scholarly journals Primary Signet Ring Cell/Histiocytoid Carcinoma of the Eyelid: Somatic Mutations in CDH1 and Other Clinically Actionable Mutations Imply Early Use of Targeted Agents

2021 ◽  
Vol 28 (1) ◽  
pp. 918-927
Author(s):  
Lei-Chi Wang ◽  
Tai-Chi Lin ◽  
Yi-Chen Yeh ◽  
Hsiang-Ling Ho ◽  
Chieh-Chih Tsai ◽  
...  

Primary signet ring cell/histiocytoid carcinoma of the eyelid is a rare ocular malignancy and its diagnosis is often delayed. This neoplasm presents as an insidious, diffusely infiltrative mass in the periocular area that later infiltrates the orbit. An exenteration is usually indicated; however, nearly one-third of patients develop local recurrence or metastasis. Morphologically, it resembles signet ring cell carcinoma of the stomach and breast, raising the possibility of mutations in CDH1, the gene encoding E-cadherin. To determine whether primary signet ring cell/histiocytoid carcinoma harbors the CDH1 mutation or other actionable mutations, we analyzed the tumor tissue via next-generation sequencing. We identified only one case of primary signet ring cell carcinoma of the eyelid with adequate DNA quality for sequencing from the pathological archive during the period 2000 to 2020. A comprehensive evaluation including histopathology, immunohistochemistry, and next-generation sequencing assay was performed on tumor tissue. Immunohistochemically, the tumor exhibited E-cadherin membranous staining with the aberrant cytoplasmic staining of β-catenin. Using next-generation sequencing, we demonstrated the mutation in the CDH1 gene. In addition, other clinically actionable mutations including ERBB2 and PIK3CA were also detected. The alterations in other actionable genes indicate a need for larger studies to evaluate the pathogenesis and potential therapies for primary signet ring cell/histiocytoid carcinoma of the eyelid.

2019 ◽  
Vol 28 (1) ◽  
pp. 51-59
Author(s):  
Kristine M. Cornejo ◽  
Ediz F. Cosar ◽  
Gladell P. Paner ◽  
Ping Yang ◽  
Keith Tomaszewicz ◽  
...  

Objectives. The rare urachal adenocarcinoma (UAC) of the bladder has striking morphologic and immunohistochemical overlap with colorectal adenocarcinoma (CAC) and bladder adenocarcinoma (BAC). To date, the mutational status in UAC and BAC has not been well investigated. Methods. We retrospectively evaluated 34 UACs (mucinous, n = 9; intestinal, n = 3; signet ring cell, n = 1; not otherwise specified, n = 21) and 4 BACs (n = 4). Next-generation sequencing analysis of 50 cancer “hotspot” gene mutations using the Ampliseq Cancer Hotspot Panel v2 was performed. Two UAC cases did not have adequate DNA quality with poor sequencing coverage and were excluded from the study. Results. RAS mutations were identified in 16 of 32 (50%) UACs (15 KRAS; 1 NRAS) and none of the BACs (0%). TP53 mutations were found in both UACs (18/32; 56%) and BACs (4/4; 100%). GNAS (n = 4), SMAD4 (n = 3), and BRAF (n = 1) mutations were only found in UACs. In contrast, APC (n = 2) mutations were only found in BACs. The mucinous subtype of UAC contained a SMAD4 mutation in 33% of cases (3/9), which was not identified in any other subtype (0/23; 0%) ( P = .0169). The only BRAF mutation was identified in the single signet ring cell subtype of UAC. There were no other differences in the mutation profile when comparing histologic subtypes of UAC. Conclusions. In summary, UAC and BAC have overlapping but distinct mutation profiles and these differences may aid in separating these 2 entities. Next-generation sequencing to identify therapeutic targets or resistance markers may aid treatment decisions.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160527 ◽  
Author(s):  
Renjie Wang ◽  
Xiaoji Ma ◽  
Yaqi Li ◽  
Yiping He ◽  
Dan Huang ◽  
...  

2006 ◽  
Vol 130 (9) ◽  
pp. 1320-1325
Author(s):  
Kyung Chul Moon ◽  
Soo Youn Cho ◽  
Hye Seung Lee ◽  
Yoon Kyung Jeon ◽  
Jin-Haeng Chung ◽  
...  

Abstract Context.—E-Cadherin and β-catenin complexes have been suggested to have critical roles in cancer development and progression. Primary signet ring cell carcinoma (SRCC) of the lung is a rare variant of pulmonary adenocarcinoma, and E-cadherin and β-catenin expressions of this tumor have not been documented, to our knowledge. Objective.—To characterize the E-cadherin and β-catenin expressions in SRCC of the lung. Design.—An immunohistochemical evaluation of E-cadherin and β-catenin expressions in 10 cases of SRCC of the lung, 10 cases of conventional pulmonary adenocarcinoma, 10 cases of gastric SRCC, and 10 cases of colorectal SRCC was performed. Results.—Membranous E-cadherin and β-catenin expressions were frequently reduced or absent in all types of tumors tested. Aberrant E-cadherin localization and nuclear β-catenin accumulation were frequently found in gastric (6/10 and 5/10, respectively) and colorectal (7/10 and 9/ 10, respectively) SRCCs, whereas SRCC of the lung rarely showed aberrant E-cadherin localization (1/10) or nuclear β-catenin accumulation (0/10). Conclusions.—Signet ring cell carcinoma of the lung rarely showed aberrant E-cadherin localization or β-catenin nuclear accumulation, which are frequent events in gastric and colorectal SRCCs. These results suggest that the biologic roles of E-cadherin and β-catenin complexes in SRCC of the lung differ from their roles in gastric or colorectal SRCCs.


2019 ◽  
Vol 30 ◽  
pp. v316
Author(s):  
H. Kim ◽  
S. Kim ◽  
J.M. Park ◽  
H.H. Lee ◽  
K.Y. Song ◽  
...  

1996 ◽  
Vol 87 (8) ◽  
pp. 843-848 ◽  
Author(s):  
Hiromi Muta ◽  
Masayuki Noguchi ◽  
Yae Kanai ◽  
Atsushi Ochiai ◽  
Hajime Nawata ◽  
...  

2009 ◽  
Vol 69 (5) ◽  
pp. 2050-2056 ◽  
Author(s):  
Bostjan Humar ◽  
Vanessa Blair ◽  
Amanda Charlton ◽  
Helen More ◽  
Iain Martin ◽  
...  

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