E. Leon Barnes

Quantitative immunohistochemical analysis of transforming growth factor-α and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck

Transforming growth factor‐α (TGF‐α) and epidermal growth factor receptor (EGFR) mRNA are up‐regulated in squamous cell carcinoma of the head and neck (SCCHN) tissues.

Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract.

To further define the clinicopathologic spectrum of epithelial-myoepithelial carcinoma (EMCa), we report the gross, histologic, and immunophenotypic characteristics of 61 tumors seen within a 30-year-period. The mean age at presentation was 60.9 years, with a female predominance (1.5:1). The most common sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%), and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. However, new morphologies in EMCa such as ancient change (8.2%), “Verocay”-like change (3.3%), and sebaceous differentiation (13.1%) were noted. Specific histologic variants were dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%). All cytokeratin cocktails selectively highlighted the epithelial component well. Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively). p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was 36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and 10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most important univariate predictors of recurrence were margin status (log rank P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with a broader morphologic spectrum than previously thought, with several key features predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting the biphasic nature of the tumor.

Management of inverted papilloma

This paper updates a 1981 report on the management of inverted papilloma. In that report, routine lateral rhinot‐omy with en bloc resection of the lateral nasal wall, including the entire schneiderian membrane, was recommended. This report emphasizes the use of computed tomography scanning in management planning.

Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.

High-grade transformation of adenoid cystic carcinoma (ACC) (previously referred to as dedifferentiation) is a rare phenomenon that does not fit into the traditional ACC grading schemes. The importance and minimal criteria for distinction from solid (grade III) ACC are not well established. We report 11 new cases and review the literature to further define the profile of this tumor. The median age was 61 years (range: 32 to 72 y) with a male predominance (male to female ratio of 1.75:1). The most commonly involved sites were sinonasal (4/11) and submandibular (4/11). Lymph nodes were pathologically positive in 4/7 (57.1%) cases. Distant metastases to the lung (n=2) and soft tissue of the shoulder (n=1) were observed. Five of 9 patients (55.6%) died, all within 5 years with a median overall survival of 12 months. Histologically, ACC with high-grade transformation was distinguished from conventional ACC by nuclear enlargement and irregularity, higher mitotic counts, and the loss of the biphasic ductal-myoepithelial differentiation. Useful supportive criteria were prominent comedonecrosis and fibrocellular desmoplasia. The most common morphologies for the high-grade component were poorly differentiated cribriform adenocarcinoma and solid undifferentiated carcinoma. Micropapillary and squamoid patterns were occasionally present. Ki-67 and p53 labeling indices were elevated in the high-grade components, though c-kit and cyclin-D1 were not. ACC–high-grade transformation is a highly aggressive salivary gland tumor with a variety of histologic patterns. The high propensity for lymph node metastases suggests a role for neck dissection in patients with this rare tumor.

Management of inverted papilloma of the nose and paranasal sinuses

Inverted papilloma of the nose and paranasal sinuses is a neoplastic growth of epithelium which inverts into the underlying stroma rather than proliferating outward from the surface. These neoplasms probably arise from the area of the lateral nasal wall. Inverted papilloma is characterized by its: A. capacity to destroy; B. tendency to recur; and C. association with malignancy.

Sjögren's syndrome in progressive systemic sclerosis.

Thirty-five consecutive patients with progressive systemic sclerosis were prospectively evaluated for evidence of Sjögrens syndrome. Six of the 35 (17%) were judged to have the disorder. This is a higher prevalence than in most reports, but much lower than that recently reportedly by Alarcón-Segovia and associates (7). An additional 17 of the 35 patients (48%) had significant fibrosis in the absence of sufficient mononuclear cell infiltrates to confirm the diagnosis of Sjögrens syndrome. This group had particularly aggressive scleroderma with serious visceral features, and five died after a short duration of illness. No significant abnormalities were found in biopsies from six patients with the mixed connective tissue disease syndrome, five with Raynauds phenomenon alone, or in 29 autopsy control subjects who had no evidence of connective tissue disease. Fibrosis in the absence of mononuclear infiltration in minor salivary glands of patients with progressive systemic sclerosis indicates a poor prognosis.

Ceruminous adenomas: A clinicopathologic study of 41 cases with a review of the literature

Background:Ceruminous gland neoplasms are rare neoplasms. To date, a large clinicopathologic study of benign ceruminous gland neoplasms has not been reported. Design:Forty-one cases of ceruminous gland adenomas diagnosed between 1970 and 2000 were retrieved from the files of the Armed Forces Institute of Pathology. Histologic features were reviewed, immunohistochemical analysis was performed (n = 21), and patient follow-up was obtained (n = 40). Results:The patients included 22 men and 19 women, 24 to 85 years of age (mean, 54.2 years). Patients presented clinically with a painless mass of the outer half of the external auditory canal (n = 33) or with hearing changes (n = 11). Symptoms were present for an average of 16.3 months. The polypoid masses affected the external auditory canal only and ranged in size from 0.4 to 2 cm in greatest dimension (mean, 1.1 cm). Histologically, the tumors demonstrated glands and small cysts lined by a tubuloglandular proliferation of inner ceruminous cells (cerumen-secreting epithelium with decapitation secretion) subtended by a spindled to cuboidal myoepithelial layer. A hyalinized stroma created an infiltrative pattern of growth; surface involvement (n = 8) was seen. Tumors were divided into ceruminous adenoma (n = 36), ceruminous pleomorphic adenoma (n = 4), and syringocystadenoma papilliferum (n = 1) types. The luminal cells were strongly and diffusely immunoreactive with CK7, while the basal cells were highlighted with CK5/6, S-100 protein, and p63. CD117 highlighted the luminal cells preferentially. The proliferation markers revealed a low index. Adenocarcinoma and middle ear adenoma are the principal differential consideration. Surgical excision was used in all patients. Four patients developed a recurrence due to incomplete excision. All patients were without evidence of disease at the last follow-up: alive (n = 28, mean 16.3 years) or dead (n = 12, mean 11.8 years). Conclusion:Ceruminous gland adenomas are the most common external auditory canal tumors. They demonstrate a dual cell population of basal myoepithelial-type cells and luminal ceruminous (ceruminal) cells. Cerumen pigment, CK7, and p63 can help to distinguish this tumor from other neoplasms that occur in the region. Complete surgical excision results in an excellent long-term clinical outcome.

Update on selected salivary gland neoplasms

CONTEXT Malignancies of the salivary gland are uncommon and account for 0.3% of all malignancies. In addition to their rarity, diagnosing these tumors can be challenging given the histologic overlap among various subtypes, their morphologic heterogeneity, and the recent recognition of new entities. OBJECTIVE To provide an overview of 4 salivary gland malignancies that we often see in consultation, with a focus on essential diagnostic features and the importance of reporting pertinent diagnostic information to ensure appropriate clinical management. DATA SOURCES Review of the literature, supplemented by the personal experience of the authors, which is based on their respective institutional experiences and consultation services. CONCLUSIONS When diagnosing carcinoma ex pleomorphic adenoma, pathologists must report several important pieces of information to allow for optimal clinical management. In addition to histologic subtype, the degree of differentiation as well as the degree of invasion, if any, must be reported because all have prognostic relevance. Polymorphous low-grade adenocarcinoma can be a challenging diagnosis on biopsy specimens. Evaluation of the tumor periphery and nuclear features should lead to the correct diagnosis in most cases. Salivary duct carcinoma is an aggressive malignancy characterized by histologic resemblance to breast carcinoma, high-grade cytologic features, and expression of androgen receptor. Benign and malignant myoepithelial neoplasms have a broad morphologic spectrum, and immunohistochemistry is important in reaching the correct diagnosis.

Cranial base surgery. Results in 183 patients

ObjectiveTo learn about the effects of cranial base surgery.DesignCohort study with a mean follow-up of 30 months.SettingPopulation-based.PatientsA consecutive sample of 183 patients who underwent cranial base surgery; 118 patients had malignant skull base tumors, majority were previously treated; 50 had benign tumors, 9 patients had congenital malformations of the skull base; 3 patients had inflammatory lesions, and 3 had traumatic defects of the skull base.Main outcome measuresDisease-free interval and overall survival as well as rate of complications and functional statusInterventionCranial base surgery was followed by radiotherapy (in previously untreated patients).ResultsAfter completion of follow-up (30 months, mean), 30 (25.4%) patients had died of their malignant tumors and 8 (6.8%) had died of other causes. One patient (0.84%) was lost to follow-up. The overall cancer survival without regard to histologic type was 67% (63% with no evidence of disease). Among the patients who were treated for benign neoplasm 72% were NED at a mean 39 months of follow-up. The group of patients with congenital malformations, inflammatory, and traumatic lesions demonstrated successful correction of their pre-surgical problem with skull base surgery. One patient (invasive aspergillosis) died of disease. The overall surgical/medical mortality was 2%, complication rate was 33% and Karnofsky performance scale was improved or unchanged postoperatively in 83% of patients. The average duration of surgery, number of blood transfusions used and the length of the hospital stay was 10 hours, 3 units, and 15 days respectively.ConclusionsCranial base surgery is a valid surgical technique for cranial base afflictions. In this study it was found to be beneficial in controlling benign as well as malignant disease and be the treatment of choice in selected congenital malformations, trauma, and inflammatory lesions.

Molecular evidence of anaplastic transformation in coexisting well-differentiated and anaplastic carcinomas of the thyroid

Anaplastic thyroid cancer is a rare but nearly universally fatal tumor. Epidemiologic data suggest that many anaplastic thyroid carcinomas arise from transformation of preexisting or coexisting well-differentiated thyroid carcinomas. At the molecular level, the mutations responsible for the anaplastic transformation are incompletely understood, although the mutational events are thought to involve tumor suppressor genes. To examine transformation from a well-differentiated thyroid carcinoma to anaplastic carcinoma, we studied coexisting well-differentiated (Hürthle cell and papillary carcinoma) and anaplastic tumors with a molecular genotyping panel of tumor suppressor genes associated with thyroid neoplasia. The patterns of allelic loss in our results showed that the majority of cases have a core of conserved mutations in the two morphologically distinct areas and substantial increases in mutation rates in the anaplastic components.