HER family receptors expression in squamous cell carcinoma of the tongue: study of the possible prognostic and biological significance.

OBJECTIVES: The squamous cell carcinoma of the tongue (SCCT) is biologically and epidemiologically distinct from other oral cavity cancers and is associated with lower overall survival rates. The role of HER family members (HER-1, HER-2/neu, HER-3 and HER-4) in the pathogenesis and progression of head and neck squamous cell carcinomas has been demonstrated but no report have focused on SCCT. This study investigated, the expression of all members of the HER family, in a series of SCCT and studied the possible prognostic value and correlation with various clinico-pathological parameters. METHODS: HER-1, HER-2/neu, HER-3 and HER-4 expression was analysed by semi-quantitative immunohistochemical staining on paraffin embedded tissue specimens from 40 patients who underwent surgery for SCCT between 1996 and 2006. RESULTS: HER-1 was overexpressed in 26 cases (65%), HER-2/neu in two (5%), HER-3 in 19 (48%) and HER-4 in three cases (8%). No significant correlation was found between clinicopathological variables and expression of HER-1 and HER-2/neu. HER-3 overexpression was significantly related to nodal stage, age (>or=64 years) and decreased overall survival (P

Mandibular condylar hyperplasia: clinical, histopathological, and treatment considerations.

Condylar hyperplasia is a rare disorder characterized by an increased volume of the condyle, ramus, and mandibular body leading to facial asymmetry. We present three cases of condylar hyperplasia: two women and one man, age range 27 to 34. Clinically, all three patients showed a deviation of the mandible to the opposite side and a protruded position of the chin, hypertrophy of the lower border of the mandible, combined with an elongation of the mandibular ramus, open-bite on the deformed side, and cross-bite on the opposite side. In all three cases, scintigraphy showed an increased uptake. Radiography and CT scanning confirmed the clinical diagnosis and patients were subjected to surgery, comprising high condylectomy on the affected side with access in the pre-tragus area. The surgical piece sent to the Institute of Pathological Anatomy for histological examination revealed a nonuniform picture, in terms of both the depth of cartilage islands and the thickness of the fibrous layer covering the joint surface. Common to all three cases, however, was the apparent evolution of fibrous tissue to cartilage, and of this to compact bone tissue. At two-four years, all cases have maintained a good occlusal response. The asymmetric deformity of the mandible resulting from the rare condition of hemimandibular hyperplasia is presented and the clinical, histopathological and therapeutic aspects discussed.

Expression of p16, p53 and Ki-67 proteins in the progression of epithelial dysplasia of the oral cavity.

BACKGROUND: The overexpression of the protein products of genes associated with the cell cycle tumour protein53 (p53), cyclin-dependent kinase inhibitor 2A (p16) and antigen identified by monoclonal antibody Ki-67 (Ki-67) is apparently of great significance. This study evaluated the immunohistochemical expression of these proteins in precancerous lesions and in carcinoma of the oral cavity. MATERIALS AND METHODS: The nuclear expression of p53 and Ki-67 and nuclear and/or cytoplasmic expression of p16 protein was examined in 54 biopsy specimens from the oral cavity obtained over a period of 3 years. The samples included 18 cases of normal/hyperplastic mucosa, 25 cases of dysplasia and 11 cases of invasive squamous cell carcinoma. The specimens were grouped into three categories: 1 = no or mild dysplasia, 2 = moderate or severe dysplasia, and 3 = invasive carcinoma. RESULTS: p16 was negative in all the group 1 specimens, while both p53 and Ki-67, when present, were limited to the cells of the basal layer. In the group 2 specimens, the number of p16-, p53-, and Ki-67-positive cells increased as the grade of dysplasia progressed. In group 3 (invasive carcinomas), p53 and p16 expression occurred respectively in 81.8% and 54.5% of cases, while Ki-67 was elevated in all the cases. CONCLUSION: The expression of the cell-cycle proteins p16 and p53 in the dysplastic epithelium, in association with Ki-67, may represent significant markers to recognize evolution of precancerous disease in the oral cavity and to improve identification of the degree of dysplasia.

Fibromatosis of the head and neck: morphological, immunohistochemical and clinical features.

The term fibromatosis indicates a proliferation of well-differentiated fibroblasts and myofibroblasts that develops in the soft tissue. This tumor has been considered locally aggressive because of the infiltrative growth pattern, but does not metastasize. Its occurrence in the head and neck region is not common, and very sporadically it may occur in the oral cavity or jaw bones. Two cases of adult fibromatosis are described here; one involving the submucosa of the middle hard palate and the other the subcutaneous area of the frontal bone. Tumor growth was rapid and bone involvement occurred in one case. Biopsies were taken and in both cases histological examination showed a tumor consisting of fibroblasts within a collagenous stroma, with rare atypia and mitoses. The patients underwent surgical resection with wide surgical margins; excised material was analyzed microscopically and a diagnosis of fibromatosis was rendered. Immunohistochemistry was positive for actin, vimentin and desmin, and negative for S-100, CD34, the progesterone receptors (PR)-A and PR-B and the estrogen receptors (ER)alpha and ERbeta. Follow-up at 5 years after surgery found both patients to be progression free. The clinical, histological and immunohistochemical features were analyzed to better characterize this form of the disease, that very rarely involves the oral cavity.

Metastatic embryonal carcinoma in the maxillary gingiva.

Gingival metastases from embryonal carcinoma are very rare and often associated with widespread disease and poor prognosis. Because of their indistinct clinical appearance, they may be difficult to discriminate from more frequent gingival hyperplastic or reactive lesions. The case of a 35-year-old man who presented with a swelling in the left maxillary gingiva, extending from the first premolar to the second molar is reported. This medical history revealed that, 2 years previously, he had been diagnosed with a testicular mixed germ cell tumor (GCTs), for which he had undergone right inguinal orchidectomy and chemotherapy, leading to complete remission. Histology revealed a metastatic embryonal carcinoma. Imaging of the chest and abdomen showed this was the only site of metastasis. He is currently undergoing chemotherapy and responding well. This case draws attention to the multiple diseases that may present as gingival masses and stresses the difficulty of making a correct diagnosis. It is emphasized that in some mixed cases of testicular GCT it may be the more aggressive component that metastasizes, without being clearly apparent.

Comparative analysis of c-erbB-2 (HER-2/neu) in squamous cell carcinoma of the tongue: does over-expression exist? And what is its correlation with traditional diagnostic parameters?

OBJECTIVES: Over-expression of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in many kinds of cancer, whereas conflicting data exist about the prevalence of HER-2/neu over-expression in squamous cell carcinoma (SCC) of the tongue. The status of Her-2/neu was evaluated in a series of SCC of the tongue to verify the frequency of over-expression of HER-2/neu and evaluate the correlation with traditional diagnostic parameters of this neoplasm. METHOD: Fourty patients with SCC of the tongue were investigated for over-expression of the protein through immunohistochemistry using CB11 antibody, the Hercep Test kit and FISH. RESULTS: Data obtained using the Hercep Test differ from published reports concerning the over-expression of Her-2/neu and there was no correlation between levels of expression of Her-2/neu and other clinico-pathological and/or prognostic parameters. Of the 40 specimens, using CB11 we obtained results in line with published reports; however, with the Hercep Test we found only 1 positive case (2.5%) (score 3+). CONCLUSION: These data, confirmed by FISH, suggest that Her-2/neu is not a suitable marker that could play a primary role in the clinical-therapeutic management of SCC of the tongue.

Ameloblastic carcinoma of the maxillary sinus.

Ameloblastic carcinoma is a very rare malignant odontogenic neoplasm of the mandible and maxilla, accounting for some 66 reported cases. The case of a 68-year-old man who presented a fistula with orosinus communication of 14-year duration that, after anti-aggregant therapy, began bleeding is reported. The initial microscopic evaluation of the biopsy and radiographic findings were consistent with benign peripheral ameloblastoma without cellular atypia and extensive fields of acantomatous pattern, but immunohistochemical investigation found strong positivity for Bcl-2, cytokeratins CAM 5 and 6, and for Ki-67/MIB-1, changing our diagnosis. The treatment consisted of left maxillary resection followed by reconstruction. Cellular features of malignancy in the surgical specimen confirmed the diagnosis of ameloblastic carcinoma. This case of an aggressive ameloblastic carcinoma of the maxillary gingiva that presented with an unusual histological pattern illustrates that these tumors can create a diagnostic challenge that may require extensive surgical sampling and/or removal to establish the diagnosis. Immunohistochemically analyzed expression of bcl-2 protein, cytokeratins CAM 5 and 6, and Ki-67/MIB-1 antigen serve to characterize the cyto-differentiation and cellular activity of ameloblastic carcinoma.

Fibrosarcoma of the jaws: two cases of primary tumors with intraosseous growth.

Fibrosarcoma (FS) is a malignant mesenchymal neoplasm of the fibroblasts that rarely affects the oral cavity. Two cases of primary FS of the jaws with intraosseous growth (2 men, aged 53 and 71 years) are described. Microscopically, in one case the tumor showed an intense proliferation of spindle-shaped cells, varying little in size and shape and arranged in parallel bands, partly crossing each other, with significant mitotic activity and nuclear pleomorphism; the second case was characterized by low cellularity comprising spindle-shaped cells, deposited in a variably fibrous and myxoid stroma. On immunohistochemistry, cells in both cases were strongly immunoreactive for MIB-1 and vimentin, focally positive for CD68, and negative for S-100 protein, pancytokeratin, HMB45, CD34, desmin, smooth muscle actin (SMA) and epithelial membrane antigen (EMA). Based on clinical, histological and immunohistochemical findings, the final diagnosis was FS in the first case, myxofibrosarcoma in the second. Treatment was radical surgery with mandibular reconstruction. After two years, the first patient displayed multiple metastases and died during the third year after the initial diagnosis; the second patient was still alive and doing well five years after treatment. We discuss the differential diagnosis versus other forms of sarcoma, examining the morphological appearance that is frequently very similar, the immunohistochemical expression of MIB-1, vimentin, S-100, CD-34, CD68, EMA, as well as conventional clinicopathological features that may help to distinguish FS from other sarcomas.

Mesenchymal chondrosarcoma of the left coronoid process: report of a unique case with clinical, histopathologic, and immunohistochemical findings, and a review of the literature.

Mesenchymal chondrosarcoma (MCS) is a rare malignant neoplasm of bone or soft tissue origin, locally aggressive, rare in the oral cavity, of which fewer than 100 cases have been reported in the English literature. This is the first case described of this type of tumor affecting the coronoid process. The report describes a unique case of MCS in a 64-year-old woman who presented with swelling and pain at the left preauricular area just anterior to the left tragus. An orthopantomograph showed a large mass in the temporomandibular joint involving the left coronoid process and extending to the left ramus of the mandible. Biopsy and histopathologic examination revealed a biphasic pattern, composed of an undifferentiated small round-cell component surrounding a myxoid of malignant cartilage; a focally pericytic vascular pattern resembling hemangiopericytoma was observed. Immunohistochemical studies were positive for CD99, S-100, and CD45 and negative for desmin, actin, chromogranin, epithelial membrane antigen (EMA), and cytokeratin. The tumor was treated by extensive hemimandibulectomy followed by reconstruction of the area. There was no evidence of disease at the 8-year follow-up. Previously reported cases are reviewed as well.

A rare case of desquamative gingivitis due to linear IgA disease: morphological and immunofluorescence features.

Linear IgA disease (LAD) is an acquired subepidermal bullous disorder, characterized by linear deposition of IgA along the basement membrane. Although the oral cavity is involved in up to 50% of cases, its exclusive involvement is very rare. The case of a 57-year-old woman with 13 months history of desquamative gingivitis chiefly located in the maxilla gingiva is presented. She had been diagnosed by her dental practitioner with an oral infection one year previously and had been receiving local anti-inflammatory and antibiotic medication, with no improvement. She was referred to our Oral Pathology Department, where the biopsy performed revealed a submucosal blister with chronic infiltrate. Direct immunofluorescence showed a linear deposition of IgA in the basal membrane zone, and a diagnosis of LAD was rendered. The patient was treated with topical cortisone, triamcinolone and systemic oral methylprednisolone at a daily dose of 32 mg, and continued at decreasing doses for 3 months. At the most recent check-up, 7 months after initial presentation, she was no longer taking any medication and remained asymptomatic and disease-free.

Hyalinizing clear cell carcinoma arising on the anterior palatoglossal arch.

Hyalinizing clear cell carcinoma (HCCC) is very rare in the oral cavity, arising more frequently in the minor salivary glands. We present the case of a 57-year-old woman with a swelling on the anterior palatoglossal arch of 2x1 cm size. An incisional biopsy was taken and histological examination revealed typical clear cells arranged in anastomosing trabeculae, cords, nests, and solid sheets with a hyalinizing stroma. These clear cells were strongly positive to periodic acid-Schiff stain (PAS) but were negative for mucicarmine. Immunohistochemically, the neoplastic cells were immunoreactive to pancytokeratin, focally positive to EMA, but negative for smooth muscle actin (SMA), vimentin and S-100 protein, HMB45, CD68, carcinoembryonic antigen (CEA) and glial fibrillary acid protein (GFAP). These findings allowed us to define this tumor as a clear cell tumor of the anterior palatoglossal arch. The tumor was subjected to radical excision and the patient is doing well at twelve months after surgery. This report focuses on the heterogeneous group of clear cell neoplasms with the intent of pointing out some aspects that may contribute to forming a diagnosis of HCCC, and which, above all enable us to distinguish this neoplasm from other very similar forms occurring in the oral cavity.

Osteoblastoma of the jaw: report of two cases and review of the literature.

Osteoblastoma is a benign bone tumor of osteoblastic origin. Two cases, an 8-year-old boy and a 24-year-old man, are presented. Both tumors were resected with wide surgical margins and neither patient had adjuvant radiation or chemotherapy. The patients showed no evidence of local recurrence after six to seven years. The clinical, radiological, histological and immunohistochemical features are described. Differential diagnosis and immunohistochemical features potentially useful for refining diagnosis of osteoblastoma are also discussed.

Liposarcoma of the oral cavity--case reports of the pleomorphic and the dedifferentiated variants and a review of the literature.

Liposarcoma is one of the commonest soft-tissue sarcomas, but very rare in the oral cavity. We present two cases of liposarcoma of the oral cavity, together with the related clinical, histopathological and immunohistochemical findings: one affecting the cheek of a 62-year-old man and the other the gingival maxillary tuber of a 41-year-old woman. At histological examination a diagnosis of liposarcoma was made in both cases. In the first case, immunohistochemical analysis revealed intense positivity for p53, MIB-1, MDM2, and focal positivity for S100 protein and CD34, but was negative for alpharsmooth muscle actin, desmin and CD68. The second case it was intensely positive for p53, MIB-1, S-100, and focal positive for MDM2, but negative for alpha smooth muscle actin, CD34, CD68 and desmin. Histological examination and immunohistochemical profiles in the first case were consistent with pleomorphic liposarcoma, whilst that in the second case with dedifferentiated liposarcoma. Both patients were subjected to surgical treatment with wide surgical margins, without adjuvant radio- or chemotherapy. The first case was lost at follow-up one year after surgery, while the second case has not undergone relapse after seven years. We discuss differential diagnosis, examining the histopathological and immunohistochemical features that are potentially useful for distinguishing this tumor from other malignant adipose tissue tumors.