PAX8-GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid.

The hyalinizing trabecular adenoma/tumor is a rare and poorly characterized follicular-derived thyroid neoplasm recently shown to harbor recurrent PAX8-GLIS1 or PAX8-GLIS3 gene fusions. Here we sought to define the repertoire of genetic alterations of hyalinizing trabecular tumors, and whether PAX8-GLIS3 fusions are pathognomonic for hyalinizing trabecular tumors. A discovery series of eight hyalinizing trabecular tumors was subjected to RNA-sequencing (n = 8), whole-exome sequencing (n = 3) or targeted massively parallel sequencing (n = 5). No recurrent somatic mutations or copy number alterations were identified in hyalinizing trabecular tumor, whereas RNA-sequencing revealed the presence of a recurrent genetic rearrangement involving PAX8 (2q14.1) and GLIS3 (9p24.2) genes in all cases. In this in-frame fusion gene, which comprised exons 1-2 of PAX8 and exons 3-11 of GLIS3, GLIS3 is likely placed under the regulation of PAX8. Reverse transcription RT-PCR and/or fluorescence in situ hybridization analyses of a validation series of 26 hyalinizing trabecular tumors revealed that the PAX8-GLIS3 gene fusion was present in all hyalinizing trabecular tumors (100%). No GLIS1 rearrangements were identified. Conversely, no PAX8-GLIS3 gene fusions were detected in a cohort of 237 control thyroid neoplasms, including 15 trabecular thyroid lesions highly resembling hyalinizing trabecular tumor from a morphological standpoint, as well as trabecular/solid follicular adenomas, solid/trabecular variants of papillary carcinoma, and Hurthle cell adenomas or carcinomas. Our data provide evidence to suggest that the PAX8-GLIS3 fusion is pathognomonic for hyalinizing trabecular tumors, and that the presence of the PAX8-GLIS3 fusion in thyroid neoplasms may be used as an ancillary marker for the diagnosis of hyalinizing trabecular tumor, thereby avoiding overtreatment in case of misdiagnoses with apparently similar malignant tumors.

Primary Ewing's sarcoma of the ethmoid sinus with intracranial and orbital extension: case report and literature review.

The Ewing's sarcoma family of tumors is a group of cancers that commonly arises in young adults during their second decade of life. It frequently involves the trunk and long bones of the body with primary Ewing's sarcoma of the paranasal sinuses being exceedingly rare. We describe the case of a 39 year-old female with primary Ewing's Sarcoma originating from the ethmoid sinus with intracranial extension into the anterior cranial fossa and the orbit. The radiologic and histopathologic profiles are presented with a review of the literature. To our knowledge, this is the second reported case with the tumor involving the anterior cranial fossa, but the only case where immunochemical staining and molecular genetic analysis are available for definitive diagnosis.

Iatrogenic oral hairy leukoplakia: report of two cases.

Oral hairy leukoplakia (OHL) presents as a white, plaque-like lesion typically occurring on the lateral border of the tongue. This condition is caused by the Epstein-Barr virus, a human herpesvirus that often establishes lifelong, asymptomatic latent infection. OHL, initially described in immunocompromised men infected with the human immunodeficiency virus (HIV), has also been described in other severely immunocompromised patients. Only rarely has OHL been reported in less profoundly immunocompromised patients primarily in the setting of corticosteroid therapy. Here we report on two additional cases of OHL attributable to immunosuppressive medications.

Papillary squamous cell carcinoma of the head and neck: a clinicopathologic series.

PURPOSE: Papillary squamous cell carcinoma (PSCC) is a rare malignancy that has been associated with human papillomavirus. We present all cases of this disease at a single academic teaching hospital over the last 30 years. MATERIALS AND METHODS: A retrospective chart review was performed for all patients with a diagnosis of PSCC. Of 65 patients identified, 52 were included after meeting established diagnostic criteria. Chart reviews were performed for patient demographics, overall survival, and disease-free survival. RESULTS: Mean age at diagnosis was 65 years, with a male to female ratio of 2.3:1. The majority of lesions (n = 34, 65.4%) arose in areas commonly affected by benign squamous papillomas, with the laryngopharynx the most commonly affected (n = 19, 36.5%), followed by the oral cavity (n = 18, 34.6%), sinonasal tract (n = 8, 15.4%), and oropharynx (n = 7, 13.5%). Two- and 5-year disease-free survival rate was 68% and 46%, respectively. Overall survival rate was 90% and 72% at 2 and 5 years, respectively. CONCLUSIONS: Papillary squamous cell carcinoma of the head and neck is a distinct variant of conventional squamous cell carcinoma with a good prognosis despite high locoregional recurrence rates. Histology and subsite localization corroborate existing evidence that human papillomavirus may be involved.

SMARCB1 (INI-1)-Deficient Adenocarcinoma of the Sinonasal Tract: A Potentially Under-Recognized form of Sinonasal Adenocarcinoma with Occasional Yolk Sac Tumor-Like Features.

The classification of sinonasal adenocarcinoma (SNAC) is complex. The high-grade, non-intestinal SNAC group is particularly heterogeneous, with tumors showing widely variable morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma is a newly described, aggressive tumor that usually resembles sinonasal undifferentiated carcinoma (SNUC) or non-keratinizing squamous cell carcinoma; however, glandular differentiation has been rarely reported and this feature may be under-recognized. We present a dedicated series of 12 SMARCB1-deficient SNACs. All tumors had an oncocytoid/plasmacytoid cytomorphology with variable degrees of glandular differentiation consisting of tubules and cribriform structures with foci of intracellular or intraluminal mucin. Three of 12 tumors exhibited foci of yolk sac tumor-like histologic features. The tumors were uniformly high-grade, with nuclear pleomorphism, elevated mitotic rates and frequent necrosis. By immunohistochemistry, all tumors were entirely SMARCB1-deficient, and 10 of 12 were CK7-positive. Occasional expression of CDX2 (4 of 12), CK20 (3 of 12), and p40 (3 of 10) was seen. Expression of yolk sac markers was variably present in tumors that harbored yolk sac-like areas but also tumors that did not: glypican-3 (10 of 11), SALL4 (6 of 11), HepPar-1 (4 of 11), PLAP (1 of 10), and AFP (1 of 11). SMARCB1-deficient sinonasal carcinoma, particularly the oncocytoid/plasmacytoid form, can demonstrate variable degrees of glandular differentiation. This unexpected morphology combined with variable immunohistochemical results may lead to misdiagnoses of high-grade intestinal or non-intestinal SNAC, myoepithelial carcinoma, or even yolk sac tumor or metastatic hepatocellular carcinoma.

Seromucinous hamartomas: a clinicopathological study of a sinonasal glandular lesion lacking myoepithelial cells.

AIMS: To describe seven cases of sinonasal seromucinous hamartoma. MATERIALS AND RESULTS: The clinicopathological and immunohistochemical features of seven seromucinous hamartomas were analysed. There were four men and three women. Six lesions involved the posterior nasal septum and one the lateral wall. Size ranged from 6 to 40 mm. Four patients had no recurrences. One patient had local recurrences 24 and 60 months after diagnosis. The masses were covered by respiratory epithelium. Their stroma was oedematous to fibrous and contained invaginated respiratory epithelium forming glands and cysts, cysts with cuboidal to flat epithelium, and small serous glands, ducts and tubules with lobular and irregular haphazard patterns. One case had numerous glands surrounded by hyalinized basement membrane with features of respiratory epithelial adenomatoid hamartoma (REAH). One case had focal REAH-like changes. Both respiratory and serous components were positive for cytokeratin (CK) 7 and CK19. The serous component lacked myoepithelial cells when stained for CK14, p63, calponin and muscle-specific antigen in five cases. CONCLUSIONS: Seromucinous hamartomas show a broader histopathological appearance than previously reported. The serous proliferation in these lesions lacks myoepithelial cells. The presence of occasional REAH-like features and common location in the posterior nasal septum suggest a spectrum from pure seromucinous hamartoma to REAH.

Squamous cell carcinoma of the bladder: a clinicopathologic analysis of 45 cases.

Squamous cell carcinoma of the bladder comprises less than 5% of all bladder cancers in the United States and its long-term prognosis has remained controversial. We examined a large series of patients who underwent radical and partial cystectomies for squamous cell carcinoma to identify associated histopathologic findings and clinical outcomes associated with these tumors. Patient age ranged from 46 to 83 years (average 68.5 y) with a male:female ratio of 3:2. Forty-three patients were white and 2 patients were African-American. No patient had a history of schistosomal infection and only 1 patient had a history of condyloma acuminatum. The majority of patients with reported signs and symptoms presented with hematuria (n=29/34), with the remainder presenting with lower urinary tract symptoms. Tumor size ranged from 0.8 to 6.4 cm (average 3.8 cm). Invasion was identified into the lamina propria (pT1, n=1/45), muscularis propria (pT2, n=14/45), perivesical fat (pT3, n=27/45), and adjacent structures (pT4, n=3/45). Concurrent metastases were identified in 11 of 45 patients (24%) to pelvic lymph nodes (n=9), perivesical lymph nodes (n=3), obturator lymph nodes (n=1), and bowel wall (n=1). Most tumors were moderately (n=29/45) or poorly (n=13/45) differentiated, whereas only 3 tumors were well differentiated (n=3/45). Keratinization was present in all cases within the invasive component and ranged from 5% to 95% of tumor bulk. Necrosis ranged from 0% to 60% and inversely correlated with tumor differentiation. Eighteen cases demonstrated a prominent giant cell reaction to keratin, and 30 tumors were associated with a desmoplastic reaction. Extensive perineural (n=11/45) and angiolymphatic invasion (n=7/45) were identified in a subset of tumors. The majority of cases demonstrated associated superficial lesions including keratinizing squamous metaplasia (n=28/45), nonkeratinizing squamous metaplasia (n=20/45), squamous cell carcinoma in situ (n=16/45), squamous metaplasia with dysplasia (n=4/45), verrucous squamous hyperplasia (n=3/45), and extensive condyloma acuminatum (n=1/45). Seven cases additionally demonstrated separate small foci of focal flat urothelial carcinoma in situ. Three cases demonstrated a markedly atypical squamous lining of the prostatic ducts at the prostatic urethra. Clinical follow-up was available on 35 patients (78%) and ranged from 1 to 175 months (average 33 mo, median 15 mo). Two patients developed recurrent local disease (n=2/35, 6%) and 13 patients developed subsequent metastatic disease (n=13/35, 37%). Ten patients were dead of disease (29%), with a time to death for most patients of less than 2 years (range 2 to 21 mo, average 10.5 mo). Thirty-seven percent of patients (n=13/35) were alive without disease. In conclusion, squamous cell carcinoma often presents at an advanced stage; however, radical cystectomy with lymph node dissection appears to offer a significant benefit in survival in a subset of patients.

High Grade (Large Cell) Neuroendocrine Carcinoma of the Nasopharynx: Novel Case Report with Touch Preparation Cytology and Positive EBV Encoded Early RNA.

Fewer than five case reports of primary large cell neuroendocrine carcinoma of the nasopharynx are known to the authors. No previous reports have included examples of cytomorphology or have proven association with Epstein-Barr virus. We herein illustrate MRI findings, histopathologic features, immunohistochemical characterization, cytologic details, and in situ hybridization studies from a unique case of primary large cell neuroendocrine carcinoma of the nasopharynx in a 38-year-old Caucasian male patient. Recognition of rare tumor types of the nasopharynx allows for refinements in disease management and prognostication.

Pathological review of turbinate tissue from functional nasal surgery: incurring costs without adding quality.

OBJECTIVE: Inferior turbinate surgery for nasal obstruction can be performed in a variety of ways. Only a few of these methods produce tissue that can be sent for pathologic analysis. According to the College of American Pathologists, turbinate tissues are not exempt from requisite pathologic evaluation. Our objectives were to evaluate the clinical value and cost implications of routine pathological examination of turbinate specimens. STUDY DESIGN: Case series with chart review. SETTING: Academic tertiary care medical center. SUBJECTS AND METHODS: Charts of patients who underwent an inferior turbinate procedure for nasal obstruction between January 2008 and August 2011 were reviewed. RESULTS: Thirteen hundred consecutive cases from 17 surgeons were identified. Among these patients, 223 (17%) underwent an isolated turbinate reduction procedure and 779 (59%) underwent a reduction procedure in conjunction with a septoplasty. The remaining patients had a turbinate procedure in addition to another head and neck procedure. Only 591 (45%) turbinate reduction procedures were performed by methods that were tissue producing, and of these, 137 (23%) were sent for pathologic analysis. All submitted specimens received a gross examination and 123 (90%) also underwent histologic analysis. No abnormalities were reported. CONCLUSION: At our institution, most surgeons did not submit turbinate tissues for pathologic examination even when a specimen was produced. Of the specimens sent, no abnormal pathologic results were identified. Our results suggest that routine pathologic evaluation of inferior turbinate specimens may not contribute to patient care and perhaps represents an unnecessary cost.

Cervical sympathetic chain paraganglioma: a report of 2 cases and a literature review.

We review 2 cases of surgically and pathologically confirmed paraganglioma of the cervical sympathetic chain. Both patients-a 46-year-old man and a 33-year-old woman-were treated surgically. Intraoperatively, both tumors were found to be hypervascular and arising from the cervical sympathetic chain. Histopathologic analysis confirmed both as paragangliomas. Paragangliomas arising from the cervical sympathetic chain are exceptionally rare, but they must be considered in the differential diagnosis of parapharyngeal masses. They often present with ipsilateral Horner syndrome and oropharyngeal fullness, and they may be associated with a higher rate of catecholamine secretion. Typical imaging characteristics include anterolateral or lateral displacement of both the carotid and jugular vessels.

Hybrid Capture 2 human papilloma virus testing for head and neck cytology specimens.

INTRODUCTION: High-risk human papilloma virus (hrHPV)-associated head and neck (HN) squamous cell carcinomas (SCCs) have important differences from non-hrHPV-related HNSCCs. A highly sensitive and specific test for HPV in cytology fine-needle aspirations (FNAs) would be useful, as it has the potential to alter therapy. MATERIALS AND METHODS: Patients with an HN FNA diagnosed as SCC or suspicious for SCC were included. Hybrid Capture 2 (HC2) was performed on residual rinse material and chromogenic in situ hybridization (CISH) for hrHPV was performed on the cell block. HC2-positive samples were genotyped for HPV types 16, 18, and 45. "Gold standard" p16 and CISH testing was performed on histologic material from the primary tumor. Tumors concordantly positive for p16 and CISH were considered hrHPV-positive, concordantly negative were considered hrHPV-negative, and discordant results were considered hrHPV-equivocal. RESULTS: A total of 96 FNAs from 95 patients were included. Surgical material was available in 80 patients. Of those, 29 patients (36%) were positive for hrHPV by "gold standard" testing, and 3 patients (4%) had equivocal results. HC2 was 72% sensitive and 100% specific for hrHPV. Sixty percent of HC2-positive aspirate samples were positive for HPV16. CISH was 61% sensitive and 79% specific for hrHPV. HC2 had a significantly better sensitivity and specificity than did CISH on paired sample analysis (P < .05). CONCLUSIONS: HC2 is a highly sensitive and specific assay for the detection of hrHPV in HN FNA samples. This new application of a familiar, widely available testing method has the potential to be clinically useful in the management of patients with HNSCC.

The presentation and clinical significance of sinonasal respiratory epithelial adenomatoid hamartoma (REAH).

BACKGROUND: Sinonasal respiratory epithelial adenomatoid hamartoma (REAH) is a benign glandular proliferation with ciliated epithelium. Little is known about REAH, with only a few published case reports appearing since its original description in 1995. Classically described as an isolated polypoid lesion arising from the nasal septum, more recent descriptions also suggest that REAH can occur among nasal polyps. We report the largest experience with REAH to date, and aim to better understand and characterize this unique entity. METHODS: In this case series, all cases of REAH diagnosed between 2006 and 2011 were reviewed. Clinical presentation, histologic and radiographic features, and operative findings were examined. RESULTS: There were 45 patients 19 females and 26 males, with a mean age of 55.9 years (range, 23-83). Most cases of REAH (33/45, 73%) were found in association with another pathologic process (sinonasal polyposis, adenoiditis, hereditary hemorrhagic telangiectasia [HHT], inverted papilloma [IP], or malignancy). Of these, REAH occurring among diffuse polyposis (79% of cases) represented the large majority. The average Harvard computed tomography (CT) stage for this cohort was 3.1. The other presentation of REAH (12/45, 27%) was an isolated sinonasal mass. In cases of isolated REAH, the majority of lesions (75%) were noted to be originating in the olfactory clefts. CONCLUSION: Isolated REAH, which may mimic a neoplasm, appears to be a different clinical entity than the more common form encountered in association with nasal polyps and inflammation. Further investigation into the etiology and clinical significance is needed.

Middle ear adenomas stain for two cell populations and lack myoepithelial cell differentiation.

Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining for myoepithelial markers has not been reported in these tumors. The archives of the Cleveland Clinic, University of Virginia and Armed Forces Institute of Pathology were retrospectively searched for tumors arising within the middle ear with material available for IHC staining. Twelve cases of MEAs, four cases of jugulotympanic paragangliomas (JPGs), 10 cases of ceruminous adenomas (CAs) and four cases of ceruminous adenocarcinomas (CACs) were obtained. IHC staining was performed for smooth muscle actin (SMA), p63, S-100 protein, cytokeratin 5/6 (CK5/6), and cytokeratin 7 (CK7). The MEAs were positive for: CK7 (92 %, luminal), CK5/6 (92 %, abluminal), p63 (83 %, abluminal), and negative for SMA and S-100 protein. The JPGs were negative for CK7, CK5/6, p63 and SMA; S-100 protein highlighted sustentacular cells. The CAs were positive for: CK7 (100 %, luminal), CK5/6 (100 %, abluminal), S-100 protein (80 %, abluminal), p63 (100 %, abluminal), and SMA (90 %, abluminal). CACs demonstrated two patterns, (1) adenoid cystic carcinoma-type: positive for CK7 (100 %, luminal), CK5/6, S-100 protein, p63, and SMA (all 100 %, abluminal); and (2) conventional-type: CK7 (50 % luminal), and no CK5/6, SMA, S-100 protein, or p63 expression. The IHC profile of MEAs suggests that these tumors harbor at least two cell populations, including luminal and basal cells. However, unlike ceruminous adenomas, MEAs lack true myoepithelial differentiation given the absence of S-100 protein and SMA staining in all cases.

Clear cell carcinoma and clear cell odontogenic carcinoma: a comparative clinicopathologic and immunohistochemical study.

Clear cell carcinoma or hyalinizing clear cell carcinoma (CCC) and clear cell odontogenic carcinoma (CCOC) are rare, low-grade and typically indolent malignancies that can be diagnostically challenging. In this study the clinicopathologic, histologic, and immunohistochemical features of 17 CCCs and 12 CCOCs are examined. The differential diagnosis of clear cell malignancies in the head and neck is discussed. The relationship of CCCs and CCOCs to other clear cell tumors on the basis of their immunohistochemical staining patterns is postulated.

Does HPV have a presence in diffuse high grade pre-malignant lesions of the larynx?

OBJECTIVE: To describe the incidence of HPV in diffuse high grade pre-cancerous lesions of the larynx. METHODS: Patient charts were searched for those who presented between October 2008 and June 2009 with diffuse vocal fold leukoplakia. Biopsy proven laryngeal lesions with high grade dysplasia or carcinoma-in-situ (CIS) were examined for patient characteristics and presence of high-risk type HPV detected by in situ hybridization technique. RESULTS: Fifteen patients with precancerous lesions were identified. Average age was 63 years and 13 were male. One lesion was identified as positive for high-risk HPV, all other lesions were negative. At current follow up, no patient has demonstrated progression to invasive carcinoma. CONCLUSION: HPV may not play a role in non-progressing diffuse high-grade lesions of the larynx.

New variants of epithelial-myoepithelial carcinoma: oncocytic-sebaceous and apocrine.

CONTEXT: Recently described variants of epithelial-myoepithelial carcinoma have not been well characterized but raise a distinct set of differential diagnostic considerations than the classic type. OBJECTIVE: To report a detailed analysis of oncocytic-sebaceous epithelial-myoepithelial carcinoma (OEMCa) and a similar, but novel, variant, apocrine epithelial-myoepithelial carcinoma (ApEMCa). DESIGN: Clinical, histologic, and immunophenotypic features of 5 OEMCas and 5 ApEMCas were analyzed. Ultrastructural examination was also performed on 3 OEMCa and 1 ApEMCa tumors. RESULTS: The mean age for OEMCa (74.4 years; range, 58-82 years) was slightly higher than for ApEMCa (61.6; range, 46-79 years). All tumors arose in the parotid glands and demonstrated a multinodular pattern of growth with an average size of 3.3 cm (range, 2.3-6.5 cm). Available follow-up (n = 6; 3 OEMCas, 3 ApEMCas) shows a favorable course (no evidence of disease; mean, 17.4 months). Both were morphologically similar, but only OEMCa had sebaceous elements. Phosphotungstic acid hematoxylin staining, antimitochondrial antibody immunohistochemistry, and ultrastructural examination confirm the abundance of mitochondria in OEMCa but not in ApEMCa. The ductal component in ApEMCa was distinguished from that of OEMCa by apical snouts, intracytoplasmic vacuoles, nuclear pleomorphism, prominent nucleoli, and androgen receptor immunoreactivity. CONCLUSIONS: Oncocytic-sebaceous epithelial-myoepithelial carcinoma and ApEMCa should be considered in the differential diagnosis of oncocytic/oncocytoid salivary gland tumors. Oncocytic-sebaceous epithelial-myoepithelial carcinoma morphology may reflect a senescent phenotype, similar to other oncocytic lesions. The ductal component of ApEMCa shares some similarities with salivary duct carcinoma and supports the notion that epithelial-myoepithelial carcinoma can serve as the progenitor tumor for hybrid tumors.

The T1799A BRAF mutation is absent in cribriform-morular variant of papillary carcinoma.

CONTEXT: Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is one of the rare types of papillary carcinoma. It has been associated with familial adenomatous polyposis, though it can also occur sporadically. The molecular pathogenesis of this tumor is incompletely understood. It appears that there can be molecular contributions from the RET/PTC translocations and from mutations in the APC gene and beta-catenin gene, which are both part of the Wnt signaling pathway. However, one of the most common mutations in papillary carcinoma, the BRAF mutation, has not been reported in this variant of papillary carcinoma. OBJECTIVE: To investigate the BRAF mutational status in CMVPTC. DESIGN: Four cases of CMVPTC (1 associated with familial adenomatous polyposis and the others apparently sporadic) were identified from the files of 3 large centers. Deoxyribonucleic acid was extracted and successfully amplified from each case. The polymerase chain reaction products were sequenced and evaluated for the T1799A BRAF mutation. RESULTS: None of the 4 cases harbored the T1799A BRAF mutation (0/4). Conclusions.-The T1799A BRAF mutation does not appear to play a role in the tumorigenesis of CMVPTC.

Oncocytic mucoepidermoid carcinoma: clinicopathologic description in a series of 12 cases.

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Oncocytic MEC (OMEC) has been rarely reported with previous cases suggesting they are largely cystic low-grade neoplasms with a favorable prognosis. The differential diagnosis of OMEC includes numerous oncocytic/"oncocytoid" neoplasms. Some are benign while others are aggressive. Recent evidence suggests that p63 is a reliable marker in the diagnosis of conventional MEC but has not been explored in OMEC. We searched the archives of various institutions for examples of OMEC to re-appraise the grade, and to evaluate p63 immunohistochemistry as a tool to separate OMEC from its potential mimics. A total of 12 cases were identified. There were 6 males and 6 females with an age range of 30 to 79 years. Most occurred in the parotid (9) with 1 each in the sublingual gland, hard palate and neck. They showed minimal cystic content and were infiltrative and solid tumors spanning all grades. All tumors had focal mucin production and were composed almost exclusively of oncocytic cells with 2 cases demonstrating conventional MEC areas. All 6 cases tested showed the majority of oncocytic cells staining with p63 in a diffuse pattern, demonstrating its utility in the diagnosis of OMEC. Of the 6 cases with follow-up information, 1 case had local recurrence 8 years after the initial surgery. Three cases showed skin or bone invasion. None had lymph node/distant metastases. In summary, OMEC behaves as a low-grade tumor, and is diffusely positive for p63, which may aid in its differential diagnosis.

Immunohistochemical evaluation of androgen receptor, HER-2/neu, and p53 in benign pleomorphic adenomas.

CONTEXT: Immunohistochemical stains for androgen receptor (AR), HER-2/neu, and p53 are used as diagnostic markers associated with malignancy in several histologic types of salivary gland tumors. These markers may be useful in differentiating pleomorphic adenoma with cytologic atypia from intracapsular carcinoma ex pleomorphic adenoma (CXPA), as these tumors are often difficult to distinguish on the basis of morphology alone. OBJECTIVE: To determine whether AR, HER-2/neu, and p53 expression can be seen in entirely benign pleomorphic adenomas. DESIGN: Androgen receptor, HER-2/neu, and p53 immunoreactivity was assessed in 41 histologically and clinically benign pleomorphic adenomas. RESULTS: A total of 3 of 41 pleomorphic adenomas exhibited multifocal areas with moderate staining for HER-2/ neu and AR. The positive staining was mainly confined to the epithelial component, where the ductal epithelium showed no cytologic atypia. Immunoreactivity for p53 was observed in the epithelial component of 5 of 41 cases, none of which stained for HER-2/neu and AR. Mean mitotic rate and Ki-67 index were 1 per 10 high-powered fields and 2.7% in HER-2/neu- and AR-positive cases and 1 per 10 high-powered fields and 2.2% in p53-positive cases. CONCLUSIONS: HER-2/neu, AR, and p53 are expressed in a subset of histologically and clinically benign pleomorphic adenomas. These markers cannot be used to reliably predict early carcinomatous transformation in pleomorphic adenoma.