Gastric‐type endocervical glandular neoplasms associated with aberrant p16 expression and <scp>K</scp>‐<scp>RAS</scp> gene mutation in <scp>P</scp>eutz‐<scp>J</scp>eghers syndrome

Ito, Shigemi; Tase, Toru; Satoh, Kennichi; Ueki, Miyuki; Sato, Iwao; Sasano, Hironobu

doi:10.1111/pin.12173

Cited by 7 publications

(3 citation statements)

References 19 publications

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“…Previous studies have reported that p16 and STK11 cell cycle-associated protein was excessively expressed in LEGH lesions. [16][17][18] The results of the present study suggest that the cell cycle in LEGH cells may occur more rapidly than in EC cells; this suggests that mitosis is initiated prior to cell growth in new cells because LEGH cells have more active nuclear division than EC cells and this may explain the smaller nuclear size in LEGH cells.…”

Section: Resultsmentioning

confidence: 57%

Image quantification technology of the heterochromatin and euchromatin region for differential diagnosis in the lobular endocervical glandular hyperplasia

Kimura

Kobayashi

Kanai

et al. 2019

Diagnostic Cytopathology

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Background Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci et al. in 1999 and is believed to be a precancerous lesion of minimal deviation adenocarcinoma and gastric‐type adenocarcinoma in the uterine cervix. LEGH lesions do not always exhibit apparent cellular and structural atypia, so are difficult to distinguish from normal endocervical cells (EC cells) with cytological examination. Therefore, we often struggle to make a definite diagnosis of LEGH. Methods We used microscopy images of cytological specimens that were diagnosed as EC cells and LEGH cells. Signal intensity in whole nuclear area and in heterochromatin and euchromatin regions, euchromatin area ratio, and nuclear morphological features were quantified in each cell nucleus of the cases. Statistical analyses were conducted to determine statistical significance. Finally, we performed linear support vector machine (LSVM) modeling as a discriminant analysis using the quantified features. Results Signal intensity in whole nuclear area, and heterochromatin and euchromatin regions of EC cell nuclei were higher than that of the LEGH cell nuclei. Morphologically, EC cell nuclei were larger than LEGH cell nuclei, and nuclei of LEGH cells had irregular nuclear respectively membrane structure and an elongated shape. The LSVM accuracy of 10‐fold cross validation and leave‐one‐case‐out cross‐validation (LOCOCV) using all measured features were 84.7% to 89.3% and 78.6% to 86.0%, respectively. Conclusions The LVSM analysis using features extracted from signal intensity and morphological analysis was useful for discrimination of EC cells vs LEGH cells. We therefore believe that this image analysis method could be used for early detection of LEGH.

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Section: Resultsmentioning

confidence: 57%

Image quantification technology of the heterochromatin and euchromatin region for differential diagnosis in the lobular endocervical glandular hyperplasia

Kimura

Kobayashi

Kanai

et al. 2019

Diagnostic Cytopathology

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“…A comprehensive literature search produced 1564 publications; 46 studies were identified that focused on lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma in patients with Peutz-Jeghers syndrome. Thirty-eight (83%) were case reports/case series that met the inclusion criteria and were included in the analysis 13 14 16 19–53. The remaining eight studies were original research (five) or reviews (three) and were excluded from the analysis.…”

Section: Resultsmentioning

confidence: 99%

Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines

Gordhandas

Kahn

Sassine

et al. 2021

Int J Gynecol Cancer

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ObjectivesTo perform a systematic review of gastric-type adenocarcinoma of the cervix and lobular endocervical glandular hyperplasia (a possible precursor lesion) in Peutz-Jeghers syndrome, and to analyze data from the literature, along with our institutional experience, to determine recommendations for screening and detection.MethodsA comprehensive literature searc and retrospective search of pathology records at our institutio were conducted. Articles were screened by two independent reviewers. Case reports/series on lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma of the cervix in Peutz-Jeghers syndrome were included. Demographic, clinical, and radiologic information was collected.ResultsA total of 1564 publications were reviewed; 38 met the inclusion criteria. Forty-nine were included in the analysis (43 from the literature, 6 from our institution). Forty-three reported on gastric-type adenocarcinoma alone, 4 on lobular endocervical glandular hyperplasia alone, and 2 on concurrent lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma. Median age at diagnosis was 17 (range, 4–52) for patients with lobular endocervical glandular hyperplasia alone and 35 (range, 15–72) for those with gastric-type adenocarcinoma. The most common presenting symptoms were abdominal/pelvic pain and vaginal bleeding/discharge. Imaging was reported for 27 patients; 24 (89%) had abnormal cervical features. Papanicolaou (Pap) smear prior to diagnosis was reported for 12 patients; 6 (50%) had normal cytology, 4 (33%) atypical glandular cells, and 2 (17%) atypical cells not otherwise specified. Patients with gastric-type adenocarcinoma (n=45) were treated with surgery alone (n=16), surgery/chemotherapy/radiation (n=11), surgery/chemotherapy (n=9), surgery/radiation (n=5), or radiation/chemotherapy (n=4). Twelve (27%) of 45 patients recurred; median progression-free survival was 10 months (range, 1–148). Twenty patients (44%) died; median overall survival was 26 months (range, 2–156). Thirteen patients (27%) were alive with no evidence of disease.ConclusionsGastric-type adenocarcinoma in Peutz-Jeghers syndrome is associated with poor outcomes and short progression-free and overall survival. Screening recommendations, including pathognomonic symptom review and physical examination, with a low threshold for imaging and biopsy, may detect precursor lesions and early-stage gastric-type adenocarcinoma, leading to better outcomes in this high-risk population.PROSPERO registration numberCRD42019118151

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“…In the visible light region, hematoxylin, EA50, and OG6 exhibited maximum absorption at red/green, green, and blue, respectively. On the other hand, LEGH with mutations in either p16 INK4a , KRAS, STK11, GNAS [20][21][22], or minimal deviation adenocarcinoma and other gastric-type adenocarcinomas in the uterine cervix with these mutations have also been reported. Therefore, LEGH is regarded as a neoplastic lesion, not a hyper-plastic lesion [23].…”

Section: Discussionmentioning

confidence: 99%

Discriminant Analysis Using Gabor Filter Sets for Lobular Endocervical Glandular Hyperplasia: Numerical Interpretation of Nuclear Atypia by Gabor Filter Features

Kimura¹,

Ohshima²,

Shirai³

et al. 2023

Acta Cytologica

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Introduction: Lobular endocervical glandular hyperplasia (LEGH) is a benign lesion; however, it is considered to be the origin of gastric-type adenocarcinoma in the uterine cervix, and early diagnosis is important. At Shinshu University Hospital, screening of LEGH cells is based on the difference in color tone of cytoplasmic mucin on Papanicolaou staining and detection of gastric mucin using HIK1083-labeled latex agglutination assay. However, it is sometimes difficult to distinguish LEGH cells with subtle nuclear atypia from endocervical (EC) cells. Methods: We calculated the Gabor filter features (mean signal value, standard deviation, skewness, kurtosis) from the nuclei of cytological specimens in EC cells (37 cases) and LEGH cells (33 cases) using microscopic images, and we performed statistical analysis and discriminant analysis by linear support vector machine (LSVM) using these features. A Gabor filter is a linear filter defined as a mathematical representation of the mammalian visual system. Gabor filters with three wavelengths and eight angles were used for analysis. Results: Gabor filter features in EC cells were higher than in LEGH cells, demonstrating that the gradient of LEGH cell nuclei was milder than that of EC cell nuclei. The accuracy calculated using all Gabor filters was 91.0% and the accuracy of four Gabor filters (λ = 2/3π and θ = 0°, 45°, 90°, 135°) was 88.9%. High accuracy with low computation costs was achieved by reducing the number of features used for LSVM. Conclusion: The application of a Gabor filter with convolutional processing resulted in the edges of LEGH cells being slightly rough and thick, whereas those of EC cells were fine and thin. Thus, it is thought that the frequency of abrupt gradients of pixels was higher in EC cells than in LEGH cells, and the gradient of chromatin distribution in LEGH cell nuclei was milder than that in EC cell nuclei. It was possible to evaluate nuclear findings of EC and LEGH cells objectively by quantifying morphological features of nuclei using Gabor filters. It was possible to differentiate EC cells from LEGH cells using LSVM using Gabor filter features.

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Gastric‐type endocervical glandular neoplasms associated with aberrant p16 expression and K‐RAS gene mutation in Peutz‐Jeghers syndrome

Cited by 7 publications

References 19 publications

Image quantification technology of the heterochromatin and euchromatin region for differential diagnosis in the lobular endocervical glandular hyperplasia

Image quantification technology of the heterochromatin and euchromatin region for differential diagnosis in the lobular endocervical glandular hyperplasia

Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines

Discriminant Analysis Using Gabor Filter Sets for Lobular Endocervical Glandular Hyperplasia: Numerical Interpretation of Nuclear Atypia by Gabor Filter Features

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