Publications by authors named "Bibianna Purgina"

45 Publications

Vertebral Ischemic Necrosis in Diabetic Lumbosacral Radiculoplexus Neuropathy.

Diabetes Care 2021 Mar 21;44(3):e53-e54. Epub 2021 Jan 21.

Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.2337/dc20-2787DOI Listing
March 2021

Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting.

Head Neck Pathol 2021 Jan 7. Epub 2021 Jan 7.

Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA.

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.
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http://dx.doi.org/10.1007/s12105-020-01262-9DOI Listing
January 2021

Subperiosteal chondromyxoid fibroma: a rare case involving the humeral diaphysis.

Skeletal Radiol 2021 Mar 15;50(3):597-602. Epub 2020 Aug 15.

Department of Radiology, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.

Initially described, in 1948, as a tumor that could be mistaken with chondrosarcoma at histopathology, chondromyxoid fibroma is now a well-recognized entity. Surface-type chondromyxoid fibroma, however, remains an extremely rare occurrence. We present a case of a 55-year-old woman, who experienced right arm pain for 5 years. After unsuccessful treatment for presumed thoracic outlet syndrome, MRI revealed a large mass abutting the anteromedial cortex of the distal humeral diaphysis in a subperiosteal location. Further characterization was made with radiography, CT, and bone scan, which were followed by ultrasound-guided biopsy. Although histopathologic features were suggestive of chondromyxoid fibroma, the diagnosis remained somewhat uncertain initially due to the very unusual location involving the diaphysis of the humerus. Surgical resection was performed, and subsequent histopathologic analysis confirmed the diagnosis of chondromyxoid fibroma. Despite being a rare entity, surface-type chondromyxoid fibroma would need to be considered in the differential when dealing with expansile surface diaphyseal lesions.
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http://dx.doi.org/10.1007/s00256-020-03581-yDOI Listing
March 2021

Putting the patient at the centre of pathology: an innovative approach to patient education-MyPathologyReport.ca.

J Clin Pathol 2020 Aug 27;73(8):454-455. Epub 2020 Feb 27.

Pathology and Laboratory Medicine, Ottawa Hospital, Ottawa, Ontario, Canada

In many centres, patients now have access to their electronic medical record (EMR) and laboratory results, including pathology reports, are amongst the most frequently accessed pieces of information. The pathology report is an important but highly technical medical document that can be difficult for patient and clinicians alike to interpret. To improve communication and patient safety, pathologists are being called upon to play a more direct role in patient care. Novel approaches have been undertaken by pathologists to address this need, including the addition of patient-friendly summaries at the beginning of pathology reports and the development of patient education tools. MyPathologyReport.ca is a novel website exclusively providing pathology education to patients. It has been designed to help patients understand the language of pathology and to effectively navigate their pathology report. At present, the website includes over 150 diagnostic articles and over 125 pathology dictionary definitions. The diagnostic articles span all body sites and include a variety of malignant, benign and non-neoplastic conditions. Since its creation, this website has been visited over 14 000 times, with cancer-related diagnoses and definitions representing the most commonly accessed articles. This website has been embedded in patient accessible EMRs and shared through partnerships with patients, caregivers and their respective advocacy groups. Our next steps involve longitudinal assessment of MyPathologyReport.ca from non-medical community members, evaluation of patient satisfaction and understanding and further collaboration with hospitals and care-providers to increase patient access to this resource.
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http://dx.doi.org/10.1136/jclinpath-2019-206370DOI Listing
August 2020

An evidence-based guideline on the application of molecular testing in the diagnosis, prediction of prognosis, and selection of therapy in non-GIST soft tissue sarcomas.

Cancer Treat Rev 2020 Apr 14;85:101987. Epub 2020 Feb 14.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address:

Aims: To make recommendations on the indications for molecular testing regarding the diagnosis, prediction of prognosis, and treatment selection in adult patients with s oft tissue sarcomas (STS) excluding gastrointestinal stromal tumour.

Materials And Methods: This guideline was developed by the Cancer Care Ontario's Program in Evidence-Based Care (PEBC) and the Sarcoma Disease Site Group (DSG). The medline, embase, and Cochrane Library databases, main guideline websites, abstracts of relevant annual meetings, and PROSPERO databases were searched (January 2005 to October 2016). Internal and external reviews were conducted, with final approval by the PEBC and the Sarcoma DSG.

Results: Based on the available evidence, we made three S trong Recommendations, 14 Recommendations, 9 Qualified Statements, and seven No Recommendations. The three Strong Recommendations include: i) MDM2 amplification by fluorescence in situ hybridization (FISH) is recommended as a sensitive and specific test to differentiate patients with atypical lipomatous tumour/well-differentiated liposarcoma, or dedifferentiated liposarcoma from lipoma or other STS in the differential diagnosis; ii) SS18 (SYT) break-apart by FISH or SS18-SSX (SYT-SSX) fusion by reverse transcription-polymerase chain reaction is recommended as a sensitive and specific test to differentiate patients with synovial sarcoma from other sarcomas; iii) CTNNB1 S45F mutation by polymerase chain reaction is recommended as a prognostic factor for poor recurrence-free survival in patients with desmoid tumours.

Conclusion: This guideline may serve as a framework for the thoughtful implementation of molecular studies at cancer centres and other jurisdictions. Some of the recommendations may need to be updated when new evidence appears in the future.
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http://dx.doi.org/10.1016/j.ctrv.2020.101987DOI Listing
April 2020

Paraneoplastic manifestations of salivary gland tumours: A case report and review.

Oral Oncol 2020 04 13;103:104582. Epub 2020 Feb 13.

Division of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada. Electronic address:

Salivary gland cancers are an uncommon and heterogenous group of malignancies, accounting for approximately 3% of head and neck tumors. We describe a case of a patient who presented with paraneoplastic Cushing's syndrome secondary to metastatic salivary ductal carcinoma (SDC). Paraneoplastic ACTH secretion initially responded to chemotherapy with complete resolution of clinical symptoms. To our knowledge, this is the first described case of an ACTH-secreting SDC. We also review other paraneoplastic syndromes (PNS) that have been reported in association with salivary gland cancers.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104582DOI Listing
April 2020

Histologic Classification and Molecular Signature of Polymorphous Adenocarcinoma (PAC) and Cribriform Adenocarcinoma of Salivary Gland (CASG): An International Interobserver Study.

Am J Surg Pathol 2020 04;44(4):545-552

Department of Pathology, Memorial Sloan-Kettering Cancer Center.

Polymorphous adenocarcinoma (PAC) shows histologic diversity with streaming and targetoid features whereas cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominantly cribriform and solid patterns with glomeruloid structures and optically clear nuclei. Opinions diverge on whether CASG represents a separate entity or a variant of PAC. We aimed to assess the level of agreement among 25 expert Head and Neck pathologists in classifying these tumors. Digital slides of 48 cases were reviewed and classified as: PAC, CASG, tumors with ≥50% of papillary architecture (PAP), and tumors with indeterminate features (IND). The consensus diagnoses were correlated with a previously reported molecular alteration. The consensus diagnoses were PAC in 18/48, CASG in16/48, PAP in 3/48, and IND in 11/48. There was a fair interobserver agreement in classifying the tumors (κ=0.370). The full consensus was achieved in 3 (6%) cases, all of which were classified as PAC. A moderate agreement was reached for PAC (κ=0.504) and PAP (κ=0.561), and a fair agreement was reached for CASG (κ=0.390). IND had only slight diagnostic concordance (κ=0.091). PAC predominantly harbored PRKD1 hotspot mutation, whereas CASG was associated with fusion involving PRKD1, PRKD2, or PRKD3. However, such molecular events were not exclusive as 7% of PAC had fusion and 13% of CASG had mutation. In conclusion, a fair to moderate interobserver agreement can be achieved in classifying PAC and CASG. However, a subset (23%) showed indeterminate features and was difficult to place along the morphologic spectrum of PAC/CASG among expert pathologists. This may explain the controversy in classifying these tumors.
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http://dx.doi.org/10.1097/PAS.0000000000001431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437128PMC
April 2020

Early and Late Complications of Percutaneous Core Needle Biopsy of Retroperitoneal Tumors at Two Tertiary Sarcoma Centers.

Ann Surg Oncol 2019 Dec 1;26(13):4692-4698. Epub 2019 Aug 1.

Department of Surgery, University of Toronto, Toronto, ON, Canada.

Background: Concern persists regarding percutaneous core needle biopsy (CNB) of a potentially malignant lesion of the retroperitoneum due to the perceived risk of immediate complications and adverse oncologic outcomes, including needle tract seeding (NTS).

Objective: The aim of this study was to evaluate the incidence of (1) early complications and (2) NTS following CNB of suspected retroperitoneal sarcoma (RPS).

Methods: Patients who underwent CNB of an RP mass with pre-biopsy suspicion of sarcoma were identified from a prospective database at two centers: (1) Princess Margaret Cancer Centre/Mount Sinai Hospital, Toronto (2009-2015); and (2) The Ottawa Hospital (1999-2015). Early complications, including bleeding, pain, infection, and organ injury, were recorded. Instances of NTS were identified from long-term follow-up of patients who underwent resection of primary RPS at these two centers after initial CNB (1996-2013).

Results: Of 358 percutaneous CNBs of suspected RPS performed over the study period, 7 (2.0%) resulted in minor bleeding with no transfusion, 3 (0.8%) resulted in significant pain, 1 (0.3%) resulted in unplanned admission to hospital for observation, and 1 (0.3%) resulted in a pneumothorax. There were no infections. In 203 patients who underwent resection of RPS following CNB, crude cumulative local recurrence was 24% at 5 years. At a median follow-up of 44 months, there was one case of NTS (approximately 0.5%).

Conclusion: This large bi-institutional experience with CNB of an RP mass demonstrates that both the early complication rate and the incidence of NTS are very low. Physicians and patients can be reassured that the benefits of CNB in diagnosing sarcoma and determining its histologic subtype and grade far outweigh the risks.
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http://dx.doi.org/10.1245/s10434-019-07656-6DOI Listing
December 2019

PAX8-GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid.

Mod Pathol 2019 12 4;32(12):1734-1743. Epub 2019 Jul 4.

Department of Oncology, University of Turin, at Città della Salute Hospital, Torino, Italy.

The hyalinizing trabecular adenoma/tumor is a rare and poorly characterized follicular-derived thyroid neoplasm recently shown to harbor recurrent PAX8-GLIS1 or PAX8-GLIS3 gene fusions. Here we sought to define the repertoire of genetic alterations of hyalinizing trabecular tumors, and whether PAX8-GLIS3 fusions are pathognomonic for hyalinizing trabecular tumors. A discovery series of eight hyalinizing trabecular tumors was subjected to RNA-sequencing (n = 8), whole-exome sequencing (n = 3) or targeted massively parallel sequencing (n = 5). No recurrent somatic mutations or copy number alterations were identified in hyalinizing trabecular tumor, whereas RNA-sequencing revealed the presence of a recurrent genetic rearrangement involving PAX8 (2q14.1) and GLIS3 (9p24.2) genes in all cases. In this in-frame fusion gene, which comprised exons 1-2 of PAX8 and exons 3-11 of GLIS3, GLIS3 is likely placed under the regulation of PAX8. Reverse transcription RT-PCR and/or fluorescence in situ hybridization analyses of a validation series of 26 hyalinizing trabecular tumors revealed that the PAX8-GLIS3 gene fusion was present in all hyalinizing trabecular tumors (100%). No GLIS1 rearrangements were identified. Conversely, no PAX8-GLIS3 gene fusions were detected in a cohort of 237 control thyroid neoplasms, including 15 trabecular thyroid lesions highly resembling hyalinizing trabecular tumor from a morphological standpoint, as well as trabecular/solid follicular adenomas, solid/trabecular variants of papillary carcinoma, and Hurthle cell adenomas or carcinomas. Our data provide evidence to suggest that the PAX8-GLIS3 fusion is pathognomonic for hyalinizing trabecular tumors, and that the presence of the PAX8-GLIS3 fusion in thyroid neoplasms may be used as an ancillary marker for the diagnosis of hyalinizing trabecular tumor, thereby avoiding overtreatment in case of misdiagnoses with apparently similar malignant tumors.
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http://dx.doi.org/10.1038/s41379-019-0313-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442035PMC
December 2019

Early squamous cell carcinoma of the oral tongue with histologically benign lymph nodes: A model predicting local control and vetting of the eighth edition of the American Joint Committee on Cancer pathologic T stage.

Cancer 2019 09 7;125(18):3198-3207. Epub 2019 Jun 7.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0).

Methods: A multi-institutional cohort of patients with early OTSCC was restaged as per AJCC8. Primary endpoints were local recurrence (LR) and locoregional recurrence (LRR). Influential variables were identified and an LR/LRR prediction model was developed.

Results: There were a total of 494 patients, with 49 LR and 73 LRR. AJCC8 pT criteria resulted in upstaging of 37.9% of patients (187 of 494 patients), including 34.5% (64 of 185 patients) from pT2 to pT3, without improving the prognostication for LR or LRR. Both LR and LRR were found to be similar for patients with AJCC8 pT2 and pT3 disease. On multivariate analysis, LR was only found to be associated with distance to the closest margin (hazard ratio, 0.36; 95% CI, 0.20-0.64 [P = .0007]) and perineural invasion (hazard ratio, 1.92; 95% CI, 1.10-0.64 [P = .046]). Based on these 2 predictors, a final proportional hazards regression model (which may be used similar to a nomogram) was developed. The proposed model appeared to be superior to AJCC pT stage for estimating the probability of LR and LRR for individual patients with early OTSCC.

Conclusions: AJCC8 pT criteria resulted in pT upstaging of patients with pN0 disease without improved LR or LRR prognostication. The proposed model based on distance to the closest margin and perineural invasion, status outperformed pT as a predictor of LR and LRR in patients with early OTSCC.
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http://dx.doi.org/10.1002/cncr.32199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723468PMC
September 2019

Metastasizing Pleomorphic Adenoma: Recurrent PLAG1/HMGA2 Rearrangements and Identification of a Novel HMGA2-TMTC2 Fusion.

Am J Surg Pathol 2019 08;43(8):1145-1151

Department of Laboratory Medicine and Pathobiology, University of Toronto.

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm. On a molecular level PA is characterized by a translocation involving PLAG1 or HMGA2. PA is considered to be a benign tumor although it can undergo malignant transformation. Alternatively, cases of histologically benign PA "metastasizing" to lymph nodes or distant body sites are well documented. Several theories have been proposed to explain this behavior. However, there is a lack of molecular data available to assess the relationship of metastasizing PA (MPA) and their benign counterparts. In this study we describe 4 cases of MPAs and perform the first molecular study linking them to conventional PA. The index case was identified in the course of routine clinical practice, while the other cases were retrieved from the archives of the authors. Slides were reviewed to confirm the diagnosis of both the primary/recurrent tumor and the metastasis. Fluorescence in situ hybridization (FISH) was performed in all cases and RNA sequencing was performed on the index case. In all cases there was a history of recurrent PA involving the parotid. Lymph node metastases were identified in 2 cases; non-lymph node metastases were identified in 3 cases. All the metastases were histologically benign. RNA sequencing performed on the index case demonstrated a novel HMGA2-TMTC2 translocation, which was confirmed by separate FISH break-apart assays for both genes. FISH performed on the remaining cases demonstrated rearrangement of PLAG1 in all 3 cases. This study demonstrates that MPA harbors the same disease-defining molecular hallmark as their benign counterparts.
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http://dx.doi.org/10.1097/PAS.0000000000001280DOI Listing
August 2019

Vaginal Vault Traumatic Neuromas.

J Minim Invasive Gynecol 2019 Nov - Dec;26(7):1219-1220. Epub 2019 Apr 10.

Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (Drs. Sunderji and Singh); Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada (Drs. Buitenhuis and Singh). Electronic address:

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http://dx.doi.org/10.1016/j.jmig.2019.04.012DOI Listing
May 2020

Pannexin 1 inhibits rhabdomyosarcoma progression through a mechanism independent of its canonical channel function.

Oncogenesis 2018 Nov 21;7(11):89. Epub 2018 Nov 21.

Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.

Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma of childhood thought to arise from impaired differentiation of skeletal muscle progenitors. We have recently identified Pannexin 1 (PANX1) channels as a novel regulator of skeletal myogenesis. In the present study, we determined that PANX1 transcript and protein levels are down-regulated in embryonal (eRMS) and alveolar RMS (aRMS) patient-derived cell lines and primary tumor specimens as compared to differentiated skeletal muscle myoblasts and tissue, respectively. While not sufficient to overcome the inability of RMS to reach terminal differentiation, ectopic expression of PANX1 in eRMS (Rh18) and aRMS (Rh30) cells significantly decreased their proliferative and migratory potential. Furthermore, ectopic PANX1 abolished 3D spheroid formation in eRMS and aRMS cells and induced regression of established spheroids through induction of apoptosis. Notably, PANX1 expression also significantly reduced the growth of human eRMS and aRMS tumor xenografts in vivo. Interestingly, PANX1 does not form active channels when expressed in eRMS (Rh18) and aRMS (Rh30) cells and the addition of PANX1 channel inhibitors did not alter or reverse the PANX1-mediated reduction of cell proliferation and migration. Moreover, expression of channel-defective PANX1 mutants not only disrupted eRMS and aRMS 3D spheroids, but also inhibited in vivo RMS tumor growth. Altogether our findings suggest that PANX1 alleviates RMS malignant properties in vitro and in vivo through a process that is independent of its canonical channel function.
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http://dx.doi.org/10.1038/s41389-018-0100-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246549PMC
November 2018

Correction to: HPV DNA in saliva from patients with SCC of the head and neck is specific for p16-positive oropharyngeal tumours.

J Otolaryngol Head Neck Surg 2018 08 2;47(1):49. Epub 2018 Aug 2.

Department of Otolaryngology - Head and Neck Surgery, The University of Ottawa and The Ottawa Hospital, Ottawa Hospital-General Campus S3, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada.

Following publication of the original article [1], the authors reported an error in one of the author names. In this Correction the incorrect and correct author names are listed.
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http://dx.doi.org/10.1186/s40463-018-0294-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074035PMC
August 2018

Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions.

Am J Surg Pathol 2018 10;42(10):1297-1305

Department of Pathology, UT Southwestern Medical Center, Dallas, TX.

Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.
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http://dx.doi.org/10.1097/PAS.0000000000001096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133728PMC
October 2018

Molecular analyses in the diagnosis and prediction of prognosis in non-GIST soft tissue sarcomas: A systematic review and meta-analysis.

Cancer Treat Rev 2018 May 22;66:74-81. Epub 2018 Apr 22.

Division of Orthopedic Surgery, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada. Electronic address:

Background: The molecular pathogenesis of many forms of soft tissue sarcomas (STS) have been rigorously characterized in the medical literature, which may be particularly important for the diagnosis and prediction of prognosis in STS.

Methods: Electronic databases (2005 to October 2016) were searched. Gastrointestinal stromal tumor and pediatric sarcomas were excluded. The eligible individual study's risk of bias and the quality of aggregate evidence were assessed. Meta-analyses were performed.

Results: Of 6674 identified articles, 70 were eligible and analyzed, covering 13 types of STS. Meta-analyses showed that the test of detecting MDM2 amplification by fluorescence in situ hybridization was accurate in differentiating atypical lipomatous tumor/well-differentiated liposarcoma/dedifferentiated liposarcoma from benign tumors (N = 971; sensitivity = 95%, 95% confidence interval [CI] 89-98; specificity = 100%, CI 89-100) or from other STS (N = 347; sensitivity = 99%, CI 72-100; specificity = 90%, CI 78-95); that the test of detecting SS18-SSX fusion by reverse transcription polymerase chain reaction (PCR) was accurate in differentiating synovial sarcoma from other STS (N = 532; sensitivity = 93%, CI 85-96; specificity = 99%, CI 96-100). The presence of a CTNNB1 S45F mutation detected by PCR was a risk factor for decreased recurrence-free survival in desmoid tumors (N = 418; hazard ratio from 3.50 [CI 1.51-8.14] to 6.20 [CI 2.24-17.15]).

Conclusions: Sarcomas are rare cancers whose molecular pathogenesis is becoming increasingly understood. The current evidence demonstrates that molecular analyses are useful in the diagnosis and prediction of prognosis in some STS.
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http://dx.doi.org/10.1016/j.ctrv.2018.04.005DOI Listing
May 2018

Measuring Depth of Invasion in Early Squamous Cell Carcinoma of the Oral Tongue: Positive Deep Margin, Extratumoral Perineural Invasion, and Other Challenges.

Head Neck Pathol 2019 Jun 26;13(2):154-161. Epub 2018 Apr 26.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

The 8th edition of American Joint Committee on Cancer (AJCC 8th) staging manual incorporated depth of invasion (DOI) into pT stage of oral cavity cancer. The aim of this study was to characterize several histological findings that may complicate measurement of DOI in early conventional squamous cell carcinomas (SCC) of the oral tongue: (1) lack of or minimal residual carcinoma following biopsy; (2) positive deep margin; (3) extratumoral perineural invasion (PNI); and (4) lymphatic or vascular invasion. Conventional SCC of the oral tongue (n = 407) with the largest dimension of ≤ 4 cm and with a negative elective cervical lymph node dissection (pN0) were reviewed. A clear plastic ruler was used to measure DOI by dropping a "plumb line" to the deepest point of the invasive tumor from the level of the basement membrane of the normal mucosa closest to the invasive tumor. Examples of identifying  reference point on the mucosal surface of oral tongue from which to measure the DOI are illustrated. In the experience of one contributing institution, the residual carcinoma was absent in 14.2% of glossectomies (34/239), while in 4.8% of cases (10/205) there was only minimal residual carcinoma. In 11.5% (21/183) of pT2 cases the deep margin was positive and thus DOI and pT may be underestimated. Of all cases with PNI, extratumoral PNI was identified in 23.1% (31/134) of cases, but represented the deepest point of invasion in only two cases. In one case, lymphatic invasion represented the deepest point of invasion and could have led to upstaging from pT1 to pT2. In conclusion, DOI measurement for SCC of the oral tongue may require re-examination of the diagnostic biopsy in up to 20% of cases due to the absence or only minimal residual carcinoma in glossectomy specimens. In 11.5% of apparently pT2 cases, DOI may be underestimated due to the positive deep margin. Rarely, extratumoral PNI or lymphatic invasion may be the deepest point of invasion. Overall, two issues (absent or minimal residual disease and positive deep margin) may confound DOI measurement in early SCCs of oral tongue.
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http://dx.doi.org/10.1007/s12105-018-0925-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514023PMC
June 2019

Human papillomavirus: An unlikely etiologic factor in sinonasal inverted papilloma.

Laryngoscope 2018 11 18;128(11):2443-2447. Epub 2018 Apr 18.

Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Objectives/hypothesis: Tenuous evidence has supported the hypothesis that sinonasal inverted papilloma (SNIP) arise from human papillomavirus (HPV) infection. To clarify the role of HPV in SNIP, all known HPV sub-types were evaluated by employing a robust polymerase chain reaction-based method in a wide variety of SNIPs from a single institution.

Study Design: Retrospective surgical specimen tumor sample analysis.

Methods: HPV positivity among SNIP samples and those with squamous cell carcinoma (SCC) were compared. Immunohistochemistry was used to quantify p16 (over)expression among tumors as a surrogate marker for HPV.

Results: HPV was detected in 10/76 (13%) SNIP specimens. Identified HPV subtypes included nononcogenic 6 and 11 (6/76, 8%) and oncogenic 16, 18, 45, 56 (4/76, 5%). There was no HPV positivity among SCC samples. Only 4/10 (40%) HPV + samples had > 75% p16 cell staining.

Conclusion: HPV is not supported as an etiological driver of SNIP development or progression to SCC. The p16 biomarker is not a sensitive indicator of HPV positivity in SNIP.

Level Of Evidence: NA Laryngoscope, 2443-2447, 2018.
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http://dx.doi.org/10.1002/lary.27207DOI Listing
November 2018

Effect of Implementing Community of Practice Modified Thyroid Imaging Reporting and Data System on Reporting Adherence and Number of Thyroid Biopsies.

Acad Radiol 2018 07 3;25(7):915-924. Epub 2018 Feb 3.

University of Ottawa-Medicine, 451 Smyth Rd, Ottawa, ON K1H 8M50; The Ottawa Hospital, 1053 Carling Ave. Ottawa ONK1R 4E9.

Rationale And Objectives: Thyroid nodules are common in the population, although the rate of malignancy is relatively low (5%-15%). The purpose of this study was to determine if introducing a modified standardized reporting format and management algorithm (Thyroid Imaging Reporting and Data System [TI-RADS]) affects radiologist reporting adherence, number of thyroid biopsies, and other measurable outcomes.

Materials And Methods: All thyroid biopsies performed over two 6-month periods were evaluated at a tertiary care hospital with Research Ethics Board approval. The first period was before implementation of TI-RADS and the second was several months after implementation of TI-RADS (using a modified version made through a multidisciplinary collaboration). The number of biopsies performed was determined in each of the two periods as well as the percent of positive malignancy, wait times, and rates of non-diagnostic/unsatisfactory and inconclusive biopsies, which included atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS).

Results: The average number of biopsies performed prior to implementing modified Kwak's TI-RADS was 74 thyroid biopsies per month and the average number of diagnostic ultrasounds was 271. After the introduction of modified Kwak's TI-RADS, the average number of thyroid biopsies decreased to 60 per month (an 18.9% reduction, P < .05), and the number of diagnostic ultrasound increased to 287 per month (a 5.9% increase from 2016 to 2017). The average wait time for a thyroid biopsy decreased from 5 to 3 weeks (P < .05). There was a slight increase in the rate of positive malignancy results (from 15% to 18%), although it was not statistically significant. The rate of non-diagnostic/unsatisfactory and inconclusive results (including AUS and FLUS) remained unchanged (18% AUS/FLUS/15% non-diagnostic/unsatisfactory before and 17% AUS/FLUS/15% non-diagnostic/unsatisfactory after TI-RADS introduction, P > .05).

Conclusions: Introduction of a multidisciplinary-approved standardized reporting system with evidence-based management recommendations led to no statistically significant change in the number of diagnostic ultrasounds but a statistically significant reduction in the number of monthly thyroid biopsies and associated reduction in wait times.
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http://dx.doi.org/10.1016/j.acra.2017.12.009DOI Listing
July 2018

Improving margin revision: Characterization of tumor bed margins in early oral tongue cancer.

Oral Oncol 2017 12 1;75:184-188. Epub 2017 Nov 1.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address:

Objectives: To improve margin revision, this study characterizes the number, fragmentation, and orientation of tumor bed margins (TBM) in patients with pT1-2 pN0 squamous cell carcinoma (SCC) of the oral tongue.

Materials And Methods: Pathology reports (n=346) were reviewed. TBM parameters were indexed. In Group 1 patients all margins were obtained from the glossectomy specimen and there were no TBM. In Revision Group/Group 2 (n=103), tumor bed was sampled to revise suboptimal margins identified by examination of the glossectomy specimen. In Group 3 (n=124), TBM were obtained before examination of the glossectomy specimen.

Results And Conclusions: Fewer TBMs were obtained per patient in Group 2 compared to Group 3 (57/103, 55% of patients with <3 vs. 117/124, 94%, ≥3 TBMs, respectively). The new margin surface was more frequently indicated in Group 2 compared to Group 3 (59/103, 57%, vs. 19/124, 15%, p<.001). If glossectomy specimen margins are accepted as the reference standard, then the TBM was 15% sensitive in Group 2 (95% confidence interval [CI], 7-29) and 32% sensitive in Group 3 (95% CI, 15-55). TBM fragmentation (23/103, 22% vs. 42/124, 34%) and frozen vs. permanent discrepancies (8/103, 3% vs. 3/124, 2%) were similar between Groups 2 and 3. The new margin surface was not indicated in 6 of 11 cases with discrepant frozen vs. permanent pathology findings, precluding judgment on final margin status. To facilitate the assessment of final margins, TBM should be represented by one tissue fragment with a marked new margin surface.
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http://dx.doi.org/10.1016/j.oraloncology.2017.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774620PMC
December 2017

Chordoma of the Head and Neck: A Review.

Head Neck Pathol 2018 Jun 4;12(2):261-268. Epub 2017 Oct 4.

Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, ON, K1H 8L6, Canada.

Chordoma is a rare malignant bone tumor that can arise anywhere along the central neural axis and many involve head and neck sites, most commonly the skull base. The relative rarity of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, pathologic, and molecular features of chordomas and describes how these features can be used to aid in formulating a differential diagnosis. Emphasis is placed on key diagnostic pitfalls and the importance of incorporating immunohistochemical information into the diagnosis.
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http://dx.doi.org/10.1007/s12105-017-0860-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953882PMC
June 2018

p16 immunohistochemistry in oropharyngeal squamous cell carcinoma: a comparison of antibody clones using patient outcomes and high-risk human papillomavirus RNA status.

Mod Pathol 2017 09 16;30(9):1194-1203. Epub 2017 Jun 16.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.

High-risk human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas have a more favorable prognosis than HPV-negative ones. p16 immunohistochemistry has been recommended as a prognostic test in clinical practice. Several p16 antibodies are available, and their performance has not been directly compared. We evaluated three commercially available p16 antibody clones (E6H4, JC8 and G175-405) utilizing 199 cases of oropharyngeal squamous cell carcinoma from a tissue microarray, read by three pathologists with three different cutoffs for positivity: any staining, >50% and >75%. Positive predictive values for high-risk HPV status by RNA in situ hybridization for the E6H4, JC8 and G175-405 clones were 98%, 100% and 99% at the 75% cutoff, but negative predictive values were much more variable at 86%, 69% and 56%, respectively. These improved using the 50% cutoff, becoming similar for all three antibodies. Intensity varied substantially, with 85% of E6H4, 72% of JC8 and 67% of G175-405 showing strong (3+) intensity. With Kaplan-Meier survival plots at the 75% cutoff, the E6H4 clone showed the largest differential in disease specific and overall survival between p16-positive and -negative results. Decreasing the cutoff to 50% increased correlation with HPV in situ hybridization and improved the survival differential for the JC8 and G175-405 clones without worsening of performance for the E6H4 clone. Interobserver agreement was also assessed by kappa scores and was highest for the E6H4 clone. Overall, these study results show modest but important performance differences between the three different p16 antibody clones, suggesting that the E6H4 clone performs best because of strongest staining intensity, greatest differential in outcomes between positive and negative results, lowest interobserver variability, and lowest background, nonspecific staining. The results also suggest that a 75% cutoff is very functional but that, in this patient population with high HPV incidence, 50% and any staining cutoffs may be more effective, particularly for the non-E6H4 clones.
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http://dx.doi.org/10.1038/modpathol.2017.31DOI Listing
September 2017

Primary Burkitt lymphoma of the supraglottic larynx: a case report and review of the literature.

J Med Case Rep 2017 Mar 10;11(1):65. Epub 2017 Mar 10.

Department of Otolaryngology - Head and Neck Surgery, University of Ottawa, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada.

Background: Burkitt lymphoma is a high-grade B cell lymphoma which accounts for less than 1% of all adult cases of non-Hodgkin lymphoma. Rare instances of Burkitt lymphoma developing secondary to prior irradiation have been described in the literature.

Case Presentation: We report a case of a 90-year-old white woman with a recent history of irradiation for Hodgkin lymphoma, who presented with primary Burkitt lymphoma of the supraglottic larynx. She underwent emergency awake tracheostomy with biopsy. A histopathological examination confirmed non-Hodgkin, B cell lymphoma of Burkitt type. Given her age and poor functional status, she underwent treatment with palliative radiotherapy.

Conclusions: A literature review was performed to clarify the clinical characteristics of radiation-induced Burkitt lymphoma in the head and neck, as well as its diagnosis and management. The present case represents the second case of radiation-induced Burkitt lymphoma in the head and neck in the reported literature, and the first in the supraglottic larynx. It highlights the need to maintain a broad differential in the assessment of malignancies of the larynx, particularly in patients with a prior history of radiation treatment.
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http://dx.doi.org/10.1186/s13256-017-1209-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345263PMC
March 2017

Distinctive Head and Neck Bone and Soft Tissue Neoplasms.

Surg Pathol Clin 2017 Mar;10(1):223-279

Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, 501 Smyth Road, 4th Floor CCW, Room 4114, Ottawa, Ontario K1H 8L6, Canada.

Benign and malignant primary bone and soft tissue lesions of the head and neck are rare. The uncommon nature of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, radiographic, and pathologic features of selected bone and soft tissue tumors involving the head and neck region, including angiofibroma, glomangiopericytoma, rhabdomyosarcoma, biphenotypic sinonasal sarcoma, chordoma, chondrosarcoma, and osteosarcoma. Emphasis is placed on key diagnostic pitfalls, differential diagnosis, and the importance of correlating clinical and radiographic information, particularly for tumors involving bone.
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http://dx.doi.org/10.1016/j.path.2016.11.003DOI Listing
March 2017

HPV DNA in saliva from patients with SCC of the head and neck is specific for p16-positive oropharyngeal tumours.

J Otolaryngol Head Neck Surg 2017 01 6;46(1). Epub 2017 Jan 6.

Department of Otolaryngology - Head and Neck Surgery, The University of Ottawa and The Ottawa Hospital, Ottawa Hospital-General Campus S3, 501 Smyth Rd, Ottawa, Ontario, K1H 8L6, Canada.

Background: Human papillomavirus (HPV) is an important cause of head and neck squamous cell carcinoma (HNSCC), especially in young people. These tumours overexpress p16 and respond well to treatment. The rapid detection of HPV in patients with HNSCC may expedite treatment when p16 status is not immediately available.

Methods: Saliva-based DNA collection kits and nested polymerase chain reaction (PCR) were used to determine the HPV status of 62 individuals with biopsy-proven HNSCC. Immunohistochemistry was used to determine tumour p16 status.

Results: A total of 62 patients were included in the study. Twenty-nine samples (47%) were positive for HPV DNA, the majority of which were high risk (HR) subtypes (79%). Patients who tested positive for HR HPV were more likely to have a tumour arising in the oropharynx compared to a non-oropharyngeal site (74 vs 26%; p = 0.003). A positive HR HPV saliva assay was 100% specific (95% CI 59-100%) and had a 100% positive predictive value (95% CI 75-100%) for a p16 positive tumour arising in the oropharynx. In contrast, a negative HR HPV assay had a 96% negative predictive value (95% CI 80-100%) for tumours arising in a non-oropharyngeal site. Independent of site, the saliva assay had a sensitivity of 77% (95% CI 54-91%) and a specificity of 94% (95% CI 77-99%), respectively, for a p16 positive tumour.

Conclusion: We show that a saliva based assay is an effective method for detecting HPV in patients with HNSCC and that a positive HR HPV test is highly specific for p16 positive tumours arising in the oropharynx. This simple and rapid test could be used in cases where a biopsy of the primary tumour is not readily available.
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http://dx.doi.org/10.1186/s40463-016-0179-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217573PMC
January 2017

Phosphaturic Mesenchymal Tumor Involving the Head and Neck: A Report of Five Cases with FGFR1 Fluorescence In Situ Hybridization Analysis.

Head Neck Pathol 2016 Sep 12;10(3):279-85. Epub 2016 Jan 12.

Department of Pathology, Presbyterian University Hospital, University of Pittsburgh Medical Center, PUH A610.3, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm; however, it is the most common cause of tumor-induced osteomalacia (TIO), a paraneoplastic syndrome characterized by renal phosphate wasting and hypophosphatemia. A subset of PMTs harbours an FGFR1 translocation although this alteration has not been demonstrated in PMT involving a head and neck site. We present a series of five PMTs involving the head and neck and demonstrate the diagnostic utility of fluorescence in situ hybridization (FISH) for detecting FGFR1 translocations. Patients' age and sex, tumor location, original diagnosis, the duration of symptoms, the presence of TIO, biochemical results, and medical management were reviewed. The median age at presentation was 45 (range, 24-58 years) and TIO was present in three cases. Four tumors involved soft tissue and one involved bone. Four out of the five tumors in our series were initially misdiagnosed. Three tumors were ultimately categorized as malignant PMT (two patients developed metastatic disease). FGFR1 translocation was present in two out of four cases and remained unknown in one case. In summary, we report on five cases of PMTs arising in the head and neck and confirm utility of FGFR1 FISH in the diagnosis of a subset of PMT.
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http://dx.doi.org/10.1007/s12105-015-0678-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972751PMC
September 2016

The Gross Appearance of a NUT Midline Carcinoma.

Int J Surg Pathol 2016 Feb 16;24(1):85-8. Epub 2015 Sep 16.

The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada

The NUT midline carcinoma (NMC) is a recently described and highly aggressive tumor that usually involves the head and neck and anterior mediastinum. Most patients with NMC present with metastases and are often treated with neoadjuvant chemotherapy and/or radiation therapy. As a consequence, surgical specimens are often piecemeal excisions demonstrating treatment effect. In this report, we provide what is to the best of our knowledge the first complete gross description of NMC resected in toto and without prior treatment. The patient in this case underwent a pneumonectomy for a lung mass with curative intent. On gross examination, the tumor was found to be arising from the mediastinum with a smooth border, and demonstrated only minimal invasion of the surrounding structures. However, lymphovascular invasion was present throughout and there was extensive involvement of surrounding lymph nodes. The gross appearance of the tumor in this case reaffirms that NMC is an aggressive malignancy that usually metastasizes before it invades locally.
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http://dx.doi.org/10.1177/1066896915606970DOI Listing
February 2016

Primary cutaneous adenoid cystic carcinoma with brain metastases: case report and literature review.

J Cutan Pathol 2016 Feb 11;43(2):137-41. Epub 2015 Sep 11.

Division of Anatomical Pathology, The Ottawa Hospital, Ottawa, Canada.

Primary cutaneous adenoid cystic carcinoma (ACC) is a rare skin tumor that is unlikely to metastasize. We present a case of primary cutaneous ACC in a 67-year-old male with axillary lymph node, pulmonary and brain metastases. To the best of our knowledge, this is the first reported case of cutaneous ACC with distant metastases to the brain.
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http://dx.doi.org/10.1111/cup.12563DOI Listing
February 2016

Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control.

JAMA Otolaryngol Head Neck Surg 2015 Dec;141(12):1104-10

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Importance: Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique.

Objective: To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC.

Design, Setting, And Participants: A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015.

Interventions: In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR.

Main Outcomes And Measures: Local recurrence.

Results: Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin.

Conclusions And Relevance: The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.
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http://dx.doi.org/10.1001/jamaoto.2015.1351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242089PMC
December 2015

The Prognostic Significance of c-MET and EGFR Overexpression in Resected Gastric Adenocarcinomas.

Am J Clin Oncol 2017 Dec;40(6):543-551

Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital, University of Ottawa.

Objectives: Epidermal growth factor receptor (EGFR) and c-MET are tyrosine kinase growth factor receptors implicated in gastric cancer (GC), and their pathways appear to be interdependent. The aim of this study was to investigate the prognostic value of EGFR and c-MET protein overexpression by immunohistochemistry in Canadian patients with resected GC and correlate it with clinicopathologic characteristics and overall survival (OS).

Materials And Methods: Tissue microarray blocks were constructed from 120 resected GCs stained with EGFR and c-MET and scored semiquantitatively (0 to 3+). Each receptor's expression was compared with clinicopathologic characteristics and survival. Descriptive statistics, Kaplan-Meyer, and Cox regression were used for statistical analyses.

Results: Of the 113 interpretable cases, overexpression of EGFR and c-MET was noted in 17 (15%) and 65 (57%), respectively; coexpression of EGFR and c-MET was observed in 12 (10%) of GC. EGFR and c-MET overexpression correlated with poor OS: median 13 versus 30 months in EGFR positive versus negative GC (hazard ratio [HR]=1.67, P=0.11); 27 versus 49 months in c-MET positive versus negative GC (HR=1.17, P=0.49), respectively. GC coexpressing EGFR and c-MET was significantly correlated with poor survival: 12 versus 29 months in double-positive versus rest of tumors both in univariate (HR=2.62, P=0.003) and multivariate analyses (HR=2.58, P=0.01).

Conclusions: This study describes the prevalence and prognostic value of EGFR and c-MET in a Canadian population of patients undergoing curative intent resection for GC. Both c-MET and EGFR overexpression trended toward poor OS, but only the group with EGFR+/c-MET+ GC reached statistical significance on multivariate analysis.
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http://dx.doi.org/10.1097/COC.0000000000000202DOI Listing
December 2017