastases to the liver without a prior history of endometriosis, accompanied by their histology, immunohistochemistry, and molecular analysis in the context of a relevant literature review.
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http://dx.doi.org/10.1016/j.prp.2018.05.008DOI Listing
October 2018

Invasive lobular carcinoma of the male breast - a systematic review with an illustrative case study.

Breast Cancer (Dove Med Press) 2017 17;9:337-345. Epub 2017 May 17.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Data 1973-2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options.
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http://dx.doi.org/10.2147/BCTT.S126341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439541PMC
May 2017

Characterisation of male breast cancer: a descriptive biomarker study from a large patient series.

Sci Rep 2017 03 28;7:45293. Epub 2017 Mar 28.

Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, UK.

Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.
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http://dx.doi.org/10.1038/srep45293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368596PMC
March 2017

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer.

Clin Cancer Res 2017 May 16;23(10):2575-2583. Epub 2016 Dec 16.

Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.

Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data Biomarkers were immunohistochemically assessed in 697 MBCs ( = 477, training; = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor. Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank = 0.013; HR = 1.77, 1.12-2.8 and = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed ( = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E = 0.016; HR = 2.38 (1.18-4.8), eIF5 = 0.022; HR = 2.55 (1.14-5.7); coexpression = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival. Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-1952DOI Listing
May 2017

Primary pulmonary/pleural melanoma in a 13 year-old presenting as pleural effusion.

Pathol Res Pract 2017 Feb 16;213(2):161-164. Epub 2016 Nov 16.

Department of Pathology & Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, S7N 0W8, Canada. Electronic address:

Melanoma in children, adolescents, and young adults is uncommon and reported almost exclusively as cutaneous melanoma. Melanoma presenting as a pleural effusion is very rare in adults and not reported in the pediatric population. Additionally, primary pulmonary melanoma is overall very rare and undocumented in pediatric patients. Furthermore, the distinction between a primary pulmonary/pleural melanoma versus a regressed cutaneous melanoma with pulmonary/pleural metastases remains extremely challenging. We discuss a case of a previously healthy 13-year-old girl that presented with a left-sided pleural effusion. Investigations revealed a large mediastinal mass, left-sided pleural and pulmonary nodules, a sacral mass, and bone marrow infiltration. The neoplasm was subsequently diagnosed by morphology and immunocytochemistry with histological correlation as malignant melanoma. As no mucosal, eye, or cutaneous lesions were identified, we deliberate the likelihood of a regressed cutaneous melanoma with metastases versus primary pulmonary/pleural melanoma with pleural effusion and discuss its diagnostic approach.
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http://dx.doi.org/10.1016/j.prp.2016.11.013DOI Listing
February 2017

Gastric biomarkers: a global review.

World J Surg Oncol 2016 Aug 11;14(1):212. Epub 2016 Aug 11.

Department of General Surgery, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK, S7N 0W8, Canada.

Background: Gastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes.

Main Body: This is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability.

Conclusion: A deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.
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http://dx.doi.org/10.1186/s12957-016-0969-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982433PMC
August 2016

Cytomegalovirus Colitis: An Uncommon Mimicker of Common Colitides.

Arch Pathol Lab Med 2016 Aug;140(8):854-8

From the Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

Cytomegalovirus latency, though ubiquitous in the human population, is known to cause colitis in both immunocompromised and immunocompetent hosts. Furthermore, the clinical, endoscopic, and histologic appearance of cytomegalovirus colitis can mimic that of inflammatory bowel disease, an extremely well-documented disease. In this context, though many reports have looked at inflammatory bowel disease with superimposed cytomegalovirus infection, less attention has been paid to cytomegalovirus as a primary cause of isolated colitis. Owing to the rarity of this phenomenon, it is important to consider this diagnosis and implement proper testing to avoid misdiagnosis and mismanagement.
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http://dx.doi.org/10.5858/arpa.2015-0176-RSDOI Listing
August 2016

Targeting synthetic lethality between the SRC kinase and the EPHB6 receptor may benefit cancer treatment.

Oncotarget 2016 Aug;7(31):50027-50042

Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, S7N 0W8, Canada.

Application of tumor genome sequencing has identified numerous loss-of-function alterations in cancer cells. While these alterations are difficult to target using direct interventions, they may be attacked with the help of the synthetic lethality (SL) approach. In this approach, inhibition of one gene causes lethality only when another gene is also completely or partially inactivated. The EPHB6 receptor tyrosine kinase has been shown to have anti-malignant properties and to be downregulated in multiple cancers, which makes it a very attractive target for SL applications. In our work, we used a genome-wide SL screen combined with expression and interaction network analyses, and identified the SRC kinase as a SL partner of EPHB6 in triple-negative breast cancer (TNBC) cells. Our experiments also reveal that this SL interaction can be targeted by small molecule SRC inhibitors, SU6656 and KX2-391, and can be used to improve elimination of human TNBC tumors in a xenograft model. Our observations are of potential practical importance, since TNBC is an aggressive heterogeneous malignancy with a very high rate of patient mortality due to the lack of targeted therapies, and our work indicates that FDA-approved SRC inhibitors may potentially be used in a personalized manner for treating patients with EPHB6-deficient TNBC. Our findings are also of a general interest, as EPHB6 is downregulated in multiple malignancies and our data serve as a proof of principle that EPHB6 deficiency may be targeted by small molecule inhibitors in the SL approach.
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http://dx.doi.org/10.18632/oncotarget.10569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226566PMC
August 2016

Paget's disease of the male breast in the 21st century: A systematic review.

Breast 2016 Oct 6;29:14-23. Epub 2016 Jul 6.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan S7N 0W8, Canada. Electronic address:

Paget's disease of the breast is characterized by eczematous changes of the nipple-areolar complex and is associated with an underlying in situ or invasive breast carcinoma in most cases. Histologically, Paget's disease is identified by epithelial cells with abundant basophilic or amphophilic, finely granular cytoplasm with a large, centrally situated nucleus, most abundant in the lower epidermal layers. Due to the rarity of the condition among breast cancers, compounded by the rarity of breast cancer in men, understanding of the disease's presentation, course, and optimal treatment in men is largely derived from case reports and extrapolation of findings from studies in female patients. Paget's disease must be differentiated from other conditions including eczema, Bowen's disease, squamous cell carcinoma, and melanoma. Recognition of Paget's disease clinically and pathologically is critical as the superficial lesion may be the only sign of an underlying ductal carcinoma and its presence may be of prognostic significance. This article provides an update on cases of Paget's disease of the breast in men reported in the published literature together with a comprehensive analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Data, 1973-2012. Current understanding and management of the disease in the context of male patients is reviewed. However, additional research is required to further understand the overall pathogenesis and molecular profile of Paget's disease to provide improved insight for personalized, precision-based therapeutic options.
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http://dx.doi.org/10.1016/j.breast.2016.06.015DOI Listing
October 2016

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)--An uncommon precursor of a common cancer?

Pathol Res Pract 2016 Feb 11;212(2):125-9. Epub 2015 Dec 11.

Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Canada. Electronic address:

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, likely under recognized entity. We report on six cases of DIPNECH that were seen in Saskatoon, SK. The cases largely have the characteristics of the typical patient profile thus far described in the literature, consistent with the limited information reported to date. Furthermore, one case had co-existing squamous cell carcinoma, which has not been previously described, and one case had concomitant adenocarcinoma. In this context, we explore the hypothesis of whether DIPNECH could play a role as an uncommon precursor in pulmonary tumorigenesis. We also propose improved diagnostic criteria for DIPNECH, which are currently ill-defined.
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http://dx.doi.org/10.1016/j.prp.2015.12.006DOI Listing
February 2016

Autoimmune-Like Hepatitis: A "Hepatitic" Manifestation of Chronic Graft Versus Host Disease in Post-Stem Cell Transplant.

Int J Surg Pathol 2016 Apr 12;24(2):146-52. Epub 2015 Oct 12.

University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

A 59-year-old female received a matched related donor stem cell transplant for chronic myelogenous leukemia. After being successfully treated with prednisone for chronic graft versus host disease that initially started 50 days posttransplant, she developed hepatic dysfunction during the steroid taper on day 531, as evidenced by jaundice, elevated liver enzymes, and increased bilirubin. Liver biopsy showed histology suggestive of autoimmune-like hepatitis, which is a rare manifestation of chronic "hepatitic" graft versus host disease.
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http://dx.doi.org/10.1177/1066896915610817DOI Listing
April 2016

Gallbladder Cancer in the 21st Century.

J Oncol 2015 1;2015:967472. Epub 2015 Sep 1.

Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada S7N 0W8.

Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC.
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http://dx.doi.org/10.1155/2015/967472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569807PMC
September 2015

Factors Associated With the Prevalence of Prostate Cancer in Rural Saskatchewan: The Saskatchewan Rural Health Study.

J Rural Health 2016 12;32(2):125-35. Epub 2015 Aug 12.

Canadian Centre for Health and Safety in Agriculture, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Purpose: Prostate cancer is the most commonly diagnosed cancer in Canadian males, and it is the third most common cause of cancer-related deaths in men. Some studies suggest that occupational exposure may be associated with prostate cancer. However, the etiology of prostate cancer is ambiguous. The purpose of this study was to assess the rural occupational exposure, including farming, as a determinant of prostate cancer in rural men. We investigated the prevalence of prostate cancer and its putative relationship between rural exposures in the Saskatchewan province of Canada.

Methods: In 2010, a baseline mailed survey was conducted of 11,982 households located in 4 geographic regions (southwest, southeast, northwest, and northeast) of rural Saskatchewan, Canada. The questionnaires collected information on individual and contextual determinants from a rural population of men. In total 2,938 males older than 45 years were included in the logistic regression analysis.

Findings: The age-standardized prevalence of prostate cancer was 3.32%. Farm residence was a significant risk factor associated with prevalence of prostate cancer while farming occupation and duration were not. Men who were exposed to insecticides and fungicides together (OR [95% CI] = 2.23 [1.15-4.33], P = .02) at work showed an increased potential risk compared to the nonexposed. The effect of farm/nonfarm residence on prevalence of prostate cancer differed depending on personal smoking history and family history of cancer.

Conclusion: Workplace exposure to insecticides and fungicides together were statistically significantly associated with prevalence of prostate cancer.
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http://dx.doi.org/10.1111/jrh.12137DOI Listing
March 2017

Diagnostic and prognostic features in adrenocortical carcinoma: a single institution case series and review of the literature.

World J Surg Oncol 2015 Mar 24;13:117. Epub 2015 Mar 24.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, Canada.

Background: Adrenocortical carcinoma is a rare cancer, with an incidence in the literature of 0.5 to 2 cases per million population per year. Adult adrenocortical carcinoma has a poor prognosis, underscoring the importance of identifying diagnostic and prognostic markers.

Methods: We searched our laboratory database for all cases in the past 15 years with a diagnosis of adrenocortical carcinoma. The original slides were then reviewed for their histopathological features. A representative paraffin block was subjected to further immunohistochemical staining for Ki-67, inhibin, steroidogenic factor-1 (SF-1), p53, and Β-catenin. These slides were scored by the study pathologist who was blinded to all clinicopathological data. In addition, a comprehensive review of the relevant English literature in the past 15 years was conducted.

Results: Eight cases were identified, including two adrenal sarcomatoid carcinomas. Seven of the eight cases had a disrupted reticulin network. Six of the eight tumors had >10% Ki-67 expression. Five of the eight tumors had >10% p53 expression. Positive inhibin immunohistochemical staining was seen in three of the eight tumors, and positive SF-1 staining was seen in five of the seven stained tumors. Abnormal Β-catenin intracellular accumulation was noted in four of the eight tumors. The two tumors in our series with sarcomatoid histology did not stain positively for SF-1 or inhibin.

Conclusions: Eight cases of adrenocortical carcinoma, including two with sarcomatoid features are presented. The two sarcomatoid adrenocortical carcinomas in our series did not stain for SF-1 which suggests a possible de novo pathway of tumorigenesis for this rare variant. The reticulin staining method was a useful tool for rapid differentiation of adrenocortical adenomas and carcinomas. Diffuse p53 staining showed a trend for positive correlation with increased Ki-67 expression. Inhibin staining was inconsistently expressed in our cases of adrenocortical carcinoma. In conclusion, as adrenocortical carcinoma is a rare disease, we recommend future multicenter studies with appropriate sample sizes to further evaluate the efficacy of these diagnostic and prognostic markers.
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http://dx.doi.org/10.1186/s12957-015-0527-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384320PMC
March 2015

Fibrolipomatous hamartoma of the median nerve: A cause of acute bilateral carpal tunnel syndrome in a three-year-old child: A case report and comprehensive literature review.

Plast Surg (Oakv) 2014 ;22(3):201-6

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, Saskatchewan;

A three-year-old boy was investigated for inexplicable incessant crying. On examination, his left wrist was mildly swollen (three to four months) and sensitive. Exploration and carpal tunnel decompression of the left wrist with incisional biopsy was performed for the presence of a fusiform swelling intimately associated with the median nerve. Histopathology revealed the presence of enlarged nerve bundles admixed with mature fat cells and diffuse fibroblastic proliferation. Three months later, he underwent urgent contralateral carpal tunnel decompression for a similar presentation. The final diagnosis was bilateral fibrolipomatous hamartoma (FLH) of the median nerves causing acute bilateral compression neuropathy. FLH of the median nerve is an extremely unusual cause of acute bilateral carpal tunnel syndrome in a young child presenting with 'incessant crying'. A comprehensive review of FLH including epidemiology, etiology, clinical presentation, differential diagnosis, imaging, pathology, treatment and prognosis is discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173870PMC
October 2014

Is routine pathological evaluation of tissue from gynecomastia necessary? A 15-year retrospective pathological and literature review.

Plast Surg (Oakv) 2014 ;22(2):112-6

Department of Pathology & Laboratory Medicine, Royal University Hospital, Saskatoon, Saskatchewan.

Objective: To reconsider the routine plastic surgical practice of requesting histopathological evaluation of tissue from gynecomastia.

Method: The present study was a retrospective histopathological review (15-year period [1996 to 2012]) involving gynecomastia tissue samples received at the pathology laboratory in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System (LIS) identified all specimens using the key search words "gynecomastia", "gynaecomastia", "gynecomazia" and "gynaecomazia". A literature review to identify all cases of incidentally discovered malignancies in gynecomastia tissue specimens over a 15-year period (1996 to present) was undertaken.

Results: The 15-year LIS search detected a total of 452 patients that included two cases of pseudogynecomastia (0.4%). Patients' age ranged from five to 92 years and 43% of the cases were bilateral (28% left sided, 29% right sided). The weight of the specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant histopathological concerns. The number of tissue blocks sampled ranged from one to 42, averaging four blocks/case (approximately $105/case), resulting in a cost of approximately $3,200/year, with a 15-year expenditure of approximately $48,000. The literature review identified a total of 15 incidental findings: ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and infiltrating ductal carcinoma (one case).

Conclusions: In the context of evidence-based literature, and because no significant pathological findings were detected in this particular cohort of 452 cases with 2178 slides, the authors believe it is time to re-evaluate whether routine histopathological examination of tissue from gynecomastia remains necessary. The current climate of health care budget fiscal restraints warrants reassessment of the current policies and practices of sending tissue samples of gynecomastia incurring negative productivity costs on routine histopathological examination.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116310PMC
August 2014

Acute cauda equina syndrome secondary to lumbar chordoma: case report and literature review.

Spine J 2013 Nov 8;13(11):e35-43. Epub 2013 Sep 8.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Royal University Hospital, 103, Hospital Drive, Saskatoon, S7N 0W8, Canada.

Background Context: Chordomas are rare tumors in the craniospinal axis arising from persistent notochordal rests commonly seen in the skull base, including the clivus and the sacrum. Chordomas in the mobile spine occur less commonly. To the best of our knowledge, the clinical presentation of acute cauda equina syndrome (CES) due to chordoma of the lumbar vertebra is not published in the English literature.

Purpose: To describe an unusual cause of acute CES resulting from chordoma of the lumbar vertebra and discuss management dilemmas in this clinical context.

Study Design: Case report with review and discussion.

Methods: We report the case of a 75-year-old man who presented with acute CES that was clinically considered a metastasis from his previously documented carcinoma of the urinary bladder treated a year ago. Clinical, radiological, and histopathological features of the case and a review of chordomas in the lumbar vertebrae in adults in the published English literature are presented.

Results: He underwent urgent surgical decompression with laminectomy of L3/L4 and L4/L5 with debulking and open biopsy of the tissue mass. Histopathological examination of the tissue mass confirmed the unsuspected diagnosis of chordoma. The salient features of chordomas in the lumbar vertebrae published in the English literature over the last 22 years are summarized. The origin, classification, clinical presentation, and management protocols for lumbar chordomas are also reviewed.

Conclusions: The clinical presentation of acute CES as the first symptom of chordoma in the lumbar vertebrae is extremely rare. Preoperative tissue diagnosis of this uncommon pathology is usually unavailable. In the face of acute CES, surgical decompression remains the primary goal of management with a planned definitive second-stage curative surgical resection for chordoma.
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http://dx.doi.org/10.1016/j.spinee.2013.06.058DOI Listing
November 2013

Expression of Toll-like receptor 9 in mouse and human lungs.

J Anat 2013 May 22;222(5):495-503. Epub 2013 Mar 22.

Department Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

Toll-like receptors (TLR) recognize conserved molecular motifs of microorganisms, and constitute an important part of the innate immune system. Numerous studies have shown the importance of these receptors, including TLR9, in establishing effective immune responses to a broad range of infections, and in disorders such as COPD. TLR9 detects unmethylated DNA and is expressed in a wide range of immune cells in mice and humans, as well as other species. Most TLR9 expression studies have been done on cultured or isolated cells, but none that we know of on intact lung. Because cell-specific expression of TLR9 is important to understand its precise role in lung physiology, we tested mouse and human lung tissues for expression of TLR9 mRNA and protein with in situ hybridization and immunohistochemistry, respectively. We found TLR9 mRNA and protein expression in bronchial epithelium, vascular endothelium, alveolar septal cells and alveolar macrophages in both species. Immuno-electron microscopy delineated TLR9 expression in plasma membrane, cytoplasm and the nucleus of various lung cells. Lungs from human cases of COPD had significantly increased numbers of TLR9-positive cells. These are the first data showing TLR9 mRNA and protein expression in intact human and mouse lungs. The data may be useful for clarifying the role of TLR9 in the contributions of specific cells to lung physiology.
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http://dx.doi.org/10.1111/joa.12039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633339PMC
May 2013

Incidental thyroid papillary carcinoma in a thyroglossal duct cyst - management dilemmas.

Int J Surg Case Rep 2013 11;4(1):58-61. Epub 2012 Oct 11.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Canada. Electronic address:

Introduction: Benign thyroglossal duct tract remnants typically thyroglossal duct cysts, (TDCs) are one of the commonest congenital childhood midline neck masses. Clinical presentation of persistent TDCs in adults is uncommon and the occurrence of incidental primary thyroid papillary carcinoma (TPC) in these cysts is rare.

Presentation Of Case: We report the case of a 32-year-old female with an asymptomatic midline neck mass compatible with a TDC that was excised by Sistrunk's procedure. Histopathological examination revealed an incidental primary intraluminal TPC arising from the wall of the TDC.

Discussion: Management dilemmas regarding the roles for total thyroidectomy, regional lymph node dissection, radioactive iodine, and suppressive thyroxine therapy are reviewed in the context of relevant evidence based literature.

Conclusion: The occurrence of incidental TPC in a TDC is rare. Though Sistrunk's procedure is adequate treatment for TDC, based on low, moderate, and high risk stratification, recommendations for further management of incidental TPC in TDC is discussed.
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http://dx.doi.org/10.1016/j.ijscr.2012.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537957PMC
January 2013

The multifaceted granulosa cell tumours-myths and realities: a review.

ISRN Obstet Gynecol 2012 13;2012:878635. Epub 2012 Sep 13.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N-0W8 ; Department of Pathology and Laboratory Medicine, Royal University Hospital, 103 Hospital Drive, Room 2868, G-Wing, Saskatoon, SK, Canada S7N-0W8.

Background. Granulosa cell tumors (GCTs), representing ~2% of ovarian tumours, are poorly understood neoplasms with unpredictable and undetermined biological behaviour. Design. 5 unusual presentations of GCT and a retrospective 14-year (1997-2011) surgical pathology review based on patient sex, age, tumour type and concurrent pathology findings are presented to discuss the "myths and realities" of GCTs in the context of relevant evidence-based literature. Results. The 5 index cases included (1) a 5 month-old boy with a left testicular mass, (2) a 7-day-old neonate with a large complex cystic mass in the abdomen, (3) a 76-year-old woman with an umbilical mass, (4) a 64-year-old woman with a complex solid-cystic pelvic mass, and (5) a 45 year-old woman with an acute abdomen. Pathological analysis confirmed the final diagnosis as (1) juvenile GCT, (2) macrofollicular GCT, (3) recurrent GCT 32 years later, (4) collision tumour: colonic adenocarcinoma and GCT, and (5) ruptured GCT. Conclusion. GCT is best considered as an unusual indolent neoplasm of low malignant potential with late recurrences that can arise in the ovaries and testicles in both the young and the old. Multifaceted clinical presentations coupled with the unpredictable biological behaviour with late relapses are diagnostic pitfalls necessitating a high degree of suspicion for accurate clinical and pathological diagnosis.
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http://dx.doi.org/10.5402/2012/878635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3449135PMC
September 2012

Molecular events in primary and metastatic colorectal carcinoma: a review.

Patholog Res Int 2012 9;2012:597497. Epub 2012 May 9.

Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 0W8 ; Royal University Hospital, Room 2868 G-Wing, 103 Hospital Drive, Saskatoon, SK, Canada S7N 0W8.

Colorectal cancer (CRC) is a heterogeneous disease, developing through a multipathway sequence of events guided by clonal selections. Pathways included in the development of CRC may be broadly categorized into (a) genomic instability, including chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP), (b) genomic mutations including suppression of tumour suppressor genes and activation of tumour oncogenes, (c) microRNA, and (d) epigenetic changes. As cancer becomes more advanced, invasion and metastases are facilitated through the epithelial-mesenchymal transition (EMT), with additional genetic alterations. Despite ongoing identification of genetic and epigenetic markers and the understanding of alternative pathways involved in the development and progression of this disease, CRC remains the second highest cause of malignancy-related mortality in Canada. The molecular events that underlie the tumorigenesis of primary and metastatic colorectal carcinoma are detailed in this manuscript.
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http://dx.doi.org/10.1155/2012/597497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357597PMC
September 2012

Fecal molecular markers for colorectal cancer screening.

Gastroenterol Res Pract 2012 17;2012:184343. Epub 2011 Nov 17.

Department of Pathology and Laboratory Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada S7N 0W8.

Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.
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http://dx.doi.org/10.1155/2012/184343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226355PMC
September 2012

Three uncommon adrenal incidentalomas: a 13-year surgical pathology review.

World J Surg Oncol 2012 Apr 27;10:64. Epub 2012 Apr 27.

Department of Pathology and Laboratory Medicine, Saskatoon, Saskatchewan, Canada.

Background: The discovery of adrenal incidentalomas due to the widespread use of sophisticated abdominal imaging techniques has resulted in an increasing trend of adrenal gland specimens being received in the pathology laboratory. In this context, we encountered three uncommon adrenal incidentalomas.The aim of this manuscript is to report in detail the three index cases of adrenal incidentalomas in the context of a 13-year retrospective surgical pathology review.

Methods: The three index cases were investigated and analyzed in detail with relevant review of the English literature as available in PubMed and Medline. A 13-year retrospective computer-based histopathological surgical review was conducted in our laboratory and the results were analyzed in the context of evidence-based literature on adrenal incidentalomas.

Results: A total of 94 adrenal specimens from incidentalomas were identified, accounting for 0.025% of all surgical pathology cases. In all 76.6% were benign and 23.4% were malignant. A total of 53 females (56.4%) and 41 males (43.6%) aged 4 to 85 years were identified. The benign lesions included cortical adenoma (43.1%), pheochromocytoma (29.3%) and inflammation/fibrosis/hemorrhage (8.3%). Metastatic neoplasms were the most common malignant lesions (50%) followed by primary adrenocortical carcinomas (31.8%) and neuroblastoma (13.6%). These cases were discovered as adrenal incidentalomas that led to surgical exploration.The three index cases of adrenal incidentalomas with unusual pathologies were encountered that included (a) adrenal ganglioneuroma, (b) periadrenal schwannoma and (c) primary adrenal pleomorphic leiomyosarcoma. These cases are discussed, with a literature and clinicopathological review.

Conclusions: Adrenal lesions are uncommon surgical specimens in the pathology laboratory. However, higher detection rates of adrenal incidentalomas aided by the ease of laparoscopic adrenalectomy has resulted in increased adrenal surgical specimens leading to unsuspected diagnostic and management dilemmas. Accurate pathological identification of common and uncommon adrenal incidentalomas is essential for optimal patient management.
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http://dx.doi.org/10.1186/1477-7819-10-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407001PMC
April 2012