Aberrant Nuclear Localization and Gene Mutation of β-catenin in Low-Grade Adenocarcinoma of Fetal Lung Type: Up-Regulation of the Wnt Signaling Pathway May Be a Common Denominator for the Development of Tumors that Form Morules

Nakatani, Yukio; Masudo, Katsuhiko; Miyagi, Yohei; Inayama, Yoshiaki; Kawano, Naomi; Tanaka, Yukichi; Kato, Keisuke; Ito, Takaaki; Kitamura, Hitoshi; Nagashima, Yoji; Yamanaka, Shōji; Nakamura, Nobuo; Sano, Jinyu; Ogawa, Norio; Ishiwa, Naoki; Notohara, Kenji; Resl, M; Mark, Eugene J.

doi:10.1038/modpathol.3880575

Cited by 104 publications

(81 citation statements)

References 35 publications

(31 reference statements)

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“…Sarcomatoid carcinomas are estimated to account for only 0.1–0.4% of all lung cancers, and of these, only 4% are pulmonary carcinosarcomas 1, 7. According to the recent World Health Organization (WHO) classification of lung tumors, carcinosarcoma is defined as a malignant tumor that consists of an admixture of non‐small cell lung carcinoma and sarcoma‐containing heterologous elements 1, 8.…”

Section: Discussionmentioning

confidence: 99%

“…Although both groups show similar histological findings, H‐FLACs show high nuclear atypia and typically lack morules 12. The pathogenesis of these two groups has been discussed, and the up‐regulation of the Wnt signaling component, including gene mutations of beta catenin, is suggested to be important for L‐FLACs/WDFAs but not for H‐FLACs 2, 7, 12. Furthermore, immunohistochemical analyses have demonstrated aberrant nuclear and cytoplasmic staining of beta catenin in the epithelial cells of L‐FLACs/WDFAs, while membranous staining in H‐FLACs 2, 3, 11, 12.…”

Section: Discussionmentioning

confidence: 99%

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Blastomatoid pulmonary carcinosarcoma: A rare case report and review of the literature

et al. 2018

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A 65‐year‐old never‐smoking woman presented to a local hospital, because an abnormal shadow was detected at the right lower lung field by annual chest X‐ray. Computed tomography (CT) revealed a 5‐cm tumor in segment 6 of her right lung and an enlarged subcarinal lymph node, suggesting metastasis. The lung tumor was diagnosed as adenocarcinoma by a CT‐guided percutaneous needle biopsy. She was referred to our hospital and underwent right lower lobectomy with lymph node dissection (ND2a‐2). A histopathological examination of the tumor showed a biphasic proliferation made of carcinomatous and sarcomatous components. The carcinomatous component consisted of glandular structures of atypical cells that possessed chromatin‐rich nuclear and clear cytoplasm, confirming high‐grade fetal adenocarcinoma. The sarcomatous component consisted of immature spindle cells that differentiated into chondrosarcoma. Immunohistochemically, the glandular structures expressed membranous beta‐catenin, and the ultimate diagnosis was blastomatoid variant of pulmonary carcinosarcoma. She received four courses of cisplatin plus vinorelbine as adjuvant chemotherapy and remained alive with neither recurrence nor distant metastasis at two and a half years after the operation. We experienced a rare case of blastomatoid pulmonary carcinoasarcoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Blastomatoid pulmonary carcinosarcoma: A rare case report and review of the literature

et al. 2018

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“…Morphologically similar structures have also been described in neoplastic lesions in other anatomic sites, such as thyroid (3), lung (4,5), stomach (6), pancreas (7), and colon (8).…”

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confidence: 85%

An Immunohistochemical Study of Morules in Endometrioid Lesions of the Female Genital Tract: CD10 Is a Characteristic Marker of Morular Metaplasia

Chiarelli

Buritica

Litta

et al. 2006

Clinical Cancer Research

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Purpose:To analyze immunohistochemically morules in endometrioid lesions to show that CD10 is a sensitive marker for morular metaplasia. Experimental Design: Immunohistochemical analysis of 53 instances of morular metaplasia comprising 1 cyclic endometrium and 52 endometrioid lesions associated with focal glandular complexity corresponding to 9 polyps, 4 atypical polypoid adenomyomas, 24 complex endometrial hyperplasias (18 with and 6 without atypia), 12 grade 1 endometrioid adenocarcinomas in early clinical stages of both uterus and ovary, and three ovarian adenofibromas. Immunohistochemistry in paraffin sections was done for CD10, h-catenin, estrogen and progesterone receptors, and cytokeratins 5-6, 7, 8, 13, 18, 19, 20, and 34h-E12. Results: Morules were negative for estrogen and progesterone receptors and had h-cateninp ositive nuclei. Cytokeratins 8, 18, 19 were positive; cytokeratins 7 and 20 were negative; and cytokeratins 5-6, 13, and 34h-E12 were weakly positive. All cases revealed strongly positive membranous CD10 staining in morules, which was absent in glands. CD10 positivity allowed easy identification of morules at low power in various types of surgical specimens and in curettings. CD10 also highlighted early morular metaplasia in glandular epithelium. In cases associated with squamous, keratinizing metaplasia, CD10 discriminated between both types of metaplasia. Conclusions: CD10 staining represents a useful marker of morules in endometrioid neoplasms of the female genital tract, permitting identification of lesions usually associated with an attenuated malignancy. Considering the immunohistochemical and genetic similarities of morules in tumors of different organs, it is likely that this marker may be also useful to diagnose morular metaplasia in similar neoplasms of extragenital locations.Morules (1) are nodular structures found in endometrial-type glands formed by a peculiar metaplastic non-keratinizing squamoid epithelium (2). Morphologically similar structures have also been described in neoplastic lesions in other anatomic sites, such as thyroid (3), lung (4, 5), stomach (6), pancreas (7), and colon (8).In both eutopic and ectopic endometrioid tissues, morules are almost invariably associated with the glandular architectural complexity of premalignant and low-grade glandular malignant lesions but are absent in high-grade ones. Thus, it can be said that the presence of morules in the endometrium relates well with an attenuated malignancy.This study deals with the immunohistochemical findings in a series of 53 cases of morular metaplasia from both uterus and ovary, showing for the first time that CD10 staining is a marker of morules, allowing its easy identification in various endometrioid lesions. Materials and MethodsA total of 53 cases of endometrioid morular metaplasia were collected from the files of the

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“…17,28 In addition, certain histological subtypes have been associated with specific molecular alterations, such as KRAS mutation in mucinous adenocarcinoma, 29 EML4-ALK translocation in cribriform mucinous and signet ring type adenocarcinoma, 30,31 and b-catenin mutations in fetal type adenocarcinoma. 32 The main utility of enumerating invasive patterns remains one of pathological communication. This communication can be helpful in the setting of future metastatic foci in which a different pathologist, potentially in a different institution, needs to assess the possibility of a new primary vs metastasis from an existing primary.…”

Section: Invasive Adenocarcinoma Patternsmentioning

confidence: 99%

Assessment of invasion in lung adenocarcinoma classification, including adenocarcinoma in situ and minimally invasive adenocarcinoma

Borczuk

2012

Modern Pathology

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Classification of adenocarcinoma has undergone recent evaluation to better align histological classification with clinical outcomes. One terminology, in particular, that of bronchioloalveolar carcinoma (BAC), has been debated for many decades. Although initial discussion surrounded the cell-of-origin of this tumor, more recent confusion has been generated from the use of this term both as a pattern of growth within an otherwise invasive adenocarcinoma and as a term for a pre-invasive tumor synonymous with adenocarcinoma in situ. As a result, adenocarcinomas with quite different radiology, gross morphology and metastatic potential have been associated with the BAC term. Focusing on invasion and using an illustrative case, we will explore the current recommendations that incorporate assessment of invasion to clarify the confusion caused by the different uses of the historical term 'BAC'.

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Aberrant Nuclear Localization and Gene Mutation of β-catenin in Low-Grade Adenocarcinoma of Fetal Lung Type: Up-Regulation of the Wnt Signaling Pathway May Be a Common Denominator for the Development of Tumors that Form Morules

Cited by 104 publications

References 35 publications

Blastomatoid pulmonary carcinosarcoma: A rare case report and review of the literature

Blastomatoid pulmonary carcinosarcoma: A rare case report and review of the literature

An Immunohistochemical Study of Morules in Endometrioid Lesions of the Female Genital Tract: CD10 Is a Characteristic Marker of Morular Metaplasia

Assessment of invasion in lung adenocarcinoma classification, including adenocarcinoma in situ and minimally invasive adenocarcinoma

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