Bruno Augusto Benevenuto de Andrade

Immunohistochemical expression of p16, p21, p27 and cyclin D1 in oral nevi and melanoma.

The acquisition of abnormalities at G1/S is considered a crucial step in the genesis and progression of melanoma. The expression of cell cycle regulators has also been used in various neoplasms as an adjunct to diagnosis. The aim of this study was to compare the expression of p16, p21, p27 and cyclin D1 in oral nevi and melanomas. Expression of these cell cycle regulatory proteins was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas. p16 and p27 were highly expressed in intramucosal nevi, whereas p21 and cyclin D1 expression was higher in oral melanomas. The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions.

Tissue microarray is a reliable method for immunohistochemical analysis of pleomorphic adenoma.

OBJECTIVE To determine the most adequate number and size of tissue microarray (TMA) cores for pleomorphic adenoma immunohistochemical studies. STUDY DESIGN Eighty-two pleomorphic adenoma cases were distributed in 3 TMA blocks assembled in triplicate containing 1.0-, 2.0-, and 3.0-mm cores. Immunohistochemical analysis against cytokeratin 7, Ki67, p63, and CD34 were performed and subsequently evaluated with PixelCount, nuclear, and microvessel software applications. RESULTS The 1.0-mm TMA presented lower results than 2.0- and 3.0-mm TMAs versus conventional whole section slides. Possibly because of an increased amount of stromal tissue, 3.0-mm cores presented a higher microvessel density. Comparing the results obtained with one, two, and three 2.0-mm cores, there was no difference between triplicate or duplicate TMAs and a single-core TMA. CONCLUSIONS Considering the possible loss of cylinders during immunohistochemical reactions, 2.0-mm TMAs in duplicate are a more reliable approach for pleomorphic adenoma immunohistochemical study.

Expression of minichromosome maintenance 2, Ki-67, and geminin in oral nevi and melanoma.

Evaluation of cell cycle using antibodies against nuclear proteins involved in regulating DNA replication has gained special interest in the effort to predict biologic behavior of benign and malignant tumors. The aim of this study was to analyze the expression of minichromosome maintenance 2, Ki-67, and geminin in oral nevi and melanomas. Expression of these cell proliferation markers was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 38 intramucosal nevi and 11 primary oral melanomas. The labeling index of each proliferation marker was assessed considering the percentage of cells expressing nuclear positivity out of the total number of cells, counting 1000 cells per slide. Minichromosome maintenance 2, Ki-67, and geminin were rarely expressed in intramucosal nevi, in contrast to oral melanomas, which showed high levels of these cell proliferation markers, particularly minichromosome maintenance 2, indicating it is a more sensitive marker in primary oral melanomas than Ki-67 and geminin. These results indicate that these markers may be involved in the pathogenesis of oral melanomas and could be eventually useful as an additional diagnostic tool for differential diagnosis of oral benign and malignant melanocytic lesions.

P63 expression in papillary cystadenoma and mucoepidermoid carcinoma of minor salivary glands

OBJECTIVE The aim of this study was to investigate the expression of p63 protein in mucoepidermoid carcinoma and papillary cystadenoma of the salivary glands, and to evaluate the usefulness of this protein in distinguishing these tumors. STUDY DESIGN Immunoexpression of p63 protein was studied and quantified in 9 formalin-fixed paraffin-embedded mucous retention cysts, 4 papillary cystadenomas, and 19 low-grade and 9 high-grade mucoepidermoid carcinomas. RESULTS All cases were positive for p63 immunoexpression; however, it was observed that p63 labeling in mucous retention cysts and papillary cystadenomas was limited to the basal layers of the cystic spaces, whereas in low-grade mucoepidermoid carcinomas, positive nuclear staining was also found diffusely in the suprabasal layers. Mucoepidermoid carcinoma presented increased immunoexpression of p63 compared with the other groups. CONCLUSIONS P63 immunohistochemical expression pattern can be helpful in distinguishing low-grade mucoepidermoid carcinoma from papillary cystadenoma of the salivary glands.

Ectomesenchymal chondromyxoid tumor: histopathologic and immunohistochemical study of two cases without a chondroid component

Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign neoplasm usually affecting the anterior dorsum of the tongue. Histopathologically, it is formed by spindle, round and/or polygonal cells embedded in a chondromyxoid matrix. Immunohistochemical positivity for vimentin, S‐100 protein, glial fibrillary acid protein and neuron‐specific enolase are helpful to confirm the diagnosis. There are 42 cases of ECT of the tongue reported in the English language literature, three of them showing no chondroid matrix. We describe two additional cases of ECT lacking the chondroid component, exhibiting areas of reticulated myxoid and cellular pattern. Considering the microscopical features, ECT can be classified in classic and ‘chondroid‐free’ variants, the latter including the reticulated myxoid and cellular patterns. It is important to consider that the cellular ECT usually exhibits predominance of an infiltrative atypical cellular component that may mimic a malignant tumor.

Expression of PROX-1 in oral Kaposi's sarcoma spindle cells

BACKGROUND The histogenesis of neoplastic spindle cells of Kaposis sarcoma is still uncertain, but some studies consider it a lymphatic vessel differentiation. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis, and it has been considered a specific and sensitive lymphatic endothelial cell marker. The aim of this study was to determine the expression of Prox-1 in oral Kaposis sarcoma comparing the results with oral benign vascular tumors including capillary hemangiomas and pyogenic granulomas. METHODS Expression of Prox-1 and HHV-8 was evaluated by immunohistochemistry in 30 oral Kaposis sarcoma, 5 oral capillary hemangiomas, and 10 oral pyogenic granulomas. The labeling index was expressed as the percentage of positive cells for each case studied. Statistical comparison was performed using the Wilcoxon-Mann-Whitney rank sum test. RESULTS Twenty-eight (93.3%) and 30 oral Kaposis sarcoma cases were positive for Prox-1 and HHV-8, respectively, while all oral benign vascular tumors were negative for these markers. The number of Prox-1 and HHV-8 oral Kaposis sarcoma-positive cells increased significantly from patch/plaque to nodular histological stages. CONCLUSION The expression of Prox-1 in the neoplastic spindle cells supports the view of a lymphatic differentiation in oral Kaposis sarcoma. Prox-1 may also be involved in the pathogenesis of oral Kaposis sarcoma as the number of positive spindle cells increased progressively from patch to nodular stages and could be eventually useful as an additional diagnostic tool for differential diagnosis between oral Kaposis sarcoma and benign oral vascular lesions.

Clear cell change in a lower lip mucocele

Oral mucocele is a common reactive lesion of the oral mucosa, which microscopically exhibits mucus extravasation surrounded by a wall of granulation tissue containing abundant foamy macrophages. Unusual variants, such as superficial mucoceles, mucoceles with myxoglobulosis-like change and mucoceles with synovial metaplasia-like change have been reported. We report a 74-year-old man who presented an asymptomatic translucent swelling on the lower labial mucosa diagnosed as mucocele showing a macrophage proliferation with extensive clear cytoplasmic vacuolation and signet-ring formation. This unusual presentation expands the microscopic spectrum of the oral mucoceles and can eventually lead to differential diagnosis with primary or metastatic clear cell neoplasms. In these cases, relevant clinical information, histochemistry and especially immunohistochemistry, are helpful for arriving at an accurate diagnosis.

Hard palate hyperpigmentation secondary to chronic chloroquine therapy: report of five cases.

Antimalarials are commonly prescribed in medical practice for conditions such as rheumatoid arthritis, lupus erythematosus, as well as malaria. They are generally well‐tolerated, but side effects, although infrequent, are well known. The antimalarial chloroquine diphosphate may be associated with a bluish‐gray to black hyperpigmentation of the oral mucosa, mainly on the hard palate. In this report we described five additional cases of palate hyperpigmentation related to the chronic use of chloroquine diphosphate. Professionals must be aware of the adverse effects of antimalarials as chloroquine diphosphate in order to make the correct diagnosis and appropriate management of the patient. Early diagnosis of oral pigmentation by antimalarials may be of great relevance, because it might be an early sign of ocular involvement, and therefore it may be helpful to prevent further complications of antimalarial therapy for the patient.

Nonlipidized juvenile xanthogranuloma: An unusual variant with a potential diagnostic pitfall

Juvenile xanthogranuloma (JXG) is a histiocytic inflammatory disorder that can present different histologic patterns. Classic JXG consists of sheets of foamy histiocytes and numerous multinucleated Touton giant cells. Nonlipidized JXG (NJXG) is one of the unusual variants of JXG, consisting of a diffuse monomorphic infiltrate of mononuclear histiocytes, suggesting an aggressive or malignant tumor due the high mitotic index. However, NJXG behaves clinically as classic JXG. We present an unusual case of a 6-year-old boy who presented an exophytic ulcerated nodule on the lower lip diagnosed as NJXG. The boy is currently well without recurrence three years after surgical excision.

Primary nasal mucosal melanoma in Brazil: clinicopathologic and immunohistochemical study of 12 patients.

Primary nasal melanoma is a rare tumor of unknown etiopathogenesis that occurs in adult and elderly patients usually diagnosed at advanced stages. The aim of this study was to analyze the clinicopathologic and immunohistochemical characteristics of 12 cases of primary nasal melanomas in Brazil. Twelve cases of primary nasal melanoma were analyzed histologically and by immunohistochemistry using the antibodies S-100 protein, HMB-45, Melan-A, CD63 (NKI/C3), CD68/KP1, fatty acid synthase (FASN), and Ki-67. The mean age of the patients was 60 years, and 7 of 12 patients were men. Microscopically, 10 cases presented level III of invasion; 4 were amelanotic; and in 7, cells were epithelioid. S-100 protein and FASN were positive in all cases, whereas 9, 8, 7, and 6 cases were positive for HMB-45, Melan-A, CD63 (NKI/C3), and CD68/KP1, respectively. Ki-67 labeling index ranged from 11.45% to 28.5% of positive cells. S-100 protein is more frequently expressed in nasal melanomas than in HMB-45, Melan-A, CD63 (NKI/C3), and CD68/KP1. FASN seems to be involved in the pathogenesis of nasal melanomas, and also, it can be helpful to confirm the diagnosis.