Aaron P. Hoschar

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.

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

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.

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

Aims:  To describe seven cases of sinonasal seromucinous hamartoma.

p63 Immunohistochemistry Differentiates Salivary Gland Oncocytoma and Oncocytic Carcinoma from Metastatic Renal Cell Carcinoma

Metastatic renal cell carcinoma (RCC) can pose diagnostic challenges in the head and neck often resembling benign and malignant oncocytic lesions. Immunohistochemical panels have been reported to help with this differential but are not entirely specific or sensitive. We have noticed that p63 routinely stains salivary gland oncocytomas but not metastatic RCC. Nineteen oncocytomas, 9 cases of oncocytosis, 9 oncocytic carcinomas and 16 head and neck metastatic RCC were studied. Morphologic features evaluated were cytoplasmic character (clear versus oncocytic), Fuhrman nuclear grade, mitotic rate, growth pattern, presence of lumens/blood lakes and stromal characteristics. Tumors were stained with antibodies to p63, renal cell carcinoma marker (RCCm), CD10, and vimentin. Eight benign oncocytic tumors (29%) had clear cell features while 6 metastatic RCC (37%) had oncocytic features. Median Fuhrman nuclear grade was 2 in oncocytoma and oncocytosis and 3 both oncocytic carcinoma and metastatic RCC. Mitotic rates were only significantly different between benign oncocytic tumors and metastatic RCC. All oncocytomas had lumina compared to half of metastatic RCC, all of which also demonstrated blood lakes. Seven benign oncocytic tumors (25%) and 5 oncocytic carcinomas (56%) had RCC-like vascular stroma. All primary salivary gland tumors were positive for p63, predominately in basal cell-type distribution. None of the metastatic RCC was positive. RCCm was entirely specific but lacked sensitivity for metastatic RCC while CD10 and vimentin showed variable sensitivity and specificity. While clinical history and morphology usually are adequate, demonstration of p63 staining can definitively exclude metastatic RCC from the differential diagnosis of similar appearing tumors in salivary glands, namely oncocytoma and oncocytic carcinoma, with 100% specificity and sensitivity. While RCCm, CD10, and vimentin performed adequately, they were significantly less reliable than p63 with both false positives and false negatives.

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.

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.

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.

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.

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.