MELF pattern invasion in endometrial carcinoma: association with low grade, myoinvasive endometrioid tumours, focal mucinous differentiation and vascular invasion

Stewart, Colin J.R.; Brennan, Barbara A.; Leung, Yee; Little, Leonie

doi:10.1080/00313020903041135

Cited by 68 publications

(86 citation statements)

References 29 publications

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“…10 However, other investigators have found an association between this pattern, lymphovascular invasion, as well as lymph node metastases. [11][12][13][14] In our experience, papillary ECa of intermediate grade, with or without MELF pattern, tends to be associated with vascular/lymphatic invasion and lymph node metastasis. Other investigators have indicated that these tumors appear to have a behavior intermediate between serous carcinoma and ECa villoglandular variant.…”

Section: Papillary Tumorsmentioning

confidence: 57%

How to approach the many faces of endometrioid carcinoma

Malpica

2016

Modern Pathology

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This article reviews the salient features of variants of endometrioid carcinoma (ECa) that can pose a diagnostic challenge and/or are associated with unique clinicopathological findings. Variants with distinct architectural and cytologic features include the following: (1) ECa with a villoglandular pattern (tumor with finger-like papillae lined by bland cells with a tendency for vascular/lymphatic invasion and lymph node metastasis once this pattern is seen within the myoinvasive component); (2) papillary ECa of intermediate grade (grade 2) (tumor that can be mistaken for serous carcinoma, as it contains papillae showing slightly irregular contours, moderately atypical cells, and it is associated with vascular/lymphatic invasion/lymph node metastasis, but with common association with mucinous metaplasia, MELF (microcystic, elongated, and fragmented) pattern of invasion, and wild p53 expression); (3) ECa with non-villous papillae (tumor containing pseudopapillae within glands with bland-appearing cytology commonly associated with abortive squamous differentiation and otherwise not different from usual ECa); (4) ECa with microglandular-like pattern (tumor that mimics microglandular hyperplasia of the cervix, often lacking the typical appearance of microglandular hyperplasia and showing Ki-67 index 410%, strong CD10 expression, and negative PAX-2, p63, and CD34); and (5) ECa with sex cord-like formations and hyalinization (tumor with interconnected cords and nests of bland epithelioid and spindled cells that merge with a typical component of low-grade ECa, usually associated with squamous differentiation and hyalinization). This tumor should be distinguished from carcinosarcoma and, in contrast to the latter, it shows nuclear β-catenin expression, ER/PR and patchy p16 positivity, tends to present at a low stage, and has a favorable prognosis and (6) dedifferentiated ECa (tumor showing a low-grade ECa juxtaposed to an undifferentiated carcinoma-the latter characterized by variably sized monotonous, often non-cohesive cells with brisk mitotic activity and usually arranged in sheets). Undifferentiated carcinoma tends to be negative for PAX8 and ER/PR with variable expression of keratins and can be associated with microsatellite instability (may be part of Lynch syndrome). Variants with distinct cytological features include the following: (1) ECa with clear cells (tumors with clearing due to 'clear' (glycogenated) squamous cells, distinct vacuoles, or not otherwise specified. EC with clear cells should be distinguished from clear cell carcinoma by the absence of the variety of architectural patterns, lack of cuboidal/flattened/hobnail cells, and lack of degree of atypia usually detected in clear cell carcinoma. In addition, they are ER/PR positive and Napsin A and p504S negative in contrast to clear cell carcinoma); (2) ECa with spindle cells (tumor with transition from spindle cells to the glandular component of a low-grade ECa. The spindle cells are keratin, ER/PR, and patchy p16 positive and show wild-type p53 expre...

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Section: Papillary Tumorsmentioning

confidence: 57%

How to approach the many faces of endometrioid carcinoma

Malpica

2016

Modern Pathology

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“…These findings illustrate the importance of considering microanatomical variation in staining and lend further support to the hypothesis that MELF pattern invasion represents an active rather than a degenerative process during the progression of endometrial carcinoma. 19,20 Expression of cyclin D1 in MELF areas would also be consistent with epithelial-mesenchymal transition as cyclin D1 is characteristically upregulated during this process in other types of carcinoma. [12][13][14]22,23 Abnormalities of b-catenin have also been shown in a significant proportion of endometrial neoplasms.…”

Section: Endometrial Carcinoma Invasionmentioning

confidence: 76%

“…11,17 We have noted earlier that endometrial carcinomas exhibiting a distinctive pattern of invasion comprising microcystic, elongated and fragmented ('MELF') glands 18 show specific pathological associations and morphological changes, some of which are suggestive of epithelial-mesenchymal transition. 19,20 Therefore, in this study, we have further explored the cellular alterations at the invasive margin of endometrial adenocarcinoma by comparing the expression of the cell-cycle-related proteins, cyclin D1, b-catenin and p16, between conventional tumor areas and foci exhibiting MELF pattern invasion. 19 and there were three subsequently identified tumors.…”

mentioning

confidence: 99%

“…19,20 Therefore, in this study, we have further explored the cellular alterations at the invasive margin of endometrial adenocarcinoma by comparing the expression of the cell-cycle-related proteins, cyclin D1, b-catenin and p16, between conventional tumor areas and foci exhibiting MELF pattern invasion. 19 and there were three subsequently identified tumors. All MELF-positive cases were low-grade (FIGO grade 1 or 2) endometrioid adenocarcinomas although three cases had separate, discreet areas of high-grade (de-differentiated) carcinoma.…”

mentioning

confidence: 99%

“…21 The MELF pattern changes were as earlier described comprising dilated (microcystic), elongated and fragmented glands, usually most evident at the deepest myoinvasive aspect of the tumors. 18,19 The cases selected for study exhibited multiple MELF-type foci in at least one tumor block that was used for the immunohistochemical evaluation.…”

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Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

et al. 2009

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Endometrial adenocarcinomas may show a distinctive pattern of invasion characterized by the presence of microcystic, elongated and fragmented glands, often most evident along the advancing tumor margin. Earlier, we have shown that these changes appear restricted to low-grade endometrioid carcinomas, many of which show focal mucinous differentiation and lymphovascular space invasion. However, the molecular alterations associated with this morphological alteration are not known. In this study, we have examined immunoreactivity for the cell cycle regulatory proteins cyclin D1, p16 and b-catenin in 22 endometrial carcinomas, specifically comparing the results in conventional tumor areas and in foci in which the glands exhibited microcystic, elongated and fragmented appearances. The conventional neoplastic glands exhibited cyclin D1 and p16 expression in most cases, with 450% tumor cells positive in 8 cases and 11 tumors, respectively. Membranous expression of b-catenin was usually preserved, with variable cytoplasmic and nuclear staining. Cyclin D1 and b-catenin predominantly stained cells at the peripheral or basal aspect of the conventional glands, whereas p16 was more uniformly expressed centrally. Tumor foci composed of microcystic, fragmented and elongated glands showed strong expression of cyclin D1 and p16, sometimes in contrast to unstained contiguous or adjacent conventional neoplastic elements, and there was also loss or fragmentation of membranous b-catenin staining. Intravascular tumor cells also expressed cyclin D1 and p16 and therefore the immunostains often highlighted subtle foci of lymphovascular invasion. The heterogenous expression of cell cycle regulatory proteins within endometrial adenocarcinoma illustrates the importance of assessing microanatomical variations in immunoreactivity, particularly at the advancing margin of tumors. The upregulation of cyclin D1 and p16, together with loss of membranous b-catenin expression in microcystic, fragmented and elongated glands, is similar to epithelial-mesenchymal transitions observed in other malignancies and suggests that this pattern of invasion represents an active rather than a degenerative cellular process. Modern Pathology (2009) 22, 725-733; doi:10.1038/modpathol.2009 published online 6 March 2009 Keywords: endometrial; carcinoma; invasion; MELF; epithelial-mesenchymal transition; immunohistochemistry Endometrial carcinomas can be divided into two major groups on the basis of clinicopathological, immunohistological and molecular features. 1,2 The more common (type 1) subgroup accounts for 80-85% of cases and mainly comprises endometrioid adenocarcinomas of low-to-intermediate grade. These tumors typically occur in perimenopausal and younger postmenopausal patients, often arise in hyperestrogenic states and are associated with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. Frequently, type 1 carcinomas are confined to the uterine corpus at the time of diagnosis (stage 1), and the prognosis in such patients is generally ...

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Preoperative Imaging Evaluation of Endometrial Cancer in FIGO 2023

Kido,

Himoto,

Kurata

et al. 2023

Magnetic Resonance Imaging

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The staging of endometrial cancer is based on the International Federation of Gynecology and Obstetrics (FIGO) staging system according to the examination of surgical specimens, and has revised in 2023, 14 years after its last revision in 2009. Molecular and histological classification has incorporated to new FIGO system reflecting the biological behavior and prognosis of endometrial cancer. Nonetheless, the basic role of imaging modalities including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography, as a preoperative assessment of the tumor extension and also the evaluation points in CT and MRI imaging are not changed, other than several point of local tumor extension. In the field of radiology, it has also undergone remarkable advancement through the rapid progress of computational technology. The application of deep learning reconstruction techniques contributes the benefits of shorter acquisition time or higher quality. Radiomics, which extract various quantitative features from the images, is also expected to have the potential for the quantitative prediction of risk factors such as histological types and lymphovascular space invasion, which is newly included in the new FIGO system. This article reviews the preoperative imaging diagnosis in new FIGO system and recent advances in imaging analysis and their clinical contributions in endometrial cancer.Evidence Level4Technical EfficacyStage 3

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MELF pattern invasion in endometrial carcinoma: association with low grade, myoinvasive endometrioid tumours, focal mucinous differentiation and vascular invasion

Cited by 68 publications

References 29 publications

How to approach the many faces of endometrioid carcinoma

How to approach the many faces of endometrioid carcinoma

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

Preoperative Imaging Evaluation of Endometrial Cancer in FIGO 2023

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