Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas.
Department of Dental Medicine, Division of Oral Pathology, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA. email@example.com
PURPOSE The purpose of this study was to determine the extent of p63 immunoreactivity in the malignant salivary gland neoplasms adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare this to the expression of this marker in the benign salivary gland tumors canalicular adenoma and basal cell adenoma. Few studies on the expression of p63 in head and neck salivary gland tumors have been published to date. P63, a selective immunohistochemical marker of basal/stem cells of stratified epithelium and of myoepithelial cells, is a p53 homologue that plays an essential role in both morphogenesis of epidermis and limb development. P63 immunoreactivity has been demonstrated in squamous cell and urothelial carcinomas. It is generally absent in most nonsquamous cell carcinomas. Study design Formalin-fixed paraffin-embedded sections from 49 salivary gland neoplasms, representing 6 canalicular adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to 2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY, were stained with an anti-p63 monoclonal antibody. RESULTS Nuclear p63 reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was also identified in the majority of cases of ACC (13/15, 87%), primarily in the nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of parotid origin stained strongly for p63, with staining localized to the peripheral tumor cells situated adjacent to the connective tissue stroma. None of the basal cell adenomas originating in the upper lip stained with p63. In native adjacent salivary gland tissue, p63 reactivity was identified focally in the nuclei of myoepithelial and basal duct cells. CONCLUSIONS P63 is strongly expressed in basal cell adenoma of parotid origin, and in ACC and PLGA. Canalicular adenoma did not demonstrate p63 staining, consistent with this tumor's putative luminal ductal cell differentiation. Our results suggest that the neoplastic cells in PLGA may represent either a population of p63-positive epithelial stem/reserve cells similar to the basal cells of stratified epithelium, or modified myoepithelial cells. Given the staining pattern of the tumors examined, p63 does not appear to be an ideal marker for distinguishing between ACC, PLGA, and basal cell adenoma.
Am J Pathol. 2011 Jul ;179 (1):391-9 21703418
Expression and regulation of the ΔN and TAp63 isoforms in salivary gland tumorigenesis clinical and experimental findings.
Yoshitsugu Mitani, Jie Li, Randal S Weber, Scott L Lippman, Elsa R Flores, Carlos Caulin, Adel K El-Naggar
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
The TP63 gene, a TP53 homologue, encodes for two main isoforms by different promoters: one retains (TA) and the other lacks (ΔN) the transactivation domain. p63 plays a critical role in the maintenance of basal and myoepithelial cells in ectodermally derived tissues and is implicated in tumorigenesis of several neoplastic entities. However, the biological and regulatory roles of these isoforms in salivary gland tumorigenesis remain unknown. Our results show a reciprocal expression between TA and ΔN isoforms in both benign and malignant salivary tumors. The most dominantly expressed were the ΔN isoforms, whereas the TA isoforms showed generally low levels of expression, except in a few tumors. High ΔNp63 expression characterized tumors with aggressive behavior, whereas tumors with high TAp63 expression were significantly smaller and less aggressive. In salivary gland cells, high expression of ΔNp63 led to enhanced cell migration and invasion and suppression of cell senescence independent of TAp63 and/or TP53 gene status. We conclude the following: i) overexpression of ΔNp63 contributes to salivary tumorigenesis, ii) ΔNp63 plays a dominant negative effect on the TA isoform in the modulation of cell migration and invasion, and iii) the ΔN isoform plays an oncogenic role and may represent an attractive target for therapeutic intervention in patients with salivary carcinomas.
Morphological heterogeneity of oral salivary gland carcinomas: a clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma.
Department of Pathology, University of Erlangen, Germany. Abbas.firstname.lastname@example.org
We analyzed 41 oral salivary gland carcinomas from consecutive 290 salivary gland carcinoma database (14%) with emphasis on the histological spectrum and clinical outcome of adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA). The cohort included 14 ACCs, 14 mucoepidermoid carcinomas (MECs), 8 PLGAs, 3 adenocarcinomas, not otherwise specified and 2 acinic cell carcinomas. Mean age was 48, 58 and 61 yrs for ACC, MEC and PLGA, respectively. Eight patients (19.5%) died of tumor at a mean interval of 66.5 months. ACC and PLGA showed similar mean age, gender distribution, predominant palatal localization, nodal metastasis, perineural invasion and MIB-1 index. However, ACC tended to show higher tumor stage and residual tumor (R1/R2) more frequently than PLGA, but this was statistically not significant. ACC and PLGA showed overlapping architectural patterns. However, ACCs displayed well organized basal-luminal differentiation, highlighted by CK5/CK7 immunostaining. In contrast, PLGA showed a disorganized histological and immunohistological pattern. C-Kit expression (CD117) was common in ACC, generally mirroring that of CK7 and virtually lacking in PLGA. Kaplan-Meier analysis demonstrated a similar clinical course for ACC and PLGA with 5 years survivals of 87% and 80%, respectively. Fluorescence in situ hybridization (FISH) performed on all 290 salivary carcinomas confirmed the specificity of the translocation t (11; 19) for MEC and its absence in all other carcinomas including ACC and PLGA. Our results emphasize the diversity of oral salivary gland carcinomas and the overlapping clinicopathological features of ACC and PLGA.
Prognostic value of quantitative p63 immunostaining in adenoid cystic carcinoma of salivary gland assessed by computerized image analysis.
Department of Pathology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. email@example.com
BACKGROUND In a long-term retrospective immunohistochemical study of adenoid cystic carcinoma (ACC) of salivary gland, we investigated the relation of p63 immunodetection to prognosis. Although it is generally agreed that the solid pattern is the most aggressive pattern of growth, ACCs with predominantly cribriform or tubular patterns have an unpredictable clinical course, with a relatively favorable 5-year survival but a low 20-year survival. METHODS Formalin-fixed paraffin sections from 35 cases of ACC showing a predominantly better differentiated histopathology, ie, cribriform or tubular patterns of growth, were immunostained for p63. Automated image analysis was used to quantify p63 positivity, using a modification of a previously developed algorithm. RESULTS Patients alive for more than 10 years had a lower extent of p63 expression than those who died of disease. Kaplan-Meier analysis revealed that separation of patients with morbidity and mortality from those alive with no evidence of disease, could be achieved at a cutoff of 35% p63 positivity (P =.0031, log-rank test). Multivariate analysis using the Cox proportional hazard model revealed p63 and tumor stage to be independent predictors of survival (P =.012 and P =.0003, respectively). CONCLUSIONS To our knowledge, the present study is the first to report prognostic significance of p63 in salivary gland ACC and the first report of a robust and well-studied immunohistochemical stain performable on routinely fixed and processed tissue with prognostic utility.
*Department of Pathology, University Health Network daggerDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada double daggerDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA section signDepartment of Pathology, Cleveland Clinic Foundation, Cleveland, OH.
Intercalated duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34 lesions in 32 patients. The IDLs were stained with CK7, estrogen receptors (ER), progesterone receptors, lysozyme, S100, calponin, and CK14. The patients ranged in age from 19 to 80 years (mean 53.8) with a 1.7:1 female predominance. The majorities of IDLs were parotid lesions (82%), were small and nodular (average size 3.1 mm) and showed 3 architectural patterns: hyperplasia (20), adenoma (9), and hybrid forms (5). In 59% of cases, IDLs were seen in conjunction with another salivary gland tumor, most commonly basal cell adenoma (8 cases), followed by EMC (3 cases). One case showed a combination of intercalated duct hyperplasia and basal cell adenoma. The IDLs stained diffusely with CK7 (100%) and S100 (73%) and focally for ER (91%) and lysozyme (100%). Calponin and CK14 highlighted a thin myoepithelial cell layer around all ducts (100%). Normal intercalated ducts were also consistently positive for CK7 and lysozyme, and focally for ER, but were S100 negative. In summary, IDLs have a variety of patterns ranging from hyperplasia to adenoma with hybrid lesions and share morphologic and immunophenotypic features with normal intercalated ducts. There is an association with basal cell adenomas and EMC, which lends credence to their role as a putative precursor lesion.
Synchronous bilateral epithelial-myoepithelial carcinoma of the parotid gland: case report and review of the literature.
Department of Otorhinolaryngology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. firstname.lastname@example.org
Synchronous bilateral malignancy in the parotid glands is extremely rare. The English literature reveals nine case reports. The most common synchronous bilateral malignancies are acinic cell carcinoma. Epithelial-myoepithelial carcinoma is an uncommon neoplasm comprising 1% of all salivary gland tumours. In this case report, we describe, to our best of knowledge, the first case of a patient with a synchronous bilateral epithelial-myoepithelial carcinoma of the parotid gland. The clinical histopathological and immunohistochemical peculiarities are elucidated. Imaging studies like ultrasonography are mandatory for both parotid glands and upper necks in the clinical presence of a unilateral parotid gland tumour.
Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma.
Department of Pathology, Ohio State University, Columbus, OH, USA. email@example.com
Distinguishing adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma of the salivary glands is important for their management. We studied the expression of several myoepithelial and basal/stem cell markers (smooth muscle actin, calponin, smooth muscle myosin heavy chain, metallothionein, maspin, and p63) by immunohistochemistry in 23 adenoid cystic carcinoma and 24 polymorphous low-grade adenocarcinoma, to identify the most useful marker or combination of markers that may help their diagnoses. The results were analyzed using hierarchical cluster analysis and chi(2) test for trend. We noted diffuse expression of smooth muscle actin in 20 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), calponin in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), smooth muscle myosin heavy chain in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P=0.001), metallothionein in 22 adenoid cystic carcinoma vs eight polymorphous low-grade adenocarcinoma (P<0.001), maspin in 22 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma, and p63 in 21 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma. Hierarchical clustering of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was virtually identical (kappa< or =0.0035), suggesting no significant advantage to their use in combination than individually. Diffuse smooth muscle actin expression showed the highest accuracy (91.5%) and positive predictive value (95.2%) for adenoid cystic carcinoma. Thus, diffuse expression of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was highly predictive of adenoid cystic carcinoma, whereas maspin and p63 were frequently expressed in both tumors. In differentiating adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, smooth muscle actin as a single ancillary test in support of the histological findings, appears to be as efficient as multiple immunohistochemical tests.
Polymorphous Low-Grade Adenocarcinoma is a rare, malignant salivary gland tumor, which is found almost exclusively in minor salivary glands. It is more frequent in the age range from 30 to 70, with a clear female predilection in a 2:1 ratio. It is usually located in the hard or soft palate, although it may be found in the rest of the oral cavity too. It is rare in major salivary glands. In general it has good prognosis, with recurrence rates in the range of 17%- 24%. Although rare, metastasis to regional lymph nodes may occur in 9% of the cases. This report describes the case of a patient that consulted at the Military Odontological Center (Central Odontológica del Ejército) due to an esthetic alteration of her dental prosthesis, which had been made 8 years before. The patient was sent to the Maxillofacial Surgery Service, where the intraoral examination showed a big mass compromising the hard palate and the alveolar ridge. During examination, a dent in her prosthesis was found to correspond to the tumor mass; it was therefore concluded that the tumor had at least an eight-year-old evolution. An incisional biopsy was carried out, and once the polymorphous low-grade adenocarcinoma diagnosis had been stated, the patient was sent to the Head and Neck Surgery Service of the Military Hospital, where the lesion was treated by wide surgical excision followed by radiation therapy.
Department of Pathology, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195-6100, USA.
Canalicular adenomas are benign neoplasms that arise from salivary glands and often present as painless enlarging nodules. They have a predilection for upper lip but can be found throughout the oropharynx. To our knowledge, canalicular adenoma arising in the esophagus has never been described in the English literature. Here we report a canalicular adenoma occurring in the esophagus.
Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
This review summarizes the new findings on salivary gland pathology under the following categories: immunohistochemistry; molecular genetics; newly recognized tumour types; known tumour entities with new findings; and progression of salivary gland tumours. In the application of immunohistochemistry, CD117 can aid in highlighting the luminal cell component of various salivary gland tumours, whereas p63 or maspin can aid in highlighting the abluminal cell component. A high Ki67 index remains the most useful marker to predict adverse outcome in salivary gland carcinoma. Specific chromosomal translocations are recognized in pleomorphic adenoma (with translocation involving PLGA1 or HMGA2 gene) and mucoepidermoid carcinoma (with MECT1-MAML2 gene fusion). Newly recognized entities include: sclerosing polycystic adenosis (with recent molecular evidence supporting its neoplastic nature), sclerosing mucoepidermoid carcinoma with eosinophilia, keratocystoma, adenoma with additional stromal component (lymphadenoma, lipoadenoma and adenofibroma), cribriform adenocarcinoma of the tongue and signet ring adenocarcinoma of minor salivary gland. Known tumour entities with new findings include: salivary duct carcinoma (with newly recognized mucinous, micropapillary and sarcomatoid variants), intraductal carcinoma (with controversies in terminology), mucoepidermoid carcinoma (with newly proposed grading parameters and oncocytic variant), epithelial-myoepithelial carcinoma (with newly recognized morphological variants), small cell carcinoma (with most cases being related to Merkel cell carcinoma), extranodal marginal zone B-cell lymphoma (with specific chromosomal translocation) and chronic sclerosing sialadenitis (being a component of IgG4-related sclerosing disease). Progression of salivary gland tumours can take the form of malignant transformation of a benign tumour, progression from low-grade to high-grade carcinoma, dedifferentiation, or stromal invasion of an in situ carcinoma.
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bldg 10/Room 2N216, 9000 Rockville Pike, Bethesda, MD 20892, USA. firstname.lastname@example.org
CONTEXT Although most prostate carcinomas are of the conventional acinar type, unusual variants have been reported. Adenoid cystic/basal cell carcinoma of the prostate is a rare tumor with distinctive histopathologic features. There are only a few publications in the literature concerning the diagnosis, treatment, and prognosis of this neoplasm. OBJECTIVE To review current literature together with the clinical, pathologic, and immunohistochemical features of adenoid cystic/basal cell carcinoma of the prostate and offer a practical approach to the diagnosis--including the differential diagnosis--of this neoplasm in surgical pathologic specimens. DATA SOURCES Adenoid cystic/basal cell carcinoma of the prostate is composed of infiltrating basaloid cells forming dilated acinar and cribriform spaces with luminal basementlike material. Differentiation of adenoid cystic/basal cell carcinoma from basal cell hyperplasia and cribriform pattern of acinar adenocarcinoma may be difficult. The use of cytokeratin 34betaE12 and prostate-specific antigen can help in difficult cases. Most cases are indolent, but metastasis has been documented in a few cases. CONCLUSIONS Various histologic and immunohistochemical features are helpful in recognizing adenoid cystic/basal cell carcinoma of the prostate. This is a rare subtype of prostate cancer and correct diagnosis is important because of the unique clinical and biological features and the implications for treatment and prognosis.
Other papers by authors:
Bilateral central giant cell granulomas of the mandible in an 8-year-old girl with Noonan syndrome (Noonan-like/multiple giant cell lesion syndrome).
Department of General Dentistry, Creighton University School of Dentistry, Omaha, NE 68178, USA. email@example.com
We report a case of an 8-year-old girl who presented with bilateral central giant cell granulomas of the posterior mandible. Characteristic facial features and a history of pulmonary stenosis led us to suspect a diagnosis of Noonan syndrome. A medical geneticist confirmed this. This case report will discuss the salient features of this diagnosis.
C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma.
Department of Dental Medicine, Long Island Jewish Medical Center, 270-05 76th Avenue, New Hyde Park, NY 11040, USA.
OBJECTIVE Differentiating between adenoid cystic carcinomas (ACCs), polymorphous low-grade adenocarcinomas (PLGAs), and the monomorphic adenomas (including canalicular adenomas, trabecular adenomas, and basal cell adenomas) can present a diagnostic challenge, especially when examining tissue obtained from small incisional or fragmented biopsies. Recent studies have revealed that overexpression of the tyrosine kinase receptor protein c-kit occurs in a narrow subset of malignant neoplasms, including gastrointestinal stromal tumors, myeloid leukemias, seminomas, and ACCs. C-kit reportedly is not expressed in PLGAs. We compared the expression of the c-kit antigen in the malignant salivary gland neoplasms ACC and PLGA with its expression in salivary gland monomorphic adenoma (including canalicular adenoma and basal cell adenoma). STUDY DESIGN Formalin-fixed paraffin-embedded sections of 49 salivary gland neoplasms (17 monomorphic adenomas, 17 PLGAs, and 15 ACCs) accessioned between 1989 and 2002 were retrieved from the files of the Department of Pathology, Long Island Jewish Medical Center, and were stained with an anti-c-kit polyclonal antibody. RESULTS C-kit reactivity was uniformly positive in the cytoplasm of luminal neoplastic cells in ACCs (15/15, 100%). Positive reactivity was also identified in the majority of PLGAs (16/17, 94%), with at least 25% of the tumor cells being positive. Similar reactivity was seen in monomorphic adenomas (16/17, 94%). CONCLUSIONS In contrast to previous reports, we find that c-kit expression was not restricted to ACC but was expressed in all 3 tumor types evaluated (ACC, PLGA, and monomorphic adenoma). Therefore, c-kit does not appear to be a useful marker for distinguishing between either ACC and PLGA in equivocal cases, or in benign and malignant salivary gland neoplasms.
University of Michigan, Ann Arbor, Michigan.
Reflections on my first year as Oral Pathology Section Editor:"the good, the less than ideal, and the downright ugly".
Editor, Oral and Maxillofacial Pathology, University of Michigan.
Recognition and management of common acute conditions of the oral cavity resulting from tooth decay, periodontal disease, and trauma: an update for the family physician.
Department of Periodontics and Oral Medicine, Faculty of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA. firstname.lastname@example.org
This article presents an overview of common and/or significant diseases of the oral cavity that the family physician is likely to encounter, with an emphasis on pathogenesis, recognition, complications, and management. Topics reviewed include the sequelae of dental caries, periodontal disease, and trauma. Prevention and early intervention strategies are emphasized. Recent updates and practical issues for the family physician are highlighted.
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA. email@example.com
University of Michigan School of Dentistry, Ann Arbor, MI, USA. firstname.lastname@example.org
Latest similar papers:
Tumour Biol. 2012 Oct 20;: 23086574
Manuela Torres Andion Vidal, Iguaracyra Barreto de Oliveira Araújo, Clarissa Araújo Silva Gurgel, Francisco De Assis Caldas Pereira, Deise Souza Vilas-Bôas, Eduardo Antônio Gonçalves Ramos, Ivan Marcelo Gonçalves Agra, Adna Conceição Barros, Valéria Souza Freitas, Jean Nunes Dos Santos
Department of Oral Pathology, Laboratory of Surgical Pathology, School of Dentistry, Federal University of Bahia, Salvador, Bahia, Brazil.
The aim of this study was to investigate the density of mast cells and microvessels in minor salivary gland tumors. Forty-one cases of minor salivary gland tumors (pleomorphic adenoma, n = 10; adenoid cystic carcinoma, n = 11; mucoepidermoid carcinoma, n = 10; and polymorphous low-grade adenocarcinoma) were investigated using immunohistochemistry for mast cell tryptase and von-Willebrand factor. Density of mast cells was higher in mucoepidermoid carcinoma; however, no differences in the number of these cells were observed between the different types of tumors (p > 0.05). The number of mast cells was higher in periparenchymal areas in all tumors, but the difference was not significant (p > 0.05). Mucoepidermoid carcinoma showed the largest number of periparenchymal mast cells, whereas pleomorphic adenomas showed the smallest number of intraparenchymal mast cells (p > 0.05). The highest microvessel density was observed in mucoepidermoid carcinomas, being this difference statistically significant when mucoepidermoid carcinoma was compared to pleomorphic adenoma (p = 0.0034) and polymorphous low-grade adenocarcinoma (p = 0.004). Microvessel density was significantly higher in adenoid cystic carcinoma when compared to pleomorphic adenoma (p = 0.0406) and polymorphous low-grade adenocarcinoma (p = 0.0123). Comparison of mast cells and microvessel densities showed no significant difference between tumors. A quantitative difference in mast cells and microvessels was observed, particularly in mucoepidermoid carcinoma, a finding supporting the aggressive behavior of malignant salivary gland tumors without myoepithelial differentiation. Further studies are needed to determine the role of mast cells in angiogenesis, as well as in the development and biological behavior of these tumors.
Diagn Mol Pathol. 2012 Jul 27;: 22847156
11q21 Rearrangement is a Frequent and Highly Specific Genetic Alteration in Mucoepidermoid Carcinoma.
Till Sebastian Clauditz, Artur Gontarewicz, Chia-Jung Wang, Adrian Münscher, Simon Laban, Maria Christina Tsourlakis, Rainald Knecht, Guido Sauter, Waldemar Wilczak
Departments of *Pathology †Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße, Hamburg, Germany.
Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. Translocation t(11;19)(q21;p13) involving the MECT1 and MAML2 genes has been suggested as a diagnostic marker in these tumors. To determine the specificity of 11q21 locus rearrangements for MEC, fluorescence in situ hybridization analysis with specific MEC-I Dual Color Break Apart Probe was performed on a tissue microarray containing samples from almost 1200 salivary gland adenomas and carcinomas. Rearrangements of 11q21 were observed in 40% of 217 MECs. The frequency of rearrangements decreased with tumor grade and was found in 53% of G1, 43% of G2, and 31% of G3 tumors (P=0.015). There were no 11q21 rearrangements found in other salivary gland carcinomas including 142 adenoid cystic carcinomas, 104 acinic cell adenocarcinomas, 76 adenocarcinoma not otherwise specified, 38 epithelial-myoepithelial carcinomas, 15 polymorphous low-grade adenocarcinomas, 18 basal cell adenocarcinomas, 19 myoepithelial carcinomas, 12 papillary cystadenocarcinomas, 6 salivary duct carcinomas, and 10 oncocytic carcinomas. Furthermore, all analyzed salivary gland adenomas, including 39 cases of Warthin tumor and control samples, either from the salivary gland or from other organs were negative for 11q21 rearrangements. It is concluded that MECT1-MAML2 gene fusion is a highly specific genetic alteration in MEC with predominance in low-grade and intermediate-grade tumors.
Minerva Stomatol. ;61 (1-2):37-43 22274309
Polymorphus low-grade adenocarcinoma of the maxilla: pathological findings and reconstructive considerations.
Department of Oral and Maxillofacial Surgery, General Hospital of Ciudad Real, Ciudad Real, Spain - email@example.com.
Polymorphous low-grade adenocarcinoma (PLGA) is a rare, malignant salivary gland tumor, which is found almost exclusively in minor salivary glands, primarily those in the palate. We report a case of PLGA arising from minor salivary gland of the palate in a 63-year-old female patient. The tumor was resected through the oral cavity performing a bilateral maxillectomy and surgical defect was reconstructed using a free radial forearm flap combined with iliac crest bone graft. The patient was free of disease at 48 months follow-up. The histopathological features of PLGA, the importance of differential diagnosis from pleomorphic adenoma and adenoid cystic carcinoma and the type of reconstruction are discussed in this article.
Acta Cytol. 2012 ;56 (1):25-33 22236742
Cytopathologic analysis of stroma-poor salivary gland epithelial/myoepithelial neoplasms on fine needle aspiration.
Department of Anatomic Pathology, The Cleveland Clinic, Cleveland, Ohio 44195, USA. firstname.lastname@example.org
OBJECTIVE Fine needle aspiration (FNA) diagnosis of salivary gland neoplasms with epithelial/myoepithelial cells but rare or no stroma is usually difficult. Our aim was to study the cytomorphology of this cohort of FNA cases and evaluate the clinical follow-up. STUDY DESIGN The diagnostic terminology for this group of aspirates was 'favor an epithelial/myoepithelial neoplasm of the salivary gland'. The cytologic smears of 32 such cases were retrieved and showed cellular smears with bland-appearing or mildly atypical epithelial and myoepithelial cells without typical chondromyxoid stroma seen in pleomorphic adenoma (PA). RESULTS Twenty of the 32 cases had histologic follow-up. Ten of these 20 cases were PAs, including 8 cellular PAs. Two cases were basal cell adenomas, 1 case myoepithelioma and 1 case benign adenoma, not otherwise specified. Among the 6 malignant tumors on surgical resections, there were 3 epithelial-myoepithelial carcinomas, 1 myoepithelial carcinoma, 1 basal cell adenocarcinoma and 1 adenoid cystic carcinoma. CONCLUSIONS Although 14 of the 20 (70%) cases were benign neoplasms, a substantial amount of cases (30%) were malignant salivary gland neoplasms. The generic diagnostic terminology of 'epithelial/myoepithelial neoplasm of the salivary gland' and appropriate clinical follow-up are recommended for these cases.
Int J Oncol. 2012 Jan ;40 (1):80-4 21901247
Studies of genomic imbalances and the MYB-NFIB gene fusion in polymorphous low-grade adenocarcinoma of the head and neck.
Sahlgrenska Cancer Center, Department of Pathology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Polymorphous low-grade adenocarcinoma (PLGA) is a malignancy predominantly originating from the minor salivary glands. The molecular events underlying the pathogenesis of PLGA is poorly understood and no recurrent genetic aberrations have so far been identified. We used genome-wide, high-resolution aCGH analysis to explore genomic imbalances in 9 cases of PLGA. Because of the well-known morphologic similarities between PLGA and adenoid cystic carcinoma (ACC) we also analyzed all tumors for expression of the recently identified ACC-associated MYB-NFIB gene fusion. aCGH analysis revealed that the PLGA genome contains comparatively few copy number alterations (CNAs). Gains/losses of whole chromosomes or chromosome arms were more than twice as common as partial CNAs. Two cases showed gain of chromosome 8 and one case each gain of chromosome 9, loss of chromosome 22 and loss of the Y chromosome. One case showed loss of the entire 6q arm and one case an interstitial deletion of a 33-Mb segment within 6q22.1-q24.3. This region contains the MYB oncogene and the candidate tumor suppressor gene PLAGL1. RT-PCR analysis revealed that one of the 9 PLGAs expressed the ACC-associated MYB-NFIB gene fusion, illustrating the diagnostic difficulties associated with the diagnosis of these morphologically partly overlapping entities. Taken together, our findings indicate that the PLGA genome is genetically stable and contains comparatively few CNAs which is in line with the clinical observation that PLGA is a slow-growing, low-grade carcinoma with low metastatic potential.
Akihiko Kawahara, Hiroshi Harada, Hideyuki Abe, Tomohiko Yamaguchi, Tomoki Taira, Kazutaka Nakashima, Hiroyuki Mihashi, Jun Akiba, Masayoshi Kage
Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan. email@example.com
BACKGROUND Nuclear localization of β-catenin is known in a wide variety of human neoplasms; however, there are few reports in basal cell adenoma of the salivary gland. Our objective was to confirm the nuclear localization of β-catenin in basal cell adenoma and to examine whether nuclear β-catenin expression could be a useful marker in the diagnosis of basal cell adenoma. METHODS To evaluate the nuclear localization of β-catenin in basal cell adenomas, immunohistochemistry (IHC) and mutation analysis of CTNNB1 were performed in 22 and 21 cases, respectively. Mutation analysis of CTNNB1 in exon 3 was performed by DNA direct sequencing. In a comparative study, IHC for β-catenin was also performed in 157 other salivary gland tumors. RESULTS Nuclear β-catenin expression was examined in 22 basal cell adenomas; scores were 2+ in 18 cases (81.8%), 1+ in three cases (13.6%), and 0 in one case (4.5%). Expression was localized in the basaloid myoepithelial cells. CTNNB1 mutation analysis was performed in 21 basal cell adenomas; mutations, including I35T and T41P, were detected in 11/21 (52%) cases. In comparison with other salivary gland tumors, one of three basal cell adenocarcinomas showed nuclear β-catenin expression, whereas there was no nuclear β-catenin expression in 154 other salivary gland tumors. CONCLUSIONS We demonstrated nuclear β-catenin expression and activation of the CTNNB1 gene in basal cell adenoma. Although nuclear β-catenin expression may be unable to distinguish basal cell adenoma from basal cell adenocarcinoma, it should be a helpful marker in the diagnosis of basal cell adenoma.
Multiple malignant salivary gland neoplasms: mucoepidermoid carcinoma of palate and adenoid cystic carcinoma of floor of mouth.
Oral and Maxillofacial Pathology, School of Dentistry, University of Missouri, 650 E. 25th Street, Kansas City, MO 64108-6489, USA. firstname.lastname@example.org
Salivary gland tumors usually occur as single lesions. To have more than one tumor is unusual. We report a case of an adult male who presented with a mucoepidermoid carcinoma involving the minor salivary glands of the palate at age 57 years, followed by an adenoid cystic carcinoma of the floor of mouth at age 63 years. The patient later succumbed to non-Hodgkin lymphoma at age 72 years. There are 31 acceptable cases of multiple malignant salivary gland neoplasms reported in the world literature. Multiple malignant tumors of the same histologic type are more common than those of different histologic type. Bilateral acinic cell adenocarcinoma was the most frequent combination of multiple salivary gland malignancy, accounting for 14 cases (10 synchronous and four metachronous). All involved the parotid glands bilaterally with the exception of one case that involved parotid and submandibular gland. Polymorphous low-grade adenocarcinoma accounted for three of the four cases of multiple malignant tumors involving minor salivary glands. Individuals with a history of malignancy are at risk for the development of additional malignant tumors and should receive appropriate clinical follow-up.
J Oral Sci. 2009 Dec ;51 (4):509-14 20032601
Comparison of immunohistochemical markers between adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma.
Department of Oral and Maxillofacial Pathology, Faculty of Dentistry and Dental Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Adenoid cystic carcinoma (AdCC) and polymorphous low-grade adenocarcinoma (PLGA) have several common histological and clinicopathological features that may create diagnostic difficulties. In this study, 10 AdCCs, 8 PLGAs, and 5 normal minor salivary glands as a control group were selected. Sections prepared from each tumor were stained using the streptavidin-biotin system for seven marker antigens: carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), muscle-specific actin (MSA), vimentin, S100, p53, and Ki-67. Data analysis showed high expression of CEA, MSA and Ki-67 in AdCCs compared with PLGAs, although CEA expression was limited to luminal cells. Ki-67 was expressed in both luminal and non-luminal cells and MSA only in non-luminal cells. Vimentin and S100 showed stronger expression in PLGAs, the expression of vimentin was more noticeable, being focal and widespread. The immunoreactivities of EMA and P53 were not helpful for distinguishing between the two tumors, although the EMA expression pattern in AdCCs was limited to luminal cells, whereas it was present in both luminal and non-luminal cells in PLGAs. Thus, immunohistochemistry can be helpful for differential diagnosis of AdCC and PLGA, particularly that for CEA, vimentin, and Ki-67.
BMC Cancer. 2009 ;9 :391 19889225
Assessment of angiogenesis by CD105 antigen in epithelial salivary gland neoplasms with diverse metastatic behavior.
Sergio V Cardoso, Kelen Christine N Souza, Paulo R Faria, Ana Lucia A Eisenberg, Fernando L Dias, Adriano M Loyola
Pathology Area, School of Dentistry, Federal University of Uberlandia, Brazil. email@example.com
BACKGROUND Information on the biology of metastasis development in salivary gland tumors is scarce. Since angiogenesis seems associated with this phenomenon in other tumors, we sought to compare salivary gland tumors with diverse metastatic behavior in order to improve the knowledge and management of these lesions. METHODS Samples from the most important salivary gland tumors were segregated according to its metastatic behavior and submitted to routine immunohistochemistry to identify vessels positive for CD105 expression. Frequency of positive cases and intratumoral microvessel density (IMD) was compared among the group of lesions. RESULTS CD105 positive vessels were absent in normal salivary gland tissue, were rare in pleomorphic adenomas and adenoid cystic carcinomas (ACC), more common in polymorphous low-grade adenocarcinomas and highest in mucoepidermoid carcinomas. Only ACC with such feature were metastatic. IMD was higher in malignant rather than benign tumors. CONCLUSION Immunostaining of CD105 in salivary gland tumors implies participation of angiogenesis in the development of malignant lesions, as well as some role for myoepithelial cells in the control of new vessel formation. In addition, suggest that ACC with positive CD105 vessels are at higher risk for metastasis.
Pathologe. 2009 Sep 26;: 19784654
Zentrum für Humangenetik, Universität Bremen, Bremen, Deutschland.
The molecular genetic background of salivary gland neoplasms has not been characterized in detail to date. However, interesting target genes which could be used as prognostic and diagnostic molecular biomarkers have already been identified, e.g. CRTC1-MAML2 in mucoepidermoid carcinoma, or PLAG1 and HMGA2 in pleomorphic adenoma. In particular, CRTC1-MAML2 has shown strong diagnostic and prognostic potential in recent years. One of the major advantages of molecular tumor markers is that valid results are obtained on minute cell and/or tissue samples. Due to high-throughput techniques like comparative genome hybridization (CGH), micro- or gene profiling array detection of new marker genes can be expected in the future. This is also true for the most frequent malignant salivary gland tumors after the mucoepidermoid carcinoma, i.e. adenoid cystic carcinomas and acinic cell carcinomas.