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.

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.

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.

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.

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.

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.

Polymorphous low grade adenocarcinoma: a clinicopathologic study of 164 cases.

BACKGROUND: Polymorphous low grade adenocarcinomas (PLGA) are minor salivary gland neoplasms with a predilection for intraoral sites. METHODS: One hundred sixty-four cases of PLGA diagnosed between 1970-1994 were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Histologic features were reviewed, immunohistochemical studies and prognostic markers were performed, and patient follow-up was obtained. The data were analyzed statistically. RESULTS: The patients included 109 women and 55 men, ages 23-94 years (average, 57.6 years). The patients usually presented clinically with a palatal mass that ranged in size from 0.4-6 cm (average, 2.2 cm). The tumors were infiltrative and characterized by a polymorphous growth pattern, with individual tumors demonstrating multiple patterns, including solid, ductotubular, cribriform, trabecular, and single file growth. Neurotropism was identified frequently. The neoplastic cells were isomorphic with vesicular nuclei. Mitotic activity was inconspicuous. At an average of 115.4 months after presentation, approximately 97.6% of all patients were either alive or had died without evidence of recurrent disease after treatment with surgical excision only. Four patients had evidence of disease at last follow-up; three had died with evidence of tumor, and one patient was alive with tumor. CONCLUSIONS: PLGA is a neoplasm of minor salivary gland origin that must be separated from adenoid cystic carcinoma and benign mixed tumor for therapeutic and prognostic considerations. Conservative but complete surgical excision is the treatment of choice for these slow-growing tumors with a low proliferation index; adjuvant therapy does not appear to alter the prognosis.

Exophytic and papillary squamous cell carcinomas of the larynx: A clinicopathologic series of 104 cases.

Exophytic and papillary squamous cell carcinomas (SCCs) are uncommon variants of SCC of the upper aerodigestive tract mucosa. The histomorphologic distinction between these variants has not been previously attempted or correlated with prognostic outcome. One hundred four cases of exophytic and papillary SCCs of the larynx were identified in the files of the Armed Forces Institute of Pathology from 1971 to 1991. The patients included 25 women and 79 men, aged 27 to 89 years (average 60.7 years). Patients had hoarseness at presentation, and many patients were using tobacco (n = 87) and/or alcohol (n = 49). Tumors measured up to 6 cm in greatest dimension. The larger tumors were associated with vocal cord impairment (n = 39). Histologically, the SCCs were divided into 2 growth patterns: papillary-frond (n = 12) or broad-based, exophytic (n = 92). Patients were treated with excisional biopsy, vocal cord stripping, and/or laryngectomy, in conjunction with radiation therapy (n = 70). Eighty-seven patients had no evidence of disease at last follow-up (average follow-up 8.6 years). Seventeen patients with an exophytic pattern died with disease (10 disseminated disease; 7 local disease). No patients with papillary patterns died of disease, although there had been 4 recurrences. In conclusion, patients with papillary and exophytic SCCs have a better prognosis than those with conventional SCCs, and the prognosis for those with papillary SCCs is even better.

Schneiderian papillomas of the pharynx.

Sixteen cases of schneiderian-type mucosal papillomas arising in the nasopharynx and oropharynx are reported. The patients include 11 men and 5 women ranging in age from 45 to 79 years (median 62 years). In 12 patients, the papilloma was discovered as an incidental finding, and 2 patients complained of nasal airway obstruction. In the remaining 2 cases, information regarding the cause that led to discovery was unavailable. None of the patients had a prior or concurrent history of sinonasal (schneiderian) papillomas. Histologically, all of the tumors were identical to sinonasal inverted papillomas. Transnasal or transoral surgical excision was the treatment of choice. In 4 of the patients, recurrent tumor occurred within 6 months of initial resection, necessitating additional surgery. Extended follow-up information was available in 9 cases. Eight of the 9 patients are alive and have been free of disease over periods ranging from 15 to 201 months (median 114 months) from diagnosis. One patient was found to have a separate nasopharyngeal squamous cell carcinoma 14 months after the diagnosis of the schneiderian-type papilloma. This patient died secondary to the squamous cell carcinoma 30 months after his initial evaluation.

Basaloid squamous cell carcinoma of the sinonasal tract.

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a high grade, aggressive variant of squamous cell carcinoma with a predilection for the larynx, hypopharynx, tonsils, and base of the tongue. To the authors' knowledge, BSCC originating in the nasal cavity and paranasal sinuses rarely has been reported. METHODS: Fourteen cases of BSCC involving the nasal cavity and paranasal sinuses were identified in the files of the Otolaryngic-Head and Neck Pathology Tumor Registry of the Armed Forces Institute of Pathology from 1975-1997. Clinical records and follow-up were available in all cases. Paraffin blocks were available for histochemical and immunohistochemical studies in all cases. RESULTS: There were 7 females and 7 males, ages 32-86 years (median, 66.5 years; mean, 62 years). The patients presented primarily with a mass lesion and unilateral nasal obstruction. In nine patients the tumor was confined to the nasal cavity. In three patients the tumor involved the sinuses alone and in two patients the tumor involved the nasal cavity and paranasal sinuses. Histologically, the tumors were widely invasive with a variety of growth patterns, including lobular, solid, trabecular, cribriform, and fascicular. The neoplastic infiltrate included predominantly pleomorphic, basaloid-appearing cells with hyperchromatic nuclei, inconspicuous to prominent nucleoli, and a variable amount of eosinophilic to clear-appearing cytoplasm. Mitotic figures, including atypical forms, were readily apparent as was necrosis (individual cell and comedo-type). Foci of squamous differentiation were limited in extent but were found in all cases and included squamous whorls, individual cell keratinization, and intercellular bridges. Intraepithelial dysplasia, carcinoma in situ, or invasive squamous carcinoma was present in all cases. Other histologic features included intercellular stromal hyalinization and peripheral nuclear palisading. In two cases, neural-type rosettes were found. Immunoreactivity for a variety of epithelial markers including cytokeratin (AE1/AE3/LP34), CAM 5.2, 34betaE12, CK7, and epithelial membrane antigen was present in all cases. Variable reactivity was present with vimentin, actins (smooth muscle and muscle specific), neuron specific enolase, S-100 protein, glial fibrillary acidic protein, CK20, carcinoembryonic antigen, Leu7, and Ewing's marker. Chromogranin, synaptophysin, neurofibrillary protein, leukocyte common antigen, HMB-45, desmin, and Epstein-Barr virus latent membrane protein were absent. Surgical resection was the treatment of choice. Eight patients had recurrent or persistent tumor and metastatic disease occurred in five patients. At last follow-up, 7 patients (50%) had died of disease with a median survival of 12 months from the time of diagnosis and 3 patients were alive with disease over periods ranging from 8 months-5 years. Of the 4 remaining patients, 2 were alive without disease at 1 month and 5 years, respectively, 1 patient was lost to follow-up with no evidence of tumor at 3 years, and 1 patient had died of unrelated causes with no evidence of disease. CONCLUSIONS: Sinonasal BSCC is a histologically distinct variant of squamous cell carcinoma with pathologic features and aggressive biologic behavior similar to BSCC localized to more common mucosal sites of the upper aerodigestive tract.

Primary ameloblastoma of the sinonasal tract: a clinicopathologic study of 24 cases.

BACKGROUND: Ameloblastomas are locally aggressive jaw tumors with a high propensity for recurrence and are believed to arise from the remnants of odontogenic epithelium. Extragnathic ameloblastomas are unusual and primary sinonasal tract origin is extraordinarily uncommon. METHODS: Twenty-four cases of ameloblastoma confined to the sinonasal tract were retrieved from the Otorhinolaryngic-Head & Neck Pathology and Oral-Maxillofacial Pathology Tumor Registries of the Armed Forces Institute of Pathology between 1956 and 1996. RESULTS: The patients included 5 females and 19 males with an age range of 43-81 years, with a mean age at presentation of 59.7 years. The patients presented with an enlarging mass in the maxillary sinus or nasal cavity (n = 24), sinusitis (n = 9), or epistaxis (n = 8). Unilateral opacification of the maxillary sinus (n = 12) was the most common radiographic finding. Histologically, the tumors exhibited the characteristic features of ameloblastoma, including peripherally palisaded columnar cells with reverse polarity. The majority of the tumors showed a plexiform growth pattern. Fifteen tumors demonstrated surface epithelial derivation. Surgical excision is the treatment of choice, ranging from conservative surgery (polypectomy) to more aggressive surgery (radical maxillectomy). Five patients experienced at least 1 recurrence, usually within 1 year of initial surgery. With follow-up intervals of up to 44 years (mean, 9.5 years), all 24 patients were alive without evidence of disease or had died of unrelated causes, without evidence of disease. CONCLUSIONS: Primary ameloblastoma of the sinonasal tract is rare. In contrast to their gnathic counterparts, sinonasal tract tumors have a predilection for older age men. Therapy should be directed toward complete surgical resection to prevent local tumor recurrence.

Thyroid papillary carcinoma of columnar cell type: a clinicopathologic study of 16 cases.

BACKGROUND: Thyroid papillary carcinoma of columnar cell type is considered an uncommon histologic subtype of papillary carcinoma characterized by its morphologic features and purportedly aggressive biologic course. METHODS: Sixteen cases of thyroid papillary carcinoma of columnar cell type were identified from the Endocrine Tumor Registry at the Armed Forces Institute of Pathology and the Washington Hospital Center. Clinical records and follow-up were available in all cases. Paraffin blocks were available for histochemical and immunohistochemical studies in 15 of the 16 cases. RESULTS: Of the 16 cases reported, 13 patients were female and 3 were male. The ages ranged from 16-76 years (average, 47 years; median, 40 years). An asymptomatic neck mass was the most common clinical presenting symptom. Macroscopically, the tumors varied from circumscribed or encapsulated to infiltrative, ranging in size from 1.5-6.5 cm. Histologically, the tumors had diverse growth patterns, including papillary, solid, microfollicular, and cribriform. A common pattern was the presence of markedly elongated follicles arranged in parallel cords. Colloid-filled follicles could be found, at least focally, in all cases. The characteristic histologic appearance included the presence of elongated cells showing nuclear stratification. Other features included the presence of vacuolated-appearing cells, spindle-shaped cells, and squamoid nests. Limited areas in the tumors showed morphologic features typical of thyroid papillary carcinoma. In 14 of the cases, the tumor was encapsulated, showed limited invasive growth, or was a microscopic tumor. In two of the cases, there was extrathyroidal invasion. Immunohistochemical studies showed consistent reactivity with cytokeratin and vimentin; varied reactivity with thyroglobulin, epithelial membrane antigen, carcinoembryonic antigen, and LeuM1; and no reactivity with calcitonin or chromogranin. Treatment was by surgical resection; supplemental radioactive iodine therapy was administered in eight patients. Follow-up was available for all patients, 13 of whom (81%) were alive and free of disease or had died of unrelated causes over periods ranging from 2-11 years (average, 5.8 years). All 13 of these patients had tumor confined completely to the thyroid gland. One patient died 4 months after diagnosis secondary to sepsis. Two patients (17%) had aggressive biologic courses. In both patients there was extrathyroidal invasion. One of these patients died of metastatic disease to the lungs 3 years after diagnosis; the other was alive with bilateral pulmonary metastases 9 years after the diagnosis. CONCLUSIONS: The findings of the current study indicate that thyroid papillary carcinoma of columnar cell type is a distinct morphologic type but not a distinct clinical type of thyroid papillary carcinoma. The biologic behavior of this tumor is predicated on clinical stage, with the presence or absence of extrathyroidal invasion being the single most important parameter. Treatment of patients with these tumors should be based on the clinical stage and not on the morphologic appearance.

Fibro-osseous, osseous, and cartilaginous lesions of the orbit and paraorbital region. Correlative clinicopathologic and radiographic features, including the diagnostic role of CT and MR imaging.

Fibro-osseous and cartilaginous lesions of the orbit and facial region share overlapping clinical, radiologic, and pathologic features that may lead to diagnostic confusion and possible misdiagnosis. The value of imaging studies in the histopathologic diagnosis of these lesions cannot be overemphasized. The histopathologic diagnosis of such lesions should not be rendered in the absence of radiographic correlation.