Pub Date : 2022-09-01Epub Date: 2022-09-13DOI: 10.4132/jptm.2022.07.11
Sharon Milton, Anne Jennifer Prabhu, V T K Titus, Rikki John, Selvamani Backianathan, Vrisha Madhuri
Background: The diagnosis of osteosarcoma (OSA) depends on clinicopathological and radiological correlation. A biopsy is considered the gold standard for OSA diagnosis. However, since OSA is a great histological mimicker, diagnostic challenges exist. Immunohistochemistry (IHC) can serve as an adjunct for the histological diagnosis of OSA. Special AT-rich sequence-binding protein 2 (SATB2) was recently described as a reliable adjunct immunohistochemical marker for the diagnosis of OSA.
Methods: We investigated the IHC expression of SATB2 in 95 OSA and 100 non-osteogenic bone and soft tissue tumors using a monoclonal antibody (clone EPNCIR30A). The diagnostic utility of SATB2 and correlation with clinicopathological parameters were analyzed.
Results: SATB2 IHC was positive in 88 out of 95 cases (92.6%) of OSA and 50 out of 100 cases (50.0%) of primary non-osteogenic bone and soft tissue tumors. Of the 59 bone tumors, 37 cases (62.7%) were positive for SATB2, and of the 41 soft tissue tumors, 13 cases (31.7%) were positive for SATB2. The sensitivity of SATB2 as a diagnostic test was 92.6%, specificity 50%, positive predictive value 63.8%, and negative predictive value 87.7%.
Conclusions: Although SATB2 is a useful diagnostic marker for OSA, other clinical, histological and immunohistochemical features should be considered for the interpretation of SATB2.
{"title":"Special AT-rich sequence-binding protein 2 (SATB2) in the differential diagnosis of osteogenic and non-osteogenic bone and soft tissue tumors.","authors":"Sharon Milton, Anne Jennifer Prabhu, V T K Titus, Rikki John, Selvamani Backianathan, Vrisha Madhuri","doi":"10.4132/jptm.2022.07.11","DOIUrl":"https://doi.org/10.4132/jptm.2022.07.11","url":null,"abstract":"<p><strong>Background: </strong>The diagnosis of osteosarcoma (OSA) depends on clinicopathological and radiological correlation. A biopsy is considered the gold standard for OSA diagnosis. However, since OSA is a great histological mimicker, diagnostic challenges exist. Immunohistochemistry (IHC) can serve as an adjunct for the histological diagnosis of OSA. Special AT-rich sequence-binding protein 2 (SATB2) was recently described as a reliable adjunct immunohistochemical marker for the diagnosis of OSA.</p><p><strong>Methods: </strong>We investigated the IHC expression of SATB2 in 95 OSA and 100 non-osteogenic bone and soft tissue tumors using a monoclonal antibody (clone EPNCIR30A). The diagnostic utility of SATB2 and correlation with clinicopathological parameters were analyzed.</p><p><strong>Results: </strong>SATB2 IHC was positive in 88 out of 95 cases (92.6%) of OSA and 50 out of 100 cases (50.0%) of primary non-osteogenic bone and soft tissue tumors. Of the 59 bone tumors, 37 cases (62.7%) were positive for SATB2, and of the 41 soft tissue tumors, 13 cases (31.7%) were positive for SATB2. The sensitivity of SATB2 as a diagnostic test was 92.6%, specificity 50%, positive predictive value 63.8%, and negative predictive value 87.7%.</p><p><strong>Conclusions: </strong>Although SATB2 is a useful diagnostic marker for OSA, other clinical, histological and immunohistochemical features should be considered for the interpretation of SATB2.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 5","pages":"270-280"},"PeriodicalIF":2.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/b7/jptm-2022-07-11.PMC9510043.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40372799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01Epub Date: 2022-09-13DOI: 10.4132/jptm.2022.08.02
Jinhee Kim, Moonsik Kim, Ji Young Park
Background: Human papillomavirus (HPV) infection is a major cause of cervical cancer and associated precursor lesions. Multiple HPV genotype infections have been reported. However, their clinicopathological characteristics still remain elusive.
Methods: For this study, 814 consecutive patients who had undergone colposcopy and HPV genotyping test using BD Onclarity HPV assay were retrospectively selected. Clinicopathological parameters of multiple HPV infections were compared with those of single HPV infection.
Results: Multiple HPV infections were found in 110 out of 814 cases (13.5%). Multiple HPV infections were associated with a significantly higher incidence of high-grade intraepithelial lesions (HSILs) compared with single HPV infection. Other high-risk HPV genotypes, in addition to HPV 16, were found more frequently in the multiple HPV infections group; these included HPV 51, 52, 33/58, 56/59/66, and 35/39/68. No specific coinfection pattern was not identified. Additionally, the number of HPV genotypes in multiple HPV infections was not associated with the progression to HSIL or squamous cell carcinoma.
Conclusions: Multiple HPV infections have distinct clinicopathological characteristics (compared with single HPV infection). As their biological behavior is uncertain, close and frequent follow-up is warranted.
{"title":"Evaluation of the characteristics of multiple human papillomavirus (HPV) infections identified using the BD Onclarity HPV assay and comparison with those of single HPV infection.","authors":"Jinhee Kim, Moonsik Kim, Ji Young Park","doi":"10.4132/jptm.2022.08.02","DOIUrl":"https://doi.org/10.4132/jptm.2022.08.02","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) infection is a major cause of cervical cancer and associated precursor lesions. Multiple HPV genotype infections have been reported. However, their clinicopathological characteristics still remain elusive.</p><p><strong>Methods: </strong>For this study, 814 consecutive patients who had undergone colposcopy and HPV genotyping test using BD Onclarity HPV assay were retrospectively selected. Clinicopathological parameters of multiple HPV infections were compared with those of single HPV infection.</p><p><strong>Results: </strong>Multiple HPV infections were found in 110 out of 814 cases (13.5%). Multiple HPV infections were associated with a significantly higher incidence of high-grade intraepithelial lesions (HSILs) compared with single HPV infection. Other high-risk HPV genotypes, in addition to HPV 16, were found more frequently in the multiple HPV infections group; these included HPV 51, 52, 33/58, 56/59/66, and 35/39/68. No specific coinfection pattern was not identified. Additionally, the number of HPV genotypes in multiple HPV infections was not associated with the progression to HSIL or squamous cell carcinoma.</p><p><strong>Conclusions: </strong>Multiple HPV infections have distinct clinicopathological characteristics (compared with single HPV infection). As their biological behavior is uncertain, close and frequent follow-up is warranted.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 5","pages":"289-293"},"PeriodicalIF":2.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/2b/jptm-2022-08-02.PMC9510038.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40372801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01Epub Date: 2022-09-13DOI: 10.4132/jptm.2022.07.26
Soyeon Choi, Yoo Jin Lee, Yunsuk Choi, Misung Kim, Hyun-Jung Kim, Ji Eun Kim, Sukjoong Oh, Seoung Wan Chae, Hee Jeong Cha, Jae-Cheol Jo
Background: The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP.
Methods: We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated.
Results: A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040).
Conclusions: Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.
{"title":"Prognostic significance of BLK expression in R-CHOP treated diffuse large B-cell lymphoma.","authors":"Soyeon Choi, Yoo Jin Lee, Yunsuk Choi, Misung Kim, Hyun-Jung Kim, Ji Eun Kim, Sukjoong Oh, Seoung Wan Chae, Hee Jeong Cha, Jae-Cheol Jo","doi":"10.4132/jptm.2022.07.26","DOIUrl":"https://doi.org/10.4132/jptm.2022.07.26","url":null,"abstract":"<p><strong>Background: </strong>The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP.</p><p><strong>Methods: </strong>We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated.</p><p><strong>Results: </strong>A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040).</p><p><strong>Conclusions: </strong>Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 5","pages":"281-288"},"PeriodicalIF":2.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/4c/jptm-2022-07-26.PMC9510039.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40372800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01Epub Date: 2022-09-13DOI: 10.4132/jptm.2022.07.23
Hisham F Bahmad, Olga Lopez, Tyson Sutherland, Marisa Vinas, Kfir Ben-David, Lydia Howard, Robert Poppiti, Sarah Alghamdi
Heterotopic mesenteric ossification (HMO) is abnormal bone formation in tissues which usually do not undergo ossification. There are approximately 75 cases reported worldwide. We present two cases of HMO. The first case is that of a 39-year-old man who presented with abdominal pain and a computerized tomography scan of the abdomen and pelvis revealed an apple core lesion resulting in small bowel obstruction. The second case is that of a 36-year-old woman who presented 2 months after undergoing robotic gastric sleeve resection complaining of weakness and emesis. An esophagogram revealed kinking at the distal esophagus. Surgical resection was performed in both, yielding the diagnosis of HMO. There are various theories as to the pathophysiology of HMO, but no clearly defined mechanism has been established. Management should be conservative whenever possible to prevent further ossification with subsequent surgical intervention.
{"title":"Heterotopic mesenteric ossification: a report of two cases.","authors":"Hisham F Bahmad, Olga Lopez, Tyson Sutherland, Marisa Vinas, Kfir Ben-David, Lydia Howard, Robert Poppiti, Sarah Alghamdi","doi":"10.4132/jptm.2022.07.23","DOIUrl":"https://doi.org/10.4132/jptm.2022.07.23","url":null,"abstract":"<p><p>Heterotopic mesenteric ossification (HMO) is abnormal bone formation in tissues which usually do not undergo ossification. There are approximately 75 cases reported worldwide. We present two cases of HMO. The first case is that of a 39-year-old man who presented with abdominal pain and a computerized tomography scan of the abdomen and pelvis revealed an apple core lesion resulting in small bowel obstruction. The second case is that of a 36-year-old woman who presented 2 months after undergoing robotic gastric sleeve resection complaining of weakness and emesis. An esophagogram revealed kinking at the distal esophagus. Surgical resection was performed in both, yielding the diagnosis of HMO. There are various theories as to the pathophysiology of HMO, but no clearly defined mechanism has been established. Management should be conservative whenever possible to prevent further ossification with subsequent surgical intervention.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 5","pages":"294-300"},"PeriodicalIF":2.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/34/jptm-2022-07-23.PMC9510041.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40372802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01Epub Date: 2022-09-13DOI: 10.4132/jptm.2022.07.05
Min-Kyung Yeo, Go Eun Bae, Dong-Hyun Kim, In-Ock Seong, Kwang-Sun Suh
Background: Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.
Methods: Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.
Results: Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.
Conclusions: Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.
{"title":"Cytopathologic features of human papillomavirus-independent, gastric-type endocervical adenocarcinoma.","authors":"Min-Kyung Yeo, Go Eun Bae, Dong-Hyun Kim, In-Ock Seong, Kwang-Sun Suh","doi":"10.4132/jptm.2022.07.05","DOIUrl":"https://doi.org/10.4132/jptm.2022.07.05","url":null,"abstract":"<p><strong>Background: </strong>Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.</p><p><strong>Methods: </strong>Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.</p><p><strong>Results: </strong>Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.</p><p><strong>Conclusions: </strong>Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 5","pages":"260-269"},"PeriodicalIF":2.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4b/ab/jptm-2022-07-05.PMC9510040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40372798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01Epub Date: 2022-09-13DOI: 10.4132/jptm.2022.06.11
Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
Background: Activating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR-tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations.
Methods: We examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response.
Results: EGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation-positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases.
Conclusions: Although PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.
{"title":"Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing.","authors":"Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung","doi":"10.4132/jptm.2022.06.11","DOIUrl":"https://doi.org/10.4132/jptm.2022.06.11","url":null,"abstract":"<p><strong>Background: </strong>Activating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR-tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations.</p><p><strong>Methods: </strong>We examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response.</p><p><strong>Results: </strong>EGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation-positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases.</p><p><strong>Conclusions: </strong>Although PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 5","pages":"249-259"},"PeriodicalIF":2.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/18/jptm-2022-06-11.PMC9510045.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40374271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Mehta, H. Diwan, G. Gupta, S. Nathany, S. Agnihotri, Surender Dhanda
Background Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people. Methods Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021. One thousand one hundred thirty-three probands were screened for germline BRCA variants by next generation sequencing. The variants were classified as per the American Society of Medical Genetics and Genomics recommendations. Pathogenic (class V) and likely pathogenic (class IV) were considered clinically relevant and utilized for cascade screening. Results Nepalese population made up a subcohort of 5.12% (58/1,133) of probands tested for germline BRCA1/2 variants. Twenty-seven of these 58 tested harbored pathogenic genetic alterations in BRCA1/2 genes, with 23 being BRCA1 mutant. Sixteen of 23 BRCA1 mutant cases shared one common pathogenic mutation c.2214_2215insT (p.Lys739Ter) (NM_007294.4). Additionally, a second highly recurrent mutation in BRCA1 gene c.5068A>T (p.Lys1690Ter) (NM_007294.4) was noted in six patients from this population. Conclusions The overwhelming abundance of the above two variants in a geographically confined population confers these two genetic alterations a status of founder mutations amongst the people of Nepal. A more extensive population-based study to reaffirm these findings will help establish a dual site-specific germline testing similar to the “Multisite-3-assay” in Ashkenazi Jews as the primary screening tool, especially in a resource-constrained environment.
{"title":"Founder BRCA1 mutations in Nepalese population","authors":"A. Mehta, H. Diwan, G. Gupta, S. Nathany, S. Agnihotri, Surender Dhanda","doi":"10.4132/jptm.2022.05.02","DOIUrl":"https://doi.org/10.4132/jptm.2022.05.02","url":null,"abstract":"Background Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people. Methods Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021. One thousand one hundred thirty-three probands were screened for germline BRCA variants by next generation sequencing. The variants were classified as per the American Society of Medical Genetics and Genomics recommendations. Pathogenic (class V) and likely pathogenic (class IV) were considered clinically relevant and utilized for cascade screening. Results Nepalese population made up a subcohort of 5.12% (58/1,133) of probands tested for germline BRCA1/2 variants. Twenty-seven of these 58 tested harbored pathogenic genetic alterations in BRCA1/2 genes, with 23 being BRCA1 mutant. Sixteen of 23 BRCA1 mutant cases shared one common pathogenic mutation c.2214_2215insT (p.Lys739Ter) (NM_007294.4). Additionally, a second highly recurrent mutation in BRCA1 gene c.5068A>T (p.Lys1690Ter) (NM_007294.4) was noted in six patients from this population. Conclusions The overwhelming abundance of the above two variants in a geographically confined population confers these two genetic alterations a status of founder mutations amongst the people of Nepal. A more extensive population-based study to reaffirm these findings will help establish a dual site-specific germline testing similar to the “Multisite-3-assay” in Ashkenazi Jews as the primary screening tool, especially in a resource-constrained environment.","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 1","pages":"212 - 216"},"PeriodicalIF":2.4,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46795357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatic carcinoma expressing inhibin is a recently described neoplasm with varied architecture, including trabecular, pseudoglandular, follicular/microcystic, organoid, solid and tubular patterns of growth. We report a case of hepatic carcinoma expressing inhibin that occurred in a 47-year-old woman presenting with epigastric and back pain. The tumor was located in the left hepatic lobe and measured 12 cm in diameter. On immunohistochemical stains, the neoplastic cells were positive for inhibin, as well as cytokeratins 7, 8/18 and 19. There was mild focal expression of synaptophysin, and lack of expression of hepatocytic markers. The histogenesis of hepatic carcinoma expressing inhibin is presently uncertain. From a practical point of view, this neoplasm can potentially cause diagnostic pitfalls by simulating other primary or metastatic tumors, such as hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and follicular carcinoma of thyroid gland. Performing inhibin immunostain could assist in the differential diagnosis of liver tumors with unusual histologic features.
{"title":"Hepatic carcinoma expressing inhibin: case report of a proposed novel entity and review of the literature","authors":"A. Syrnioti, E. Athanasiou, P. Hytiroglou","doi":"10.4132/jptm.2022.04.07","DOIUrl":"https://doi.org/10.4132/jptm.2022.04.07","url":null,"abstract":"Hepatic carcinoma expressing inhibin is a recently described neoplasm with varied architecture, including trabecular, pseudoglandular, follicular/microcystic, organoid, solid and tubular patterns of growth. We report a case of hepatic carcinoma expressing inhibin that occurred in a 47-year-old woman presenting with epigastric and back pain. The tumor was located in the left hepatic lobe and measured 12 cm in diameter. On immunohistochemical stains, the neoplastic cells were positive for inhibin, as well as cytokeratins 7, 8/18 and 19. There was mild focal expression of synaptophysin, and lack of expression of hepatocytic markers. The histogenesis of hepatic carcinoma expressing inhibin is presently uncertain. From a practical point of view, this neoplasm can potentially cause diagnostic pitfalls by simulating other primary or metastatic tumors, such as hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and follicular carcinoma of thyroid gland. Performing inhibin immunostain could assist in the differential diagnosis of liver tumors with unusual histologic features.","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 1","pages":"225 - 230"},"PeriodicalIF":2.4,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41416974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruno Henrique Bressan da Costa, A. Becker, L. Neder, P. G. Gonçalves, Cristiane Carla de Oliveira, A. Polverini, C. Clara, G. Teixeira, R. Reis, L. Bidinotto
Background Despite the advances in glioblastoma (GBM) treatment, the average life span of patients is 14 months. Therefore, it is urgent to identity biomarkers of prognosis, treatment response, or development of novel treatment strategies. We previously described the association of high epidermal growth factor-like domain multiple 7 (EGFL7) expression and unfavorable outcome of pilocytic astrocytoma patients. The present study aims to analyze the prognostic potential of EGFL7 in GBM isocitrate dehydrogenase (IDH)-wildtype, using immunohistochemistry and in silico approaches. Methods Spearman’s correlation analysis of The Cancer Genome Atlas RNA sequencing data was performed. The genes strongly correlated to EGFL7 expression were submitted to enrichment gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, EGFL7 expression was associated with patient overall survival. The expression of EGFL7 was analyzed through immunohistochemistry in 74 GBM IDH-wildtype patients’ samples, and was associated with clinicopathological data and overall survival. Results In silico analysis found 78 genes strongly correlated to EGFL7 expression. These genes were enriched in 40 biological processes and eight KEGG pathways, including angiogenesis/vasculogenesis, cell adhesion, and phosphoinositide 3-kinase–Akt, Notch, and Rap1 signaling pathways. The immunostaining showed high EGFL7 expression in 39 cases (52.7%). High immunolabelling was significantly associated with low Karnofsky Performance Status and poor overall survival. Cox analysis showed that GBMs IDH-wildtype with high EGFL7 expression presented a higher risk of death compared to low expression (hazard ratio, 1.645; 95% confidence interval, 1.021 to 2.650; p = .041). Conclusions This study gives insights regarding the genes that are correlated with EGFL7, as well as biological processes and signaling pathways, which should be further investigated in order to elucidate their role in glioblastoma biology.
{"title":"EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome","authors":"Bruno Henrique Bressan da Costa, A. Becker, L. Neder, P. G. Gonçalves, Cristiane Carla de Oliveira, A. Polverini, C. Clara, G. Teixeira, R. Reis, L. Bidinotto","doi":"10.4132/jptm.2022.04.22","DOIUrl":"https://doi.org/10.4132/jptm.2022.04.22","url":null,"abstract":"Background Despite the advances in glioblastoma (GBM) treatment, the average life span of patients is 14 months. Therefore, it is urgent to identity biomarkers of prognosis, treatment response, or development of novel treatment strategies. We previously described the association of high epidermal growth factor-like domain multiple 7 (EGFL7) expression and unfavorable outcome of pilocytic astrocytoma patients. The present study aims to analyze the prognostic potential of EGFL7 in GBM isocitrate dehydrogenase (IDH)-wildtype, using immunohistochemistry and in silico approaches. Methods Spearman’s correlation analysis of The Cancer Genome Atlas RNA sequencing data was performed. The genes strongly correlated to EGFL7 expression were submitted to enrichment gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, EGFL7 expression was associated with patient overall survival. The expression of EGFL7 was analyzed through immunohistochemistry in 74 GBM IDH-wildtype patients’ samples, and was associated with clinicopathological data and overall survival. Results In silico analysis found 78 genes strongly correlated to EGFL7 expression. These genes were enriched in 40 biological processes and eight KEGG pathways, including angiogenesis/vasculogenesis, cell adhesion, and phosphoinositide 3-kinase–Akt, Notch, and Rap1 signaling pathways. The immunostaining showed high EGFL7 expression in 39 cases (52.7%). High immunolabelling was significantly associated with low Karnofsky Performance Status and poor overall survival. Cox analysis showed that GBMs IDH-wildtype with high EGFL7 expression presented a higher risk of death compared to low expression (hazard ratio, 1.645; 95% confidence interval, 1.021 to 2.650; p = .041). Conclusions This study gives insights regarding the genes that are correlated with EGFL7, as well as biological processes and signaling pathways, which should be further investigated in order to elucidate their role in glioblastoma biology.","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 1","pages":"205 - 211"},"PeriodicalIF":2.4,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44475535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Na, Dong Chul Kim, D. Song, H. An, H. Koh, Jeong-Hee Lee, Jong Sil Lee, J. Yang, Min Hye Kim
Background Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis. Methods We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated. Results Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors. Conclusions Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.
{"title":"Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma","authors":"J. Na, Dong Chul Kim, D. Song, H. An, H. Koh, Jeong-Hee Lee, Jong Sil Lee, J. Yang, Min Hye Kim","doi":"10.4132/jptm.2022.03.19","DOIUrl":"https://doi.org/10.4132/jptm.2022.03.19","url":null,"abstract":"Background Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis. Methods We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated. Results Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors. Conclusions Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"56 1","pages":"199 - 204"},"PeriodicalIF":2.4,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48581485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}