Applied immunohistochemistry & molecular morphology : AIMM最新文献

{"title":"Screening Strategy for Detecting Double-Hit Lymphoma in a Resource-Limited Setting.","authors":"Balamurugan Thirunavukkarasu,&nbsp;Amanjit Bal,&nbsp;Gaurav Prakash,&nbsp;Pankaj Malhotra,&nbsp;Harmandeep Singh,&nbsp;Ashim Das","doi":"10.1097/PAI.0000000000000967","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000967","url":null,"abstract":"<p><strong>Aim: </strong>High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements [double-hit lymphomas (DHL)] are aggressive lymphomas. Current literature recommends fluorescent in-situ hybridization analysis (FISH) in all cases of diffuse large B-cell lymphoma (DLBCL) to identify cases of DHL. However, this approach is not feasible in a resource-limited setting. We analyzed cases of de novo high-grade B-cell non-Hodgkin lymphoma using histomorphology, immunohistochemistry and FISH to identify which cases need to undergo FISH testing in a resource-limited setting.</p><p><strong>Materials and methods: </strong>Cases of de novo high-grade B-cell non-Hodgkin lymphoma that included DLBCL, not otherwise specified and B-cell lymphoma unclassifiable (BCLU) with features intermediate between DLBCL and Burkitt lymphoma diagnosed over a period of 5 years were analyzed by Hans algorithm, MYC, BCL2, and Ki67. MYC, BCL2, and BCL6 break apart FISH was tested in selected cases.</p><p><strong>Results: </strong>One hundred and nine cases were obtained, of which 102 had DLBCL morphology and 7 had BCLU/blastoid morphology. BCL2 expression was noted in 48 cases (44%), MYC in 33 cases (30.3%) and MYC/BCL2 co-expression in 24 cases (22%). FISH testing could be done in 42 consecutive cases, of which 5 cases had MYC and BCL2 co-rearrangement (11.9%) (double-hit) and 2 cases showed rearrangement for only MYC (4.7%) (single-hit). Single-hit lymphoma/DHL showed significant independent positive correlation with BCLU/blastoid morphology, CD10 expression, germinal center B-cell phenotype, and MYC/BCL2 co-expression. The sensitivity and specificity of each parameters include BCLU/blastoid morphology (42% vs. 94%), CD10 positive (50% vs. 88%), germinal center B-cell phenotype (57% vs. 82%), MYC/BCL2 co-expression (85% vs. 80%). Selected candidates for FISH (any one of the above parameters) using this strategy showed a sensitivity and specificity of 100% and 68%, respectively (P=0.001).</p><p><strong>Conclusion: </strong>We propose a highly sensitive screening strategy for detection of MYC/BCL2 rearrangement in high-grade B-cell lymphoma in a resource-limited setting (pending validation in a larger cohort).</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"49-55"},"PeriodicalIF":1.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39366018","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}

{"title":"Prognostic and Clinicopathologic Associations of LAG-3 Expression in Triple-negative Breast Cancer.","authors":"Elisabeth S Stovgaard,&nbsp;Iben Kümler,&nbsp;Kamille List-Jensen,&nbsp;Anne Roslind,&nbsp;Ib J Christensen,&nbsp;Estrid Høgdall,&nbsp;Dorte Nielsen,&nbsp;Eva Balslev","doi":"10.1097/PAI.0000000000000954","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000954","url":null,"abstract":"<p><p>The immune checkpoint molecule lymphocyte activation gene 3 (LAG-3) is currently being investigated as a possible target for immunotherapy in triple-negative breast cancer (TNBC), frequently as an addition to treatment with programmed cell death protein 1/programmed death ligand 1 (PD-L1) inhibition. However, expression of LAG-3, the frequency of coexpression with PD-L1, and the prognostic significance of this marker have not been studied extensively in TNBC. For this study, tissue microarrays (TMAs) were constructed from surgical specimens of 514 patients with TNBC. TMAs were stained immunohistochemically for LAG-3 and PD-L1 expression. Tumor-infiltrating lymphocytes (TILs) were evaluated on full glass slides. LAG-3 expression was significantly associated with improved overall survival and relapse-free survival. When adjusted for clinicopathologic factors, each increment of 10 LAG-3-positive intratumoral lymphocytes per TMA core was associated with improved overall survival (hazard ratio=0.93, 95% confidence interval: 0.89-0.97, P=0.002), and recurrence-free survival (hazard ratio=0.91, 95% confidence interval: 0.85-0.97, P=0.002). PD-L1 expression on immune cells and PD-L1 expression evaluated with the combined positive score and TILs were also associated with improved survival in both univariate and multivariate analyses. PD-L1 expression on tumor cells was only associated with improved survival in univariate analysis. LAG-3 expression was associated with both TILs and PD-L1 expression. Coexpression of LAG-3 and PD-L1 did not confer additional survival benefits. In conclusion, LAG-3 expression is associated with improved survival in TNBC. LAG-3 is often coexpressed with PD-L1, confirming that TNBC is likely a suitable candidate for cotreatment with LAG-3 and programmed cell death protein 1/PD-L1 inhibitors. However, coexpression does not confer additional survival benefits.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"62-71"},"PeriodicalIF":1.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38977370","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}

{"title":"Claudin-18 Immunohistochemical Staining Facilitates the Identification of Metastatic Carcinoma of Gastric or Pancreatic Origin in Effusion Specimens.","authors":"Yu-Jou Yang,&nbsp;Yung-Ming Jeng,&nbsp;Ching-Yao Yang,&nbsp;Hsiang-Wei Hu","doi":"10.1097/PAI.0000000000000971","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000971","url":null,"abstract":"<p><p>Determining the primary origin of a malignant effusion remains a common challenge for cytopathologists. Although immunohistochemical (IHC) markers are available for most primary sites, ideal IHC markers for metastatic gastric adenocarcinoma and pancreatic ductal adenocarcinoma are lacking, and related interpretation is often hindered by mesothelial cells. We recently revealed that claudin-18 IHC staining is useful for identifying the stomach and pancreas as the primary sites of metastatic adenocarcinoma. Thus, we assessed the use of claudin-18 IHC staining in 111 cell blocks obtained from various metastatic cancers and specimens negative for malignancy. Positive membranous claudin-18 staining was noted in all 10 (100%) metastatic pancreatic ductal adenocarcinomas, 9 (90%) of 10 gastric adenocarcinomas, and 1 (9%) of 11 nonmucinous lung adenocarcinomas. The cases of metastatic mucinous carcinomas of lung origin (1 case) and ovarian origin (1 case) were also positive for claudin-18. The other remaining 89 cases showed variable cytoplasmic staining on some cells (73 cases) or complete absence of staining (16 cases). After normalization to the tumor frequency, the sensitivity and specificity for identifying the stomach or pancreas as primary tumor sites in ascites were 95% (confidence interval: 0.83-0.99) and 99% (confidence interval: 0.94-1), respectively. In conclusion, membranous claudin-18 staining is a useful marker for metastatic gastric adenocarcinoma and pancreatic ductal adenocarcinoma in effusion specimens.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"8-13"},"PeriodicalIF":1.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39703602","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}

{"title":"PD-L1 Tumor Cell Expression in Upper Tract Urothelial Carcinomas is Associated With Higher Pathologic Stage.","authors":"Michael Ward,&nbsp;Daniel Albertson,&nbsp;Larissa V Furtado,&nbsp;Georgios Deftereos","doi":"10.1097/PAI.0000000000000957","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000957","url":null,"abstract":"<p><strong>Background: </strong>Upper tract urothelial carcinomas (UTUCs) are a rare and unique subset of urothelial carcinoma (UC). Patients with UTUC may qualify for treatment with immune checkpoint inhibitors if their tumor cells express programmed death ligand-1 (PD-L1). While several large studies have looked at PD-L1 expression in UC, most have not investigated UTUC as a separate group, and most have not used Food and Drug Administration approved PD-L1 stains and scoring systems. Moreover, comparison between studies of PD-L1 expression is challenging as a wide variety of different PD-L1 antibody clones, testing platforms, and cutoff values have been used in the literature.</p><p><strong>Methods: </strong>This is a retrospective study of 37 cases of resected UTUC. Representative tissue from each case was compiled into tissue microarrays and immunohistochemical stains for PD-L1 (Dako antibody clones 22C3 and 28-8) were performed. PD-L1 staining was evaluated using several established Food and Drug Administration approved scoring systems: tumor proportion score (TPS), combined positive score, and immune cell score. Associations between PD-L1 expression and clinicopathologic features were investigated.</p><p><strong>Results: </strong>Overall expression of PD-L1 in UTUC was 29.7% when using a TPS cutoff of ≥1%. Total of, 55.6% of cases with higher pathologic stage (pT3 or pT4) were positive for PD-L1, compared with only 5.3% of cases with lower pathologic stage (pTis, pT1, or pT2; P=0.0011). When using a combined positive score cutoff of ≥10, there was no significant association between tumor stage and PD-L1 expression. There was no association between PD-L1 positivity and tumor grade, tumor location, sex, or age. There was 100% concordance between 22C3 and 28-8 in terms of positivity rate.</p><p><strong>Conclusions: </strong>Our study using approved testing methods shows that PD-L1 expression in UTUC is more often associated with high pathologic stage, which may reflect an immune response evasion mechanism that UC cells acquire later in disease progression. In addition we show that 29.7% of UTUCs are positive for PD-L1 TPS expression, comparable to the 20% to 30% reported in UC literature. Finally, PD-L1 22C3 and 28-8 clones show similar overall patterns of staining in this setting.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"56-61"},"PeriodicalIF":1.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39118290","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}

{"title":"Intratumoral Budding and Tumor Microenvironment in Pretreatment Rectal Cancer Biopsies Predict the Response to Neoadjuvant Chemoradiotherapy.","authors":"Xiaoyun Wen,&nbsp;Sui Y Zee,&nbsp;Kenneth R Shroyer,&nbsp;Jela Bandovic","doi":"10.1097/PAI.0000000000000966","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000966","url":null,"abstract":"<p><p>Tumor budding at the invasive tumor front (peritumoral budding) is an established prognostic factor in colorectal cancer. However, the significance of intratumoral budding (ITB) in pretreatment biopsies is still uncertain. Our study aims to investigate the association of ITB and tumor microenvironment in pretreatment rectal cancer biopsies with pathologic response to neoadjuvant chemoradiotherapy. Pretreatment biopsies of low-grade rectal cancer from 37 patients who underwent resection after neoadjuvant chemoradiotherapy were retrospectively reviewed to evaluate ITB, type of tumor stroma, and intraepithelial lymphocytes. ITB was counted on a single hotspot in 1 HPF upon pan-keratin immunohistochemical staining. Intraepithelial lymphocytes was graded semiquantitatively as \"absent\" (≤2/HPF) or \"present\" (>2/HPF). The tumor stroma was classified as either immature type or maturing type. In pretreatment biopsies, ITB was observed in 34/37 patients (92%). High-grade ITB was significantly associated with a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P<0.001; and higher posttreatment T stage, P=0.002). Immature type of stroma was significantly associated with both high-grade ITB in biopsies (P=0.02) and a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P=0.005). In multivariate analysis, ITB and the type of stroma remained the significant parameters for prediction of response to neoadjuvant treatment. Our study indicates that ITB and tumor microenvironment in pretreatment biopsies are strong predictors of response to neoadjuvant chemoradiotherapy, which may assist risk stratification and clinical management in rectal cancer patients.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"1-7"},"PeriodicalIF":1.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39294704","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}

{"title":"Reliability and Role of Mutation-specific H3F3A (Histone 3-3) G34W Immunohistochemistry to Differentiate Giant Cell Tumor of Bone From its Clinicoradiologic and Histologic Mimics: An Institutional Study.","authors":"Sunil Pasricha,&nbsp;Manish Pruthi,&nbsp;Ankush Jajodia,&nbsp;Ankur Kumar,&nbsp;Gurudutt Gupta,&nbsp;Anila Sharma,&nbsp;Akshay Tiwari,&nbsp;Himanshu Rohela,&nbsp;Garima Durga,&nbsp;Meenakshi Kamboj,&nbsp;Venkata P B Koyyala,&nbsp;Anurag Mehta","doi":"10.1097/PAI.0000000000000964","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000964","url":null,"abstract":"<p><p>Giant cell tumor of bone (GCTB) is a benign neoplasm, which can sometimes be a diagnostic challenge, especially in small biopsies, due to its histologic benign and malignant mimics. We evaluated the role of H3.3 G34W immunohistochemistry (IHC) antibody in diagnosing GCTB and its role in differentiating it from its close histologic mimics. A total of 120 cases (80 cases of GCTB and 40 cases of histologic mimics) were retrieved and subjected to IHC. Of 80 cases of GCTB, 72 cases showed a positive nuclear immunoexpression, while all 40 cases of histologic mimics of GCTB showed a negative staining for H3.3 G34W IHC. Sensitivity and specificity of this mutation-specific antibody for diagnosis of GCTB was 90% and 100%, respectively, while, the positive predictive value and the negative predictive value were 100% and 83.3%, respectively. A positive expression of H3.3 G34W was seen in all 5 cases of GCTB, postdenosumab therapy, as well as, in all 3 cases of malignant giant cell tumor. The presented study showed that H3.3 G34W mutation-specific IHC is a reliable and specific marker for GCTB and can help distinguish it from the histologic mimics due to distinct therapeutic implications.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"36-41"},"PeriodicalIF":1.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39274729","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}

{"title":"Immunodetection of Epithelial-Mesenchymal Transition and Tumor Proliferation Markers in GLi-1-positive Oral Squamous Cell Carcinoma.","authors":"Rebeca C M Dantas,&nbsp;Vanessa S N Guimarães,&nbsp;Renata O de Souza,&nbsp;Ludmila F Valverde,&nbsp;Manuela T A Vidal,&nbsp;Raphael L R Nogueira,&nbsp;Leonardo O S da Rocha,&nbsp;Giovana T Araújo,&nbsp;Jean N Dos Santos,&nbsp;Clarissa A G Rocha","doi":"10.1097/PAI.0000000000000866","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000866","url":null,"abstract":"<p><p>In oral squamous cell carcinoma (OSCC), involvement and activation of the Hedgehog pathway (HH) may be related to epithelial-mesenchymal transition and cell proliferation. The present study aimed to evaluate epithelial-mesenchymal transition and proliferative potential in OSCC cases demonstrating activation of the HH pathway. Twenty-three GLi-1-positive OSCC cases were submitted to immunohistochemical detection of Snail, Slug, N-cadherin, E-cadherin, β-catenin, and MCM3 proteins. Clinical-pathologic immunoexpression data were obtained from the invasion front and tumor islets, and then compared. At the invasion front, OSCC cases presented positive Snail, Slug, and MCM3 expression in the nuclei of tumor cells. Loss of membrane and cytoplasmic expression of E-cadherin and β-catenin was also observed. Positive N-cadherin expression was observed in 31.78% of the cases. GLi-1 immunoexpression was associated with loss of membrane E-cadherin (P<0.001), membrane β-catenin (P<0.001), and cytoplasmic β-catenin (P=0.02) expression. In the tumor islets, we observed nuclear expression of GLi-1, Snail, Slug, and MCM3. E-cadherin and β-catenin showed positivity in tumor cell membranes. Statistically significant positive correlations between GLi-1 and Snail (P=0.05), E-cadherin (P=0.01), and cytoplasmic β-catenin (P=0.04) were found. GLi-1 was associated with clinical staging, while membrane β-catenin expression was related to the presence of metastasis in lymph nodes and to clinical staging. The HH pathway may be involved in regulating the expression of the mesenchymal phenotype. The loss of membrane E-cadherin and β-catenin expression was observed at the tumor front region, whereas cell adhesion protein expression was detected in tumor islets regardless of MCM3.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"335-344"},"PeriodicalIF":1.6,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40565449","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}

{"title":"Expression of Cyclooxygenase-2 in Human Epithelial Skin Lesions: A Systematic Review of Immunohistochemical Studies.","authors":"Łukasz Kuźbicki,&nbsp;Anna A Brożyna","doi":"10.1097/PAI.0000000000000871","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000871","url":null,"abstract":"<p><p>Permanent, elevated expression of cyclooxygenase-2 (COX-2) in keratinocytes of epidermis can stimulate its hyperplasia and constitute a factor promoting cancer development, as demonstrated in animal models. Intratumoral level and localization of COX-2 in epithelial lesions of human skin was examined immunohistochemically in 26 studies. In squamous cell carcinomas (SCCs), strong staining was observed with great compatibility. High COX-2 detectability throughout the entire tumor mass could be helpful in the finding of SCC cells. However, in basal cell carcinomas, and precancerous lesions, frequency and detection level of this protein, as well as the type and/or localization of stained cells within the tumor, varied among different research groups. The discrepancies may be due to the heterogeneity of each of these 2 groups of lesions. However, differences in COX-2 staining in normal skin indicate also possible methodological reasons. In general, COX-2 levels were significantly decreased in basal cell carcinomas compared with SCCs, which could be used in the differential diagnosis of these cancers. Reduced, although heterogenous, COX-2 expression in precancerous lesions may suggest its association with SCC development. These observations are consistent with data on the efficacy of preventive and therapeutic effects of nonsteroidal anti-inflammatory drugs that are COX-2 inhibitors.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"163-174"},"PeriodicalIF":1.6,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40554418","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}

{"title":"The Profile and Role of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: An Immunohistochemical Study.","authors":"Hala S El-Rebey,&nbsp;Asmaa G Abdou,&nbsp;Mervat M Sultan,&nbsp;Shymaa H Ibrahim,&nbsp;Nanis S Holah","doi":"10.1097/PAI.0000000000000865","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000865","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Tumor-infiltrating lymphocytes (TILs) are a class of cells that form the tumor microenvironment and thus have an effect on carcinogenesis. The aim of this study was to investigate the immunohistochemical expression of CD8, CD4, cytotoxic T lymphocyte-associated protein-4 (CTLA-4), and granzyme B in HCC and their correlation with clinicopathologic parameters and prognosis. This study was carried out on 112 cases of HCC. High percentage of CD8+ TILs was associated with large tumors and adjacent noncirrhotic liver. High percentage of CD4+ TILs and high CD4 to CD8 ratio were associated with nonviral etiology, low alpha fetoprotein, and direct acting antiviral treatment. High percentage of CTLA-4-positive TILs tended to be associated with high-grade HCC, while a high percentage of CTLA-4 in tumor cells was associated with multiple lesions and low tumor grade. High percentage of granzyme B+ TILs was associated with low grade, early stage, and absence of tumor recurrence. High CD4 percentage and high CD4/CD8 ratio affected patients' overall survival. There is a dynamic interaction between the different subsets of lymphocytes in the environment of HCC manifested by coparallel expression of CD4 and CD8 augmenting the expression of CTLA-4, and only CD8 augments the expression of granzyme B. This opens the gate for the beneficial role of immunotherapy in the management of HCC, reducing recurrence and improving survival.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"188-200"},"PeriodicalIF":1.6,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40453833","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}

{"title":"Aberrant Immunostaining of Breast Carcinoma by MRQ-50 PAX8 Antibody.","authors":"Kamaljeet Singh,&nbsp;Katrine Hansen,&nbsp;M Ruhul Quddus","doi":"10.1097/PAI.0000000000000682","DOIUrl":"https://doi.org/10.1097/PAI.0000000000000682","url":null,"abstract":"melanoma. The tumor did not present BRAFV600 mutations but did have a NRAS mutation in codon 61, Q61R (nucleotide change c.182A>G). The previously excised lentigo maligna melanoma was reviewed and compared with the ankle melanoma. This tumor presented a higher atypia degree and 1 mitosis per square millimeter was found. The 4-probe FISH assay showed gains of 11q13 (CCND1). The tumor also failed to show a BRAFV600 mutation, but a different NRAS mutation was detected on codon 61, Q61K (nucleotide change c.181C>A). The melanoma of the ankle was finally diagnosed as nonulcerated nevoid melanoma (Breslow 2.5mm). Two months after the excision of the lesion the patient presented systemic progression of the melanoma and eventually died. Although histopathologic study is the gold standard for the diagnosis of melanoma, the biological behavior of some melanocytic lesions can be extremely difficult to accurately predict on the basis of the histopathologic features, even for expert dermatopathologists.3 To address these difficulties, immunohistochemistry and molecular techniques have been developed as adjunctive tools. In our case, the histopathology and immunohistochemical results were concerning but the commercially available FISH panel did not give abnormalities. This 4-color probe set FISH identifies the most recurrent genomic aberrations in cutaneous melanomas, including copy number increases of 6p25 (RREB1) and 11q13 (CCND1) and deletion of 6q23 (MYB). It has shown to be useful in the differential diagnosis between nevus and melanoma in different settings, including the diagnosis of ambiguous melanocytic lesions4 and nevoid melanomas.5 We were finally able to confirm the diagnosis of melanoma by the study of the genomic copy number array. Several chromosomal abnormalities were observed in loci that are not tested with FISH, being concordant with the diagnosis of melanoma. The arraybased test for DNA copy number aberration analyses the entire genome in a single assay, thereby having a higher sensitivity than FISH for the diagnosis of challenging melanocytic lesions.6 In conclusion, the diagnosis of nevoid melanomas can be challenging and can require the molecular exploration of the tumor. These molecular studies are also useful to differentiate primary from metastatic tumors.","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"e37-e38"},"PeriodicalIF":1.6,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0000000000000682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40532250","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}