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D R Gnepp

Publications and source records attributed to D R Gnepp.

At least 37 records · Page 2Linked to original sources

Dedifferentiated acinic cell carcinoma of the parotid gland: a distinct rarely described entity.

A case of dedifferentiated acinic cell carcinoma of the parotid gland is presented. A 46-year-old man presented with a parotid gland mass. At surgery the tumor was found adherent to the temporal bone and cervical adenopathy was present. Treatment included radical parotidectomy and intraoperative radiotherapy. Histologically, the tumor was a composite of a usual low-grade acinic cell carcinoma and high-grade, poorly differentiated carcinoma. Cervical lymph node metastases were composed entirely of high-grade carcinoma. Immunohistochemically, both low- and high-grade malignant components were negative for p53 oncoprotein expression. Moreover, polymerase chain reaction and nonisotopic single-stranded conformational polymorphism analyses were consistent with a germ line configuration of the p53 gene, exons five through eight, in both low- and high-grade elements of the tumor. The literature on this unusual variant of acinic cell carcinoma is reviewed.

Carcinoma, Acinar Cell↗

Polymorphous low-grade adenocarcinoma: glial fibrillary acidic protein staining in the differential diagnosis with cellular mixed tumors.

Polymorphous low-grade adenocarcinoma is a recently recognized salivary gland carcinoma arising primarily within the oral cavity. Most of these tumors are readily diagnosed; occasionally, however, they may be confused histologically with cellular mixed tumors. The difficulty stems from the bland cytologic nature of cellular mixed tumors and their organizational diversity, together with the irregular pushing growth at their interface with adjacent soft tissues, on histologic examination. Because of this diagnostic problem, we evaluated the use of glial fibrillary acidic protein localization in the differential diagnosis of polymorphous low-grade adenocarcinoma and cellular mixed tumor. Twelve oral polymorphous low-grade adenocarcinomas (polymorphous low-grade adenocarcinoma) and twelve cellular mixed tumors were selected and stained for glial fibrillary acidic protein (glial fibrillary acidic protein) using a strept-avidin-biotin system and examined independently by each investigator. In addition, five tumors with limited material (three cellular mixed tumors and two polymorphous low-grade adenocarcinoma) from the consultation service of one author were evaluated using the same techniques. Two polymorphous low-grade adenocarcinoma stained positive in very focal areas and only in the epithelial component; staining did not occur in the stroma. Fourteen of fifteen mixed tumors focally to diffusely expressed glial fibrillary acidic protein. Only one tumor did not express glial fibrillary acidic protein. In mixed tumors with only focal staining, the most helpful differential diagnostic feature was positive staining of the mesenchyme-like cells adjacent to epithelial nests. We did not find this latter staining pattern in any of the polymorphous low-grade adenocarcinoma.

Adenocarcinoma↗

Cigarette smoking and nasopharyngeal cancer: an analysis of the relationship according to age at starting smoking and age at diagnosis.

To examine whether the association between smoking and nasopharyngeal cancer varies according to age at starting smoking and age at diagnosis of the disease, we compared 113 men with nasopharyngeal cancer diagnosed between 31 and 59 years old who lived within eight cancer registry areas to 1,910 controls selected by random-digit telephone dialing. Compared to smoking which began at the age of 22 years or older, the risk estimates were 0.4 (95% confidence interval (CI) 0.2-0.9) and 0.8 (95%CI 0.4-1.5) for smoking begun at the ages of 18-21 and 17 years or younger, when adjusted for pack-years smoked and other potential confounders (p for trend > 0.8). In contrast, the risk estimates adjusted for age at starting smoking and other variables were 1.3 (95%CI 0.7-2.6), 1.9(95%CI 0.9-4.0) and 3.0(95%CI 1.4-6.2) for 15-29.9, 30-44.9 and 45 or over, relative to 15 or less pack-years smoked (p for trend < 0.005). The analyses were repeated for subgroups in terms of age at diagnosis. The relative risks of ever-smoking and the dose-effect relation between pack-years and the risk of the disease were not significantly different between men whose cancer was diagnosed at the age 49 or younger and those whose tumor was diagnosed between the ages 50 and 59. This study suggests that the magnitude of the risk for nasopharyngeal cancer may not vary significantly with the age at which smoking begins, and age at which the disease is diagnosed.

Adult↗

Desmoid fibromatosis of the sinonasal tract and nasopharynx. A clinicopathologic study of 25 cases.

BACKGROUND: Desmoid fibromatoses are a group of nonmetastasizing, well differentiated, unencapsulated fibrous tissue proliferations that have a tendency for local invasion and recurrence. Biologically, they fall in an intermediate category between benign fibrous lesions and fibrosarcoma. Because of the rarity of this lesion in the upper respiratory tract and inadequate characterization of its biologic potential in the literature, this study was undertaken. METHODS: The files of the Armed Forces Institute of Pathology were reviewed for cases of fibromatosis involving the sinonasal and nasopharyngeal areas that occurred between 1885 and 1985. For each case, histologic materials were reviewed, clinical data tabulated, and follow-up obtained. RESULTS: Twenty-five cases were identified. Sixteen patients were male and 9 female, ranging in age from 8 months to 62 years (mean, 29 years and 11 months). A single site was involved in 18 patients and multiple contiguous adjacent sites in 7. The maxillary sinus was the site most frequently involved (22 patients), followed by the nasal cavity (5 patients), the ethmoid sinus (4 patients), orbit (4 patients), sphenoid and frontal sinuses (2 patients each), and the nasopharynx (1 patient). Twenty-four patients were followed for periods ranging from 1 year to 20 years and 7 months (median, 6 years and 9 months; mean, 8 years and 2 months). At last follow-up, 18 patients were alive and well with no evidence of disease, 2 patients were alive with unknown disease histories, and 3 patients were alive with recurrent or residual disease. One patient died without evidence of disease. Five patients (21%) (4 adults and 1 child) developed recurrences; 3 patients had 1 recurrence at 6, 16, and 34 months, respectively, 1 patient had 2 recurrences at 3.5 and 5.5 months, and 1 patient was alive with recurrent disease at 6.5 years. One patient was lost to follow-up. CONCLUSIONS: Twenty-five cases of desmoid fibromatosis involving the sinonasal tract and nasopharynx were described. These lesions appear to have lower recurrence rates and morbidity than desmoid fibromatoses arising in many other areas of the body.

Adult↗

Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident.

Starting 4 years after the Chernobyl accident, a dramatic increase in incidence of thyroid carcinoma was noticed in children from contaminated areas. The incidence of benign thyroid lesions in the exposed population was also increased. To study the possible role of ras and p53 genes in radiation-induced thyroid tumorigenesis, 33 papillary carcinomas, one follicular carcinoma and 22 benign lesions removed from children aged 5-19 were screened for point mutations of H-, K-, and N-ras, as well as of p53 (exons 5-8) using single strand conformation polymorphism (SSCP) analysis. Ras point mutations were detected in 1/1 case of follicular carcinoma (N-ras codon 61 CAAgln-->AAAlys), and in 3/7 follicular adenomas (N-ras codon 61 CAAgln-->CGAarg x 2, CAAgln-->AAAlys). None of the cases of papillary thyroid carcinoma was positive for ras oncogene abnormalities. The lack of K-ras mutations was confirmed by allele-specific oligonucleotide hybridization (ASOH), and by sequencing in five cases. Somatic point mutations in p53 were found by SSCP in 2/33 papillary thyroid carcinomas, with one missense mutation (exon 5, codon 160 ATGmet-->GTGval) and another silent mutation (codon 182, TGCcys-->TGTcys). Immunohisto-chemically, focally positive p53 staining was found in four papillary carcinomas being primarily confined to solid and poorly-differentiated areas in tumors. These data demonstrate that as opposed to the few reports on tumors arising after therapeutic external irradiation, ras mutations are not primary events in the development of post-Chernobyl thyroid papillary carcinomas. p53 mutations do not appear to be important in the development of these tumors, but may in some cases have a role in progression to a more aggressive phenotype that has not yet fully manifested in these pediatric neoplasms.

Adolescent↗

Cytogenetic analysis of salivary gland type tumors.

Fourteen salivary gland type tumors were analyzed with a combination of conventional cytogenetics via GTG-banding, molecular cytogenetics via fluorescent in situ hybridization, and chromosome morphometry. Nine tumors were benign (eight pleomorphic adenomas and one Warthin tumor) five tumors were malignant (one carcinoma ex pleomorphic adenoma, two adenoid cystic carcinomas including one from the breast, a basal cell adenocarcinoma, and an acinic cell carcinoma). Thirteen specimens grew in tissue culture; the basal cell adenocarcinoma did not grow. The Warthin tumor had a normal karyotype, one pleomorphic adenoma was normal, one had a clone with a missing Y chromosome, and the other pleomorphic adenomas had structural chromosomal abnormalities including the following: translocations between chromosomes 3 and 8, chromosomes 6 and 16, chromosomes 8 and 9, chromosomes 8 and 12, chromosomes 8 and 14, and chromosomes 8 and 21. Of the four malignant tumors with karyotypes, the acinic cell carcinoma and one adenoid cystic carcinoma were normal, the second adenoid cystic carcinoma showed a normal polymorphic variant, whereas the carcinoma ex pleomorphic adenoma demonstrated the following karyotype: 46,XX,dir ins(8;5)(q12;q12q35), add(12)(p13)/46,XX. In conclusion, 66% of the benign tumors and 25% of the malignant tumors demonstrated abnormal karyotypes.

Adenolymphoma↗

Thyroid lesions in children and adolescents after the Chernobyl disaster: implications for the study of radiation tumorigenesis.

Eight years after the Chernobyl nuclear accident, the most obvious effect is manifested by an increase in the prevalence of thyroid gland diseases in the exposed children and adolescents. In this study, we describe a comparative analysis of epidemiological, clinical, and morphological features of 92 malignant and 59 benign thyroid lesions from patients 5-18 yr of age exposed to radiation in Belarus as a result of the Chernobyl disaster. All of them were operated at the same institution during the period from September 1991 through December 1992. The highest number of patients that subsequently developed thyroid carcinomas was in the group that was less that 1 yr of age at the time of Chernobyl, and this number decreased progressively through age 12 yr. Conversely, none of the patients with benign lesions only was less than 2 yr old at the time of the accident, and an exposure age of 5-6 yr was a threshold separating significant prevalence of malignant tumors in younger children from the more frequent benign lesions in older patients (P < 0.001). Fifty-two percent of children with carcinomas and only 24% with benign lesions (P < 0.005) were residents of the Gomel region, which is the most contaminated in Belarus. The morphology of thyroid tissue adjacent to carcinomas showed a high prevalence of multinodular and diffuse changes, but not of adenomas or solitary adenomatoid nodules. There was a high prevalence of focal micropapillary hyperplasia with graded degrees of severity, which we hypothesize may correspond to precursors for papillary thyroid carcinoma in post-Chernobyl radiation-associated tumors.

Adolescent↗

Characteristics of follicular tumors and nonneoplastic thyroid lesions in children and adolescents exposed to radiation as a result of the Chernobyl disaster.

BACKGROUND: In addition to the previously reported increase in incidence of thyroid carcinomas in Belarussian children after the Chernobyl disaster in April, 1986, benign thyroid lesions were also found to be increased in the exposed population. METHODS: A total of 60 follicular neoplasms and benign nonneoplastic thyroid lesions arising after the Chernobyl disaster in children and adolescents of 7 to 18 years of age were studied. RESULTS: The primary diagnoses in this series were follicular carcinoma in 1 (2%) case, follicular adenoma in 9 (15%), cystic adenomatoid nodule with papillae in 18 (30%), multinodular goiter in 18 (30%), diffuse hyperplasia in 2 (3%), diffuse hyperplasia with atypia and nodularity in 5 (8%), lymphocytic thyroiditis in 6 (10%), and thyroid cyst in 1 patient (2%). Additional histologic changes in thyroid glands from these patients were similar to those reported after radiation exposure, and included perifollicular fibrosis (72%), focal epithelial hyperplasia (73%), colloid accumulation (47%), follicular atrophy (33%), and cellular atypia (25%). Vascular abnormalities were found more often (75%) than previously reported in the thyroid gland after irradiation, and had a somewhat different appearance. They affected primarily medium-size arteries and were characterized by damage of the internal elastic lamina in addition to intimal fibrosis. CONCLUSIONS: The first case of thyroid follicular carcinoma in the exposed Belarussian children was diagnosed after a latent period of 6.5 years, as compared with 4 years of minimal latency for post-Chernobyl papillary carcinomas. Among benign thyroid lesions, cystic adenomatoid nodules of papillary type and diffuse hyperplasia with cellular atypia and nodularity seem to be commonly associated with radiation exposure to the thyroid gland.

Adenocarcinoma, Follicular↗

A population-based case-control study of the relationship between cigarette smoking and nasopharyngeal cancer (United States).

This case-control investigation, based on the Selected Cancers Study, assesses the association between cigarette smoking and nasopharyngeal cancer, a relatively rare neoplasm in the United States. Men who were diagnosed pathologically with nasopharyngeal cancer during 1984-88 were included as cases in the analysis if they were 15 to 39 years old in 1968, and lived in the areas covered by eight cancer registries in the US (n = 113). Control men were selected by random-digit telephone dialing (n = 1,910). Using logistic regression analysis with adjustment for potential confounding factors, it was found that relative to nonsmokers, the risks of nasopharyngeal cancer were 2.3 (95 percent confidence interval [CI] = 1.3-4.0) and 1.4 (CI = 0.8-2.6) for former and current smokers, respectively. Using pack-years as a measure, adjusted odds ratio (OR) estimates were 1.3, 1.8, 2.5, and 3.9 for smoking for less than 15, 15-29, 30-44, and 45 or more pack-years, respectively. When squamous cell carcinoma was used as an outcome, the smoking/nasopharyngeal-cancer association became stronger. The analysis did not show interactions between smoking and alcohol consumption, or prior nasal diseases. The results of this study suggest that cigarette smoking may be related to the occurrence of nasopharyngeal cancer (especially squamous cell carcinoma) among US men.

Adolescent↗

Composite follicular variant of papillary carcinoma and mucoepidermoid carcinoma of the thyroid. Report of a case and review of the literature.

The follicular variant of papillary carcinoma of the thyroid gland is a commonly recognized, well-defined entity. However, primary mucoepidermoid carcinoma of the thyroid is rare, with only 21 cases reported. We describe a 29-year-old woman who presented with a mass in the right lobe of the thyroid. The tumor was classified as the follicular variant of papillary carcinoma of the thyroid with several foci of mucoepidermoid carcinoma. Both components were invading the capsule and had spread to regional lymph nodes. This is the first reported case in which both the papillary and mucoepidermoid carcinomas were present in the primary tumor and in the metastases.

Adult↗

Pediatric thyroid cancer after the Chernobyl disaster. Pathomorphologic study of 84 cases (1991-1992) from the Republic of Belarus.

BACKGROUND: During the initial period after the Chernobyl accident, large amounts of radioactive iodine were released in fallout, resulting in serious exposure to the thyroid gland in the residents of areas around the nuclear power station. Beginning in 1990, a definite increase in the incidence of thyroid cancer was noted in children of the Republic of Belarus. METHODS: Morphologic and clinical features of 84 cases of post-Chernobyl thyroid carcinoma in Belarussian children from 5 to 14 years of age are reported. The latent period for tumor development was 4-6 years, with a mean of 5.8 years. RESULTS: Papillary carcinoma was found in 83 patients and medullary carcinoma in one. Besides typical papillary carcinoma (14%), solid (34%), follicular (33%), mixed (10%), and diffuse sclerosing (9%) variants were observed. The follow-up period ranged from 8 months to 2.5 years. One patient died, local recurrence developed in 2, and cervical lymph node metastases developed in 10. To date, the incidence of local recurrence or metastatic disease after surgery was significantly higher in patients 5-8 years of age and in residents of areas nearest to the Chernobyl station. CONCLUSIONS: Post-Chernobyl pediatric thyroid carcinoma is characterized by a short latency, a higher proportion of tumors arising in young children, and an almost equal sex ratio. Microscopically, these tumors were usually aggressive, often demonstrating intraglandular tumor dissemination (92%), thyroid capsular and adjacent soft tissue invasion (89%), and cervical lymph node metastases (88%). Papillary carcinoma was diagnosed in 99% of cases, with an unusually high frequency of solid growth patterns. Morphologic changes in nonneoplastic thyroid tissue were present in 90% of the glands, and the most specific findings were vascular changes and perifollicular fibrosis.

Accidents↗

Hyalinizing clear cell carcinoma of salivary gland.

We describe 11 patients with a distinctive salivary gland neoplasm. Most of the patients were adult women who presented with a painless mass. Nine tumors arose in minor salivary glands of the oral cavity (82%). Microscopically, they were characterized by the formation of trabeculae, cords, islands, and/or nests of monomorphic clear cells that were glycogen rich and mucin negative and were surrounded by hyalinized bands with foci of myxohyaline stroma. Cells with eosinophilic and granular cytoplasm were also noted. Both cell types showed minimal nuclear pleomorphism and a very low mitotic index. The neoplasms all had infiltrative borders. Immunohistochemically, the tumor cells expressed cytokeratins and epithelial membrane antigen, but not S-100 protein and smooth muscle actin. Ultrastructurally, the tumor cells contained abundant glycogen, desmosomes, peripheral tonofilaments, and prominent interdigitating microvilli without actin myofilaments or dense bodies. These immunohistochemical and ultrastructural findings provide evidence of epithelial differentiation without myoepithelial differentiation. For these tumors, we propose the name, hyalinizing clear cell carcinoma (HCCC). These are low-grade malignant neoplasms. Two patients had ipsilateral cervical lymph node metastases at presentation, but with surgical excision and either preoperative or post-operative radiotherapy in three cases, eight of 10 patients with clinical follow-up are alive and well without evidence of recurrence. The mean clinical follow-up is 3.6 years, with a range of 6 months to 11 years. One patient died as a result of surgery, another died of unrelated causes, and one patient was lost to follow-up.

Adenocarcinoma, Clear Cell↗

Expanded polytetrafluoroethylene (Gore-Tex soft-tissue patch) in facial augmentation.

BACKGROUND: Expanded polytetrafluoroethylene (EPTFE) (Gore-Tex soft-tissue patch) has received favorable clinical reports for use in facial augmentation procedures. We evaluated the EPTFE soft-tissue patch in short-term (3-week), intermediate-term (6-month), and long-term (12-month) animal models. METHODS: Nine pathogen-free male and female New Zealand white rabbits weighing 2 to 4 kg were used. After implantation of the EPTFE soft-tissue patch, the animals were carefully observed on a daily basis for signs of wound infection, seroma, or hematoma formation. The stability of the implant was evaluated and graded after the animals were killed. Tissue specimens, including skin, implant, and underlying bone, were removed en bloc. These blocks were sectioned and stained for histologic evaluation. A portion of these blocks were used for scanning electron microscopy. RESULTS: The material increased in stability over time and showed minimal inflammatory cell response and only a delicate fibrous capsule, even in long-term implants. Ultrastructural analysis demonstrated close apposition of the material to tissue, suggesting good interface bioactivity. CONCLUSIONS: The EPTFE soft-tissue patch appears to be safe and reliable material for augmentation, demonstrating high biocompatibility, low tissue reactivity, and increasing stability over time.

Animals↗

Sinonasal fibrosarcomas, malignant schwannomas, and "Triton" tumors. A clinicopathologic study of 67 cases.

BACKGROUND: Sinonasal fibrosarcomatous neoplasms are uncommon tumors and there are no previous studies of a large number of such cases. The clinical and histologic features of 67 fibrosarcomatous neoplasms of the nasal cavity and paranasal sinuses are reported. METHODS: Multiple clinical and histologic parameters (including immunostain results) were analyzed to characterize the features important for histologic recognition of the tumors and for correlation with patient outcomes. RESULTS: Some tumors could be classified as malignant schwannomas or malignant "Triton" tumors, but their behavior was similar to that of the fibrosarcomas. Histologically, most tumors were very low-grade malignant neoplasms; however, 22% of patients died of their tumors. Factors that correlated with death were mitotic rate (greater than 4 mitoses per 50 high-power fields), increased tumor cellularity, and male sex. CONCLUSIONS: Many tumors originally were diagnosed as benign (by others), probably causing initial undertreatment of some patients. Proper recognition and histologic evaluation of the tumor are important to ensure the best therapy and optimal patient survival.

Adolescent↗

Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis.

Among salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize; they have been called metastasizing mixed tumor (MZMT) of salivary glands. We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT. At the time of discovery of metastatic disease, the patients, six women and five men, ranged in age from 20 to 83 years. Primary sites of involvement included the parotid gland (eight cases), submandibular gland (two cases), and the nasal septum (one case). With one exception, all the patients had at least a single recurrences of their primary mixed tumor, but two or more recurrences were the norm before development of metastatic foci. The metastases were discovered from six to 52 years following the occurrence of the primary tumor. Metastatic deposits were identified in bone, lung, regional lymph nodes, skin, kidney, retroperitoneum, oral cavity, pharynx, calvarium, and central nervous system. The metastases either occurred simultaneously with an episode of recurrent mixed tumor (n = 5) or from 5 to 29 years after a recurrence (n = 6). The treatment of the primary, recurrent, and metastatic neoplasms was surgical excision. Follow-up, ranging from 8 months to 16 years following the diagnosis of MZMT, revealed seven patients to be alive without disease (64%) and two dead of causes unrelated to metastatic disease (18%). Two patients (18%) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors. Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases. Aneuploid DNA cell content was identified in two of the cases. DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors. Retrospective analysis of histologic parameters (mitotic rate, cellular pleomorphism, infiltrative growth, vascular or lymphatic invasion) and flow cytometric analysis failed to identify criteria to predict the development of metastasis in these neoplasms.

Actins↗

Small cell neuroendocrine carcinoma of the larynx. A critical review of the literature.

Small cell neuroendocrine carcinoma is an unusual laryngeal carcinoma accounting for slightly less than 0.5% of carcinomas. To date, approximately 125 cases have been reported. These tumors most often present in the 6th and 7th decades in men who are heavy cigarette smokers. Patients usually complain of hoarseness and almost 50% present with cervical lymph node metastases. These tumors are biologically aggressive with at least 73% of patients dying with widespread tumor metastases. Two- and 5-year survivals are 16 and 5%, respectively. Combined radiation and chemotherapy offer the best hope of survival.

Aged↗