Dedifferentiation in low-grade mucoepidermoid carcinoma of the parotid gland
ABSTRACT Mucoepidermoid carcinoma (MEC), a common malignant salivary gland neoplasm, is generally divided into low-, intermediate-, and high-grade types according to the histologic features. To our knowledge, the present report describes the first case of dedifferentiation occurring in a low-grade MEC. A 55-year-old man presented with a biphasic neoplasm of the right parotid gland composed of low-grade MEC and dedifferentiated high-grade anaplastic undifferentiated carcinoma. Immunohistochemically, carcinoembryonic antigen expression was restricted to the low-grade MEC portion. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade component. On image cytometric analysis, the low-grade MEC was diploid, whereas the dedifferentiated carcinoma was aneuploid. Although the patient was alive 10 years after the initial diagnosis, the tumor has recurred twice, at 3 months and 7 months after the initial resection. It is important to recognize that dedifferentiation can occur in a low-grade MEC, similar to other low-grade salivary gland carcinomas.
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- "The immunoprofile of the dedifferentiation/high-grade transformation in salivary gland tumors has been evaluated in many studies (Table 1), however, with variable and therefore inconclusive results, possibly due to the small number of cases. The marker that best distinguished between the transformed and the conventional components was Ki-67, since, in all salivary gland tumors studied, an increased proliferation index was detected in the transformed component when compared to the conventional counterpart                  . However, a distinct cut-off for the proliferation index that could identify the transformed component has "
ABSTRACT: The concept of dedifferentiation had previously been used in salivary gland carcinomas. Recently, the term "high-grade transformation" was introduced for adenoid cystic carcinoma, acinic cell carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma and may better reflect this phenomenon, although transformation into moderately differentiated adenocarcinoma (i.e., not "high grade") has also been described. Among the immunohistochemical markers, Ki-67 seems to be the only one that can help distinguish between the conventional and transformed components; however, the combination of morphological criteria is still sovereign. The overexpression of p53 was observed in the transformed component in all tumor types studied, despite few cases having been demonstrated to carry mutations or deletions in TP53 gene. Genetic studies in salivary gland tumors with dedifferentiation/high-grade transformation are rare and deserve further investigation. This paper aims at providing an overview on the recent concepts in histopathological classification of salivary gland tumors, complemented by immunohistochemical and genetic findings.08/2011; 2011:325965. DOI:10.4061/2011/325965
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ABSTRACT: Low-grade endometrioid carcinomas, either of the endometrium or the ovaries, usually have an excellent prognosis. The association of this type of tumor with undifferentiated carcinoma is rare. In this study, we present the clinicopathologic features of 25 such cases. The age of the patients ranged from 30 to 82 years (median, 51 years). At presentation, the patients had either vaginal bleeding or pelvic pain. The endometrioid carcinoma involved the endometrium in 14 cases, the endometrium and 1 or both ovaries in 9 cases, and the ovaries in 2 cases. Undifferentiated carcinoma associated with low-grade endometrioid carcinoma was found at presentation in 19 grade 1 or 2 endometrioid carcinomas: 15 in the endometrium and 5 in the ovary. In one of these cases, undifferentiated carcinoma was found in the endometrium and the ovary. Undifferentiated carcinoma was found after resection of low-grade endometrioid carcinoma in six cases, involving the retroperitoneum, pelvis, vagina, or liver. The undifferentiated carcinoma was composed exclusively of diffuse sheets and solid nests of epithelial cells in l0 cases. Epithelial cells with isolated foci of keratinization were seen in nine cases and rhabdoid cells in a myxoid background in six cases. Twenty-four patients were treated with total abdominal hysterectomy and with bilateral salpingo-oophorectomy. Twenty-two patients received additional therapy as follows: chemotherapy (), radiotherapy (), and tamoxifen (). Follow-up showed that 15 patients died of disease in 1 to 60 months (median, 6 months), and 5 patients are alive with progressive disease with a follow-up between 6 and 8 months; 1 patient is alive with no evidence of disease at 104 months. In four cases, the diagnosis was made recently, with short follow-ups of 3 and 4 months. Foci of undifferentiated carcinoma may be confused with solid endometrioid adenocarcinoma erroneously leading to the diagnosis of a grade 3 or a significantly less aggressive grade 2 endometrioid carcinoma. The recognition of undifferentiated carcinoma in an otherwise low-grade endometrioid adenocarcinoma is extremely important because it indicates aggressive behavior. In asynchronous cases, being aware of this association can explain the absence of a second primary.International Journal of Gynecological Pathology 02/2006; 25(1):52-8. DOI:10.1097/01.pgp.0000183048.22588.18 · 1.63 Impact Factor
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ABSTRACT: Mucoepidermoid carcinomas (MECs) of the salivary and bronchial glands are characterized by a recurrent t(11;19)(q21;p13) translocation resulting in a MECT1-MAML2 fusion in which the CREB-binding domain of the CREB coactivator MECT1 (also known as CRTC1, TORC1 or WAMTP1) is fused to the transactivation domain of the Notch coactivator MAML2. To gain further insights into the molecular pathogenesis of MECs, we cytogenetically and molecularly characterized a series of 29 MECs. A t(11;19) and/or an MECT1-MAML2 fusion was detected in more than 55% of the tumors. Several cases with cryptic rearrangements that resulted in gene fusions were detected. In fusion-negative MECs, the most common aberration was a single or multiple trisomies. Western blot and immunohistochemical studies demonstrated that the MECT1-MAML2 fusion protein was expressed in all MEC-specific cell types. In addition, cotransfection experiments showed that the fusion protein colocalized with CREB in homogeneously distributed nuclear granules. Analyses of potential downstream targets of the fusion revealed differential expression of the cAMP/CREB (FLT1 and NR4A2) and Notch (HES1 and HES5) target genes in fusion-positive and fusion-negative MECs. Moreover, clinical follow-up studies revealed that fusion-positive patients had a significantly lower risk of local recurrence, metastases, or tumor-related death compared to fusion-negative patients (P = 0.0012). When considering tumor-related deaths only, the estimated median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients. These findings suggest that molecularly classifying MECs on the basis of an MECT1-MAML2 fusion is histopathologically and clinically relevant and that the fusion is a useful marker in predicting the biological behavior of MECs.Genes Chromosomes and Cancer 05/2006; 45(5):470-81. DOI:10.1002/gcc.20306 · 3.84 Impact Factor