Pub Date : 2019-10-22DOI: 10.1097/PAS.0000000000001389
M. Yoshimoto, Yuichi Yamada, S. Ishihara, Kenichi Kohashi, Y. Toda, Yoshihiro Ito, Hidetaka Yamamoto, M. Furue, Y. Nakashima, Y. Oda
Supplemental Digital Content is available in the text. Myxofibrosarcoma (MFS) is a malignant fibroblastic/myofibroblastic neoplasm with the prominent myxoid area. It has the clinical features of frequent local recurrence and occasional distant metastasis. Morphologically, MFS is occasionally difficult to distinguish from undifferentiated pleomorphic sarcoma (UPS), especially in the case of high-grade MFS. Here, we reviewed clinical and histologic data of 162 MFS cases and 43 UPS cases. MFS was distinguished from UPS with the criterion of 10% myxoid area as a cutoff value. Overall, 52 MFS (34.4%) and 9 UPS (20.9%) cases showed local recurrence, 18 MFS (12.2%) and 19 UPS (44.2%) cases developed distant metastasis, and 13 MFS (9.5%) and 14 UPS (32.6%) cases resulted in tumor-related death. Statistically, MFS had a better prognosis than UPS. Moreover, MFS with less myxoid area had a tendency to present a poorer prognosis. FNCLCC grade was a statistically significant prognostic factor (distant metastasis: P=0.0021, tumor-related death: P=0.0021). Cellularity and nuclear atypia had only a statistical tendency for associations with a poorer prognosis. The overall survival rate of MFS after transformation into a UPS-like condition (<10% myxoid area) was close to that of UPS. It was suggested that MFS is a biologically distinct tumor from UPS, and MFS with less myxoid area had a tendency to present a poorer prognosis. We considered that evaluation of the amount of myxoid area, cellularity, and nuclear atypia may be important as prognostic predictors. MFS may become similar to histologic malignancy of UPS in terms of morphology and biology via local recurrence.
{"title":"Comparative Study of Myxofibrosarcoma With Undifferentiated Pleomorphic Sarcoma","authors":"M. Yoshimoto, Yuichi Yamada, S. Ishihara, Kenichi Kohashi, Y. Toda, Yoshihiro Ito, Hidetaka Yamamoto, M. Furue, Y. Nakashima, Y. Oda","doi":"10.1097/PAS.0000000000001389","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001389","url":null,"abstract":"Supplemental Digital Content is available in the text. Myxofibrosarcoma (MFS) is a malignant fibroblastic/myofibroblastic neoplasm with the prominent myxoid area. It has the clinical features of frequent local recurrence and occasional distant metastasis. Morphologically, MFS is occasionally difficult to distinguish from undifferentiated pleomorphic sarcoma (UPS), especially in the case of high-grade MFS. Here, we reviewed clinical and histologic data of 162 MFS cases and 43 UPS cases. MFS was distinguished from UPS with the criterion of 10% myxoid area as a cutoff value. Overall, 52 MFS (34.4%) and 9 UPS (20.9%) cases showed local recurrence, 18 MFS (12.2%) and 19 UPS (44.2%) cases developed distant metastasis, and 13 MFS (9.5%) and 14 UPS (32.6%) cases resulted in tumor-related death. Statistically, MFS had a better prognosis than UPS. Moreover, MFS with less myxoid area had a tendency to present a poorer prognosis. FNCLCC grade was a statistically significant prognostic factor (distant metastasis: P=0.0021, tumor-related death: P=0.0021). Cellularity and nuclear atypia had only a statistical tendency for associations with a poorer prognosis. The overall survival rate of MFS after transformation into a UPS-like condition (<10% myxoid area) was close to that of UPS. It was suggested that MFS is a biologically distinct tumor from UPS, and MFS with less myxoid area had a tendency to present a poorer prognosis. We considered that evaluation of the amount of myxoid area, cellularity, and nuclear atypia may be important as prognostic predictors. MFS may become similar to histologic malignancy of UPS in terms of morphology and biology via local recurrence.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123164105","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}
Pub Date : 2019-10-22DOI: 10.1097/PAS.0000000000001391
B. Lawson, E. Euscher, R. Bassett, Jinsong Liu, P. Ramalingam, Y. Zhong, N. Fleming, A. Malpica
The chemotherapy response score (CRS) is used to score histopathologic response to neoadjuvant chemotherapy (NACT) of patients with extrauterine high-grade serous carcinoma. This study was undertaken to determine if the CRS in the omentum, adnexa or when combined correlates with (1) progression-free survival (PFS) or overall survival (OS), (2) laparoscopic score of abdominal disease, (3) Cancer antigen 125 levels, (4) BRCA status, and (5) platinum-resistant disease. A total of 158 cases were retrospectively collected that received NACT between April 2013 and February 2018 at a single institution. The 3-tier Böhm CRS system was applied to the omentum and adnexa. Survival outcomes between scored subgroups were analyzed using Cox proportional hazards regression. Spearman rank correlation analyses were used to assess CRS and clinical data. A total of 119 cases were treated only with carboplatin/paclitaxel. Omental CRS was: 1 (23 cases, 19.3%), 2 (65 cases, 54.6%), and 3 (31 cases, 26.1%), whereas adnexal CRS was: 1 (50 cases, 42%), 2 (48 cases, 40.3%) and 3 (21 cases, 17.6%). The omental CRS was significantly associated with PFS as a 2-tier score (hazard ratio [HR]=0.612, 95% confidence interval [CI]: 0.378-0.989, P=0.045) but not associated with the PFS using the 3-tier score or with OS using either system. Adnexal CRS was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.49, 95% CI: 0.263-0.914, P=0.025) and 2-tier scores (HR=0.535, 95% CI: 0.297-0.963, P=0.037). The combined score was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.348, 95% CI: 0.137-0.88, P=0.026) and 2-tier scores (HR=0.364, 95% CI: 0.148-0.896, P=0.028). No CRS system used associated with laparoscopic assessment of disease. CRS in the omentum had no significant association with platinum resistance; however, the adnexal CRS 1/2 were 3 times as likely to develop platinum resistance compared with CRS 3 (relative risk=3.94, 95% CI: 1.03-15.09, P=0.046). The CRS, when used on the omentum, adnexa, and as a combined score, was significantly associated with PFS but not with OS. Adnexal CRS 1/2 are more likely to develop platinum-resistant disease. Therefore, the use of this pathology parameter may be useful for clinical management.
{"title":"A 3-Tier Chemotherapy Response Score for Ovarian/Fallopian Tube/Peritoneal High-grade Serous Carcinoma","authors":"B. Lawson, E. Euscher, R. Bassett, Jinsong Liu, P. Ramalingam, Y. Zhong, N. Fleming, A. Malpica","doi":"10.1097/PAS.0000000000001391","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001391","url":null,"abstract":"The chemotherapy response score (CRS) is used to score histopathologic response to neoadjuvant chemotherapy (NACT) of patients with extrauterine high-grade serous carcinoma. This study was undertaken to determine if the CRS in the omentum, adnexa or when combined correlates with (1) progression-free survival (PFS) or overall survival (OS), (2) laparoscopic score of abdominal disease, (3) Cancer antigen 125 levels, (4) BRCA status, and (5) platinum-resistant disease. A total of 158 cases were retrospectively collected that received NACT between April 2013 and February 2018 at a single institution. The 3-tier Böhm CRS system was applied to the omentum and adnexa. Survival outcomes between scored subgroups were analyzed using Cox proportional hazards regression. Spearman rank correlation analyses were used to assess CRS and clinical data. A total of 119 cases were treated only with carboplatin/paclitaxel. Omental CRS was: 1 (23 cases, 19.3%), 2 (65 cases, 54.6%), and 3 (31 cases, 26.1%), whereas adnexal CRS was: 1 (50 cases, 42%), 2 (48 cases, 40.3%) and 3 (21 cases, 17.6%). The omental CRS was significantly associated with PFS as a 2-tier score (hazard ratio [HR]=0.612, 95% confidence interval [CI]: 0.378-0.989, P=0.045) but not associated with the PFS using the 3-tier score or with OS using either system. Adnexal CRS was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.49, 95% CI: 0.263-0.914, P=0.025) and 2-tier scores (HR=0.535, 95% CI: 0.297-0.963, P=0.037). The combined score was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.348, 95% CI: 0.137-0.88, P=0.026) and 2-tier scores (HR=0.364, 95% CI: 0.148-0.896, P=0.028). No CRS system used associated with laparoscopic assessment of disease. CRS in the omentum had no significant association with platinum resistance; however, the adnexal CRS 1/2 were 3 times as likely to develop platinum resistance compared with CRS 3 (relative risk=3.94, 95% CI: 1.03-15.09, P=0.046). The CRS, when used on the omentum, adnexa, and as a combined score, was significantly associated with PFS but not with OS. Adnexal CRS 1/2 are more likely to develop platinum-resistant disease. Therefore, the use of this pathology parameter may be useful for clinical management.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124001473","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}
Pub Date : 2019-10-22DOI: 10.1097/PAS.0000000000001388
M. Treffel, Émilie Lardenois, F. Larousserie, M. Karanian, A. Gomez-Brouchet, C. Bouvier, F. Le Loarer, S. Aubert, G. de Pinieux, V. Audard, Maria Rios, F. Sirveaux, J. Vignaud, G. Gauchotte, B. Marie
Supplemental Digital Content is available in the text. Denosumab, an antibody directed against receptor activator of nuclear factor-κB ligand (RANKL), has recently been introduced in the treatment strategy of giant cell tumor of bone. In this study, we assessed the tumor changes induced by denosumab in a national multicentric series of 35 cases (French Bone Pathology Group network—ResOs). Tissue specimens collected before and after denosumab treatment were investigated for RANKL, H3.3 G34W, p63, and Ki-67 expression, and for H3F3A mutation. These parameters were put in correspondance with clinical and radiologic presentation to identify prognostic factors, and more specifically, predictive markers of an optimal histologic response to denosumab, identified as a ≥50% loss in giant cells with fibrosis and ossification. The main changes in posttreatment specimens showed an induction of ossification (P=2.10−5), an increased fibrosis (P=3.10−5), and a major decrease in giant cells (P=6.10−11). No significant change in mononuclear tumor cell density and in patterns of expression of RANKL (P=0.061) and H3.3 G34W was observed (P=0.061). An optimal histologic response to denosumab treatment was associated with an enhanced progression-free survival (P=0.010 in univariate analyses; P=0.040 in multivariate analyses). The initial number of giant cells was predictive of the histologic response to treatment (P=0.016). In summary, denosumab treatment induced radical changes in the tumor. The histologic response, despite the absence of objective regression of the mononuclear cells, was associated with an enhanced progression-free survival. Greater numbers of giant cells represented the only predictive indication of an optimal histologic response to denosumab treatment.
补充数字内容可在文本中找到。Denosumab是一种针对核因子-κB配体受体激活剂(receptor activator of nuclear factor-κB ligand, RANKL)的抗体，最近被引入骨巨细胞瘤的治疗策略。在这项研究中，我们评估了denosumab在35例国家多中心系列病例(法国骨病理组网络- resos)中引起的肿瘤变化。在denosumab治疗前后收集组织标本，检测RANKL、H3.3 G34W、p63和Ki-67的表达以及H3F3A的突变。这些参数与临床和放射学表现相一致，以确定预后因素，更具体地说，是对denosumab的最佳组织学反应的预测标记，确定为纤维化和骨化的巨细胞损失≥50%。处理后标本的主要变化表现为诱导骨化(P=2.10−5)，纤维化增加(P=3.10−5)，巨细胞大量减少(P=6.10−11)。单核肿瘤细胞密度、RANKL表达谱(P=0.061)、H3.3 G34W表达谱(P=0.061)无显著变化。对denosumab治疗的最佳组织学反应与提高的无进展生存期相关(单变量分析中P=0.010;多变量分析P=0.040)。巨细胞的初始数量可以预测对治疗的组织学反应(P=0.016)。综上所述，denosumab治疗可诱导肿瘤发生根治性变化。组织学上的反应，尽管没有客观的单核细胞消退，但与无进展生存期的提高有关。大量巨细胞是对地诺单抗治疗的最佳组织学反应的唯一预测指标。
{"title":"Denosumab-treated Giant Cell Tumors of Bone: A Clinicopathologic Analysis of 35 Cases From the French Group of Bone Pathology","authors":"M. Treffel, Émilie Lardenois, F. Larousserie, M. Karanian, A. Gomez-Brouchet, C. Bouvier, F. Le Loarer, S. Aubert, G. de Pinieux, V. Audard, Maria Rios, F. Sirveaux, J. Vignaud, G. Gauchotte, B. Marie","doi":"10.1097/PAS.0000000000001388","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001388","url":null,"abstract":"Supplemental Digital Content is available in the text. Denosumab, an antibody directed against receptor activator of nuclear factor-κB ligand (RANKL), has recently been introduced in the treatment strategy of giant cell tumor of bone. In this study, we assessed the tumor changes induced by denosumab in a national multicentric series of 35 cases (French Bone Pathology Group network—ResOs). Tissue specimens collected before and after denosumab treatment were investigated for RANKL, H3.3 G34W, p63, and Ki-67 expression, and for H3F3A mutation. These parameters were put in correspondance with clinical and radiologic presentation to identify prognostic factors, and more specifically, predictive markers of an optimal histologic response to denosumab, identified as a ≥50% loss in giant cells with fibrosis and ossification. The main changes in posttreatment specimens showed an induction of ossification (P=2.10−5), an increased fibrosis (P=3.10−5), and a major decrease in giant cells (P=6.10−11). No significant change in mononuclear tumor cell density and in patterns of expression of RANKL (P=0.061) and H3.3 G34W was observed (P=0.061). An optimal histologic response to denosumab treatment was associated with an enhanced progression-free survival (P=0.010 in univariate analyses; P=0.040 in multivariate analyses). The initial number of giant cells was predictive of the histologic response to treatment (P=0.016). In summary, denosumab treatment induced radical changes in the tumor. The histologic response, despite the absence of objective regression of the mononuclear cells, was associated with an enhanced progression-free survival. Greater numbers of giant cells represented the only predictive indication of an optimal histologic response to denosumab treatment.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128318187","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}
Pub Date : 2019-10-22DOI: 10.1097/PAS.0000000000001394
M. Pittman, Erika Hissong, P. Katz, R. Yantiss
Lymphocytic esophagitis is a well-known manifestation of Crohn disease among children but is not considered to be an immune-mediated mucositis in adults. We hypothesize that adult-onset lymphocyte-predominant esophagitis is also an immune-mediated inflammatory pattern, the nature of which has been masked by other conditions that feature esophageal lymphocytosis and occur in older patients. We performed this study to consolidate diagnostic criteria for lymphocyte-predominant esophagitis and determine its clinical significance. We identified 61 patients with lymphocyte-rich inflammation in the mid or proximal esophagus, none of whom had another explanation for esophageal lymphocytosis. Affected patients were usually older adults and 72% were women. Most (56%) presented with dysphagia and 34% had eosinophilic esophagitis-like changes with rings, exudates, and/or edematous mucosa and linear furrows. Intraepithelial lymphocytosis was accompanied by mucosal injury featuring edema, basal zone hyperplasia, and scattered dyskeratotic cells. Some cases displayed occasional neutrophils or even superficial microabscesses; eosinophils were consistently infrequent. Most (67%) patients had at least 1 systemic immune-mediated disorder, particularly Crohn disease (30%) and connective tissue diseases (23%); only 1 had mucocutaneous lichen planus. We conclude that mild mucosal lymphocytosis (ie, ≥20 lymphocytes/HPF) alone is a frequent and nonspecific finding; criteria for lymphocyte-predominant esophagitis should include evidence of mucosal injury and allow for more than the occasional neutrophil. When this diagnosis is limited to cases that feature lymphocytosis unattributed to acid reflux, motility disorders, or infection, lymphocyte-predominant esophagitis may represent an immune-mediated disorder with characteristic clinical manifestations and a predilection for middle-aged women.
{"title":"Lymphocyte-predominant Esophagitis","authors":"M. Pittman, Erika Hissong, P. Katz, R. Yantiss","doi":"10.1097/PAS.0000000000001394","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001394","url":null,"abstract":"Lymphocytic esophagitis is a well-known manifestation of Crohn disease among children but is not considered to be an immune-mediated mucositis in adults. We hypothesize that adult-onset lymphocyte-predominant esophagitis is also an immune-mediated inflammatory pattern, the nature of which has been masked by other conditions that feature esophageal lymphocytosis and occur in older patients. We performed this study to consolidate diagnostic criteria for lymphocyte-predominant esophagitis and determine its clinical significance. We identified 61 patients with lymphocyte-rich inflammation in the mid or proximal esophagus, none of whom had another explanation for esophageal lymphocytosis. Affected patients were usually older adults and 72% were women. Most (56%) presented with dysphagia and 34% had eosinophilic esophagitis-like changes with rings, exudates, and/or edematous mucosa and linear furrows. Intraepithelial lymphocytosis was accompanied by mucosal injury featuring edema, basal zone hyperplasia, and scattered dyskeratotic cells. Some cases displayed occasional neutrophils or even superficial microabscesses; eosinophils were consistently infrequent. Most (67%) patients had at least 1 systemic immune-mediated disorder, particularly Crohn disease (30%) and connective tissue diseases (23%); only 1 had mucocutaneous lichen planus. We conclude that mild mucosal lymphocytosis (ie, ≥20 lymphocytes/HPF) alone is a frequent and nonspecific finding; criteria for lymphocyte-predominant esophagitis should include evidence of mucosal injury and allow for more than the occasional neutrophil. When this diagnosis is limited to cases that feature lymphocytosis unattributed to acid reflux, motility disorders, or infection, lymphocyte-predominant esophagitis may represent an immune-mediated disorder with characteristic clinical manifestations and a predilection for middle-aged women.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124457672","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}
Pub Date : 2019-10-22DOI: 10.1097/PAS.0000000000001397
Margaret L. Compton, J. Cates
Supplemental Digital Content is available in the text. The eighth edition of the American Joint Committee on Cancer (AJCC) staging system has introduced major changes for the staging of skeletal sarcomas. However, it is unclear if these changes improve the predictive value for chondrosarcomas of the nonpelvic appendicular and nonspinal axial skeleton. Specifically, there is no clear evidence that supports the use of the proposed binary size cutoff of 8 cm for risk stratification, nor is a rationale provided for the categorization of grade 2 chondrosarcomas as high grade. The prognostic value of various anatomic and pathologic factors including tumor size, histologic grade, site of metastasis, and local tumor extent was evaluated using a cohort of patients derived from the National Cancer Database (N=3946). A simplified evidence-based staging system for chondrosarcoma (the Vanderbilt Staging System) was developed based on histologic subtype, histologic grade, and presence of metastatic disease. The predictive accuracy for 5-year overall survival was evaluated for the AJCC 8th edition, Musculoskeletal Tumor Society, and Vanderbilt Staging Systems by comparing areas under receiver operating characteristic curves generated from logistic regression analysis. Three different concordance indices and Bayesian information criterion were also calculated for model comparisons. The Vanderbilt Staging System showed significantly improved predictive accuracy for 5-year survival (82±2%) compared with the AJCC (79±2%; P=0.0075) and Musculoskeletal Tumor Society systems (76±2%; P<0.00005) in a separate validation cohort. Furthermore, the Vanderbilt Staging System showed significantly higher concordance with clinical outcomes for 2 of 3 examined indices and significantly greater extent of explained variation compared with the other 2 staging systems.
{"title":"Evidence-based Tumor Staging of Skeletal Chondrosarcoma","authors":"Margaret L. Compton, J. Cates","doi":"10.1097/PAS.0000000000001397","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001397","url":null,"abstract":"Supplemental Digital Content is available in the text. The eighth edition of the American Joint Committee on Cancer (AJCC) staging system has introduced major changes for the staging of skeletal sarcomas. However, it is unclear if these changes improve the predictive value for chondrosarcomas of the nonpelvic appendicular and nonspinal axial skeleton. Specifically, there is no clear evidence that supports the use of the proposed binary size cutoff of 8 cm for risk stratification, nor is a rationale provided for the categorization of grade 2 chondrosarcomas as high grade. The prognostic value of various anatomic and pathologic factors including tumor size, histologic grade, site of metastasis, and local tumor extent was evaluated using a cohort of patients derived from the National Cancer Database (N=3946). A simplified evidence-based staging system for chondrosarcoma (the Vanderbilt Staging System) was developed based on histologic subtype, histologic grade, and presence of metastatic disease. The predictive accuracy for 5-year overall survival was evaluated for the AJCC 8th edition, Musculoskeletal Tumor Society, and Vanderbilt Staging Systems by comparing areas under receiver operating characteristic curves generated from logistic regression analysis. Three different concordance indices and Bayesian information criterion were also calculated for model comparisons. The Vanderbilt Staging System showed significantly improved predictive accuracy for 5-year survival (82±2%) compared with the AJCC (79±2%; P=0.0075) and Musculoskeletal Tumor Society systems (76±2%; P<0.00005) in a separate validation cohort. Furthermore, the Vanderbilt Staging System showed significantly higher concordance with clinical outcomes for 2 of 3 examined indices and significantly greater extent of explained variation compared with the other 2 staging systems.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125422924","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}
Pub Date : 2019-10-22DOI: 10.1097/PAS.0000000000001395
A. Pasanen, T. Ahvenainen, T. Pellinen, P. Vahteristo, M. Loukovaara, R. Bützow
Programmed death-ligand 1 (PD-L1) is a biomarker that may predict the response to anti-programmed death 1/PD-L1 immunotherapy. We evaluated the expression of PD-L1 in carcinoma cells (Ca) and immune cells (ICs) across histopathologic and The Cancer Genome Atlas (TCGA) molecular subgroups of endometrial carcinoma (EC). Our study included 842 patients with EC. Direct sequencing of polymerase epsilon (POLE) exonuclease domain hot spots and conventional immunohistochemistry (MLH1, PMS2, MSH2, MSH6, p53) were conducted to identify TCGA classification–based molecular subgroups of EC: POLE-mutated, mismatch repair deficient, no specific molecular profile, and p53 aberrant. Multiplex immunohistochemistry was performed to evaluate PD-L1 expression in Ca and tumor-infiltrating ICs. PD-L1 expression in Ca and in ICs was detected in 8.6% and 27.7% of the cases, respectively. A combined positive score (CPS) was ≥1% in 19.4% of the samples. PD-L1 positivity in Ca and ICs, and CPS correlated with tumor T-cell density (P<0.001). POLE-mutated and mismatch repair-deficient tumors were more likely to present PD-L1-expressing ICs, CPS positivity, and abundant tumor-infiltrating lymphocytes compared with other TCGA subgroups (P<0.001). No differences existed in Ca-PD-L1 expression (P=0.366). Within various histotypes, non-endometrioid carcinomas displayed the highest Ca-PD-L1, ICs, and CPS (P<0.03). Advanced cancers showed more frequent Ca-PD-L1 positivity (P=0.016), and CPS (P=0.029) and IC≥1% (P=0.037) positivity compared with early disease. In conclusion, PD-L1 expression profiles differ between molecular subclasses, histologic subtypes, and disease stage of EC. Prospective studies are needed to explore the predictive value of various PD-L1 scoring systems within the subgroups of EC. CPS presents methodological advantages over cell type–specific scoring systems.
{"title":"PD-L1 Expression in Endometrial Carcinoma Cells and Intratumoral Immune Cells","authors":"A. Pasanen, T. Ahvenainen, T. Pellinen, P. Vahteristo, M. Loukovaara, R. Bützow","doi":"10.1097/PAS.0000000000001395","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001395","url":null,"abstract":"Programmed death-ligand 1 (PD-L1) is a biomarker that may predict the response to anti-programmed death 1/PD-L1 immunotherapy. We evaluated the expression of PD-L1 in carcinoma cells (Ca) and immune cells (ICs) across histopathologic and The Cancer Genome Atlas (TCGA) molecular subgroups of endometrial carcinoma (EC). Our study included 842 patients with EC. Direct sequencing of polymerase epsilon (POLE) exonuclease domain hot spots and conventional immunohistochemistry (MLH1, PMS2, MSH2, MSH6, p53) were conducted to identify TCGA classification–based molecular subgroups of EC: POLE-mutated, mismatch repair deficient, no specific molecular profile, and p53 aberrant. Multiplex immunohistochemistry was performed to evaluate PD-L1 expression in Ca and tumor-infiltrating ICs. PD-L1 expression in Ca and in ICs was detected in 8.6% and 27.7% of the cases, respectively. A combined positive score (CPS) was ≥1% in 19.4% of the samples. PD-L1 positivity in Ca and ICs, and CPS correlated with tumor T-cell density (P<0.001). POLE-mutated and mismatch repair-deficient tumors were more likely to present PD-L1-expressing ICs, CPS positivity, and abundant tumor-infiltrating lymphocytes compared with other TCGA subgroups (P<0.001). No differences existed in Ca-PD-L1 expression (P=0.366). Within various histotypes, non-endometrioid carcinomas displayed the highest Ca-PD-L1, ICs, and CPS (P<0.03). Advanced cancers showed more frequent Ca-PD-L1 positivity (P=0.016), and CPS (P=0.029) and IC≥1% (P=0.037) positivity compared with early disease. In conclusion, PD-L1 expression profiles differ between molecular subclasses, histologic subtypes, and disease stage of EC. Prospective studies are needed to explore the predictive value of various PD-L1 scoring systems within the subgroups of EC. CPS presents methodological advantages over cell type–specific scoring systems.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"120 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124168169","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}
Pub Date : 2019-10-22DOI: 10.1097/PAS.0000000000001396
B. Chang, Lin Yu, Wen-wen Guo, W. Sheng, Lei Wang, I. Lao, Dan Huang, Q. Bai, Jian Wang
A malignant gastrointestinal neuroectodermal tumor (GNET) is rare, and it is therefore yet to be completely understood. This study aimed to present the clinicopathologic features of GNET, including treatment information. We included 19 patients with GNET with a mean tumor size of 4.2 cm. The most common site of tumor origin was the small intestine (57.9%), followed by the stomach (15.8%), colon (10.5%), ileocecal junction (5.3%), lower esophagus (5.3%), and anal canal (5.3%). Microscopically, the tumors were composed of epithelioid cells with eosinophilic or clear cytoplasm arranged in nest, sheet-like, papillary, or pseudoalveolar patterns and/or spindle tumor cells with eosinophilic cytoplasm arranged in a fascicular pattern. Immunohistochemically, the tumor cells stained positively for S100 (19/19,100%), SOX10 (14/15, 93.3%), vimentin (17/17, 100%), synaptophysin (Syn) (7/17, 41.2%), CD56 (4/13, 30.8%), CD99 (1/5, 20%), and CD117 (1/15, 6.7%), and negatively for HMB45, Melan A, DOG1, CD34, AE1/AE3, CAM5.2, chromogranin A, smooth muscle actin, and desmin. In total, 14/15 (93.3%) cases showed split Ewing sarcoma breakpoint region 1 gene (EWSR1) signals consistent with a chromosomal translocation involving EWSR1. Within a mean follow-up of 29.7 months (range: 3 to 63 mo), 2/15 (13.3%) patients died of disease, 5 (33.3%) were alive with disease, and 8 (53.3%) had no evidence of disease. Two and 1 patients showed partial response to apatinib and anlotinib, respectively. In conclusion, GNET has distinctive morphologic, immunohistochemical, and molecular genetic features and should be distinguished from other gastrointestinal tract malignancies. Apatinib and anlotinib might be effective for the treatment of advanced GNET and could prolong patient survival.
{"title":"Malignant Gastrointestinal Neuroectodermal Tumor","authors":"B. Chang, Lin Yu, Wen-wen Guo, W. Sheng, Lei Wang, I. Lao, Dan Huang, Q. Bai, Jian Wang","doi":"10.1097/PAS.0000000000001396","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001396","url":null,"abstract":"A malignant gastrointestinal neuroectodermal tumor (GNET) is rare, and it is therefore yet to be completely understood. This study aimed to present the clinicopathologic features of GNET, including treatment information. We included 19 patients with GNET with a mean tumor size of 4.2 cm. The most common site of tumor origin was the small intestine (57.9%), followed by the stomach (15.8%), colon (10.5%), ileocecal junction (5.3%), lower esophagus (5.3%), and anal canal (5.3%). Microscopically, the tumors were composed of epithelioid cells with eosinophilic or clear cytoplasm arranged in nest, sheet-like, papillary, or pseudoalveolar patterns and/or spindle tumor cells with eosinophilic cytoplasm arranged in a fascicular pattern. Immunohistochemically, the tumor cells stained positively for S100 (19/19,100%), SOX10 (14/15, 93.3%), vimentin (17/17, 100%), synaptophysin (Syn) (7/17, 41.2%), CD56 (4/13, 30.8%), CD99 (1/5, 20%), and CD117 (1/15, 6.7%), and negatively for HMB45, Melan A, DOG1, CD34, AE1/AE3, CAM5.2, chromogranin A, smooth muscle actin, and desmin. In total, 14/15 (93.3%) cases showed split Ewing sarcoma breakpoint region 1 gene (EWSR1) signals consistent with a chromosomal translocation involving EWSR1. Within a mean follow-up of 29.7 months (range: 3 to 63 mo), 2/15 (13.3%) patients died of disease, 5 (33.3%) were alive with disease, and 8 (53.3%) had no evidence of disease. Two and 1 patients showed partial response to apatinib and anlotinib, respectively. In conclusion, GNET has distinctive morphologic, immunohistochemical, and molecular genetic features and should be distinguished from other gastrointestinal tract malignancies. Apatinib and anlotinib might be effective for the treatment of advanced GNET and could prolong patient survival.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131192263","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}
Pub Date : 2019-10-16DOI: 10.1097/PAS.0000000000001393
C. Lezcano, M. Pulitzer, A. Moy, T. Hollmann, A. Jungbluth, K. Busam
The distinction of metastatic melanoma from melanocytic nevi in lymph nodes can on occasion be difficult. As diffuse immunohistochemical (IHC) PRAME (PReferentially expressed Antigen in MElanoma) expression is detected in the majority of primary and metastatic melanomas, but rarely in nevi, we reasoned that PRAME could be a useful adjunct marker for the diagnosis of melanocytes in lymph nodes. In this study, we examined 45 nodal melanocytic deposits comprising 30 nodal nevi and 15 melanoma metastases. The latter were diagnostically not straightforward because they either coexisted with nodal nevi or were present in perinodal fibrous tissue. All nodal nevi (30/30) were negative for PRAME, whereas all melanoma metastases (15/15) were diffusely positive for PRAME IHC. We additionally report the novel use of a PRAME/Melan A dual-label immunostain. Our results show that PRAME IHC may be useful in the assessment of diagnostically challenging nodal melanocytic deposits, such as intraparenchymal nodal nevi, metastases confined to the capsular fibrous tissue, or in the setting of small metastases coexisting with a nodal nevus in the same lymph node.
{"title":"Immunohistochemistry for PRAME in the Distinction of Nodal Nevi From Metastatic Melanoma","authors":"C. Lezcano, M. Pulitzer, A. Moy, T. Hollmann, A. Jungbluth, K. Busam","doi":"10.1097/PAS.0000000000001393","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001393","url":null,"abstract":"The distinction of metastatic melanoma from melanocytic nevi in lymph nodes can on occasion be difficult. As diffuse immunohistochemical (IHC) PRAME (PReferentially expressed Antigen in MElanoma) expression is detected in the majority of primary and metastatic melanomas, but rarely in nevi, we reasoned that PRAME could be a useful adjunct marker for the diagnosis of melanocytes in lymph nodes. In this study, we examined 45 nodal melanocytic deposits comprising 30 nodal nevi and 15 melanoma metastases. The latter were diagnostically not straightforward because they either coexisted with nodal nevi or were present in perinodal fibrous tissue. All nodal nevi (30/30) were negative for PRAME, whereas all melanoma metastases (15/15) were diffusely positive for PRAME IHC. We additionally report the novel use of a PRAME/Melan A dual-label immunostain. Our results show that PRAME IHC may be useful in the assessment of diagnostically challenging nodal melanocytic deposits, such as intraparenchymal nodal nevi, metastases confined to the capsular fibrous tissue, or in the setting of small metastases coexisting with a nodal nevus in the same lymph node.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130119663","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}
In this study, we aimed to present the clinicopathologic and molecular features of a distinct group of hemangioma with GNA mutations that exhibited prominent thrombosis and organization changes with florid intravascular endothelial cell proliferation that we provisionally termed “thrombotic hemangioma with organizing/anastomosing features.” Twenty-six cases were included. No sex predilection was seen (male:female=13:13). Patients’ age ranged from 17 to 89 years (median: 51 y). All but 1 occurred in the skin whereas the remaining tumor involved the neck soft tissue. Remarkably, the majority (18) occurred in the lower abdominal/inguinal regions. Histologically, thrombotic hemangioma with organizing/anastomosing features were circumscribed tumors composed of variably sized and congested thin-walled vessels. The most striking features were prominent thrombosis and organization with florid intravascular endothelial cell proliferation. The proliferating endothelial cells exhibit a streaming pattern with focal anastomosing–like feature resembling anastomosing hemangioma. The stroma was sclerotic or hyalinized but could also be myxoid/edematous. Other features included vessels with nuclear hobnailing and perivascular hyalinization, cherry hemangioma–like component, cavernous-like or sinusoidal hemangioma–like areas, Masson hemangioma–like feature, and spindle cell fascicular pattern. Mitotic activity was usually low and nuclei were bland but 2 tumors exhibited moderate nuclear atypia and higher mitotic activity. Extramedullary hematopoiesis and hyaline globules were not identified. Genetically, by Sanger sequencing and MassARRAY analysis, mutually exclusive GNAQ, GNA11, and GNA14 exon 5 mutations were identified in 15, 5, and 2 tumors, respectively, with a combined mutation rate of 85% (22/26). In conclusion, we described a distinct group of hemangioma and expanded the clinicopathologic features of GNA-mutated hemangiomas.
{"title":"Thrombotic Hemangioma With Organizing/Anastomosing Features","authors":"Jau-Yu Liau, Jen-Chieh Lee, J. Tsai, Chih-Chi Chen, Ying-Hao Wang, Yung-Chuan Chung","doi":"10.1097/PAS.0000000000001392","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001392","url":null,"abstract":"In this study, we aimed to present the clinicopathologic and molecular features of a distinct group of hemangioma with GNA mutations that exhibited prominent thrombosis and organization changes with florid intravascular endothelial cell proliferation that we provisionally termed “thrombotic hemangioma with organizing/anastomosing features.” Twenty-six cases were included. No sex predilection was seen (male:female=13:13). Patients’ age ranged from 17 to 89 years (median: 51 y). All but 1 occurred in the skin whereas the remaining tumor involved the neck soft tissue. Remarkably, the majority (18) occurred in the lower abdominal/inguinal regions. Histologically, thrombotic hemangioma with organizing/anastomosing features were circumscribed tumors composed of variably sized and congested thin-walled vessels. The most striking features were prominent thrombosis and organization with florid intravascular endothelial cell proliferation. The proliferating endothelial cells exhibit a streaming pattern with focal anastomosing–like feature resembling anastomosing hemangioma. The stroma was sclerotic or hyalinized but could also be myxoid/edematous. Other features included vessels with nuclear hobnailing and perivascular hyalinization, cherry hemangioma–like component, cavernous-like or sinusoidal hemangioma–like areas, Masson hemangioma–like feature, and spindle cell fascicular pattern. Mitotic activity was usually low and nuclei were bland but 2 tumors exhibited moderate nuclear atypia and higher mitotic activity. Extramedullary hematopoiesis and hyaline globules were not identified. Genetically, by Sanger sequencing and MassARRAY analysis, mutually exclusive GNAQ, GNA11, and GNA14 exon 5 mutations were identified in 15, 5, and 2 tumors, respectively, with a combined mutation rate of 85% (22/26). In conclusion, we described a distinct group of hemangioma and expanded the clinicopathologic features of GNA-mutated hemangiomas.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"81 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132060315","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}
Pub Date : 2019-10-11DOI: 10.1097/PAS.0000000000001385
Anne Grabenstetter, Sandra B Brennan, E. D. Salagean, M. Morrow, E. Brogi
Flat epithelial atypia (FEA) is an alteration of terminal duct lobular units by a proliferation of ductal epithelium with low-grade atypia. No consensus exists on whether the diagnosis of FEA in core needle biopsy (CNB) requires excision (EXC). We retrospectively identified all in-house CNBs obtained between January 2012 and July 2018 with FEA. We reviewed all CNB slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma (IC) and/or ductal carcinoma in situ in the EXC. The EXC slides of all upgraded cases were rereviewed. Out of ∼15,700 consecutive CNBs in the study period, 106 CNBs from 106 patients yielded FEA alone or with classic lobular neoplasia (LN). We excluded 52 CNBs (40 patients with prior/concurrent carcinoma and 12 without EXC). After rereview, we reclassified 14 cases (2 marked nuclear atypia, 10 focal atypical ductal hyperplasia, 2 benign). The final FEA study cohort consisted of 40 CNBs from 40 women. The CNB targeted mammographic calcifications in 36 (90%) cases, magnetic resonance imaging nonmass enhancement in 3 (8%), and 1 (2%) sonographic mass. All CNBs were deemed radiologic-pathologic concordant. FEA was present alone in 34 CNBs and with LN in 6. EXC yielded 2 low-grade IC, each spanning <2 mm, identified in tissue sections without biopsy site changes. The remaining 38 cases had no upgrade. Classic LN did not affect the upgrade. The upgrade rate of FEA was 5%; both minute, low-grade “incidental” IC. We conclude that nonsurgical management may be considered in patients without prior/concurrent carcinoma and radiologic-pathologic concordant CNB diagnosis of FEA.
{"title":"Flat Epithelial Atypia in Breast Core Needle Biopsies With Radiologic-Pathologic Concordance","authors":"Anne Grabenstetter, Sandra B Brennan, E. D. Salagean, M. Morrow, E. Brogi","doi":"10.1097/PAS.0000000000001385","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001385","url":null,"abstract":"Flat epithelial atypia (FEA) is an alteration of terminal duct lobular units by a proliferation of ductal epithelium with low-grade atypia. No consensus exists on whether the diagnosis of FEA in core needle biopsy (CNB) requires excision (EXC). We retrospectively identified all in-house CNBs obtained between January 2012 and July 2018 with FEA. We reviewed all CNB slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma (IC) and/or ductal carcinoma in situ in the EXC. The EXC slides of all upgraded cases were rereviewed. Out of ∼15,700 consecutive CNBs in the study period, 106 CNBs from 106 patients yielded FEA alone or with classic lobular neoplasia (LN). We excluded 52 CNBs (40 patients with prior/concurrent carcinoma and 12 without EXC). After rereview, we reclassified 14 cases (2 marked nuclear atypia, 10 focal atypical ductal hyperplasia, 2 benign). The final FEA study cohort consisted of 40 CNBs from 40 women. The CNB targeted mammographic calcifications in 36 (90%) cases, magnetic resonance imaging nonmass enhancement in 3 (8%), and 1 (2%) sonographic mass. All CNBs were deemed radiologic-pathologic concordant. FEA was present alone in 34 CNBs and with LN in 6. EXC yielded 2 low-grade IC, each spanning <2 mm, identified in tissue sections without biopsy site changes. The remaining 38 cases had no upgrade. Classic LN did not affect the upgrade. The upgrade rate of FEA was 5%; both minute, low-grade “incidental” IC. We conclude that nonsurgical management may be considered in patients without prior/concurrent carcinoma and radiologic-pathologic concordant CNB diagnosis of FEA.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"173 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126285654","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}
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