Salivary acinic cell carcinoma: reappraisal and update.

Epidemiologic and clinicopathologic features, therapeutic strategies, and prognosis for acinic cell carcinoma of the major and minor salivary glands are critically reviewed. We explore histopathologic, histochemical, electron microscopic and immunohistochemical aspects and discuss histologic grading, histogenesis, animal models, and genetic events. In the context of possible diagnostic difficulties, the relationship to mammary analog secretory carcinoma is probed and a classification is suggested. Areas of controversy or uncertainty, which may benefit from further investigations, are also highlighted.

Differential expression of p16(INK4A) and cyclin D1 in benign and malignant salivary gland tumors: a study of 44 Cases.

Salivary gland tumors (SGT) are a heterogeneous group of lesions. There is conflicting data concerning the molecular events involving the tumour suppressor retinoblastoma protein (pRb) pathway in these tumors. Few studies examined the alterations in components of the Rb pathway by immunohistochemical (IHC) methods in benign and malignant SGTs. Furthermore, recent evidence implicates human papillomavirus (HPV) in mucoepidermoid carcinoma (MEC) carcinogenesis. The purpose of our study is to examine p16(INK4A) and cyclin D1 expression in a variety of benign and malignant salivary gland tumors, and to investigate p16(INK4A) expression as a surrogate marker for HPV infection in MEC. Our series includes 30 malignant tumors [14 MEC, 6 acinic cell carcinomas (ACC), 5 polymorphous low grade adenocarcinomas (PLGA), 5 (AdCC)] and 14 benign tumors (4 benign cysts, 5 Warthin tumors and 5 pleomorphic adenomas (PA). All cases were tested by IHC for p16(INK4A) and cyclin D1. Testing for HPV wide spectrum (HPV-WS) was performed by in situ hybridization in all MEC cases. Staining intensity was recorded semi quantitatively (on a scale from 0 to 4+). Fisher's exact test and Pearson X2 test with a p < 0.05 were used. Cyclin D1 and p16(INK4A) are expressed similarly in malignant and benign tumors (p = 0.146 and p = 0.543, respectively). None of the MEC cases showed nuclear reactivity for HPV-WS. Statistical analysis showed positive correlation between cyclin D1 and p16(INK4A) expression. Our findings suggest that p16(INK4A) overexpression is likely secondary to cyclin D1 gene upregulation or amplification. Further molecular studies are warranted.

Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience.

BACKGROUND: Locoregionally advanced, stage IV head and neck cancer has traditionally carried a poor prognosis. We sought to assess changes in patterns of failure, prognostic factors for recurrence, and overall outcome, using two different strategies of chemoradiotherapy conducted in prospective, multi-institutional phase II trials. PATIENTS AND METHODS: Three hundred and thirty-seven stage IV patients were treated from 1989 to 1998. We compared locoregional and distant recurrence rates, overall survival and progression-free survival from two different treatment strategies: intensive induction chemotherapy followed by split-course chemoradiotherapy (type 1, n=127), or intensified, split-course, hyperfractionated multiagent chemoradiotherapy alone (type 2, n=210). Univariate and multivariate analyses of 12 chosen covariates were assessed separately for the two study types. RESULTS: The pattern of failure varied greatly between study types 1 and 2 (5-year locoregional failure of 31% and 17% for study types 1 and 2, respectively, P=0.01; 5-year distant failure rate of 13% and 22% for study types 1 and 2, P=0.03). Combined 5-year overall survival was 47% [95% confidence interval (CI) 41% to 53%) and progression-free survival was 60% (95% CI 55% to 66%). Both treatment strategies yielded similar survival rates. Poor overall survival and distant recurrence were best predicted by advanced nodal stage. Locoregional recurrence was extremely rare for patients with T0-T3 tumor stage, regardless of lymph-node stage. CONCLUSIONS: This analysis suggests that pattern of failure in primary head and neck cancer may be dependent upon treatment strategy. Randomized clinical trials of induction chemotherapy are warranted as a means to determine if a decrease in distant metastases can lead to an increase in survival rates in the setting of effective chemoradiotherapy for locoregional control. Additionally, this analysis provides impetus for randomized clinical trials of organ preservation chemoradiotherapy in sites outside the larynx and hypopharynx.

Nodular fasciitis of the external ear region: a clinicopathologic study of 50 cases.

Nodular fasciitis (NF), uncommon in the auricular area, is a benign reactive myofibroblastic proliferation that may be mistaken for a neoplastic proliferation. Fifty cases of NF of the auricular region were identified in the files of the Otorhinolaryngic-Head and Neck Tumor Registry of the Armed Forces Institute of Pathology. The patients included 22 females and 28 males, aged 1 to 76 years (mean, 27.4 years). The patients usually presented clinically with a mass lesion (n = 49). Five patients recalled antecedent trauma. The lesions were dermal (n = 28) or subcutaneous (n = 11) in those cases where histologic determination was possible, measuring 1.9 cm on average. The majority of the lesions were circumscribed (n = 38), composed of spindle-shaped to stellate myofibroblasts arranged in a storiform growth pattern, juxtaposed to hypocellular myxoid tissue-culture-like areas with extravasation of erythrocytes. Dense, keloid-like collagen and occasional giant cells were seen (n = 18). Mitotic figures (without atypical forms) were readily identifiable. By immunohistochemical staining, myofibroblasts were reactive with vimentin, actins, and CD68. All patients had surgical excision. Four patients (9.3%) developed local recurrence and were alive and disease free at last follow-up. All patients with follow-up (n = 43) were alive or had died of unrelated causes, without evidence of disease an average 13.4 years after diagnosis. Nodular fasciitis of the auricular area occurs most often in young patients. Because NF is more often dermally situated than extremity NF, it may present with superficial ulceration and/or bleeding. Local recurrence is more frequent because of the difficulty in obtaining complete surgical excision around the ear.

Adrenal oncocytic pheochromocytoma.

We report a case of adrenal oncoctyic pheochromocytoma in a 37-year-old woman. The patient presented with a 2-year history of an increase in abdominal girth. Computed tomographic studies revealed a large left adrenal mass, which was subsequently excised. Grossly, the tumor measured 17 x 14 x 8.5 cm, weighed 1,150 g, and had a solid, brown cut surface. Histologically, it consisted of large polygonal tumor cells containing eosinophilic granular cytoplasm and arranged in nesting, alveolar, and trabecular patterns. Electron microscopy revealed closely packed mitochondria and dense-core membrane-bound granules in almost all tumor cells. The latter were immunohistochemically positive for chromogranin, synaptophysin, neuron-specific enolase, neurofilament, serotonin, bombesin, ACTH, vimentin, desmin, S-100 protein, and cytokeratins, including AE1/3, CAM 5.2, cytokeratin 7, and cytokeratin 20. To the best of our knowledge, this is the first reported case of adrenal oncocytic pheochromocytoma confirmed by ultrastructural study. The immunoreactivity of this tumor adds several unusual features to the wide immunohistochemical spectrum of pheochromocytoma.

Resection of cancer of the tongue base and tonsil via the transhyoid approach.

OBJECTIVE: To assess whether transhyoid resection of the tongue base and tonsil lesions is an effective approach to tumors involving this region compared with more traditional anterior surgical approaches that arbitrarily involve either segmental resection or division of the mandible. STUDY DESIGN: Retrospective review. METHODS: Since 1988, we have used a combined transhyoid and transoral approach to resect lesions involving the tongue base, tonsil, or both. Forty-one patients were identified who underwent surgical resection of lesions involving this region via this combined approach during this period. A stage-matched group of 41 patients was also identified in which patients underwent resection via traditional composite or mandibulotomy approaches and was used as a basis for comparison. Factors assessed included status of surgical margins, postoperative complications, degree of postoperative dysphagia, and long-term outcome. RESULTS: Comparison between the two groups revealed similar rates of negative surgical margins. Levels of postoperative dysphagia, notably severe primarily in patients with either T4 or recurrent disease, were also similar between groups. Complication rates, especially with regard to fistula occurrence and mandible-healing problems, were significantly lower in the transhyoid group. Analysis of long-term outcome revealed similar patterns with regard to disease status in both groups. CONCLUSIONS: The combined transhyoid and transoral approach is an effective surgical option for a number of lesions affecting the tongue base, tonsil, or both. Although similar to other approaches with regard to postoperative function and disease outcome, the transhyoid approach is associated with decreased postoperative morbidity. However, tumors that extend to involve the mandible or pterygoid musculature or skull base are probably best suited for traditional approaches that involve division of the mandible.

Tonsillar lymphangiomatous polyps: a clinicopathologic series of 26 cases.

BACKGROUND: Lymphangiomatous polyps are uncommon benign tumors of the tonsils. METHODS: Twenty-six cases of lymphangiomatous polyps diagnosed between 1980 and 1999 were retrieved from the files of the Otorhinolaryngic-Head and Neck Tumor Registry of the Armed Forces Institute of Pathology. Hematoxylin and eosin-stained slides were reviewed to characterize the histologic features of these tumors. Immunohistochemical stains were performed on 15 cases. Clinical follow-up data were obtained. RESULTS: The patients included 13 males and 13 females, ages 3 to 63 years (mean, 25.2 years). Patients experienced dysphagia, sore throat, and the sensation of a mass in the throat. Symptoms were present from a few weeks to years. The tonsillar masses were unilateral in all cases. Clinically, the lesions were frequently mistaken for a neoplasm (n = 18 patients). Grossly, all of the lesions were polypoid and measured 0.5 to 3.8 cm (mean, 1.6 cm). Histologically, the polyps were covered by squamous epithelium showing variable epithelial hyperplasia, dyskeratosis, and lymphocytic epitheliotropism. The masses showed a characteristic submucosal proliferation of small to medium-sized, endothelial-lined, lymph-vascular channels lacking features of malignancy. Collagen, smooth muscle, and adipose tissue were present in the stroma. Intravascular proteinaceous fluid and lymphocytes were noted. Immunohistochemical findings confirmed the endothelial origin of the vascular proliferation and a mixed lymphoid population. The differential diagnosis included fibroepithelial polyp, lymphangioma, juvenile angiofibroma, and squamous papilloma. In all patients with follow-up, complete surgical excision was curative (mean follow-up, 5.4 years; range, 1 mo to 14 years). CONCLUSIONS: We detail the clinical and pathologic features of tonsillar lymphangiomatous polyps. These tumors are uncommon and may clinically be mistaken for a malignant neoplasm. The characteristic histologic features should allow for its correct diagnosis and differentiation from similar appearing tonsillar lesions.

Amyloidosis of the larynx: a clinicopathologic study of 11 cases.

Laryngeal amyloidosis (LA) is uncommon and poorly understood, with limited long-term clinicopathologic and immunophenotypic studies in the literature. Eleven cases of LA were retrieved from the files of the Otorhinolaryngic-Head & Neck Tumor Registry from 1953 to 1990. The histology, histochemistry, immunohistochemistry, and follow-up were reviewed. All patients (three women and eight men) presented with hoarseness at an average age of 37.8 years. The lesions, polypoid or granular, measured an average of 1.6 cm and involved the true vocal cords only (n = 4), false vocal cord only (n = 1), or were transglottic (n = 6). An acellular, amorphous, eosinophilic material was present in the stroma, often accentuated around vessels and seromucous glands, which reacted positively with Congo red. A sparse lymphoplasmacytic infiltrate was present in all cases that demonstrated light chain restriction by immunohistochemistry in three cases (kappa = 2, lambda = 1). Serum and urine electrophoreses were negative in all patients. Treatment was limited to surgical excision, including a single laryngectomy. Six patients manifested either recurrent and/or multifocal/systemic disease: two patients with light chain restriction were dead with recurrent disease (mean, 11.1 years); two patients were dead with no evidence of disease (mean, 31.7 years); and two patients were alive, one with light chain restriction and recurrent and multifocal disease (41.6 years) and one with no evidence of disease after a single recurrence (43.4 years). The remaining five patients were either alive or had died with no evidence of disease an average of 32.4 years after diagnosis. No patient developed multiple myeloma or an overt B-cell lymphoma. LA is an uncommon indolent lesion that may be associated with multifocal disease (local or systemic). The presence of an associated monoclonal lymphoplasmacytic infiltrate and recurrent/multifocal disease in the respiratory or gastrointestinal tract of a few cases and the lack of development of a systemic plasma cell dyscrasia or overt systemic B-cell malignancy suggest that some LA may be the result of an immunocyte dyscrasia or tumor of mucosa-associated lymphoid tissue.

Pharyngeal suspension suture with repose bone screw for obstructive sleep apnea.

OBJECTIVE: Multilevel surgery for obstructive sleep apnea syndrome (OSA) may improve success. This study's goal is to prospectively evaluate the feasibility and short-term subjective effectiveness of a new tongue-suspension technique. METHODS: A multicenter nonrandomized open enrollment trial used the Repose device to treat tongue obstruction in 39 snoring and OSA patients. Outcomes include 1- and 2-month subjective reports of general health, snoring, and sleep. RESULTS: Twenty-three patients completed 1 month and 19 completed 2 months of follow-up. In OSA patients, activity level, energy/fatigue, and sleepiness improved. Two-month outcomes were less (activity level, energy/fatigue, and sleepiness). Fewer changes were observed in snorers than in OSA patients. There were 6 complications (18%), including sialadenitis (4), gastrointestinal bleeding (1), and dehydration (1) after the procedure. CONCLUSION: A pharyngeal suspension suture changes subjective outcomes. Improvement is incomplete. The procedure is nonexcisional, but significant complications may occur. Further evaluation is required to demonstrate effectiveness.

Influence of tobacco and alcohol on the stage of laryngeal cancer at diagnosis.

OBJECTIVE: This study sought to examine the influence of cigarette smoking and alcohol consumption on the stage of laryngeal cancer at diagnosis. STUDY DESIGN: A retrospective review of 499 laryngeal cancer patients diagnosed between 1978 and 1997 was conducted. METHODS: Parameters that included smoking history, history of alcohol consumption, and the tumor stage and location at diagnosis were analyzed using the proportional odds model, correlation coefficient, and Student t test. RESULTS: Three hundred sixteen patients met the inclusion criteria, and 180 (56%) had advanced-stage disease at the time of presentation. The statistical model demonstrated a small but significant relationship between tobacco and alcohol on the stage of laryngeal cancer at diagnosis. Patients diagnosed with an advanced-stage tumor (stage III or IV) smoked a significantly greater amount and were more likely to be heavy drinkers than those diagnosed with a localized laryngeal cancer. CONCLUSIONS: Our results demonstrate that for every incremental increase in pack years of smoking, there is a small but measurable increase in the odds that a patient's laryngeal cancer will be stage III or IV at diagnosis. Likewise, being a "heavy" drinker as opposed to a "social" drinker raises the likelihood of an advanced tumor. Given the preventable nature of these risk factors, the moderation of alcohol consumption and cessation of smoking is prudent advice that should be conveyed to all patients.

Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential.

Solid-pseudopapillary tumors are uncommon neoplasms of low malignant potential generally occurring in young women. They often cause few symptoms and may reach a large size by the time they are detected. Degenerative cystic changes are common, and the clinical presentation is often that of a cystic pancreatic tumor. Pathological features include solid, cellular, hypervascular regions without gland formation, and degenerative pseudopapillae. The cells contain eosinophilic granules rich in alpha-1-antitrypsin and the nuclei are typically grooved. Despite its characteristic microscopic appearance, the immunophenotype (positive for vimentin, alpha-1-antitrypsin, and neuron specific enolase) is not specific and does not define a line of differentiation corresponding to any normal pancreatic cell type. Ultrastructural studies have also failed to identify specific differentiated features. Nonetheless, the biological behavior of solid-pseudopapillary tumor is well established. The tumor is indolent, with infrequent metastases to liver or peritoneum and usually long survival, even in the presence of disseminated disease.

Sentinel lymph node radiolocalization in head and neck squamous cell carcinoma.

OBJECTIVES: To determine the feasibility of sentinel node radiolocalization in stage N0 in head and neck squamous cell carcinoma and to gain insight as to whether the sentinel node could be prognostic of regional micrometastatic disease. STUDY DESIGN: A prospective report on the application sentinel node radiolocalization in eight patients with N0 squamous cell carcinoma of the head and neck region. METHODS: For each patient a peritumoral submucosal injection of filtered technetium (99mTc) prepared with sulfur colloid was performed immediately following intubation. After at least 30 minutes, focal areas of accumulation corresponding to a sentinel node were marked on the skin surface. Complete neck dissections were performed, and the sentinel nodes were identified for later histological evaluation and comparison to the remaining lymphadenectomy specimen. RESULTS: Sentinel node radiolocalization accurately identified two or more sentinel lymph nodes in all eight cases. In one patient, two of the three lymph nodes containing micrometastatic disease were sentinel lymph nodes. There was no instance in which sentinel node was negative for micrometastatic disease while being positive in a nonsentinel lymph node. CONCLUSIONS: Accurate localization of the sentinel lymph node using radiolabeled sulfur-colloid is feasible in patients with squamous cell carcinoma of the head and neck region. Although sentinel node radiolocalization in head and neck squamous cell cancer may potentially reduce the time, cost, and morbidity of regional lymph node management, more experience with technique is required before its role can be determined.

Pancreatic mucinous cystic neoplasms with sarcomatous stroma: molecular evidence for monoclonal origin with subsequent divergence of the epithelial and sarcomatous components.

Neoplasms with mixed carcinomatous and sarcomatous growth patterns occur in many organs and tissues. The pathogenesis of these cancers is thought to be either the result of two independent neoplastic processes merging to form a single tumor, or a neoplasm of monoclonal origin that develops phenotypic diversity. To address this issue, we characterized molecular alterations in separately microdissected epithelial and sarcomatous areas in three cases of pancreatic mucinous cystic neoplasms with sarcomatous stroma. Using microsatellite markers for six chromosomal loci commonly deleted in infiltrating ductal adenocarcinomas of the pancreas, we found genetic alterations to be virtually identical between the sarcomatous and epithelial components of two of the three neoplasms. In the third neoplasm, we found allelic losses and retentions to be identical at five of the six chromosomal loci, but at a single locus, we noted allelic loss in the neoplastic epithelial component but not the sarcomatous component. The same neoplasms were also analyzed for activating point mutations in codon 12 of the K-ras gene by using mutant-enriched polymerase chain reaction and allele-specific oligonucleotide hybridization. A K-ras mutation was identified in the epithelial component of one of the three neoplasms (the same tumor with an additional allelic loss in the neoplastic epithelial cells), but the sarcomatous component of this tumor was wild-type at codon 12 of K-ras, as were both components of the other two neoplasms. Overall, these results suggest a monoclonal origin with subsequent divergence of the neoplastic epithelial and sarcomatous portions of these neoplasms.

Salvage treatment for recurrent squamous cell carcinoma of the oral cavity.

BACKGROUND: Squamous cell carcinoma (SCCA) of the oral cavity recurs with a frequency of 25%-48%, a fact that usually portends a poor prognosis. Recent studies have reported salvage cure rates as high as 67%. Investigators have also claimed that restaging recurrent tumors provides useful prognostic information, although this has not been demonstrated with tumors of the oral cavity. The purposes of this study were: (1) to report the patterns of recurrent SCCA of the oral cavity; (2) to examine the benefit of restaging oral cavity tumors, and (3) to compare different treatment modalities in the management of recurrent SCCA of the oral cavity. Materials and Methods Thirty-eight patients who developed recurrent SCCA of the oral cavity were reviewed. Salvage treatment consisted of surgery, chemotherapy, radiation therapy, or a combination of these modalities. Survival analysis was based on the stage of the primary and recurrent tumors and the type of salvage treatment received. RESULTS: The overall recurrence rate was 28%. Local recurrence was most common (58%) followed by locoregional (27%) and regional recurrence (16%). Patients who recurred more than 6 months after completion of their primary treatment had improved survival compared with those who recurred within 6 months of initial treatment. Individuals with stage I-II primary tumors had significantly improved salvage time and total survival time compared with those with stage III-IV primary tumors (p < 0.005 and p < 0.001). Conversely, the stage of the recurrent tumor was not predictive of either improved salvage time or total survival time. Patients who underwent salvage surgery had significantly improved salvage time and total survival time compared with those who received chemotherapy and/or radiation therapy (p < 0.001 and p < 0.002). The overall salvage cure rate was 21%. Neither the stage of the primary or recurrent tumors nor the type of salvage treatment received significantly correlated with an improved cure rate. However, the group of patients who underwent salvage surgery approached a statistically significant improvement in cure rate (p = 0.08). CONCLUSIONS: Squamous cell carcinoma of the oral cavity is most likely to recur at the primary site. The stage of the primary tumor is significantly correlated with survival even after recurrence, but the stage of the recurrent tumor is not significantly correlated with survival. Patients most likely to benefit from retreatment are those who (1) have primary tumors stage I-II, (2) recur greater than 6 months after their initial treatment, and (3) develop recurrences that are amenable to salvage surgery.

Nasopharyngeal carcinoma.

Nasopharyngeal carcinoma represents a morphologic spectrum of neoplasms localized to the nasopharynx and arising from nasopharyngeal epithelium. Nasopharyngeal carcinomas have rather unique clinical, epidemiologic, pathologic, and biologic features. The morphologic spectrum of nasopharyngeal carcinoma includes keratinizing, nonkeratinizing, and undifferentiated subtypes. The separation of these morphologic types is not an academic exercise, but has practical importance relative to differential diagnosis, management, and prognosis. A similar morphologic classification applies to carcinomas arising in the palatine tonsils and the base of tongue. The nasopharynx, palatine tonsils, and base of tongue are collectively designated as Waldeyer's tonsillar tissues. Awareness of the morphologic spectrum of Waldeyer's ring carcinomas may assist in suggesting the primary tumor site in the face of an occult metastatic carcinoma to cervical neck lymph nodes.