Pub Date : 2019-08-28DOI: 10.1097/PAS.0000000000001351
A. Akki, Wei Zhang, Kathryn E. Tanaka, S. Chung, Qiang Liu, N. Panarelli
Many gallbladder adenocarcinomas (ACs) are detected incidentally in routine cholecystectomy specimens, yet sampling practices vary when intestinal metaplasia (IM) or dysplasia are found via routine sampling. Our practice has been to submit 5 additional sections when IM is found, but cases with dysplasia are entirely submitted. We sought to determine an appropriate sampling protocol when encountering these findings. We retrospectively identified cholecystectomy specimens with these features over a 26-month period, yielding 48 of 4059 (1%) cases. Four pathologists independently classified the (2 longitudinal and 1 cystic duct margin) original sections into 1 of 3 categories (IM, low-grade dysplasia [LGD] or high-grade dysplasia [HGD]); initial findings were correlated with final diagnoses. Sixteen (33%) cases had additional findings upon further sampling, including LGD (n=10) or HGD (n=4) and AC (n=2). HGD always accompanied malignancy. We prospectively analyzed 39 of 3133 (1%) additional cholecystectomy specimens, initially submitting the same routine sections. We submitted 5 random sections from cases with IM. Cases with LGD were first examined with 1 additional section per centimeter. All remaining tissue was submitted in all of these cases and separately reviewed. Cases with HGD were entirely submitted as both test cases with HGD in initial sections ultimately showed carcinoma. This protocol detected all cases of HGD and AC. Patients with clear cystic duct margins did not experience neoplastic progression, even if dysplasia was present elsewhere. We conclude gallbladders with HGD should be entirely submitted, LGD may be representatively sampled, and routine sampling is adequate for IM.
{"title":"Systematic Selective Sampling of Cholecystectomy Specimens Is Adequate to Detect Incidental Gallbladder Adenocarcinoma","authors":"A. Akki, Wei Zhang, Kathryn E. Tanaka, S. Chung, Qiang Liu, N. Panarelli","doi":"10.1097/PAS.0000000000001351","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001351","url":null,"abstract":"Many gallbladder adenocarcinomas (ACs) are detected incidentally in routine cholecystectomy specimens, yet sampling practices vary when intestinal metaplasia (IM) or dysplasia are found via routine sampling. Our practice has been to submit 5 additional sections when IM is found, but cases with dysplasia are entirely submitted. We sought to determine an appropriate sampling protocol when encountering these findings. We retrospectively identified cholecystectomy specimens with these features over a 26-month period, yielding 48 of 4059 (1%) cases. Four pathologists independently classified the (2 longitudinal and 1 cystic duct margin) original sections into 1 of 3 categories (IM, low-grade dysplasia [LGD] or high-grade dysplasia [HGD]); initial findings were correlated with final diagnoses. Sixteen (33%) cases had additional findings upon further sampling, including LGD (n=10) or HGD (n=4) and AC (n=2). HGD always accompanied malignancy. We prospectively analyzed 39 of 3133 (1%) additional cholecystectomy specimens, initially submitting the same routine sections. We submitted 5 random sections from cases with IM. Cases with LGD were first examined with 1 additional section per centimeter. All remaining tissue was submitted in all of these cases and separately reviewed. Cases with HGD were entirely submitted as both test cases with HGD in initial sections ultimately showed carcinoma. This protocol detected all cases of HGD and AC. Patients with clear cystic duct margins did not experience neoplastic progression, even if dysplasia was present elsewhere. We conclude gallbladders with HGD should be entirely submitted, LGD may be representatively sampled, and routine sampling is adequate for IM.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132794263","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 : 2019-08-28DOI: 10.1097/PAS.0000000000001348
Emily A Goebel, Silvia Hernandez Bonilla, Fei Dong, B. Dickson, L. Hoang, D. Hardisson, M. Lacambra, F. Lu, C. Fletcher, C. Crum, C. Antonescu, M. Nucci, D. Kolin
Supplemental Digital Content is available in the text. Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study. Fluorescence in situ hybridization for NCOA1, NCOA2, NCOA3, ESR1 and GREB1, and targeted RNA sequencing was performed on 17 and 8 UTROSCTs, respectively. Eight cases underwent massively parallel sequencing to detect single nucleotide variants (SNV), copy number variations, and structural variants using a targeted hybrid-capture based assay. NCOA1-3 rearrangement was identified in 81.8% (18/22) of cases. The most common fusion was ESR1-NCOA3, occurring in 40.9% (9/22). GREB1-NCOA1 (n=4), ESR1-NCOA2 (n=3), and GREB1-NCOA2 (n=1) rearrangements were also identified. No recurrent SNVs were identified and no tumor had SNVs in FOXL2, DICER1, STK11, or AKT1, which can be seen in ovarian sex cord-stromal tumors. Copy number variations were infrequent. Clinical follow-up was available for 11 cases with a mean follow-up interval of 94.4 (range, 1 to 319) months. Only one case had a recurrence 66 months after the initial diagnosis and this was the single case with a GREB1-NCOA2 fusion. This study reports the morphologic spectrum of UTROSCT and confirms the recently reported recurrent NCOA2-3 gene fusions, in addition to identifying novel rearrangements involving NCOA1 in these tumors.
{"title":"Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT)","authors":"Emily A Goebel, Silvia Hernandez Bonilla, Fei Dong, B. Dickson, L. Hoang, D. Hardisson, M. Lacambra, F. Lu, C. Fletcher, C. Crum, C. Antonescu, M. Nucci, D. Kolin","doi":"10.1097/PAS.0000000000001348","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001348","url":null,"abstract":"Supplemental Digital Content is available in the text. Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study. Fluorescence in situ hybridization for NCOA1, NCOA2, NCOA3, ESR1 and GREB1, and targeted RNA sequencing was performed on 17 and 8 UTROSCTs, respectively. Eight cases underwent massively parallel sequencing to detect single nucleotide variants (SNV), copy number variations, and structural variants using a targeted hybrid-capture based assay. NCOA1-3 rearrangement was identified in 81.8% (18/22) of cases. The most common fusion was ESR1-NCOA3, occurring in 40.9% (9/22). GREB1-NCOA1 (n=4), ESR1-NCOA2 (n=3), and GREB1-NCOA2 (n=1) rearrangements were also identified. No recurrent SNVs were identified and no tumor had SNVs in FOXL2, DICER1, STK11, or AKT1, which can be seen in ovarian sex cord-stromal tumors. Copy number variations were infrequent. Clinical follow-up was available for 11 cases with a mean follow-up interval of 94.4 (range, 1 to 319) months. Only one case had a recurrence 66 months after the initial diagnosis and this was the single case with a GREB1-NCOA2 fusion. This study reports the morphologic spectrum of UTROSCT and confirms the recently reported recurrent NCOA2-3 gene fusions, in addition to identifying novel rearrangements involving NCOA1 in these tumors.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121758693","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 : 2019-08-20DOI: 10.1097/PAS.0000000000001345
Shun Sato, T. Kimura, T. Yorozu, H. Onuma, K. Iwatani, S. Egawa, M. Ikegami, Hiroyuki Takahashi
Supplemental Digital Content is available in the text. Recent discussions have suggested expanding the inclusion criteria for active prostate cancer surveillance to include cases with a Gleason score (GS) of 3+4=7. In this study, we examined this proposed use of a limited percent Gleason pattern 4 (%GP4) to identify candidates of active surveillance among 315 patients who underwent radical prostatectomy for prostate cancer with a GS of 6 or 3+4=7 via needle biopsy. The latter cases were divided into 4 groups using highest or overall %GP4 cut-off values of 5% and 10% as determined from prostate needle biopsies. The frequency of adverse pathology and risk of biochemical recurrence were compared between the GS 6 and both GS 3+4=7 groups. Adverse pathology was defined as a GS 4+3=7 or higher, pT3b staging or positive lymph node metastasis. Notably, the Gleason pattern 4 <5% and GS 6 groups did not differ significantly in terms of the frequency of adverse pathology and risk of biochemical recurrence by the highest method. However, other highest Gleason pattern 4 categories had significantly higher frequencies and risks. Using the overall method, even the Gleason pattern 4 <5% group had a significantly higher frequency of adverse pathology and risk of biochemical recurrence relative to the GS 6 group. In conclusion, our findings suggest that patients with a GS 3+4=7 on biopsy with a highest %GP4 <5% are similar candidates for active surveillance to men with GS 6 cancers.
{"title":"Cases Having a Gleason Score 3+4=7 With <5% of Gleason Pattern 4 in Prostate Needle Biopsy Show Similar Failure-free Survival and Adverse Pathology Prevalence to Gleason Score 6 Cases in a Radical Prostatectomy Cohort","authors":"Shun Sato, T. Kimura, T. Yorozu, H. Onuma, K. Iwatani, S. Egawa, M. Ikegami, Hiroyuki Takahashi","doi":"10.1097/PAS.0000000000001345","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001345","url":null,"abstract":"Supplemental Digital Content is available in the text. Recent discussions have suggested expanding the inclusion criteria for active prostate cancer surveillance to include cases with a Gleason score (GS) of 3+4=7. In this study, we examined this proposed use of a limited percent Gleason pattern 4 (%GP4) to identify candidates of active surveillance among 315 patients who underwent radical prostatectomy for prostate cancer with a GS of 6 or 3+4=7 via needle biopsy. The latter cases were divided into 4 groups using highest or overall %GP4 cut-off values of 5% and 10% as determined from prostate needle biopsies. The frequency of adverse pathology and risk of biochemical recurrence were compared between the GS 6 and both GS 3+4=7 groups. Adverse pathology was defined as a GS 4+3=7 or higher, pT3b staging or positive lymph node metastasis. Notably, the Gleason pattern 4 <5% and GS 6 groups did not differ significantly in terms of the frequency of adverse pathology and risk of biochemical recurrence by the highest method. However, other highest Gleason pattern 4 categories had significantly higher frequencies and risks. Using the overall method, even the Gleason pattern 4 <5% group had a significantly higher frequency of adverse pathology and risk of biochemical recurrence relative to the GS 6 group. In conclusion, our findings suggest that patients with a GS 3+4=7 on biopsy with a highest %GP4 <5% are similar candidates for active surveillance to men with GS 6 cancers.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134523043","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 : 2019-08-20DOI: 10.1097/PAS.0000000000001347
Jenny C. Hoffmann, Chieh-Yu Lin, Siddhartha Bhattacharyya, O. Weinberg, Karen M. Chisholm, M. Bayerl, Michael J. Cascio, G. Venkataraman, K. Allison, M. Troxell, C. Chang, A. Bagg, T. George, D. O’Malley, R. Ohgami
Supplemental Digital Content is available in the text. Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (<1/50 HPF) to numerous (>50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.
{"title":"Rosai-Dorfman Disease of the Breast With Variable IgG4+ Plasma Cells","authors":"Jenny C. Hoffmann, Chieh-Yu Lin, Siddhartha Bhattacharyya, O. Weinberg, Karen M. Chisholm, M. Bayerl, Michael J. Cascio, G. Venkataraman, K. Allison, M. Troxell, C. Chang, A. Bagg, T. George, D. O’Malley, R. Ohgami","doi":"10.1097/PAS.0000000000001347","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001347","url":null,"abstract":"Supplemental Digital Content is available in the text. Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (<1/50 HPF) to numerous (>50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128581497","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 : 2019-08-14DOI: 10.1097/PAS.0000000000001344
B. Esmaeli, M. L. Rubin, Shiqiong Xu, R. Goepfert, J. Curry, V. Prieto, J. Ning, M. Tetzlaff
Supplemental Digital Content is available in the text. Identifying tumor characteristics that correlate with metastasis and survival in patients with conjunctival melanoma can potentially lead to better outcomes through a better selection of patients for adjuvant treatments including potentially life-saving new melanoma therapy. The objective of this study was to validate the conjunctival melanoma staging criteria in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (8th edition) and explore the prognostic importance of tumor thickness, histologic ulceration, and sentinel lymph node biopsy (SLNB) findings in patients with conjunctival melanoma. This is a case series of 88 consecutive patients with conjunctival melanoma. Clinicopathologic characteristics were analyzed. Associations between pathologic characteristics and outcomes were studied using Kaplan-Meier survival analysis. Local recurrence, lymph node metastasis, distant metastasis, and disease-specific survival (DSS) were the main outcome measures. The study included 56 women and 32 men; the median age was 62 years. At presentation, 41 patients had T1 disease, 23 had T2 disease, 23 had T3, and 1 had T4 disease. Sixty-six patients had invasive conjunctival melanoma (median thickness, 1.56 mm), 17 had conjunctival melanoma in situ, and in 5 patients, tumor thickness could not be determined. Overall, 22 patients had ulceration. In total, 31 patients underwent SLNB, and 4 had a positive sentinel lymph node (SLN). The median follow-up time was 46.6 months. Overall, 12 patients had nodal metastasis at presentation or during follow-up, 19 patients had distant metastasis at last follow-up, and 14 patients died of the disease. Tumor thickness and ulceration were associated with increased risks of nodal metastasis, distant metastasis, and death from the disease. Overall, greater clinical T category at presentation was associated with increased risks of distant metastasis and disease-related death; however, the risks of distant metastasis and disease-related death did not differ between T1 (bulbar) and T2 (nonbulbar) tumors or between T2c,d (caruncular) and T1-T2a,b (noncaruncular) tumors. In patients who underwent SLNB, a positive SLN was associated with worse distant metastasis free survival and DSS. Consideration should be given to adding ulceration and emphasizing tumor thickness as the main determinants of pathologic T category for conjunctival melanoma in future AJCC classifications. The significant association between a positive SLN and worse DSS highlights the importance of SLNB for prognosis in patients with conjunctival melanoma and selecting high-risk patients for adjuvant drug treatment.
{"title":"Greater Tumor Thickness, Ulceration, and Positive Sentinel Lymph Node Are Associated With Worse Prognosis in Patients With Conjunctival Melanoma","authors":"B. Esmaeli, M. L. Rubin, Shiqiong Xu, R. Goepfert, J. Curry, V. Prieto, J. Ning, M. Tetzlaff","doi":"10.1097/PAS.0000000000001344","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001344","url":null,"abstract":"Supplemental Digital Content is available in the text. Identifying tumor characteristics that correlate with metastasis and survival in patients with conjunctival melanoma can potentially lead to better outcomes through a better selection of patients for adjuvant treatments including potentially life-saving new melanoma therapy. The objective of this study was to validate the conjunctival melanoma staging criteria in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (8th edition) and explore the prognostic importance of tumor thickness, histologic ulceration, and sentinel lymph node biopsy (SLNB) findings in patients with conjunctival melanoma. This is a case series of 88 consecutive patients with conjunctival melanoma. Clinicopathologic characteristics were analyzed. Associations between pathologic characteristics and outcomes were studied using Kaplan-Meier survival analysis. Local recurrence, lymph node metastasis, distant metastasis, and disease-specific survival (DSS) were the main outcome measures. The study included 56 women and 32 men; the median age was 62 years. At presentation, 41 patients had T1 disease, 23 had T2 disease, 23 had T3, and 1 had T4 disease. Sixty-six patients had invasive conjunctival melanoma (median thickness, 1.56 mm), 17 had conjunctival melanoma in situ, and in 5 patients, tumor thickness could not be determined. Overall, 22 patients had ulceration. In total, 31 patients underwent SLNB, and 4 had a positive sentinel lymph node (SLN). The median follow-up time was 46.6 months. Overall, 12 patients had nodal metastasis at presentation or during follow-up, 19 patients had distant metastasis at last follow-up, and 14 patients died of the disease. Tumor thickness and ulceration were associated with increased risks of nodal metastasis, distant metastasis, and death from the disease. Overall, greater clinical T category at presentation was associated with increased risks of distant metastasis and disease-related death; however, the risks of distant metastasis and disease-related death did not differ between T1 (bulbar) and T2 (nonbulbar) tumors or between T2c,d (caruncular) and T1-T2a,b (noncaruncular) tumors. In patients who underwent SLNB, a positive SLN was associated with worse distant metastasis free survival and DSS. Consideration should be given to adding ulceration and emphasizing tumor thickness as the main determinants of pathologic T category for conjunctival melanoma in future AJCC classifications. The significant association between a positive SLN and worse DSS highlights the importance of SLNB for prognosis in patients with conjunctival melanoma and selecting high-risk patients for adjuvant drug treatment.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"88 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133037062","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 : 2019-08-12DOI: 10.1097/PAS.0000000000001343
Zainab I. Alruwaii, Yang Zhang, Tatianna C. Larman, J. A. Miller, E. Montgomery
Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferation that occurs in nodal and extranodal sites. Rare examples of the disease involving the digestive system have been described. To characterize the digestive tract manifestations of this disease, 12 specimens from 11 patients with extranodal RDD affecting the digestive organs were analyzed. Hematoxylin and eosin sections and available immunohistochemical stains were reviewed, and the clinical information was obtained from patients’ electronic or submitted records. Eight patients were female and 3 male (median age, 65 y; range, 17 to 76 y). Abdominal pain was the most frequent symptom. Six patients had an associated immunologic or malignant disease. Nine lesions arose in the gastrointestinal tract (1 involving the appendix, 2 right colon, 6 left colon), 2 in the pancreas, and 1 in the liver. Two patients had the coexistent nodal disease, and 1 had bone and soft-tissue involvement. The lesions were generally composed of polygonal to spindle-shaped histiocytes with eosinophilic to clear cytoplasm admixed with lymphoplasmacytic cells. The inflammatory cells formed lymphoid aggregates in 7 cases and included focally scattered or small collections of neutrophils in 6 cases. Fibrosis was variable, and 4 cases had a storiform pattern. Vasculopathy in the form of a thickened capillary wall, medium-sized arterial wall infiltration by lesional and inflammatory cells and phlebitis was seen in 10, 5, and 2 cases, respectively. All cases were reactive for S100-protein. Of the 5 patients with follow-up, 1 developed immunoglobulin A nephropathy and died of renal failure.
{"title":"Rosai-Dorfman Disease of the Digestive System—Beware Vasculopathy","authors":"Zainab I. Alruwaii, Yang Zhang, Tatianna C. Larman, J. A. Miller, E. Montgomery","doi":"10.1097/PAS.0000000000001343","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001343","url":null,"abstract":"Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferation that occurs in nodal and extranodal sites. Rare examples of the disease involving the digestive system have been described. To characterize the digestive tract manifestations of this disease, 12 specimens from 11 patients with extranodal RDD affecting the digestive organs were analyzed. Hematoxylin and eosin sections and available immunohistochemical stains were reviewed, and the clinical information was obtained from patients’ electronic or submitted records. Eight patients were female and 3 male (median age, 65 y; range, 17 to 76 y). Abdominal pain was the most frequent symptom. Six patients had an associated immunologic or malignant disease. Nine lesions arose in the gastrointestinal tract (1 involving the appendix, 2 right colon, 6 left colon), 2 in the pancreas, and 1 in the liver. Two patients had the coexistent nodal disease, and 1 had bone and soft-tissue involvement. The lesions were generally composed of polygonal to spindle-shaped histiocytes with eosinophilic to clear cytoplasm admixed with lymphoplasmacytic cells. The inflammatory cells formed lymphoid aggregates in 7 cases and included focally scattered or small collections of neutrophils in 6 cases. Fibrosis was variable, and 4 cases had a storiform pattern. Vasculopathy in the form of a thickened capillary wall, medium-sized arterial wall infiltration by lesional and inflammatory cells and phlebitis was seen in 10, 5, and 2 cases, respectively. All cases were reactive for S100-protein. Of the 5 patients with follow-up, 1 developed immunoglobulin A nephropathy and died of renal failure.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115608615","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 : 2019-08-09DOI: 10.1097/PAS.0000000000001341
L. Clinton, T. Plesec, J. Goldblum, Kaveh Hajifathalian, E. Downs‐Kelly, Deepa T. Patil
Metastatic invasive lobular carcinoma (mILC) may masquerade as primary diffuse gastric adenocarcinoma (PDGA) by demonstrating significant clinical and pathologic overlap. Accurate distinction is of therapeutic and prognostic significance. On the basis of anecdotal cases of mILC that lacked estrogen receptor and/or GATA3 expression, we analyzed the cytoarchitectural features of 28 mILC and 44 PDGA specimens obtained from women to assess features that would help in this distinction and prompt ancillary work-up. In addition to performing an interobserver agreement analysis among 3 pathologists, we also evaluated SATB2 expression in this setting. Eighteen of 20 (90%) patients had a history of ILC. The mean interval between initial diagnosis of breast cancer and metastasis was 7.3 years (range: 1 to 36 y). Compared with mILC, PDGA was significantly associated with full-thickness mucosal involvement (47% vs. 80%; P=0.015), a nested/sheet-like growth pattern (32% vs. 68%; P=0.004), anastomosing cords (0% vs. 100%; P=0.001), multivacuolated cells (0% vs. 61%; P<0.0001), pleomorphic nuclei (4% vs. 70%; P<0.0001) and enlarged nuclei (4% vs. 70%; P<0.0001). Single file growth pattern (P<0.0001) and superficial lamina propria involvement (P=0.009) were more common in mILC. Estrogen receptor and GATA3 were expressed in all but 5 mILC cases; SATB2 was only seen in 30% of PDGA cases. Our results demonstrate that in a biopsy specimen, careful morphologic assessment can be extremely helpful in distinguishing mILC from PDGA and guiding ancillary work-up, especially when a history of breast cancer may not be readily available or when the neoplasm lacks expression of conventional breast markers.
转移性浸润性小叶癌(mILC)可以伪装成原发性弥漫性胃腺癌(PDGA)，表现出明显的临床和病理重叠。准确区分对治疗和预后有重要意义。基于缺乏雌激素受体和/或GATA3表达的mILC轶事病例，我们分析了28例mILC和44例女性PDGA标本的细胞结构特征，以评估有助于这种区分和及时辅助检查的特征。除了对3名病理学家进行观察者间一致性分析外，我们还评估了SATB2在这种情况下的表达。20例患者中18例(90%)有ILC病史。乳腺癌的初次诊断和转移之间的平均间隔为7.3年(范围:1至36年)。与mILC相比，PDGA与全层粘膜受累显著相关(47% vs. 80%;P=0.015)，嵌套式/片状增长模式(32% vs. 68%;P=0.004)，吻合索(0% vs. 100%;P=0.001)，多空泡细胞(0% vs. 61%;P<0.0001)，多形性核(4% vs. 70%;P<0.0001)和细胞核增大(4% vs. 70%;P < 0.0001)。单排生长模式(P<0.0001)和浅表固有层受累(P=0.009)在mILC中更为常见。除5例mILC外，其余均表达雌激素受体和GATA3;SATB2仅见于30%的PDGA病例。我们的研究结果表明，在活检标本中，仔细的形态学评估可以非常有助于区分mILC和PDGA，并指导辅助检查，特别是当乳腺癌病史可能不容易获得或肿瘤缺乏常规乳腺标志物表达时。
{"title":"Specific Histopathologic Features Aid in Distinguishing Diffuse-type Gastric Adenocarcinoma From Metastatic Lobular Breast Carcinoma","authors":"L. Clinton, T. Plesec, J. Goldblum, Kaveh Hajifathalian, E. Downs‐Kelly, Deepa T. Patil","doi":"10.1097/PAS.0000000000001341","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001341","url":null,"abstract":"Metastatic invasive lobular carcinoma (mILC) may masquerade as primary diffuse gastric adenocarcinoma (PDGA) by demonstrating significant clinical and pathologic overlap. Accurate distinction is of therapeutic and prognostic significance. On the basis of anecdotal cases of mILC that lacked estrogen receptor and/or GATA3 expression, we analyzed the cytoarchitectural features of 28 mILC and 44 PDGA specimens obtained from women to assess features that would help in this distinction and prompt ancillary work-up. In addition to performing an interobserver agreement analysis among 3 pathologists, we also evaluated SATB2 expression in this setting. Eighteen of 20 (90%) patients had a history of ILC. The mean interval between initial diagnosis of breast cancer and metastasis was 7.3 years (range: 1 to 36 y). Compared with mILC, PDGA was significantly associated with full-thickness mucosal involvement (47% vs. 80%; P=0.015), a nested/sheet-like growth pattern (32% vs. 68%; P=0.004), anastomosing cords (0% vs. 100%; P=0.001), multivacuolated cells (0% vs. 61%; P<0.0001), pleomorphic nuclei (4% vs. 70%; P<0.0001) and enlarged nuclei (4% vs. 70%; P<0.0001). Single file growth pattern (P<0.0001) and superficial lamina propria involvement (P=0.009) were more common in mILC. Estrogen receptor and GATA3 were expressed in all but 5 mILC cases; SATB2 was only seen in 30% of PDGA cases. Our results demonstrate that in a biopsy specimen, careful morphologic assessment can be extremely helpful in distinguishing mILC from PDGA and guiding ancillary work-up, especially when a history of breast cancer may not be readily available or when the neoplasm lacks expression of conventional breast markers.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134060260","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 : 2019-08-09DOI: 10.1097/PAS.0000000000001340
Elaine Zhong, E. Cheng, M. Goldfischer, S. Hoda
Supplemental Digital Content is available in the text. Papillary lesions of the male breast (PLMB) are uncommon. To date, PLMB have been reported as individual case reports and in relatively small series. We reviewed cases of PLMB diagnosed at our medical center over a 19-year (2000-2019) period. A total of 117 cases were identified, with an age range of 7 months to 88 years. These cases included 3 of papillary ductal hyperplasia, 5 intraductal papillomas, 1 adenomyoepithelioma, 5 atypical papillomas (ie, papillomas with atypia), 51 papillary ductal carcinoma in situ, 14 encapsulated papillary carcinomas, 38 solid papillary carcinomas, and 8 invasive papillary carcinomas. Malignant papillary neoplasms, including invasive and noninvasive ones, had a mean size of 1.3 cm (range: 0.3 to 4.4 cm), and all were ER+ and HER2−. Fifty-four percent (19/35) of carcinomas were treated with excision alone, 46% (16/35) underwent mastectomy, and 63% (22/35) had axillary lymph node sampling. Only one case had metastatic involvement of axillary lymph nodes. Of the cases with follow-up, no (0/8) invasive carcinoma showed distant metastasis or proved fatal, and no (0/23) noninvasive papillary carcinoma recurred. Two notable cases of PLMB were encountered: one of a 7-month-old boy with NF1 mutation and florid papillary hyperplasia, and another of a 57-year-old man with Klippel-Feil syndrome and bilateral solid papillary carcinoma, invasive and oligometastatic on one side and noninvasive on the other. On the basis of this study of PLMB cases, the largest to date, and review of literature, we conclude that PLMB span a broad clinicopathologic spectrum, and that both invasive and noninvasive papillary carcinomas have relatively good prognosis.
{"title":"Papillary Lesions of the Male Breast","authors":"Elaine Zhong, E. Cheng, M. Goldfischer, S. Hoda","doi":"10.1097/PAS.0000000000001340","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001340","url":null,"abstract":"Supplemental Digital Content is available in the text. Papillary lesions of the male breast (PLMB) are uncommon. To date, PLMB have been reported as individual case reports and in relatively small series. We reviewed cases of PLMB diagnosed at our medical center over a 19-year (2000-2019) period. A total of 117 cases were identified, with an age range of 7 months to 88 years. These cases included 3 of papillary ductal hyperplasia, 5 intraductal papillomas, 1 adenomyoepithelioma, 5 atypical papillomas (ie, papillomas with atypia), 51 papillary ductal carcinoma in situ, 14 encapsulated papillary carcinomas, 38 solid papillary carcinomas, and 8 invasive papillary carcinomas. Malignant papillary neoplasms, including invasive and noninvasive ones, had a mean size of 1.3 cm (range: 0.3 to 4.4 cm), and all were ER+ and HER2−. Fifty-four percent (19/35) of carcinomas were treated with excision alone, 46% (16/35) underwent mastectomy, and 63% (22/35) had axillary lymph node sampling. Only one case had metastatic involvement of axillary lymph nodes. Of the cases with follow-up, no (0/8) invasive carcinoma showed distant metastasis or proved fatal, and no (0/23) noninvasive papillary carcinoma recurred. Two notable cases of PLMB were encountered: one of a 7-month-old boy with NF1 mutation and florid papillary hyperplasia, and another of a 57-year-old man with Klippel-Feil syndrome and bilateral solid papillary carcinoma, invasive and oligometastatic on one side and noninvasive on the other. On the basis of this study of PLMB cases, the largest to date, and review of literature, we conclude that PLMB span a broad clinicopathologic spectrum, and that both invasive and noninvasive papillary carcinomas have relatively good prognosis.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124919259","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 : 2019-08-06DOI: 10.1097/PAS.0000000000001342
Leiming Wang, Lina Liu, Hainan Li, PeiPei Wang, Zeliang Hu, Yukui Wei, Ming Zhang, Wenjuan Wen, Zhi Li, Li Liu, Lihong Zhao, D. Lu, L. Teng
Supplemental Digital Content is available in the text. Supratentorial extraventricular ependymomas (STEEs) are relatively rare ependymomas, and their pathologic and genetic characteristics are still poorly understood. The aim of this study was to determine the histologic, immunohistochemical, and RELA fusion features, as well as to clarify in more detail the clinical courses of STEEs. Data from a total of 43 patients with STEEs was analyzed retrospectively. The status of RELA fusion was evaluated using fluorescence in situ hybridization. The expression levels of L1CAM, p65, cyclin D1, and p53 were assessed using immunohistochemistry. Progression-free survival and overall survival were calculated via Kaplan-Meier estimation using the log-rank test. Among all 43 STEEs, 65.1% (28/43) are positive for RELA fusion. Interestingly, almost half of the patients with RELA fusion–positive ependymomas are adults (13/28), and 89.3% (25/28) cases are anaplastic ependymomas, which suggests that RELA fusion testing is necessary in adults with STEEs. We investigated the immunohistochemical status of p65, L1CAM and CCND1 protein expression for their ability to predict RELA fusion status. RELA fusion–positive STEEs are frequently associated with expression of p65 (85.2%), L1CAM (85.2%), and CCND1 (81.5%). The accuracy of predicting RELA fusion status was much higher when the expression of p65 and L1CAM was combined, that is, when both were immunopositive. The status of RELA fusion, p53 overexpression, and extent of tumor resection are significantly associated with prognosis.
{"title":"RELA Fusion in Supratentorial Extraventricular Ependymomas: A Morphologic, Immunohistochemical, and Molecular Study of 43 Cases","authors":"Leiming Wang, Lina Liu, Hainan Li, PeiPei Wang, Zeliang Hu, Yukui Wei, Ming Zhang, Wenjuan Wen, Zhi Li, Li Liu, Lihong Zhao, D. Lu, L. Teng","doi":"10.1097/PAS.0000000000001342","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001342","url":null,"abstract":"Supplemental Digital Content is available in the text. Supratentorial extraventricular ependymomas (STEEs) are relatively rare ependymomas, and their pathologic and genetic characteristics are still poorly understood. The aim of this study was to determine the histologic, immunohistochemical, and RELA fusion features, as well as to clarify in more detail the clinical courses of STEEs. Data from a total of 43 patients with STEEs was analyzed retrospectively. The status of RELA fusion was evaluated using fluorescence in situ hybridization. The expression levels of L1CAM, p65, cyclin D1, and p53 were assessed using immunohistochemistry. Progression-free survival and overall survival were calculated via Kaplan-Meier estimation using the log-rank test. Among all 43 STEEs, 65.1% (28/43) are positive for RELA fusion. Interestingly, almost half of the patients with RELA fusion–positive ependymomas are adults (13/28), and 89.3% (25/28) cases are anaplastic ependymomas, which suggests that RELA fusion testing is necessary in adults with STEEs. We investigated the immunohistochemical status of p65, L1CAM and CCND1 protein expression for their ability to predict RELA fusion status. RELA fusion–positive STEEs are frequently associated with expression of p65 (85.2%), L1CAM (85.2%), and CCND1 (81.5%). The accuracy of predicting RELA fusion status was much higher when the expression of p65 and L1CAM was combined, that is, when both were immunopositive. The status of RELA fusion, p53 overexpression, and extent of tumor resection are significantly associated with prognosis.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122717072","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 : 2019-08-02DOI: 10.1097/PAS.0000000000001337
Steven M. Johnson, Jessica P Vanleer, S. O'Connor, S. Maygarden
Many physicians share the perception that the work required to evaluate breast pathology specimens is undervalued by Current Procedural Terminology (CPT) codes. To examine this issue, we compared slide volumes from an equal number of breast and nonbreast specimens assigned 88305, 88307, or 88309 CPT codes during four 2.5-week periods over 1 year. For each specimen, a number of initial hematoxylin and eosin–stained sections (H&Es), preordered additional H&E sections (levels), H&E sections ordered after initial slide review (recuts), and specimen type were recorded. Slides associated with ancillary stains were not considered. In total, 911 breast and 911 nonbreast specimens, each assigned 88305 (n=580), 88307 (n=320), and 88309 (n=11) CPT codes, were compared. Breast 88305 specimens were mainly core biopsies and margins and generated 2.3 and 6.4 times the H&Es and recuts, respectively, than did nonbreast specimens (P<0.01). Breast 88307 specimens were mainly lymph nodes and lumpectomies and generated 1.8 times the total slides than did nonbreast specimens (P<0.01). Eleven modified radical mastectomies (88309) generated 2.1 times the total slides than nonbreast 88309 specimens (P<0.01). In total (n=911 in each cohort), breast specimens generated 1.9, 4.0, and 1.7 times the H&Es, recuts, and total slides (P<0.01) than did nonbreast specimens. At our academic institution, the slide volume for breast specimens is nearly twice that of similarly coded nonbreast specimens. These results have significant implications for workload management and assessing pathologist productivity, particularly in subspecialty practices.
{"title":"Current Procedural Terminology Coding in an Academic Breast Pathology Service","authors":"Steven M. Johnson, Jessica P Vanleer, S. O'Connor, S. Maygarden","doi":"10.1097/PAS.0000000000001337","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001337","url":null,"abstract":"Many physicians share the perception that the work required to evaluate breast pathology specimens is undervalued by Current Procedural Terminology (CPT) codes. To examine this issue, we compared slide volumes from an equal number of breast and nonbreast specimens assigned 88305, 88307, or 88309 CPT codes during four 2.5-week periods over 1 year. For each specimen, a number of initial hematoxylin and eosin–stained sections (H&Es), preordered additional H&E sections (levels), H&E sections ordered after initial slide review (recuts), and specimen type were recorded. Slides associated with ancillary stains were not considered. In total, 911 breast and 911 nonbreast specimens, each assigned 88305 (n=580), 88307 (n=320), and 88309 (n=11) CPT codes, were compared. Breast 88305 specimens were mainly core biopsies and margins and generated 2.3 and 6.4 times the H&Es and recuts, respectively, than did nonbreast specimens (P<0.01). Breast 88307 specimens were mainly lymph nodes and lumpectomies and generated 1.8 times the total slides than did nonbreast specimens (P<0.01). Eleven modified radical mastectomies (88309) generated 2.1 times the total slides than nonbreast 88309 specimens (P<0.01). In total (n=911 in each cohort), breast specimens generated 1.9, 4.0, and 1.7 times the H&Es, recuts, and total slides (P<0.01) than did nonbreast specimens. At our academic institution, the slide volume for breast specimens is nearly twice that of similarly coded nonbreast specimens. These results have significant implications for workload management and assessing pathologist productivity, particularly in subspecialty practices.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115463547","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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