Pub Date : 2019-11-08DOI: 10.1097/PAS.0000000000001403
Jennifer Pors, Julie Ho, Leah M Prentice, E. Thompson, D. Cochrane, Evan Gibbard, D. Huntsman, B. Gilks, L. Hoang
Mesonephric carcinoma is a rare malignancy, thought to derive from Wolffian remnants. To date, no targeted molecular therapeutic options have been identified. On the basis of limited case reports, c-KIT immunohistochemical expression has been reported in female adnexal tumors of Wolffian origin, and targeted therapy with Imatinib has been attempted with mixed success. Currently, it is unclear whether c-KIT immunohistochemical expression is seen in mesonephric carcinoma, a tumor that is thought to be related to female adnexal tumors of Wolffian origin, and how this correlates with KIT mutational status. In this study, we assessed the immunohistochemical expression of c-KIT and KIT mutational status, in a series of 13 mesonephric neoplasms (5 cervical [including 2 cervical carcinosarcomas], 3 uterine corpora, 4 ovarian, and 1 vaginal/pelvic). The intensity of staining and proportion of cells showing cytoplasmic/membranous staining for c-KIT were recorded. KIT was sequenced using a next-generation sequencing panel that targeted 120 hotspots and 17 exons in 33 known actionable cancer genes. This panel included KIT exons 9, 11, and 13, and 6 hotspots (T670, D816, D820, N822, Y823, A829). Although c-KIT immunohistochemical expression was observed in the majority of mesonephric carcinomas (10/12 cases; 83%), no KIT mutations were detected. This cautions pathologists against the use of c-KIT immunohistochemistry as a surrogate marker for KIT-activating mutations in this setting. Consistent with previous studies, the majority of mesonephric neoplasms (10/13; 77%) harbored KRAS mutations. Additional mutations were found in CTNNB1 (2/13, 15%), TP53 (2/13, 15%), and PIK3CA (1/13, 8%).
{"title":"c-KIT Analysis and Targeted Molecular Sequencing of Mesonephric Carcinomas of the Female Genital Tract","authors":"Jennifer Pors, Julie Ho, Leah M Prentice, E. Thompson, D. Cochrane, Evan Gibbard, D. Huntsman, B. Gilks, L. Hoang","doi":"10.1097/PAS.0000000000001403","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001403","url":null,"abstract":"Mesonephric carcinoma is a rare malignancy, thought to derive from Wolffian remnants. To date, no targeted molecular therapeutic options have been identified. On the basis of limited case reports, c-KIT immunohistochemical expression has been reported in female adnexal tumors of Wolffian origin, and targeted therapy with Imatinib has been attempted with mixed success. Currently, it is unclear whether c-KIT immunohistochemical expression is seen in mesonephric carcinoma, a tumor that is thought to be related to female adnexal tumors of Wolffian origin, and how this correlates with KIT mutational status. In this study, we assessed the immunohistochemical expression of c-KIT and KIT mutational status, in a series of 13 mesonephric neoplasms (5 cervical [including 2 cervical carcinosarcomas], 3 uterine corpora, 4 ovarian, and 1 vaginal/pelvic). The intensity of staining and proportion of cells showing cytoplasmic/membranous staining for c-KIT were recorded. KIT was sequenced using a next-generation sequencing panel that targeted 120 hotspots and 17 exons in 33 known actionable cancer genes. This panel included KIT exons 9, 11, and 13, and 6 hotspots (T670, D816, D820, N822, Y823, A829). Although c-KIT immunohistochemical expression was observed in the majority of mesonephric carcinomas (10/12 cases; 83%), no KIT mutations were detected. This cautions pathologists against the use of c-KIT immunohistochemistry as a surrogate marker for KIT-activating mutations in this setting. Consistent with previous studies, the majority of mesonephric neoplasms (10/13; 77%) harbored KRAS mutations. Additional mutations were found in CTNNB1 (2/13, 15%), TP53 (2/13, 15%), and PIK3CA (1/13, 8%).","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131894653","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 : 2019-11-01DOI: 10.1097/PAS.0000000000001402
D. Xing, Minghao Zhong, F. Ye, Michael T. O’Malley, Shao-Ming Li, R. Vang, B. Ronnett
Supplemental Digital Content is available in the text. Trophoblastic neoplasms involving the ovary are uncommon and include gestational tumors, which are either metastatic from the uterus or ectopic and nongestational tumors, which include those of germ cell type/origin and somatic tumors with trophoblastic differentiation; in all these types, most are pure choriocarcinoma. Intermediate trophoblastic tumors, which include placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT), are rare in the ovary, with most assumed to be gestational; this is the only category formally recognized in 2014 World Health Organization (WHO) classification, likely due to few well-documented nongestational examples. We report the clinicopathologic features of 6 ovarian intermediate trophoblastic tumors, including 3 PSTTs, 2 ETTs, and 1 ETT with choriocarcinomatous differentiation. DNA-based short tandem repeat genotyping identified 4 of these as nongestational (3 PSTTs and 1 ETT), as evidenced by sharing of alleles between tumor and normal tissue at all informative loci. Interestingly, all 3 of the nongestational PSTTs coexisted with mature cystic teratoma. The remaining 2 tumors (1 ETT and 1 ETT with some choriocarcinomatous differentiation) were gestational (likely ectopic due to lack of evidence of a uterine tumor), as evidenced by the presence of both maternal and novel/nonmaternal alleles at informative loci in tumor compared with normal tissue. It is important to recognize a distinct category of primary ovarian nongestational intermediate trophoblastic tumors of germ cell type/origin, including PSTT and ETT, in classification systems to guide clinical management, as gestational and nongestational tumors have different genetic origins and may require different therapy. Genotyping is useful for classification as nongestational versus gestational, particularly as traditional clinicopathologic findings cannot always predict the nature of a trophoblastic tumor.
{"title":"Ovarian Intermediate Trophoblastic Tumors","authors":"D. Xing, Minghao Zhong, F. Ye, Michael T. O’Malley, Shao-Ming Li, R. Vang, B. Ronnett","doi":"10.1097/PAS.0000000000001402","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001402","url":null,"abstract":"Supplemental Digital Content is available in the text. Trophoblastic neoplasms involving the ovary are uncommon and include gestational tumors, which are either metastatic from the uterus or ectopic and nongestational tumors, which include those of germ cell type/origin and somatic tumors with trophoblastic differentiation; in all these types, most are pure choriocarcinoma. Intermediate trophoblastic tumors, which include placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT), are rare in the ovary, with most assumed to be gestational; this is the only category formally recognized in 2014 World Health Organization (WHO) classification, likely due to few well-documented nongestational examples. We report the clinicopathologic features of 6 ovarian intermediate trophoblastic tumors, including 3 PSTTs, 2 ETTs, and 1 ETT with choriocarcinomatous differentiation. DNA-based short tandem repeat genotyping identified 4 of these as nongestational (3 PSTTs and 1 ETT), as evidenced by sharing of alleles between tumor and normal tissue at all informative loci. Interestingly, all 3 of the nongestational PSTTs coexisted with mature cystic teratoma. The remaining 2 tumors (1 ETT and 1 ETT with some choriocarcinomatous differentiation) were gestational (likely ectopic due to lack of evidence of a uterine tumor), as evidenced by the presence of both maternal and novel/nonmaternal alleles at informative loci in tumor compared with normal tissue. It is important to recognize a distinct category of primary ovarian nongestational intermediate trophoblastic tumors of germ cell type/origin, including PSTT and ETT, in classification systems to guide clinical management, as gestational and nongestational tumors have different genetic origins and may require different therapy. Genotyping is useful for classification as nongestational versus gestational, particularly as traditional clinicopathologic findings cannot always predict the nature of a trophoblastic tumor.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115129855","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 : 2019-11-01DOI: 10.1097/PAS.0000000000001404
B. Luzar, S. Billings, A. de la Fouchardière, D. Pissaloux, L. Alberti, E. Calonje
The proliferation of cells with melanocytic lineage and a nested pattern has traditionally been regarded as a characteristic feature of a wide range of benign and malignant melanocytic proliferations. Herein, we report a series of 4 clear cell sarcomas, including 3 primary cutaneous and 1 metastatic to the skin, associated with a clear-cut intraepidermal proliferation of tumor cells representing a serious potential diagnostic pitfall. All patients were male individuals, aged from 17 to 71 years (mean: 42 y). The size of the tumors ranged from 8 to 55 mm (mean: 22.2 mm, median: 13 mm). Two tumors arose on a lower extremity and 1 each on the scalp and chest. Cutaneous metastasis developed on the limb proximal to the amputation site. Histologically, all tumors were variably circumscribed nodular or multinodular proliferations within the dermis, focally extending into the subcutis. They were composed of nests and fascicles of pale spindled and epithelioid cells with finely granular or pale cytoplasm, elongated nuclei with a single prominent nucleolus, featuring mild nuclear pleomorphism, and surrounded by delicate fibrous septa. Scattered wreath-like giant cells were present in all cases. Mitotic activity was low (mean and median: 3.5 mitoses/mm2). The intraepidermal component consisted in all 4 cases of nests of tumor cells localized at the dermal-epidermal junction. Nests were well-defined and composed of spindled or epithelioid cells with irregular hyperchromatic nuclei, prominent nucleoli, and scant to moderately abundant eosinophilic to pale cytoplasm. Lentiginous proliferation of epithelioid tumor cells was coupled with focal upward migration of isolated tumor cells in a single case. By immunohistochemistry, all tumors were S100 protein, melan A, and HMB45 positive. By fluorescence in situ hybridization analysis, 3 tumors displayed rearrangements in the EWSR1 gene, whereas reverse transcriptase polymerase chain reaction confirmed EWSR1(e8)/ATF1(e4) translocation in the remaining case. In conclusion, an epidermal component in primary cutaneous clear cell sarcomas, or cutaneous metastasis of the tumor, is exceptional and represents a potential diagnostic pitfall. Careful attention to the salient morphologic features in the dermal component of the tumor, as well as confirmation of EWSR1 gene rearrangement by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction, is necessary for correct recognition of the tumor and to avoid erroneous diagnosis of a benign or malignant melanocytic proliferation.
{"title":"Compound Clear Cell Sarcoma of the Skin—A Potential Diagnostic Pitfall","authors":"B. Luzar, S. Billings, A. de la Fouchardière, D. Pissaloux, L. Alberti, E. Calonje","doi":"10.1097/PAS.0000000000001404","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001404","url":null,"abstract":"The proliferation of cells with melanocytic lineage and a nested pattern has traditionally been regarded as a characteristic feature of a wide range of benign and malignant melanocytic proliferations. Herein, we report a series of 4 clear cell sarcomas, including 3 primary cutaneous and 1 metastatic to the skin, associated with a clear-cut intraepidermal proliferation of tumor cells representing a serious potential diagnostic pitfall. All patients were male individuals, aged from 17 to 71 years (mean: 42 y). The size of the tumors ranged from 8 to 55 mm (mean: 22.2 mm, median: 13 mm). Two tumors arose on a lower extremity and 1 each on the scalp and chest. Cutaneous metastasis developed on the limb proximal to the amputation site. Histologically, all tumors were variably circumscribed nodular or multinodular proliferations within the dermis, focally extending into the subcutis. They were composed of nests and fascicles of pale spindled and epithelioid cells with finely granular or pale cytoplasm, elongated nuclei with a single prominent nucleolus, featuring mild nuclear pleomorphism, and surrounded by delicate fibrous septa. Scattered wreath-like giant cells were present in all cases. Mitotic activity was low (mean and median: 3.5 mitoses/mm2). The intraepidermal component consisted in all 4 cases of nests of tumor cells localized at the dermal-epidermal junction. Nests were well-defined and composed of spindled or epithelioid cells with irregular hyperchromatic nuclei, prominent nucleoli, and scant to moderately abundant eosinophilic to pale cytoplasm. Lentiginous proliferation of epithelioid tumor cells was coupled with focal upward migration of isolated tumor cells in a single case. By immunohistochemistry, all tumors were S100 protein, melan A, and HMB45 positive. By fluorescence in situ hybridization analysis, 3 tumors displayed rearrangements in the EWSR1 gene, whereas reverse transcriptase polymerase chain reaction confirmed EWSR1(e8)/ATF1(e4) translocation in the remaining case. In conclusion, an epidermal component in primary cutaneous clear cell sarcomas, or cutaneous metastasis of the tumor, is exceptional and represents a potential diagnostic pitfall. Careful attention to the salient morphologic features in the dermal component of the tumor, as well as confirmation of EWSR1 gene rearrangement by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction, is necessary for correct recognition of the tumor and to avoid erroneous diagnosis of a benign or malignant melanocytic proliferation.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116493880","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 : 2019-11-01DOI: 10.1097/PAS.0000000000001307
Sounak Gupta, P. Argani, A. Jungbluth, Ying-bei Chen, S. Tickoo, S. Fine, A. Gopalan, H. Al-Ahmadie, S. Sirintrapun, Alejandro Sanchez, A. Hakimi, Tiffany Mcfarlane, Paulo Salazar, S. Williamson, S. Skala, R. Mehra, O. Hes, C. Antonescu, M. Ladanyi, M. Arcila, V. Reuter
TFEB is overexpressed in TFEB-rearranged renal cell carcinomas as well as in renal tumors with amplifications of TFEB at 6p21.1. As recent literature suggests that renal tumors with 6p21.1 amplification behave more aggressively than those with rearrangements of TFEB, we compared relative TFEB gene expression in these tumors. This study included 37 TFEB-altered tumors: 15 6p21.1-amplified and 22 TFEB-rearranged (including 5 cases from The Cancer Genome Atlas data set). TFEB status was verified using a combination of fluorescent in situ hybridization (n=27) or comprehensive molecular profiling (n=13) and digital droplet polymerase chain reaction was used to quantify TFEB mRNA expression in 6p21.1-amplified (n=9) and TFEB-rearranged renal tumors (n=19). These results were correlated with TFEB immunohistochemistry. TFEB-altered tumors had higher TFEB expression when normalized to B2M (mean: 168.9%, n=28), compared with non–TFEB-altered controls (mean: 7%, n=18, P=0.005). Interestingly, TFEB expression in tumors with rearrangements (mean: 224.7%, n=19) was higher compared with 6p21.1-amplified tumors (mean: 51.2%, n=9; P=0.06). Of note, classic biphasic morphology was only seen in TFEB-rearranged tumors and when present correlated with 6.8-fold higher TFEB expression (P=0.00004). Our results suggest that 6p21.1 amplified renal tumors show increased TFEB gene expression but not as much as t(6;11) renal tumors. These findings correlate with the less consistent/diffuse expression of downstream markers of TFEB activation (cathepsin K, melan A, HMB45) seen in the amplified neoplasms. This suggests that the aggressive biological behavior of 6p21.1 amplified renal tumors might be secondary to other genes at the 6p21.1 locus that are co-amplified, such as VEGFA and CCND3, or other genetic alterations.
TFEB在TFEB重排的肾细胞癌和肾肿瘤中过表达，TFEB在6p21.1处扩增。由于最近的文献表明6p21.1扩增的肾肿瘤比TFEB重排的肾肿瘤更具侵袭性，我们比较了这些肿瘤中TFEB基因的相对表达。本研究纳入37例tfeb改变的肿瘤:15例6p21.1扩增，22例tfeb重排(其中5例来自The Cancer Genome Atlas数据集)。采用荧光原位杂交(n=27)或综合分子分析(n=13)验证TFEB状态，并采用数字液滴聚合酶链反应定量6p21.1扩增(n=9)和TFEB重排肾肿瘤(n=19)中TFEB mRNA的表达。这些结果与TFEB免疫组织化学相关。与未改变TFEB的对照组(平均7%，n=18, P=0.005)相比，TFEB改变的肿瘤与B2M归一化后TFEB表达更高(平均值:168.9%，n=28)。有趣的是，TFEB在重排肿瘤中的表达(平均:224.7%，n=19)高于6p21.1扩增肿瘤(平均:51.2%，n=9;P = 0.06)。值得注意的是，经典的双相形态仅在TFEB重排的肿瘤中可见，当存在时，与TFEB表达高6.8倍相关(P=0.00004)。我们的研究结果表明，6p21.1扩增肾肿瘤TFEB基因表达增加，但不像t(6;11)肾肿瘤那么多。这些发现与在扩增肿瘤中观察到的TFEB激活的下游标记物(组织蛋白酶K、黑色素A、HMB45)的不一致/弥漫性表达有关。这表明，6p21.1扩增肾肿瘤的侵袭性生物学行为可能是继发于6p21.1位点上的其他共同扩增基因，如VEGFA和CCND3，或其他遗传改变。
{"title":"TFEB Expression Profiling in Renal Cell Carcinomas","authors":"Sounak Gupta, P. Argani, A. Jungbluth, Ying-bei Chen, S. Tickoo, S. Fine, A. Gopalan, H. Al-Ahmadie, S. Sirintrapun, Alejandro Sanchez, A. Hakimi, Tiffany Mcfarlane, Paulo Salazar, S. Williamson, S. Skala, R. Mehra, O. Hes, C. Antonescu, M. Ladanyi, M. Arcila, V. Reuter","doi":"10.1097/PAS.0000000000001307","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001307","url":null,"abstract":"TFEB is overexpressed in TFEB-rearranged renal cell carcinomas as well as in renal tumors with amplifications of TFEB at 6p21.1. As recent literature suggests that renal tumors with 6p21.1 amplification behave more aggressively than those with rearrangements of TFEB, we compared relative TFEB gene expression in these tumors. This study included 37 TFEB-altered tumors: 15 6p21.1-amplified and 22 TFEB-rearranged (including 5 cases from The Cancer Genome Atlas data set). TFEB status was verified using a combination of fluorescent in situ hybridization (n=27) or comprehensive molecular profiling (n=13) and digital droplet polymerase chain reaction was used to quantify TFEB mRNA expression in 6p21.1-amplified (n=9) and TFEB-rearranged renal tumors (n=19). These results were correlated with TFEB immunohistochemistry. TFEB-altered tumors had higher TFEB expression when normalized to B2M (mean: 168.9%, n=28), compared with non–TFEB-altered controls (mean: 7%, n=18, P=0.005). Interestingly, TFEB expression in tumors with rearrangements (mean: 224.7%, n=19) was higher compared with 6p21.1-amplified tumors (mean: 51.2%, n=9; P=0.06). Of note, classic biphasic morphology was only seen in TFEB-rearranged tumors and when present correlated with 6.8-fold higher TFEB expression (P=0.00004). Our results suggest that 6p21.1 amplified renal tumors show increased TFEB gene expression but not as much as t(6;11) renal tumors. These findings correlate with the less consistent/diffuse expression of downstream markers of TFEB activation (cathepsin K, melan A, HMB45) seen in the amplified neoplasms. This suggests that the aggressive biological behavior of 6p21.1 amplified renal tumors might be secondary to other genes at the 6p21.1 locus that are co-amplified, such as VEGFA and CCND3, or other genetic alterations.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126754573","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 : 2019-11-01DOI: 10.1097/PAS.0000000000001325
M. Chui, D. Xing, F. Zeppernick, Zoe Q Wang, Charlotte G Hannibal, K. Frederiksen, S. Kjaer, L. Cope, R. Kurman, I. Shih, Tian-Li Wang, R. Vang
Although risk factors have been established for the development of serous carcinoma after a diagnosis of serous borderline tumor (SBT), comprising atypical proliferative serous tumor (APST) (ie, conventional SBT) and noninvasive low-grade serous carcinoma (niLGSC) (ie, micropapillary SBT), subsequent invasive carcinoma still occurs in a subset of women who are not at increased risk. Whether subsequent serous carcinoma in women with a prior SBT represents malignant progression/recurrence or an independent primary tumor is unclear, and the combined clinicopathologic and molecular features of SBTs and their subsequent carcinomas have not been fully characterized. In this study, we analyzed a cohort of 42 women initially diagnosed with SBT who subsequently developed serous carcinoma of a total of 1025 cases of ovarian SBT from a nationwide population-based cohort. Review of the diagnostic slides was performed from this subset of SBTs and matched metachronous invasive serous carcinomas (39 low grade, 3 high grade). DNA was extracted from tissue blocks available for 41 cases (both SBT and carcinoma, n=36; SBT only, n=3; carcinoma only, n=2). Samples were subjected to digital droplet PCR to analyze mutation hotspots in KRAS (codon 12) and BRAF (V600E), which are frequently found in low-grade serous tumors. Eighty-one percent of SBTs (34/42) were APST, and 19% (8/42) were niLGSC. Forty percent of cases (17/42) were FIGO stage I, the majority of which were APST (14/17; 82%). The median time to development of carcinoma was 9 years (range, 0.6 to 25 y). Mutations in SBTs were distributed as follows: 5/39 (13%) BRAF mutant, 22/39 (56%) KRAS mutant, and 12/39 (31%) wild-type for both genes. There was a significant relationship between SBT gene mutation and histologic type, with BRAF mutations occurring exclusively in APST and a higher frequency of niLGSC among SBTs wild-type for BRAF and KRAS (P=0.01). The diffuse presence of tumor cells with abundant eosinophilic cytoplasm was significantly associated with the BRAF mutation (P=0.001). Mutational analyses of matched SBT/carcinoma pairs revealed concordant profiles in 33/36 (92%) cases, of which 19 (53%) were KRAS mutant, 4 (11%) were BRAF mutant, and 10 (28%) were wild type for both genes. The 3 discordant cases consisted of a wild-type niLGSC with a subsequent BRAF-mutant invasive LGSC, a KRASG12V-mutant APST with a KRASG12C-mutant LGSC, and a BRAF-mutant APST with subsequent development of a KRASG12D-mutant high-grade serous carcinoma. In conclusion, some women with SBTs can subsequently develop serous carcinoma, occasionally over 10 years later. Most subsequent carcinomas are low grade, but a small subset can be high grade. The type of gene mutation in SBT correlates with various histologic features. While most cases of serous carcinoma developing after a diagnosis of SBT probably represent tumor progression, a minority are independent primary tumors, presumably arising from endosalpingiosis.
{"title":"Clinicopathologic and Molecular Features of Paired Cases of Metachronous Ovarian Serous Borderline Tumor and Subsequent Serous Carcinoma","authors":"M. Chui, D. Xing, F. Zeppernick, Zoe Q Wang, Charlotte G Hannibal, K. Frederiksen, S. Kjaer, L. Cope, R. Kurman, I. Shih, Tian-Li Wang, R. Vang","doi":"10.1097/PAS.0000000000001325","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001325","url":null,"abstract":"Although risk factors have been established for the development of serous carcinoma after a diagnosis of serous borderline tumor (SBT), comprising atypical proliferative serous tumor (APST) (ie, conventional SBT) and noninvasive low-grade serous carcinoma (niLGSC) (ie, micropapillary SBT), subsequent invasive carcinoma still occurs in a subset of women who are not at increased risk. Whether subsequent serous carcinoma in women with a prior SBT represents malignant progression/recurrence or an independent primary tumor is unclear, and the combined clinicopathologic and molecular features of SBTs and their subsequent carcinomas have not been fully characterized. In this study, we analyzed a cohort of 42 women initially diagnosed with SBT who subsequently developed serous carcinoma of a total of 1025 cases of ovarian SBT from a nationwide population-based cohort. Review of the diagnostic slides was performed from this subset of SBTs and matched metachronous invasive serous carcinomas (39 low grade, 3 high grade). DNA was extracted from tissue blocks available for 41 cases (both SBT and carcinoma, n=36; SBT only, n=3; carcinoma only, n=2). Samples were subjected to digital droplet PCR to analyze mutation hotspots in KRAS (codon 12) and BRAF (V600E), which are frequently found in low-grade serous tumors. Eighty-one percent of SBTs (34/42) were APST, and 19% (8/42) were niLGSC. Forty percent of cases (17/42) were FIGO stage I, the majority of which were APST (14/17; 82%). The median time to development of carcinoma was 9 years (range, 0.6 to 25 y). Mutations in SBTs were distributed as follows: 5/39 (13%) BRAF mutant, 22/39 (56%) KRAS mutant, and 12/39 (31%) wild-type for both genes. There was a significant relationship between SBT gene mutation and histologic type, with BRAF mutations occurring exclusively in APST and a higher frequency of niLGSC among SBTs wild-type for BRAF and KRAS (P=0.01). The diffuse presence of tumor cells with abundant eosinophilic cytoplasm was significantly associated with the BRAF mutation (P=0.001). Mutational analyses of matched SBT/carcinoma pairs revealed concordant profiles in 33/36 (92%) cases, of which 19 (53%) were KRAS mutant, 4 (11%) were BRAF mutant, and 10 (28%) were wild type for both genes. The 3 discordant cases consisted of a wild-type niLGSC with a subsequent BRAF-mutant invasive LGSC, a KRASG12V-mutant APST with a KRASG12C-mutant LGSC, and a BRAF-mutant APST with subsequent development of a KRASG12D-mutant high-grade serous carcinoma. In conclusion, some women with SBTs can subsequently develop serous carcinoma, occasionally over 10 years later. Most subsequent carcinomas are low grade, but a small subset can be high grade. The type of gene mutation in SBT correlates with various histologic features. While most cases of serous carcinoma developing after a diagnosis of SBT probably represent tumor progression, a minority are independent primary tumors, presumably arising from endosalpingiosis.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"133 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114695363","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 : 2019-11-01DOI: 10.1097/PAS.0000000000001320
Atsushi Kihara, Y. Amano, T. Yoshimoto, D. Matsubara, N. Fukushima, H. Fujiwara, T. Niki
Supplemental Digital Content is available in the text. Atypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear β-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions.
{"title":"Stromal p16 Expression Helps Distinguish Atypical Polypoid Adenomyoma From Myoinvasive Endometrioid Carcinoma of the Uterus","authors":"Atsushi Kihara, Y. Amano, T. Yoshimoto, D. Matsubara, N. Fukushima, H. Fujiwara, T. Niki","doi":"10.1097/PAS.0000000000001320","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001320","url":null,"abstract":"Supplemental Digital Content is available in the text. Atypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear β-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"2021 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124386338","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 : 2019-10-29DOI: 10.1097/PAS.0000000000001398
Anthony P. Martinez, M. Zapata, P. North, A. Folpe, S. Weiss
We report 21 cases of a distinctive and unique vascular tumor which we propose to be a pure lymphatic-type angiosarcoma characterized by architectural and growth characteristics of angiosarcoma, cytologic, and immunohistochemical features of lymphatic differentiation, a prominent lymphocytic infiltrate, and variable nuclear grade. Patients included 12 males and 9 females with a median age of 65 years (range: 32 to 95 y). Tumors involved the head and neck (n=11), lower extremities (n=5), trunk (n=4), and upper extremity (n=1) and were located superficially in the dermis and/or subcutis. Tumors were designated “low grade” (n=10) when the nuclear grade was low, and vascular channel formation was evident throughout but with multilayering of endothelium within the vessels. Cases were designated “high grade” (n=11) when nuclei appeared higher grade with more rounded contours and prominent nucleoli and when solid areas predominated over vascular channel formation. A striking feature of both groups was the presence of a dense, lymphocytic infiltrate with occasional germinal center formation. All cases strongly and diffusely expressed at least 1 lymphatic marker (21/21) with podoplanin (17/19) and Prox-1 (11/11) more commonly expressed than LYVE-1 (5/10). No consistent molecular alteration was identified. Follow-up on 17 patients (median: 41 mo, mean: 54 mo) showed 10 patients were alive without disease, 5 were alive with disease, 1 died of other cause, and 1 died of disease. Local recurrence developed in 9 cases and metastasis in 2 cases, although neither correlated with grade as defined. On the basis of clinical follow-up to date, the natural history of lymphatic-type angiosarcoma appears to be more favorable than other forms of cutaneous angiosarcoma.
{"title":"Lymphatic-type “Angiosarcoma” With Prominent Lymphocytic Infiltrate","authors":"Anthony P. Martinez, M. Zapata, P. North, A. Folpe, S. Weiss","doi":"10.1097/PAS.0000000000001398","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001398","url":null,"abstract":"We report 21 cases of a distinctive and unique vascular tumor which we propose to be a pure lymphatic-type angiosarcoma characterized by architectural and growth characteristics of angiosarcoma, cytologic, and immunohistochemical features of lymphatic differentiation, a prominent lymphocytic infiltrate, and variable nuclear grade. Patients included 12 males and 9 females with a median age of 65 years (range: 32 to 95 y). Tumors involved the head and neck (n=11), lower extremities (n=5), trunk (n=4), and upper extremity (n=1) and were located superficially in the dermis and/or subcutis. Tumors were designated “low grade” (n=10) when the nuclear grade was low, and vascular channel formation was evident throughout but with multilayering of endothelium within the vessels. Cases were designated “high grade” (n=11) when nuclei appeared higher grade with more rounded contours and prominent nucleoli and when solid areas predominated over vascular channel formation. A striking feature of both groups was the presence of a dense, lymphocytic infiltrate with occasional germinal center formation. All cases strongly and diffusely expressed at least 1 lymphatic marker (21/21) with podoplanin (17/19) and Prox-1 (11/11) more commonly expressed than LYVE-1 (5/10). No consistent molecular alteration was identified. Follow-up on 17 patients (median: 41 mo, mean: 54 mo) showed 10 patients were alive without disease, 5 were alive with disease, 1 died of other cause, and 1 died of disease. Local recurrence developed in 9 cases and metastasis in 2 cases, although neither correlated with grade as defined. On the basis of clinical follow-up to date, the natural history of lymphatic-type angiosarcoma appears to be more favorable than other forms of cutaneous angiosarcoma.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126198225","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 : 2019-10-29DOI: 10.1097/PAS.0000000000001390
W. Chuang, Sheng-Tsung Chang, Chang-Tsu Yuan, G. Chang, Hung Chang, Chi‐Ju Yeh, S. Ueng, Hsiao-Wen Kao, Tong-Hong Wang, Y. Wan, L. Shih, S. Chuang, C. Hsueh
Pleomorphic mantle cell lymphoma (PMCL) can closely mimic diffuse large B-cell lymphoma (DLBCL) morphologically, and expression of CD5 and cyclin D1 is helpful for differential diagnosis. To date, no cases of CD5/cyclin D1 double-negative PMCL have been reported. Four cases of B-cell lymphoma with an immunophenotype of CD5(−) cyclin D1(−) SOX11(+) and morphologic features compatible with DLBCL were included. Two were previously identified, and the other 2 were screened from 500 cases of B-cell lymphoma. We analyzed their clinicopathologic, immunophenotypic, genetic, and gene expression features. Cases of cyclin D1-positive PMCL, cyclin D1-negative PMCL, germinal center B-cell (GCB) DLBCL, and activated B cell (ABC) DLBCL were also studied for comparison. Similar to other PMCL cases, these 4 patients were mainly elderly male individuals with an aggressive clinical course. None of these tumors had detectable translocations involving CCND1, CCND2, CCND3, CCNE1, CCNE2, MYC, BCL2, or BCL6. The genome-wide copy number profile of these 4 cases was similar to that of cyclin D1-negative PMCL. None of these tumors had high expression of cyclin D1, cyclin D2, or cyclin D3. Similar to cyclin D1-negative PMCL, these cases had higher expression of cyclin E1 and cyclin E2 compared with cyclin D1-positive PMCL. The gene expression pattern of these tumors was also similar to that of cyclin D1-negative PMCL. Here we report for the first time 4 cases of CD5/cyclin D1 double-negative PMCL. SOX11 positivity is useful to identify these rare tumors, and further genetic and gene expression analysis can be used to confirm the diagnosis.
{"title":"Identification of CD5/Cyclin D1 Double-negative Pleomorphic Mantle Cell Lymphoma","authors":"W. Chuang, Sheng-Tsung Chang, Chang-Tsu Yuan, G. Chang, Hung Chang, Chi‐Ju Yeh, S. Ueng, Hsiao-Wen Kao, Tong-Hong Wang, Y. Wan, L. Shih, S. Chuang, C. Hsueh","doi":"10.1097/PAS.0000000000001390","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001390","url":null,"abstract":"Pleomorphic mantle cell lymphoma (PMCL) can closely mimic diffuse large B-cell lymphoma (DLBCL) morphologically, and expression of CD5 and cyclin D1 is helpful for differential diagnosis. To date, no cases of CD5/cyclin D1 double-negative PMCL have been reported. Four cases of B-cell lymphoma with an immunophenotype of CD5(−) cyclin D1(−) SOX11(+) and morphologic features compatible with DLBCL were included. Two were previously identified, and the other 2 were screened from 500 cases of B-cell lymphoma. We analyzed their clinicopathologic, immunophenotypic, genetic, and gene expression features. Cases of cyclin D1-positive PMCL, cyclin D1-negative PMCL, germinal center B-cell (GCB) DLBCL, and activated B cell (ABC) DLBCL were also studied for comparison. Similar to other PMCL cases, these 4 patients were mainly elderly male individuals with an aggressive clinical course. None of these tumors had detectable translocations involving CCND1, CCND2, CCND3, CCNE1, CCNE2, MYC, BCL2, or BCL6. The genome-wide copy number profile of these 4 cases was similar to that of cyclin D1-negative PMCL. None of these tumors had high expression of cyclin D1, cyclin D2, or cyclin D3. Similar to cyclin D1-negative PMCL, these cases had higher expression of cyclin E1 and cyclin E2 compared with cyclin D1-positive PMCL. The gene expression pattern of these tumors was also similar to that of cyclin D1-negative PMCL. Here we report for the first time 4 cases of CD5/cyclin D1 double-negative PMCL. SOX11 positivity is useful to identify these rare tumors, and further genetic and gene expression analysis can be used to confirm the diagnosis.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"60 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121504061","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 : 2019-10-29DOI: 10.1097/PAS.0000000000001400
F. Zito Marino, G. Rossi, M. Montella, G. Botti, R. De Cecio, A. Morabito, C. La Manna, A. Ronchi, M. Micheli, Giuseppe Salatiello, P. Micheli, D. Rocco, M. Accardo, R. Franco
Immune checkpoint inhibitors against programmed cell death protein 1/programmed death-ligand 1 (PD-L1) have proven to be remarkably effective in non–small cell lung cancer. PD-L1 represents a predictive biomarker in lung cancer, although its heterogenous expression represents an emerging challenge for accurate biomarker-based patient selection. Lung adenocarcinomas (ADCs) show a high rate of intratumor morphologic heterogeneity that may reflect a heterogenous molecular and immunophenotypic profile. The aim of our study was to analyze the expression of PD-L1 in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas (mADCs) and adenosquamous lung carcinomas (AdSqLCs). As many as 73 mADCs and 6 AdSqLCs were selected. Comprehensive histologic subtyping was performed, and PD-L1 expression was assessed by immunohistochemistry assay using different primary antibodies and automated immunostainers. Overall, PD-L1 expression was observed in 37 of 79 cases (39.2%) (31 mADCs and all AdSqLCs). PD-L1 expression was heterogenous in 22 of 37 PD-L1-positive cases (23.2% mADC and 83% AdSqLC). PD-L1 expression was observed more frequently in ADC with solid pattern. Heterogeneity of PD-L1 expression was significantly related to the presence of micropapillary (P=0.028) and solid (P=0.017) patterns. All PD-L1-positive cases were epidermal growth factor receptor wild-type, 2 cases harbored concomitantly PD-L1 expression and ALK rearrangement. Our data suggest that PD-L1 expression is quite heterogenous in mADCs and AdSqLCs, partly contributing to explaining the discrepant results between biopsy and surgical resections and discordant clinical effectiveness in regard to PD-L1-positive or negative ADC diagnosed on cytology/small biopsy.
{"title":"Heterogeneity of PD-L1 Expression in Lung Mixed Adenocarcinomas and Adenosquamous Carcinomas","authors":"F. Zito Marino, G. Rossi, M. Montella, G. Botti, R. De Cecio, A. Morabito, C. La Manna, A. Ronchi, M. Micheli, Giuseppe Salatiello, P. Micheli, D. Rocco, M. Accardo, R. Franco","doi":"10.1097/PAS.0000000000001400","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001400","url":null,"abstract":"Immune checkpoint inhibitors against programmed cell death protein 1/programmed death-ligand 1 (PD-L1) have proven to be remarkably effective in non–small cell lung cancer. PD-L1 represents a predictive biomarker in lung cancer, although its heterogenous expression represents an emerging challenge for accurate biomarker-based patient selection. Lung adenocarcinomas (ADCs) show a high rate of intratumor morphologic heterogeneity that may reflect a heterogenous molecular and immunophenotypic profile. The aim of our study was to analyze the expression of PD-L1 in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas (mADCs) and adenosquamous lung carcinomas (AdSqLCs). As many as 73 mADCs and 6 AdSqLCs were selected. Comprehensive histologic subtyping was performed, and PD-L1 expression was assessed by immunohistochemistry assay using different primary antibodies and automated immunostainers. Overall, PD-L1 expression was observed in 37 of 79 cases (39.2%) (31 mADCs and all AdSqLCs). PD-L1 expression was heterogenous in 22 of 37 PD-L1-positive cases (23.2% mADC and 83% AdSqLC). PD-L1 expression was observed more frequently in ADC with solid pattern. Heterogeneity of PD-L1 expression was significantly related to the presence of micropapillary (P=0.028) and solid (P=0.017) patterns. All PD-L1-positive cases were epidermal growth factor receptor wild-type, 2 cases harbored concomitantly PD-L1 expression and ALK rearrangement. Our data suggest that PD-L1 expression is quite heterogenous in mADCs and AdSqLCs, partly contributing to explaining the discrepant results between biopsy and surgical resections and discordant clinical effectiveness in regard to PD-L1-positive or negative ADC diagnosed on cytology/small biopsy.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130345856","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 : 2019-10-29DOI: 10.1097/PAS.0000000000001399
J. Chapman, Jessica P Alvarez, Kyle White, Sandra Sanchez, M. Khanlari, Khaled J Algashaamy, Daniel P. Cassidy, Jing-Hong Peng, Yao‐Shan Fan, A. Alencar, J. Alderuccio, I. Lossos, F. Vega
Follicular lymphoma (FL) is one of the most frequently diagnosed lymphomas in the United States and Europe. The definition of and basic approach to diagnosis and grading of FL is essentially unchanged in the recently updated revision of the World Health Organization (WHO) classification. FL is a biologically and histopathologically heterogeneous disease. Although there is an improved understanding of some FL variants and specific subtypes, there are cases whose recognition is particularly challenging, either because they have unusual features or represent examples of new or rare variants. Herein, we share a series of unusual and difficult to recognize FLs with the goal of increasing awareness of the expanding histopathologic variability in FL. Unusual FL discussed here include: FL with Castleman-like changes, FL with plasmacytic differentiation, and immunoglobulin G4-positive plasma cells in the setting of immunoglobulin G4-related disease, FL with marginal zone differentiation and involving mucosa-associated lymphoid tissue sites, diffuse FL variant expressing CD23 with STAT6 mutation, large B-cell lymphoma with IRF4 rearrangement, CD10-negative and MUM1-positive aggressive FL, and Epstein-Barr virus–positive FL.
{"title":"Unusual Variants of Follicular Lymphoma","authors":"J. Chapman, Jessica P Alvarez, Kyle White, Sandra Sanchez, M. Khanlari, Khaled J Algashaamy, Daniel P. Cassidy, Jing-Hong Peng, Yao‐Shan Fan, A. Alencar, J. Alderuccio, I. Lossos, F. Vega","doi":"10.1097/PAS.0000000000001399","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001399","url":null,"abstract":"Follicular lymphoma (FL) is one of the most frequently diagnosed lymphomas in the United States and Europe. The definition of and basic approach to diagnosis and grading of FL is essentially unchanged in the recently updated revision of the World Health Organization (WHO) classification. FL is a biologically and histopathologically heterogeneous disease. Although there is an improved understanding of some FL variants and specific subtypes, there are cases whose recognition is particularly challenging, either because they have unusual features or represent examples of new or rare variants. Herein, we share a series of unusual and difficult to recognize FLs with the goal of increasing awareness of the expanding histopathologic variability in FL. Unusual FL discussed here include: FL with Castleman-like changes, FL with plasmacytic differentiation, and immunoglobulin G4-positive plasma cells in the setting of immunoglobulin G4-related disease, FL with marginal zone differentiation and involving mucosa-associated lymphoid tissue sites, diffuse FL variant expressing CD23 with STAT6 mutation, large B-cell lymphoma with IRF4 rearrangement, CD10-negative and MUM1-positive aggressive FL, and Epstein-Barr virus–positive FL.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122435634","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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