scholarly journals Primary Signet Ring Cell/Histiocytoid Carcinoma of the Eyelid: Clinicopathologic Analysis with Evaluation of the E-Cadherin/β-Catenin Complex and Associated Genetic Alterations

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Maria Del Valle Estopinal ◽  
Lavinia P. Middleton ◽  
Bita Esmaeli ◽  
Keyur P. Patel ◽  
Sara Nowroozizadeh ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Somatic Mutations ◽  
Genetic Alterations ◽  
Signet Ring Cell ◽  
Cancer Center ◽  
Diffuse Gastric Cancer ◽  
Cytoplasmic Staining ◽  
Signet Ring ◽  
Ring Cell ◽  
E Cadherin

Signet Ring Cell (SRC)/Histiocytoid carcinoma of the eyelid is a rare neoplasm that shares histological and immunohistochemical similarities with diffuse gastric cancer and breast lobular carcinoma. The CDH1 gene, which encodes the E-cadherin protein, is the best known gene associated with these tumors. The structural and functional integrity of E-cadherin is regulated by interconnecting molecular pathways which might participate in the development of this disease. Hence, we analyzed the protein expression in key genes in E-cadherin-related pathways associated with primary SRC/Histiocytoid carcinoma of the eyelid. SRC/Histiocytoid carcinoma diagnosed in the eyelid/orbit at MD Anderson Cancer Center from 1990 to 2016 were evaluated. Clinicopathologic findings were studied to confirm the primary site of origin. Immunohistochemical studies for the expression of E-cadherin, β-catenin, c-Myc, Cyclin D1, Src, and p53 were analyzed. Next generation sequencing for the detection of somatic mutations was performed on each tumor with matched normal tissue, examining 50 cancer-related genes. Four primary SRC/Histiocytoid carcinomas of the eyelid were diagnosed in four male patients aged 40-82 years. Immunohistochemically, two tumors with loss of E-cadherin expression had weak β-catenin and low cytoplasmic staining for Src while the other two cases with intact E-cadherin showed strong β-catenin expression and high cytoplasmic expression for Src. Cyclin D1 was focally positive in three cases. Somatic mutations in CDH1, PIK3CA, and TP53 genes were detected in two cases. Our results suggest an abnormality in the convergence of E-cadherin/β-catenin pathways which may promote tumorigenesis by inducing expression of oncogenes such as Cyclin D1 and C-Myc. Mutations in CDH1, PIK3CA, and TP53 genes could induce E-cadherin dysfunction which takes part in the development and progression of this malignancy.

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 ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Cell Carcinoma ◽  
Tumor Tissue ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Next Generation ◽  
Signet Ring ◽  
Ring Cell ◽  
Generation Sequencing ◽  
E Cadherin

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.

scholarly journals Wernicke Encephalopathy Due to Prolonged Total Parenteral Nutrition in A Child with Signet Ring Cell Gastric Carcinoma

2020 ◽  
pp. 30-33
Author(s):  
Buket KARA ◽  
Ayse KARTAL ◽  
Mehmet ÖZTÜRK ◽  
Yavuz KÖKSAL
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Parenteral Nutrition ◽  
Total Parenteral Nutrition ◽  
Signet Ring Cell ◽  
Diffuse Gastric Cancer ◽  
Wernicke Encephalopathy ◽  
Signet Ring ◽  
Ring Cell

Signet ring cell gastric carcinoma is extremely rare during childhood. One of the most important problems in these patients is nutritional difficulty and impairment, and these patients are often supported by total parenteral nutrition. Herein, the authors report a case of Wernicke encephalopathy due to prolonged total parenteral nutrition in a 13-year-old girl with diffuse gastric cancer with signet ring cell.

scholarly journals The Clinicopathological Characteristics And Genetic Alterations of Signet-ring Cell Carcinoma in Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2318
Author(s):  
Kuo-Hung Huang ◽  
Ming-Huang Chen ◽  
Wen-Liang Fang ◽  
Chien-Hsing Lin ◽  
Yee Chao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Liver Metastasis ◽  
Cell Carcinoma ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Akt Pathway ◽  
Signet Ring ◽  
Ring Cell

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients.

scholarly journals Confocal Endomicroscopy Diagnostic Criteria for Early Signet-Ring Cell Carcinoma in Hereditary Diffuse Gastric Cancer

2021 ◽  
Author(s):  
Nastazja D. Pilonis ◽  
Maria O’Donovan ◽  
Susan Richardson ◽  
Rebecca C. Fitzgerald ◽  
Massimiliano Pietro
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Diagnostic Criteria ◽  
Interobserver Agreement ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Video Sequences ◽  
Diffuse Gastric Cancer ◽  
Signet Ring ◽  
Ring Cell

Abstract Background Recognition of early signet-ring cell carcinoma (SRCC) in patients with hereditary diffuse gastric cancer (HDGC) undergoing endoscopic surveillance is challenging. We hypothesized that probe-based confocal laser endomicroscopy (pCLE) might help diagnose early cancerous lesions in the context of HDGC. The aim of this study was to identify pCLE diagnostic criteria for early SRCC. Methods Patients with HDGC were prospectively recruited and pCLE assessment was performed on areas suspicious for early SRCC and control regions. Targeted biopsies were taken for gold standard histologic assessment. In Phase I two investigators assessed video sequences off-line to identify pCLE features related to SRCC. In Phase II pCLE diagnostic criteria were evaluated in an independent video set by the investigators blinded to the histologic diagnosis. Sensitivity, specificity, accuracy, and interobserver agreement were calculated. Results 42 video sequences from 16 HDGC patients were included in Phase I. Four pCLE patterns associated to SRCC histologic features were identified: (A) glands with attenuated margins, (B) glands with spiculated or irregular shape, (C) heterogenous granular stroma with sparse glands, (D) enlarged vessels with tortuous shape. In Phase II, 38 video sequences from 15 patients were assessed. Criteria A and B and C had the highest diagnostic accuracy, with a κ for interobserver agreement ranging from 0.153 to 0.565. A panel comprising these 3 criteria with a cut-off of at least one positive criterion had a sensitivity of 80.9% (95%CI:58.1 - 94.5%) and a specificity of 70.6% (95%CI:44.0 - 89.7%) for a diagnosis of SRCC. Conclusions We have generated and validated off-line pCLE criteria for early SRCC. Future real-time validation of these criteria is required.

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