Bruno Tavares Sedassari

Embryonic stem cells markers Oct4 and Nanog correlate with perineural invasion in human salivary gland mucoepidermoid carcinoma

BACKGROUND Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and is successfully treated by surgery and radiation. However, some patients have recurrent tumours and in these cases, few treatments options are available. Cancer stem cells (CSC) have been observed and isolated from different solid tumours based on the expression of stem cell markers. These cells are associated with tumour initiation, progression as well as treatment resistance. In this study, the expression of stem cell markers CD44, Bmi1, Oct4 and Nanog was evaluated in non-neoplastic salivary tissue and in MEC. METHODS Twenty-eight samples of MEC and their corresponding non-neoplastic salivary tissue were examined by immunohistochemistry and the stem cell markers expression was correlated with histological and clinical parameters. RESULTS CD44 was expressed in the membrane of serous and mucous acini as well as in the ductal cells in normal gland tissue. Bmi1, Oct4 and Nanog were mainly expressed in ductal structures. In MEC, CD44 and Bmi1 showed strong expression in all types of neoplastic cells and both markers revealed intense expression in tumour invasive front. Oct4 and Nanog protein expression was associated with desmoplasia and perineural invasion. Only Oct4 positive tumours were associated with dissociative growth pattern and committed margins. CONCLUSION The stem cell markers CD44, Bmi1, Oct4 and Nanog are frequently expressed in MEC in relation to normal salivary gland and Oct4 and Nanog expression may contribute to aggressiveness and worst prognosis in MEC patients.

Carcinoma ex pleomorphic adenoma of minor salivary glands with major epithelial-myoepithelial component: clinicopathologic and immunohistochemical study of 3 cases

In the present study, 3 cases of very rare intraoral carcinomas ex pleomorphic adenomas showing a striking differentiation of the malignant component towards epithelial-myoepithelial carcinoma were described. The tumors occurred in 2 men and 1 woman with median age of 56 years. Involved sites included palate and buccal mucosa. Two patients experienced local recurrences, of which one died of disease complications. In all cases, residual pleomorphic adenoma was present. The malignant component in all cases shared morphological aspects with epithelial-myoepithelial carcinoma. Those areas were characterized by eosinophilic duct-forming cells surrounded by layers of clear cells. The studied immunohistochemical markers highlighted a biphasic cell population. Duct-forming cells expressed pan-cytokeratin, cytokeratin 7, and focally cytokeratin 14, whereas the clear cell component strongly stained to cytokeratin 14, vimentin, and p63 but weakly stained to pan-cytokeratin and focally to α-smooth muscle actin, an immunophenotype compatible with both epithelial and myoepithelial differentiation. The Ki-67 proliferation index was up to 40% in malignant areas. Carcinoma ex pleomorphic adenomas of minor salivary glands with major epithelial-myoepithelial component are rare, locally aggressive, and potentially lethal tumors. The peculiar morphological and immunohistochemical aspects described may raise problems in diagnosis and classification of such cases, particularly in incisional biopsies.

Carcinoma ex pleomorphic adenoma of the palate composed of invasive micropapillary salivary duct carcinoma and adenoid cystic carcinoma components: an unusual case with immunohistochemical approach.

AbstractCarcinoma ex pleomorphic adenoma (CXPA) is an unusual epithelial malignancy that develops from a primary or recurrent pleomorphic adenoma (PA), the most common tumor of salivary glands, and constitutes about 11.5% of all carcinomas that affect these glands. Intraoral minor salivary glands and seromucous glands of the oropharynx are uncommon locations of CXPA. On histopathological examination, the tumor comprises a wide morphological spectrum with a variable proportion between the benign and malignant components with the latter often predominating and overlapping the PA, which may cause misdiagnosis. Here, we report a case of palatal minor salivary gland CXPA composed of invasive micropapillary salivary duct carcinoma and adenoid cystic carcinoma components with multiple nodal metastases in a 74-year-old woman. Neoplastic cells showed heterogeneous immunohistochemical profile with both luminal and myoepithelial differentiation. The invasive micropapillary salivary duct carcinoma component demonstrated overexpression of the oncoprotein human epidermal growth factor receptor-2. This feature should be considered and evaluated as a possible target for adjuvant therapy in case of metastatic disease.

Neuroblastoma-like schwannoma of the lower labial mucosa: a rare morphologic variant of peripheral nerve sheath tumor

Neuroblastoma-like schwannoma is a rare variant of benign nerve sheath neoplasia, which is histologically characterized by small round neoplastic Schwann cells radially arranged around collagenous cores with a configuration of rosette-like structures. We report the first documented case of neuroblastoma-like schwannoma of the oral cavity in a 26-year-old male patient who presented with swelling in the lower labial mucosa.

Doing more with less: the challenging diagnosis of polymorphous low-grade adenocarcinoma in incisional biopsy samples.

The diagnosis of polymorphous low‐grade adenocarcinoma (PLGA) remains difficult for general pathologists, particularly in cases of small biopsy samples. We aimed to characterize the histopathological spectrum and immunohistochemical aspects by using an accessible immunohistochemical panel of cytoskeletal proteins in limited samples of PLGA.

Prognostic implications of CD44, NANOG, OCT4, and BMI1 expression in tongue squamous cell carcinoma

Tongue squamous cell carcinoma (SCC) contains a cell subpopulation referred to as cancer stem cells (CSCs), which are responsible for tumor growth, metastasis, and resistance to chemotherapy and radiotherapy. The CSC markers have been used to isolate these cells and as biomarkers to predict overall survival.

Fatal hepatocellular carcinoma presenting with oral metastasis in a patient with synchronic primary malignancies of prostate and liver.

BACKGROUND Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer and its occurrence in the oral cavity as a metastatic neoplasm is a rare event. We describe a fatal case of HCC with oral metastasis in a patient firstly diagnosed with prostatic and hepatic carcinomas. The histopathological examination revealed a hepatocyte-like tumour cells arranged in organoid structures as well as positivity to cytokeratin 8 and Hep Par 1. The present findings highlight the importance of a complete medical evaluation of the patient to identify possible oral repercussions of primary diseases.

Peripheral ameloblastoma with dystrophic calcification: an unusual feature in non-calcifying odontogenic tumors.

Peripheral ameloblastoma is a rare extraosseous counterpart of central ameloblastoma that occurs in soft tissues and may cause bone crest resorption. This study reports a peripheral ameloblastoma on the buccal gingiva of a 56-year-old man, which presented extensive squamous metaplasia areas, keratinization and dystrophic calcifications in the neoplastic islands. It is emphasized the need of a detailed imaging study and a long follow-up period to exclude bone involvement whenever peripheral ameloblastoma diagnosis is considered.

Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland

IntroductionCripto-1 is a member of the epidermal growth factor—Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. Objective: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands.MethodsA total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0–3). For statistical analysis, Mann–Whitney and Kruskal–Wallis tests were performed and a significance level of p ≤ 0.05 was established.ResultsMost CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294).ConclusionThe results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.

The Stem Cell Marker Bmi-1 Is Sensitive in Identifying Early Lesions of Carcinoma ex Pleomorphic Adenoma.

AbstractIn the present study, we evaluated and described the sensitivity of the stem cell marker B cell-specific moloney murine leukemia virus integration site 1 (Bmi-1) in identifying early lesions of carcinoma ex pleomorphic adenoma (CXPA). While invasive CXPAs are tumors with a prominent and easily recognizable malignant component, the identification of early carcinomatous changes in PA remains a diagnostic challenge due to the lack of objective morphological criteria. The immunohistochemical expression of Bmi-1 was assessed in both adenomatous and carcinomatous components of 9 CXPA cases at an early phase of histological progression (6 intracapsular and 3 minimally invasive) grouped according to the cellular differentiation as luminal (7 cases) or myoepithelial (2 cases). A selective nuclear expression of Bmi-1 was found exclusively in the malignant component of 8 cases (6 luminal type and 2 myoepithelial type), including intraductal carcinoma areas, except for 1 case in which scarce cells of the remnant PA were positive. Thus, Bmi-1 is expressed from the earliest morphologically detectable stages of PA malignant transformation. When faced with atypical features in PA, evaluation of Bmi-1 expression can provide more objective criteria for identification and diagnosis of early lesions of CXPA. This is applied to carcinomas with luminal or myoepithelial differentiation.