Bringing digital teaching materials into residency training programs has seen slow adoption, expe... more Bringing digital teaching materials into residency training programs has seen slow adoption, expected for many new technologies. The COVID-19 pandemic dramatically shifted the paradigm for many resident teaching modalities as institutions instituted social distancing to prevent spread of the novel coronavirus. The impact of this shift on pathology trainee education has not been well studied. We conducted an online survey of pathology trainees, program directors, and faculty to assess pre- and post-COVID-19 use of, and response to, various digital pathology modalities. Responses were solicited through both social media and directed appeals. A total of 261 respondents (112 faculty, 52 program directors, and 97 trainees) reported a dramatic and significant increase in the use of digital pathology-related education tools. A significant majority of faculty and program directors agreed that this shift had adversely affected the quality (59% and 62%, respectively) and effectiveness (66%) o...
The clinical outcomes of IDH-wild type (IDH-wt) lower-grade glioma (LGG) have been the subject of... more The clinical outcomes of IDH-wild type (IDH-wt) lower-grade glioma (LGG) have been the subject of debate for some time. In this meta-analysis, we aimed to assess the prognostic values of several known genetic markers (eg, TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. Four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival (OS) were calculated using random effect model weighted by inverse variance method. Eleven studies were finally selected from 2274 articles for meta-analyses. Several genetic alterations were demonstrated to have a negative impact on prognosis of IDH-wt LGGs, specifically TERT promoter mutation (HR = 1.96; 95% CI = 1.42 - 2.70), H3F3A mutation (HR = 3.21; 95% CI = 1.86 - 5.55) and EGFR amplification (HR = 1.67; 95% CI = 1.02 - 2.74). On the other hand, CDKN loss, ATRX muta...
The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma ... more The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15-1.67) and progression-free survival (PFS) (HR=1.31; 95% CI=1.06-1.63) in glioma patients. In studying its reaction with IDH, TERT promoter mutation was associated with reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH...
Distant metastasis (DM) is not a frequent event in differentiated thyroid carcinoma (DTC) but has... more Distant metastasis (DM) is not a frequent event in differentiated thyroid carcinoma (DTC) but has an adverse impact on mortality of patients with DTC. In the current study, we aimed to conduct a comprehensive systematic review and meta-analysis to investigate the risk factors for DM in DTCs and for each histological subtype. Five electronic databases were searched from inception to December 2016 for relevant articles. Pooled odd ratios and 95% confidence interval were calculated using random-effect model. Thirty-four articles with 73,219 patients were included for meta-analyses. In DTCs, male gender, age ≥45 years, tumor size ≥4 cm, multifocality, vascular invasion (VI), extrathyroidal extension (ETE), lymph node metastasis (LNM), and lateral LNM were demonstrated to be associated with significant risks for DM. In addition, several clinicopathological factors such as age ≥45 years, VI, ETE, and LNM were shown to be significant risk factors for DM in both PTC and FTC subgroups. Our s...
The use of molecular markers, especially BRAF and TERT promoter mutations, for risk stratificatio... more The use of molecular markers, especially BRAF and TERT promoter mutations, for risk stratification in papillary thyroid carcinoma (PTC) is subject to continuing debate. In this study, we aimed to investigate the clinicopathological implication of each genotype when combining BRAF and TERT promoter mutations in PTCs. We searched four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library for relevant studies. Pooled estimates of odds ratios and corresponding 95% confidence intervals were calculated using random-effect model. From 111 results, we finally included 11 studies with 3911 PTC patients for meta-analyses. Our results demonstrated that PTCs with concurrent BRAF and TERT promoter mutations were associated with increased tumour aggressiveness in comparison with PTCs harbouring BRAF or TERT promoter mutation alone. The combination of BRAF and TERT promoter mutations could classify PTCs into four distinct risk groups with decreasing aggressivenes...
Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of h... more Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (...
Liposclerosing myxofibrous tumor is a benign fibro-osseous lesion, with distinct radiographic and... more Liposclerosing myxofibrous tumor is a benign fibro-osseous lesion, with distinct radiographic and clinical features and diverse histologic patterns. This lesion occurs in the fourth decade of life, with equal male and female incidence. Most lesions are discovered incidentally, but patients can present with bone pain or fracture. Liposclerosing myxofibrous tumor exhibits a very strong predilection for the proximal femur with characteristic radiographic findings, often providing an initial clue to diagnosis. Microscopically, this tumor is characterized by a variety of patterns, including myxofibrous tissue, fibrous dysplasia-like features, and ischemic ossification. It can be mistaken for many other fibro-osseous lesions; therefore, this unique lesion should be included in the differential diagnosis of fibro-osseous lesions, particularly in this location. Patients with this lesion are generally successfully treated by curettage and bone graft and have a favorable prognosis. A small ri...
Archives of Pathology Laboratory Medicine, Aug 1, 2010
The site-specific cancer checklists developed by the College of American Pathologists have the po... more The site-specific cancer checklists developed by the College of American Pathologists have the potential to improve the quality of data derived from pathology reports and incorporated into cancer registry databases and are now mandated report elements by various accrediting bodies. A pilot project, funded by the Centers for Disease Control National Project for Cancer Registries in 2004, brought 4 pathology services in 3 states, with differing baseline implementations of the checklists, the opportunity to partner with their state National Project for Cancer Registry and their laboratory information system vendors to evaluate the feasibility of using electronically encoded College of American Pathologists cancer checklists for melanoma and tumors of the breast and prostate.
International Journal of Clinical and Experimental Pathology, 2013
We recently reported three cases of metastatic melanoma that does not express S100, HMB45, Melan ... more We recently reported three cases of metastatic melanoma that does not express S100, HMB45, Melan A and Tyrosinase. A concurrent cutaneous scalp primary melanoma was identified later in one of the cases, which showed strong expression of these markers. The difference in immunophenotype between the primary melanoma and its metastasis in the parotid gland in this case raised the question of the biological significance of the expression of these markers and metastatic potential. To address this question, we utilized microarray comparative genomic hybridization (aCGH) to compare the cytogenetic features between the primary and metastatic melanoma. We observed chromosomal gains including 6p, entire chromosome 7, and 8q11.1-q24.3 in both primary and metastatic tumors. However, the metastatic lesion showed unique additional copy of chromosomal 7q, and loss of chromosome 9p24.3-q13 and chromosome 4, which included Melan A encoding gene region in 9p24.1. The above findings suggest the unique cytogenetic changes in the parotid lesion are most likely related to the metastatic behavior, as well as responsible for loss of multiple melanocytic marker expression in the metastatic melanoma for this case.
International Journal of Clinical and Experimental Pathology, 2013
Metastatic malignant melanoma has a wide spectrum of histopathologic patterns and often lacks mel... more Metastatic malignant melanoma has a wide spectrum of histopathologic patterns and often lacks melanin pigment. Without a known primary tumor, the diagnosis of metastatic malignant melanoma relies on a combination of morphology and immunohistochemical profile. Infrequently, commonly used markers for melanoma (S100, HMB45, Melan-A and Tyrosinase A) are negative. These cases pose critical diagnostic challenges. Recent studies show that Microphthalmia Transcription Factor (MITF) has high sensitivity (88-100%) and specificity for metastatic melanoma. We are reporting here three cases of high grade tumors that were studied by a comprehensive immunohistochemical panel including cytokeratins, S100, HMB-45, Melan A, Tyrosinase, and MITF. All three tumors were also analyzed for the presence of BRAF mutations. All three metastatic tumors were negative for S100, Melan A, HMB-45 and Tyrosinase but positive for MITF. Subsequent to the diagnoses, previously existing or concurrent primary melanomas were identified in 2 of the 3 cases. Interestingly, S100, Melan A, and HMB-45 were positive in the primary tumors. No BRAF (V600E) mutations were identified in the three metastatic melanomas and CD 117 (c-kit) was positive in one of the cases. In summary, our experience shows that MITF can be a valuable adjunct in the diagnosis of metastatic tumors that are suspicious for melanoma but negative for other melanoma markers.
International Journal of Clinical and Experimental Pathology, 2014
Human melanoma contains multipotent stem cells that express the neural crest stem cell marker CD2... more Human melanoma contains multipotent stem cells that express the neural crest stem cell marker CD271. CD271-expressing melanoma cells in murine xenografts give rise to metastatic tumor. However, a comprehensive clinical investigation of its role in different stages of melanomagenesis has not been well studied. We studied CD271 expression with immunohistochemistry in 11 cases of banal melanocytic nevus, 9 cases of primary cutaneous melanoma, 10 cases of primary mucosal melanoma, 5 cases of metastatic melanoma in regional lymph nodes, and 11 cases of metastatic melanoma in the brain. In addition, 9 cases of metastatic, high-grade adenocarcinomas from breast and lung to the brain were studied as controls. The staining was scored based on the number of positive cells and analyzed by student t-test. All banal melanocytic nevi showed negative to equivocal staining. Primary cutaneous melanomas showed variable patterns, mucosal melanomas were mostly negative, and metastases to lymph nodes ranged from negative to moderate positivity. In contrast, all 11 cases of metastatic melanoma to the brain showed moderate (4 cases) to strong positivity (7 cases). Metastases from lung and breast origin were used as controls and showed negative to weakly positive staining in all but one case. Statistically, CD271 has significantly increased expression in metastatic melanoma to the brain when compared to the other groups studied (P < 0.05). The findings suggest that CD271 expression is specifically increased in metastatic melanoma to the brain. Further prospective study for the role of CD271 in prediction of melanoma brain metastasis as well as prognosis assessment will be of great clinical significance.
Bringing digital teaching materials into residency training programs has seen slow adoption, expe... more Bringing digital teaching materials into residency training programs has seen slow adoption, expected for many new technologies. The COVID-19 pandemic dramatically shifted the paradigm for many resident teaching modalities as institutions instituted social distancing to prevent spread of the novel coronavirus. The impact of this shift on pathology trainee education has not been well studied. We conducted an online survey of pathology trainees, program directors, and faculty to assess pre- and post-COVID-19 use of, and response to, various digital pathology modalities. Responses were solicited through both social media and directed appeals. A total of 261 respondents (112 faculty, 52 program directors, and 97 trainees) reported a dramatic and significant increase in the use of digital pathology-related education tools. A significant majority of faculty and program directors agreed that this shift had adversely affected the quality (59% and 62%, respectively) and effectiveness (66%) o...
The clinical outcomes of IDH-wild type (IDH-wt) lower-grade glioma (LGG) have been the subject of... more The clinical outcomes of IDH-wild type (IDH-wt) lower-grade glioma (LGG) have been the subject of debate for some time. In this meta-analysis, we aimed to assess the prognostic values of several known genetic markers (eg, TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. Four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival (OS) were calculated using random effect model weighted by inverse variance method. Eleven studies were finally selected from 2274 articles for meta-analyses. Several genetic alterations were demonstrated to have a negative impact on prognosis of IDH-wt LGGs, specifically TERT promoter mutation (HR = 1.96; 95% CI = 1.42 - 2.70), H3F3A mutation (HR = 3.21; 95% CI = 1.86 - 5.55) and EGFR amplification (HR = 1.67; 95% CI = 1.02 - 2.74). On the other hand, CDKN loss, ATRX muta...
The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma ... more The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15-1.67) and progression-free survival (PFS) (HR=1.31; 95% CI=1.06-1.63) in glioma patients. In studying its reaction with IDH, TERT promoter mutation was associated with reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH...
Distant metastasis (DM) is not a frequent event in differentiated thyroid carcinoma (DTC) but has... more Distant metastasis (DM) is not a frequent event in differentiated thyroid carcinoma (DTC) but has an adverse impact on mortality of patients with DTC. In the current study, we aimed to conduct a comprehensive systematic review and meta-analysis to investigate the risk factors for DM in DTCs and for each histological subtype. Five electronic databases were searched from inception to December 2016 for relevant articles. Pooled odd ratios and 95% confidence interval were calculated using random-effect model. Thirty-four articles with 73,219 patients were included for meta-analyses. In DTCs, male gender, age ≥45 years, tumor size ≥4 cm, multifocality, vascular invasion (VI), extrathyroidal extension (ETE), lymph node metastasis (LNM), and lateral LNM were demonstrated to be associated with significant risks for DM. In addition, several clinicopathological factors such as age ≥45 years, VI, ETE, and LNM were shown to be significant risk factors for DM in both PTC and FTC subgroups. Our s...
The use of molecular markers, especially BRAF and TERT promoter mutations, for risk stratificatio... more The use of molecular markers, especially BRAF and TERT promoter mutations, for risk stratification in papillary thyroid carcinoma (PTC) is subject to continuing debate. In this study, we aimed to investigate the clinicopathological implication of each genotype when combining BRAF and TERT promoter mutations in PTCs. We searched four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library for relevant studies. Pooled estimates of odds ratios and corresponding 95% confidence intervals were calculated using random-effect model. From 111 results, we finally included 11 studies with 3911 PTC patients for meta-analyses. Our results demonstrated that PTCs with concurrent BRAF and TERT promoter mutations were associated with increased tumour aggressiveness in comparison with PTCs harbouring BRAF or TERT promoter mutation alone. The combination of BRAF and TERT promoter mutations could classify PTCs into four distinct risk groups with decreasing aggressivenes...
Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of h... more Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (...
Liposclerosing myxofibrous tumor is a benign fibro-osseous lesion, with distinct radiographic and... more Liposclerosing myxofibrous tumor is a benign fibro-osseous lesion, with distinct radiographic and clinical features and diverse histologic patterns. This lesion occurs in the fourth decade of life, with equal male and female incidence. Most lesions are discovered incidentally, but patients can present with bone pain or fracture. Liposclerosing myxofibrous tumor exhibits a very strong predilection for the proximal femur with characteristic radiographic findings, often providing an initial clue to diagnosis. Microscopically, this tumor is characterized by a variety of patterns, including myxofibrous tissue, fibrous dysplasia-like features, and ischemic ossification. It can be mistaken for many other fibro-osseous lesions; therefore, this unique lesion should be included in the differential diagnosis of fibro-osseous lesions, particularly in this location. Patients with this lesion are generally successfully treated by curettage and bone graft and have a favorable prognosis. A small ri...
Archives of Pathology Laboratory Medicine, Aug 1, 2010
The site-specific cancer checklists developed by the College of American Pathologists have the po... more The site-specific cancer checklists developed by the College of American Pathologists have the potential to improve the quality of data derived from pathology reports and incorporated into cancer registry databases and are now mandated report elements by various accrediting bodies. A pilot project, funded by the Centers for Disease Control National Project for Cancer Registries in 2004, brought 4 pathology services in 3 states, with differing baseline implementations of the checklists, the opportunity to partner with their state National Project for Cancer Registry and their laboratory information system vendors to evaluate the feasibility of using electronically encoded College of American Pathologists cancer checklists for melanoma and tumors of the breast and prostate.
International Journal of Clinical and Experimental Pathology, 2013
We recently reported three cases of metastatic melanoma that does not express S100, HMB45, Melan ... more We recently reported three cases of metastatic melanoma that does not express S100, HMB45, Melan A and Tyrosinase. A concurrent cutaneous scalp primary melanoma was identified later in one of the cases, which showed strong expression of these markers. The difference in immunophenotype between the primary melanoma and its metastasis in the parotid gland in this case raised the question of the biological significance of the expression of these markers and metastatic potential. To address this question, we utilized microarray comparative genomic hybridization (aCGH) to compare the cytogenetic features between the primary and metastatic melanoma. We observed chromosomal gains including 6p, entire chromosome 7, and 8q11.1-q24.3 in both primary and metastatic tumors. However, the metastatic lesion showed unique additional copy of chromosomal 7q, and loss of chromosome 9p24.3-q13 and chromosome 4, which included Melan A encoding gene region in 9p24.1. The above findings suggest the unique cytogenetic changes in the parotid lesion are most likely related to the metastatic behavior, as well as responsible for loss of multiple melanocytic marker expression in the metastatic melanoma for this case.
International Journal of Clinical and Experimental Pathology, 2013
Metastatic malignant melanoma has a wide spectrum of histopathologic patterns and often lacks mel... more Metastatic malignant melanoma has a wide spectrum of histopathologic patterns and often lacks melanin pigment. Without a known primary tumor, the diagnosis of metastatic malignant melanoma relies on a combination of morphology and immunohistochemical profile. Infrequently, commonly used markers for melanoma (S100, HMB45, Melan-A and Tyrosinase A) are negative. These cases pose critical diagnostic challenges. Recent studies show that Microphthalmia Transcription Factor (MITF) has high sensitivity (88-100%) and specificity for metastatic melanoma. We are reporting here three cases of high grade tumors that were studied by a comprehensive immunohistochemical panel including cytokeratins, S100, HMB-45, Melan A, Tyrosinase, and MITF. All three tumors were also analyzed for the presence of BRAF mutations. All three metastatic tumors were negative for S100, Melan A, HMB-45 and Tyrosinase but positive for MITF. Subsequent to the diagnoses, previously existing or concurrent primary melanomas were identified in 2 of the 3 cases. Interestingly, S100, Melan A, and HMB-45 were positive in the primary tumors. No BRAF (V600E) mutations were identified in the three metastatic melanomas and CD 117 (c-kit) was positive in one of the cases. In summary, our experience shows that MITF can be a valuable adjunct in the diagnosis of metastatic tumors that are suspicious for melanoma but negative for other melanoma markers.
International Journal of Clinical and Experimental Pathology, 2014
Human melanoma contains multipotent stem cells that express the neural crest stem cell marker CD2... more Human melanoma contains multipotent stem cells that express the neural crest stem cell marker CD271. CD271-expressing melanoma cells in murine xenografts give rise to metastatic tumor. However, a comprehensive clinical investigation of its role in different stages of melanomagenesis has not been well studied. We studied CD271 expression with immunohistochemistry in 11 cases of banal melanocytic nevus, 9 cases of primary cutaneous melanoma, 10 cases of primary mucosal melanoma, 5 cases of metastatic melanoma in regional lymph nodes, and 11 cases of metastatic melanoma in the brain. In addition, 9 cases of metastatic, high-grade adenocarcinomas from breast and lung to the brain were studied as controls. The staining was scored based on the number of positive cells and analyzed by student t-test. All banal melanocytic nevi showed negative to equivocal staining. Primary cutaneous melanomas showed variable patterns, mucosal melanomas were mostly negative, and metastases to lymph nodes ranged from negative to moderate positivity. In contrast, all 11 cases of metastatic melanoma to the brain showed moderate (4 cases) to strong positivity (7 cases). Metastases from lung and breast origin were used as controls and showed negative to weakly positive staining in all but one case. Statistically, CD271 has significantly increased expression in metastatic melanoma to the brain when compared to the other groups studied (P < 0.05). The findings suggest that CD271 expression is specifically increased in metastatic melanoma to the brain. Further prospective study for the role of CD271 in prediction of melanoma brain metastasis as well as prognosis assessment will be of great clinical significance.
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Papers by Lewis Hassell