Immunohistochemical profile of oral mucosal and head and neck cutaneous melanoma.

BACKGROUND: In addition to ultraviolet radiation exposure, various molecular markers may differ between oral mucosal and cutaneous head and neck melanomas and lead to variations in their biologic behavior and prognosis. The aim of this study was to compare four such markers, namely microphthalmia transcription factor (MITF), P75, P53, and Ki-67 in malignant melanomas originating from the oral cavity and head and neck skin. METHODS: A total of 19 oral mucosal and 23 head and neck cutaneous melanomas were subjected to immunohistochemical analysis using antibodies against MITF, P75, P53, and Ki-67. Statistical comparison of data was performed by t-test and chi-square analysis (P < 0.05). RESULTS: Significant differences in MITF (P = 0.016) and Ki-67 (P = 0.002) were observed between oral mucosal and cutaneous melanomas. P75 (P = 0.80) and P53 (P = 0.76) did not differ significantly, between these locations. CONCLUSIONS: According to the results obtained in this study, the biological properties of cutaneous and mucosal melanoma differ, especially regarding MITF and Ki-67.

Mammary analog secretory carcinoma of salivary gland with high-grade histology arising in hard palate, report of a case and review of literature.

Mammary gland analog secretary carcinoma (MASC) of salivary gland is typically a tumor of low histologic grade and behaves as a low-grade malignancy with relatively benign course. This tumor shares histologic features, immunohistochemical profile, and a highly specific genetic translocation, ETV6-NTRK3, with secretory carcinoma of breast. Histologically, it is often mistaken as acinic cell carcinoma, adenocarcinoma not otherwise specified, and other primary salivary gland tumors. Here we report a case of MASC with high-grade transformation and cervical lymph node metastases confirmed with ETV6-NTRK3 translocation arising in the hard palate of a 41 year-old adult. Interestingly, the metastatic carcinoma has lower grade than the original tumor which strongly support malignant transformation of the original tumor. Most commonly, MASC arises from the parotid gland and less often in minor salivary glands. Metastasis is relatively uncommon and high-grade histology has only been reported in four cases with three of them arising from the parotid gland and the location of the fourth one has not been reported. This is the first case with high grade histology that arise from minor salivary gland and it emphasizes the importance of molecular screening of salivary gland tumor with high-grade histology for ETV6-NTRK3 translocation. In our literature of 115 cases that includes the current case, MASC occurred predominantly in adult with only a few cases under 18 years of age and a male to female ratio of 1.2:1. Parotid gland is more commonly affected but there is also significant occurrence in minor salivary glands. Except for the cases with high grade histology, the overall prognosis is good.

Non pigmented melanocytic nevus of the oral cavity: a case report with emphasis on the surgical excision procedures.

We report a case of a 37-year-old caucasian woman presenting a 1 cm pinkish nodular asymptomatic lesion of the hard palate, slowly growing in the last years. The lesion underwent to biopsy. Histological analysis showed the nevus tissue layered under a continuous squamous epithelium. The stroma contained nests of medium-sized round cells, with regular monomorphous nuclei. The nevus cells were immunohistochemically positive for S-100 protein, while melanin, visualized by Masson-Fontana silver staining, was absent. Therefore a diagnosis of non pigmented melanocytic nevus was formulated. Because of its rarity and to avoid any risk of malignant transformation, a surgical treatment with wide excision was chosen; the surgical wound was previously covered with a membrane of fibrin and autologous platelets, and subsequently sutured, resulting in a total heal. This procedure seems to be the most reliable to approach melanocytic lesions of the oral cavity. Clinical diagnosis of non-pigmented nevi, either flat or protruding, is difficult, because the nevus shows a pinkish colour that is indistinguishable from that of the surrounding mucosa. Moreover, attention is required when similar clinical evidence occurs, because the localization inside the oral cavity may offer several problems of differential diagnosis.

Squamous cell carcinoma arising within verrucous carcinoma of the oral cavity: a case report.

The author herein reports a case of squamous cell carcinoma (SCC) arising within verrucous carcinoma (VC) of the hard palate. An 84-year-old woman was admitted to our hospital complaining of oral discomfort. Oral examination revealed a pedunculated verrucous tumor (15 x 15 mm) in the hard palate. A biopsy revealed verrucous tumor. Resection of the lesion with wide margins was performed. Grossly, the palate tumor was pedunculated and verrucous, but a depressed area (8 x 7 mm) was recognized. Microscopically, the verrucous ares showed verrucous proliferation of squamous epithelium with little cellular atypia, and was interpreted as VC without invasion. The depressed lesion was obvious SCC with invasion. There were direct transitions between the VC and SCC. Immunohistochemically, the VC and SCC tumor cells were negative for human papilloma virus antigens. P53 protein was expressed in both VC and SCC, though the expression in SCC was much more strong and broad than that in VC. The Ki-67 antigen was also expressed in the VC and SCC, and Ki-67 labeling index ranged was 12% in VC and 64% in SCC. These findings indicate that SCC may arise within VC.

[Solitary fibrous tumour of the smooth palate]. / Tumor fibroso solitario del paladar blando.

The solid fibrous solitary tumour of the oral cavity is an extremely rare entity. It is also of complicated diagnosis because of its extensive morphologic diversity (especially when there is a small amount of biopsied tissue) and because of its similarity to many mesenchymal injuries, mostly with hemangiopericytoma. The prognosis is reserved because of the few cases reported, mainly depending on tumour location and size.

Cystadenoma of the palate: immunohistochemistry of mucins.

Cystadenoma is a relatively rare benign epithelial tumor of the salivary glands, and described herein is an additional case. A 51-year-old Japanese man had noticed a mass of the left hard palate 25 years previously. Macroscopically, the resected specimen was a multicystic lesion. Histologically, the tumor was composed of bilayered columnar epithelium with cystic change and partial solid growth of glandular structures with clear cells. The tumor cells had mild cellular atypia, but the tumor lacked papillary growth and a fibrous capsule. Immunohistochemistry was positive for cytokeratins, epithelial membrane antigen, MUC1, MUC4 and MUC6, but negative for myoepithelial markers, MUC2, MUC5AC and MUC5B. Such MUC expression patterns suggested that cystadenoma occurs from excretory ducts.

Possible involvement of stem cell factor and endothelin-1 in the emergence of pigmented squamous cell carcinoma in oral mucosa.

We present here the clinical, morphological and immunohistochemical features of a pigmented squamous cell carcinoma (SCC) in the oral mucosa of the hard palate of a 76-year-old Japanese man. He underwent a partial resection of the maxilla subsequent to radiotherapy. The tumor was typical, moderately well-differentiated SCC but had many melanocytes (melanocytosis) within it. Immunohistochemical analysis for stem cell factor (SCF) and endothelin-1, both of which are known to stimulate proliferation and differentiation of melanocytes, revealed prominent expression of both factors in the neoplastic squamous cells of the pigmented SCC, while the non-pigmented oral SCC showed little sign of either factor. These findings strongly suggest that SCF and endothelin-1 secreted by neoplasmic squamous cells are involved in the emergence of a rare variant of oral SCC.

Sialadenoma papilliferum: immunohistochemical study.

Sialadenoma papilliferum (SP) is a rare benign tumour of salivary gland origin, which has been included among the ductal papillomas in the latest classification of tumours by the World Health Organisation. Two SP from the minor salivary gland of the palate of middle age patients were presented and studied by immunohistochemical. Our results showed presence of cytokeratins (CKs) 13, 14, 7, 8, 19 and absence of vimentin and smooth muscle actin. This immunoprofile is similar to the excretory duct of salivary gland.

Expression of Rb, pRb2/p130, p53, and p16 proteins in malignant melanoma of oral mucosa.

We previously reported that pRb2/p130 gene, one of the Rb family members, was immunohistochemically abundantly expressed in well-differentiated oral squamous cell carcinomas, whereas in undifferentiated ones the expression was low. Oral malignant melanoma is extremely rare, however the prognosis is poor because it tends to locally invade tissue or metastasize and its biological behavior appears to be different from cutaneous malignant melanoma. The present study dealt with the expression of pRb2/p130, Rb, p53, and p16 in 13 cases of malignant melanoma of oral mucosa as revealed by immunohistochemical staining. The stage classification of the 13 patients was as follows; stage II: eight patients, stage III: three patients, and stage IV: two patients. pRb2/p130 was expressed in only two stage II-cases, neither of which have shown any evidence of recurrence or metastasis for over 14 years. Positive staining for Rb was found in three cases consisting of one stage II-case, one stage III-case, and one stage IV-case. p53 was expressed in two cases, one a stage II and the other a stage IV. Positive staining for p16 was found in seven cases consisting of four stage II-cases, two stage III-cases, and one stage IV-case. pRb2/p130 may be inversely correlated with the malignancy of oral malignant melanoma, but further study is needed.

Angiomyolipoma of the palate. Report of a case.

Angiomyolipoma (AML) is a tumour or an hamartomatous growth that usually affects the kidney. Only rarely has AML been described in the oral cavity. The authors report a case of AML located in the palate in a 43-year-old patient. AML is composed of smooth muscle cells, blood vessels and mature fat cells. In 50% of cases, AML presents with symptoms of tuberous sclerosis. Renal AML are often invasive, may involve regional nodes and may recur, while, on the contrary, AML are most often well circumscribed and easily resected. AML seems to follow an entire benign course.

Squamous cell carcinoma of the oropharynx: Ki-67 and p53 can identify patients at high risk for local recurrence after surgery and postoperative radiotherapy.

PURPOSE: To assess the prognostic value of biologic (p53, Ki-67) and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). METHODS AND MATERIALS: Between 1985 and 1995, a total of 102 patients with 104 tumor sites were entered onto the study. Fifty-five primary tumors (53%) involved the tonsils, 26 (25%) the soft palate, and 23 (22%) the base of the tongue. Median age was 53 years (range 36-80 years). The clinical T- and N-categories (UICC 1997) were: T1 (30), T2 (47), T3 (22), T4 (5), N0 (33), N1 (28), N2 (42), and N3 (1). Histologically-clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given, to a total of 60 Gy in 6 weeks, and single daily fractions of 2 Gy. The expression of the nuclear p53- and Ki-67-labeling index (LI) was investigated by immunostaining using the monoclonal antibodies DO-7 and MIB 1. The nuclear p53-intensity (p53-I) was graded into 4 categories (0/+/++/) by densitometry. Median follow-up was 43 months (range 14-132 months). RESULTS: Cancer-specific survival, disease-free survival, and locoregional tumor control rates were 74%, 69%, and 75%, respectively, at 5 years. Significant prognostic factors for disease-free survival were: T-category (T1/2: 77% vs. T3/4: 53%, p = 0.02), tumor site (tonsils: 79% vs. soft palate: 70% vs. base of tongue: 45%, p = 0.05), duration of RT (< or = 46 days: 80% vs. > 46 days: 60%, p = 0.04), Ki-67 LI (< or = 20%: 84% vs. > 20%: 49%, p = 0.006) and p53-I (0/+: 56% vs. ++/ : 79%, p = 0.008). A significant prognostic impact on locoregional control was noted for the duration of RT (< or = 46 days: 86% vs. > 46 days: 68%, p = 0.01), tumor site (tonsils: 88% vs. soft palate: 67% vs. base of tongue: 51%, p = 0.02), Ki-67 LI (< or = 20% LI: 87% vs. > 20% LI: 56%, p = 0.018), and the p53-I (0/+: 58% vs. ++/ : 88%, p = 0.0006). On multivariate analysis, the p53 nuclear intensity (p = 0.002) and the Ki-67 index (p = 0.01) remained the only significant factors for locoregional control. CONCLUSION: Ki-67 labeling index above 20% and a weak p53 nuclear intensity (0/+) are both able to identify patients with squamous cell carcinoma of the oropharynx being at high risk for local recurrence after surgery and postoperative RT. Consequently, in this subgroup an intensification of treatment may be contemplated in prospective trials.

Extranodal follicular dendritic cell sarcoma of the palate.

Follicular dendritic cell tumors are uncommon and usually occur in lymph nodes. We report the case of a follicular dendritic cell tumor that occurred in the palate of a 14-year-old boy and manifested itself as a nodular mass. Histologically, the neoplasm consisted of spindle-shaped or oval-shaped cells with eosinophilic cytoplasms and nuclei with delicate, dispersed chromatin. The lesional cells were principally arranged in diffuse, fascicular patterns with vaguely whorled or storiform areas. Focal multinucleate tumor giant cells and lymphocytes were observed throughout the neoplasm. Immunohistochemically, tumor cells were positive for the follicular dendritic cell markers CD21, CD35, and CD23 and for S-100 protein, CD68, and muscle-specific actin. Tumor cells were negative for LCA, CD20, EMA, CK (AE1/AE3), HMB45, and CD34. Lymphocytes were positive for LCA and CD45RO. Although follicular dendritic cell sarcoma is a very uncommon tumor, it should be included in the differential diagnosis of tumors in this location.

Malignant plasmacytoid myoepithelioma of the palate: histological observations compared to benign predominant plasmacytoid myoepithelial cells in pleomorphic adenoma of the palate.

Predominant benign plasmacytoid myoepithelial cells in pleomorphic adenoma and malignant plasmacytoid myoepithelioma cells were investigated morphologically. The cells of both tumors were plasmacytoid in appearance and sheet-like. Immunohistochemically, they were positive for keratin, vimentin, and S-100 protein, and negative for alpha-smooth muscle actin. In the malignant cells, large nuclei with irregular nuclear membranes and distinct nucleoi and occasional intranuclear inclusions and nuclear grooves were seen. Ultrastructural findings showed that the benign cells were richer in intermediate filaments and had fewer mitochondria. The intranuclear inclusions and nuclear grooves of the malignant cells were caused by invagination of the irregular nuclear membranes. Taken in their entirety, the above light microscopical nuclear findings may be useful as an adjunct for distinguishing malignant from benign plasmacytoid neoplastic myoepithelial cells of the salivary gland.

Merkel cell carcinoma of palatal mucosa in a young adult: immunohistochemical and ultrastructural features.

The first case report of a merkel cell carcinoma arising from the palatal mucosa in a young adult is presented. The histopathological similarities of this tumour in skin and oral mucosa are also discussed. The patient was a 14-year-old female with a non-symptomatic painful swelling in the left molar region of the maxilla. Under the diagnosis of a malignant tumour, a partial maxillary resection was performed, but there was a recurrence, and finally the patient died of cerebral metastasis. The tumor was composed mainly of uniform small cells. Immunohistologically, a large number of the cells were reactive to neuron specific enolase (NSE) and cytokeratin CK19, and some of the cells were positive to CK8, CK13, CK20, PGP9.5 and CEA focally and slightly. Pseudo-rosette formation and squamous differentiation were frequently detected. The ultrastructure of the tumour cells showed abundant Golgi bodies associated with neurosecretory granules. We conclude that it is the first case of a Merkel cell tumour arising from palatal mucosa and invading underlying bone with reactive hyperplasia. These findings closely resemble those of the same tumour occurring in the skin

Pseudocyst formation by adenoid cystic carcinoma cells in collagen gel culture and in SCID mice.

In order to reconstruct the characteristic three-dimensional architecture of adenoid cystic carcinoma, we cultured ACC2 cells, a cell system established from a human adenoid cystic carcinoma of the palate, in collagen gel matrix and transplanted them in SCID mice. In the collagen gel culture, the cells formed spherical colonies measuring 75.6 +/- 14.6 microns in diameter by 6 days after seeding. The tumor cell nests contained vacuolar structures that were immunopositive for heparan sulfate proteoglycan, type III collagen, type IV collagen, and fibronectin. The rim of the nests was argyrophilic and immunopositive for type I collagen, type IV collagen, laminin, and fibronectin. Transplants of ACC2 cells in SCID mice grew to form tumor masses in which pseudocysts were formed. The results indicate that our collagen gel culture system provides physiological conditions for ACC2 cells to secrete particular extracellular matrix molecules and form pseudocystic spaces.

An immunohistochemical study of two cases of either peripheral odontogenic fibroma (WHO type) or peripheral ameloblastoma.

Two cases of either peripheral odontogenic fibroma (POF) (WHO type) or peripheral ameloblastoma are reported. Their immunohistochemical characteristics were investigated in an attempt to clarify their histogenesis. The results showed that the epithelial component of this neoplasm tended to retain its distinct odontogenic character and expressed a keratin profile different from that of the overlying oral epithelium from which both cases most probably originated. The connective tissue element of these tumors was vimentin-positive and S-100 protein negative, confirming their mesodermal nature but precluding the possibility of ectomesenchymal derivation. No reactivity for desmin was noted.

Myoepithelial carcinoma arising in a benign myoepithelioma: immunohistochemical, ultrastructural, and flow-cytometrical study.

A case of myoepithelial carcinoma arising in a benign myoepithelioma of the minor salivary gland in a 71-year-old patient is reported. The tumor presented initially on the palate and had been diagnosed as "benign lesion" 40 years before. It recurred 22, 36, and 40 years after initial presentation, and a similar histopathological diagnosis was rendered. One year after the last recurrence, the tumor recurred showing typical changes of malignant transformation, and the diagnosis was malignant myoepithelioma. The light microscopy and ultrastructural features of the initial tumor were typical of plasmocytoid myoepithelioma. There were abundant round cells and rare spindle cells with uniform dispersed filaments, sometimes arranged in parallel streams without evidence of dense bodies. These cells showed micropinocytotic vesicles along the cell membrane with poorly developed intercellular junctions and were surrounded by a basal membrane. The malignant counterpart showed fewer plasmocytoid cells and a rather epithelial pattern with marked nuclear pleomorphism and formation of small, or rarely large, glandular lumina. The immunohistochemical features were similar for the benign and malignant tumors, with positivity for S-100 protein, vimentin, cytokeratins, and CAM 5.2, and were negative for GFAP, muscle-specific actin, CEA, and desmin. Flow cytometry showed a change in the DNA content profile. The benign myoepithelioma had a diploid DNA content with a low S-phase fraction of 3.9% and proliferative index of 9.1%, while the myoepithelial carcinoma had an evident aneuploid DNA stem line and an increased S-phase fraction of 8.3% with a proliferative index of 18.1%.