p16 Expression in Squamous and Trophoblastic Lesions of the Upper Female Genital Tract

Chew, Ivy; Post, Miriam D.; Carinelli, Silvestro; Campbell, Sharon; Ye, Di; Soslow, Robert A.; Oliva, Esther

doi:10.1097/pgp.0b013e3181e2fe70

Cited by 22 publications

(11 citation statements)

References 71 publications

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“…In the context of the available data in the literature 2–4, 17–20 , our results show that for squamous cell carcinomas that would typically be considered in the differential diagnosis of epithelioid trophoblastic tumor (cervix and lung), GATA-3 is expressed in only a subset of cases, often with limited extent and sometimes weak intensity. Therefore, in combination with other immunohistochemical stains (including p16, 21–22 actins, desmin, cytokeratins, and/or other trophoblast-specific markers), GATA-3 can be a useful and discriminatory marker when smooth muscle tumors or squamous cell carcinomas are in the differential diagnosis of a trophoblastic neoplasm. However, it should be noted that some markers frequently positive in squamous cell carcinomas, such as p63 and p40, may be expressed in trophoblastic neoplasms.…”

Section: Discussionmentioning

confidence: 99%

GATA-3 Expression in Trophoblastic Tissues

Banet¹,

Gown²,

Shih³

et al. 2015

American Journal of Surgical Pathology

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Immunohistochemical expression of GATA-3 is seen predominantly in non-neoplastic bladder and breast epithelium and their respective carcinomas; however, data on expression in normal and lesional trophoblastic tissues are limited. Immunohistochemical staining for GATA-3 was assessed in a range of normal/lesional trophoblastic tissues and tumors in the differential diagnosis (n=445), including non-molar products of conceptions/2nd and 3rd trimester placentas/ ectopic pregnancies, hydatidiform moles, placental site nodules, normal/exaggerated implantation sites, choriocarcinomas, epithelioid trophoblastic tumors, placental site trophoblastic tumors, atypical smooth muscle tumors (including leiomyosarcoma), and cervical and pulmonary squamous cell carcinomas. The extent of expression (0 to 4+) and intensity (weak to strong) were recorded. All cases with developing trophoblast/non-neoplastic trophoblastic proliferations and 81% of trophoblastic neoplasms were positive. Of all non-neoplastic trophoblast cell types, expression was observed in cytotrophoblast in 89% of cases, syncytiotrophoblast in 50%, intermediate trophoblast in 100%, and villous trophoblastic columns in 100%. Increasing gestational age was associated with a decrease in extent/intensity of expression in non-neoplastic cytotrophoblast and syncytiotrophoblast while intermediate trophoblast maintained diffuse and strong expression from early to late gestation (p<0.0001). Eighty-nine percent of normal/exaggerated implantation sites showed 3+ or 4+ expression while staining in 55% of placental site nodules was 1+ or 2+. Staining for GATA-3 was present in 78% of choriocarcinomas, 95% of epithelioid trophoblastic tumors, and 71% of placental site trophoblastic tumors. While the number of choriocarcinomas and placental site trophoblastic tumors that showed a spectrum of expression ranging from negative to diffuse was relatively evenly distributed, 81% of epithelioid trophoblastic tumors had 3+ or 4+ staining. None of the atypical smooth muscle tumors and 3% of squamous cell carcinomas were positive, all of which exhibited weak staining. We conclude that GATA-3 is frequently expressed in normal and lesional trophoblastic tissues. It is also differentially expressed in intermediate trophoblast and cytotrophoblast/syncytiotrophoblast, which varies according to time during pregnancy. This study expands the spectrum of neoplasms known to express GATA-3. Thus, recognition of expression in trophoblastic tumors is important because it can present a diagnostic pitfall in the assessment of suspected metastatic bladder or breast carcinomas involving the gynecologic tract. In the evaluation of diagnostically problematic tumors for which trophoblastic neoplasms are in the differential diagnosis, such as leiomyosarcoma and squamous cell carcinoma, GATA-3 can be included as part of an immunohistochemical panel particularly when other trophoblastic markers are either not available or yield ambiguous results.

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Section: Discussionmentioning

confidence: 99%

GATA-3 Expression in Trophoblastic Tissues

Banet¹,

Gown²,

Shih³

et al. 2015

American Journal of Surgical Pathology

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“…These trophoblastic tumors also express cytokeratins, and may express CD10 and p16 as leiomyosarcomas. [112][113][114] Placental site trophoblastic tumors have a very characteristic infiltrative growth of single cells or small aggregates of cells that dissect individual muscle fibers and often replace endothelial cells with associated fibrinoid change recapitulating the physiologic implantation site. 115,116 The finding of islands or nests of cells surrounded by extensive necrosis or hyaline-like matrix that are p63-positive support the diagnosis of epithelioid trophoblastic tumor.…”

Section: Tumor Cell Necrosismentioning

confidence: 99%

Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia

Oliva

2016

Modern Pathology

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Among mesenchymal tumors of the uterus, smooth muscle neoplasms are most common. The wide morphologic spectrum, especially within the category of leiomyomas, is responsible for diagnostic problems more frequently with leiomyosarcoma (including mitotically active, apoplectic, and leiomyoma with bizarre nuclei) but also with endometrial stromal tumors. In the former scenario, clinical information, gross appearance as well as strict utilization of morphologic criteria including cytologic atypia, mitotic activity, and tumor cell necrosis are clues in establishing the correct diagnosis. It is important to keep in mind that mitotic rate thresholds vary for the different subtypes of leiomyosarcoma. Of note, p16 should be used with caution in supporting a diagnosis of leiomyosarcoma as it is often positive in leiomyomas with bizarre nuclei and leiomyomas with apoplectic change (in the latter most frequently and more intense near areas of necrosis). MED12 mutations have also a very limited role in this differential diagnosis. Endometrial stromal tumors are by far, less common than smooth muscle tumors, but can be confused with leiomyosarcomas if they are associated with an undifferentiated uterine sarcoma and the low-grade component is overlooked or they have a myxoid/fibroblastic morphology. The differential diagnosis may be confounded if the latter is associated with a high-grade endometrial stromal sarcoma. It is important to highlight that CD10 is not a reliable marker in these differentials and should be used as a part of a panel of antibodies that also includes desmin and h-caldesmon. Two other recently categorized tumors in the uterus that merit special mention are PEComa and inflammatory myofibroblastic tumor as they enter in the differential diagnosis of smooth muscle tumors. PEComa may be part of the tuberous sclerosis syndrome and may show either a predominantly epithelioid or spindle morphology or combination thereof. Rarely, it may contain melanin pigment. There is variable positivity for HMB-45, MelanA, MiTF, and CathepsinK, and some tumors have been shown to express TFE-3 especially when associated with "clear cell" morphology. Patients with adverse outcome have tumors with ≥ 2 of the following features: ≥ 5 cm, infiltration, high-grade cytologic features, mitotic rate ≥ 1/50 high-power fields, necrosis, or lymphovascular invasion. Inflammatory myofibroblastic tumor is important to recognize as it often mimics myxoid smooth muscle tumors, either benign or malignant. The presence of an associated lymphoplasmacytic infiltrate should alert to that possibility and ALK studies (immunostain or FISH) are helpful in establishing this diagnosis. These tumors can behave in a malignant manner if large, associated with abundant myxoid change, brisk mitotic rate or show tumor cell necrosis.

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“…Further, four of ten tumors were positive for p16, a tumor suppressor protein that has been associated with malignancy‐inducing human papillomaviruses in the female genital tract . Endometrioid adenocarcinomas typically express estrogen receptors, p53 is associated with clear cell and papillary serous endometrial carcinomas, and both p53 and cyclin D1 are associated with tumor progression in endometrial cancer …”

Section: Discussionmentioning

confidence: 99%

“…11 Endometrioid adenocarcinomas typically express estrogen receptors, p53 is associated with clear cell and papillary serous endometrial carcinomas, and both p53 and cyclin D1 are associated with tumor progression in endometrial cancer. 6,8 Further, given the rarity of this condition, there is no consensus for the best way to manage these patients with PSCCE. A review of the literature yields sparse reporting of treatment data and associated outcome.…”

Section: Postoperative Follow-upmentioning

confidence: 99%

Primary squamous cell carcinoma of the endometrium: Two cases and a review of the literature

Goodrich

Kebria-Moslemi

Broshears

et al. 2012

Diagnostic Cytopathology

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Primary squamous cell carcinoma of the endometrium (PSCCE) is a rare entity, with fewer than 100 cases reported in the literature. We report two cases of PSCCE and review the literature regarding associated markers and treatment outcomes. Many different markers have been tested for association with PSCCE, with mixed results. Thus, it is likely that several etiologic factors are responsible for the development of PSCCE. Further, due to the rarity of the condition, the optimal postoperative management of patients with PSCCE remains to be defined.

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p16 Expression in Squamous and Trophoblastic Lesions of the Upper Female Genital Tract

Cited by 22 publications

References 71 publications

GATA-3 Expression in Trophoblastic Tissues

GATA-3 Expression in Trophoblastic Tissues

Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia

Primary squamous cell carcinoma of the endometrium: Two cases and a review of the literature

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