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1.
Head Neck Pathol ; 9(3): 360-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25563452

ABSTRACT

Spindle cell carcinoma (SpCC) is an uncommon head and neck squamous cell carcinoma (SCC) variant consisting of spindled and/or pleomorphic cells with epithelial differentiation. Epidermal growth factor receptor (EGFR) is expressed by >90 % of conventional SCC, and high level expression is associated with a poorer prognosis. Anti-EGFR therapies are commonly used to treat head and neck SCC. However, no studies have evaluated EGFR expression in SpCC. Cases of SpCC were retrieved from department files. The diagnosis required either a biphasic lesion with a squamous neoplastic component, or a purely spindle cell or pleomorphic tumor with immunohistochemical positivity for epithelial markers. EGFR immunohistochemistry was performed and was quantified in quartiles. Medical records were reviewed for clinical follow up information. EGFR was expressed in 21/30 (70 %) cases, including in the squamous component in 18/19 (95 %) and the spindle cell component in only 12/30 (40 %). Where the spindle cell component was positive, the intensity and distribution were lower than for the squamous component. Recurrent tumors were predominantly (80-90 %) of the spindle cell component, and had low (or absent) EGFR expression. Kaplan-Meier survival analysis showed no statistically significant differences in overall or disease free survival between the EGFR expressing and non-expressing groups (p = 0.414 and 0.19, respectively). SpCCs of the head and neck have a poor prognosis, and markedly reduced EGFR expression. EGFR-specific therapies may not be ideal for SpCC patients, which may lack EGFR expression, but further studies are needed.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , ErbB Receptors/biosynthesis , Head and Neck Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Disease-Free Survival , ErbB Receptors/analysis , Female , Head and Neck Neoplasms/mortality , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Squamous Cell Carcinoma of Head and Neck
2.
Head Neck Pathol ; 7(3): 250-7, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23536041

ABSTRACT

Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma characterized by spindled or pleomorphic cells which appear to be a true sarcoma but are actually epithelial. Some head and neck squamous cell carcinoma variants can be human papillomavirus (HPV)-related and have improved outcomes. We sought to determine if spindle cell carcinomas are associated with transcriptionally-active HPV. Cases of spindle cell carcinoma were retrieved from department files. Transcriptionally-active HPV was determined by mRNA in situ hybridization for high risk HPV E6 and E7 transcripts and by a surrogate marker, p16 immunohistochemistry, with a 50% staining cutoff. RT-PCR for high risk HPV mRNA was performed on the cases that were technical failures by in situ hybridization. Medical records and follow up information were retrieved for all patients. Of 31 cases, 5 were from the oropharynx, 12 from the oral cavity, and 14 from the larynx or hypopharynx. One purely spindled oral cavity spindle cell carcinoma was HPV positive. It was also diffusely positive for p16. Another laryngeal spindle cell carcinoma was HPV positive in both the squamous and spindle cell components, but was negative for p16. None of the five oropharyngeal spindle cell carcinomas were positive for p16 or HPV RNA. The HPV positive patients both presented at high stage (IV) and died with disease within 2 years of diagnosis. The majority of spindle cell carcinomas of the head and neck, including those arising in the oropharynx, are not related to transcriptionally active HPV. Although the number of cases is too small for any definitive conclusions, for the rare HPV positive spindle cell carcinoma cases, positive viral status does not appear to confer any prognostic benefit.


Subject(s)
Carcinoma, Squamous Cell/virology , Head and Neck Neoplasms/virology , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Female , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , In Situ Hybridization , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction
3.
Z Rheumatol ; 60(3): 148-55, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11475602

ABSTRACT

INTRODUCTION: This study was undertaken to evaluate the role of ultrasound (US), conventional color (CD) and power Doppler (PD) in the detection and quantification of inflammatory signs of the knee in children with juvenile idiopathic arthritis (JIA) and to correlate these findings with patient history, clinical, laboratory and radiological findings. PATIENTS AND METHODS: Thirty patients with JIA who had clinical signs of knee involvement as well as 15 healthy children as a control group where subjected to full clinical examination and laboratory investigations on the same day of US examination. The knee joints were evaluated with plain radiography, US, and color Doppler in 13 patients, while the remaining 17 were assessed with power Doppler. Fourteen patients were subjected to follow-up assessment. RESULTS: A highly significant difference in synovial thickening and cartilage thickness detected by US between JIA affected knees and those of controls (p < 0.0001). Knee effusion was demonstrated in 93% of patients. Synovial vessels were detected by Doppler in 76.7% of patients. A significant correlation was detected between the degree of vascularity detected by PD and knee score (p < 0.05), and JAFAR score (P < 0.05). On comparing the findings of the follow-up with those of the initial examination, a significant positive correlation was detected between the differences in the knee score and those in synovial thickness (p < 0.05), and with the vascularity scale detected by PD (p < 0.05). CONCLUSION: This study suggests the Doppler sonography as a non-invasive, low-cost, and readily available tool for the evaluation and follow-up of articular involvement in knees of JIA patients.


Subject(s)
Arthritis/diagnostic imaging , Knee Joint/diagnostic imaging , Synovitis/diagnostic imaging , Ultrasonography, Doppler, Color , Adolescent , Arthritis/etiology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Hyperemia/diagnostic imaging , Infant , Male , Neovascularization, Pathologic/diagnostic imaging , Reference Values , Sensitivity and Specificity , Synovial Membrane/diagnostic imaging , Synovitis/etiology
4.
Laryngoscope ; 111(6): 1079-87, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11404625

ABSTRACT

OBJECTIVE: To determine the impact of delayed regional metastases, distant metastases, and second primary tumors on the therapeutic outcomes in squamous cell carcinomas of the larynx and hypopharynx. STUDY DESIGN: Chart review and statistical analysis. METHODS: A retrospective tumor registry analysis was made of patients with squamous cell carcinomas of the larynx and hypopharynx who were treated with curative intent in the Department of Otolaryngology-Head and Neck Surgery and the Radiation Oncology Center of the Washington University School of Medicine (St. Louis, MO) between January 1971 and December 1991 and developed delayed regional metastases (2 y after treatment), distant metastases, and second primary malignancies. RESULTS: In 2550 patients, the mean age (59.8 y), sex (8.5 male patients and 1 female patient), and tumor differentiation did not affect the incidence of delayed distant, regional, or second primary malignancies. The overall incidence of delayed regional metastases was 12.4% (317/2550 patients); distant metastases, 8.5% (217/2550); and second primary tumors, 8.9% (228/2550), with a 5-year disease-specific survival of 41%, 6.4%, and 35%, respectively. Second primary malignancies were not statistically related to the origin of the primary tumor, tumor staging, or delayed regional and distant metastases (P =.98). Delayed regional metastases and distant metastases were related to advanced primary disease (T4 stage), lymph node metastases (node positive [N+]), tumor location (hypopharynx), and locoregional tumor recurrence (P < or =.028). Advanced regional metastases at initial diagnosis (N2 and N3 disease) increased the incidence of delayed and distant metastases threefold (P =.017). These two metastatic parameters were significantly greater in hypopharyngeal tumors than in laryngeal tumors (P =.037). The incidences of delayed regional metastases by anatomical location of the primary tumor were as follows: glottic, 4.4%; supraglottic, 16%; subglottic, 11.5%; aryepiglottic fold, 21.9%; pyriform sinus, 31.1%; and posterior hypopharyngeal wall, 18.5%. The incidences of distant metastases were as follows: glottic, 4%; supraglottic, 3.7%; subglottic, 14%; aryepiglottic fold, 16%; pyriform fossa, 17.2%; and posterior hypopharyngeal wall, 17.6%. Seventeen hypopharyngeal tumors (2%) presented with M1 disease. Delayed regional metastases to the ipsilateral treated neck had a significantly worse survival prognosis than delayed metastases to the contralateral nontreated neck (P =.001). CONCLUSIONS: Conclusions are as follows: 1) The incidence of second primary tumors is independent from the primary tumor staging and distant and delayed regional metastases. The highest incidence occurred in patient groups with the highest disease-free survival rates (P =.0378). 2) Highest incidence of delayed and distant metastases occurred in hypopharyngeal tumors and was three times greater than in laryngeal cancers (P =.028). 3) Salvage therapeutic rates were poor for delayed metastases to the ipsilateral treated nodes and distant metastases as compared with contralateral neck metastases and second primary tumors (P =.001). 4) Delayed and distant lymph node metastases were significantly higher in advanced primary disease (T4 stage), locoregional recurrences, and regional disease (N2 and N3) (P =.028) in both the larynx and hypopharynx. 5) The higher incidence of delayed and distant metastatic disease was related to more advanced initial tumor presentation in hypopharyngeal cancer as compared with laryngeal cancer (P =.039). 6) Incidence of distant metastases was greatest between 1.5 and 6 years after initial treatment with a mean incidence being less than or equal to 3.2 years.


Subject(s)
Carcinoma, Squamous Cell/pathology , Hypopharyngeal Neoplasms/pathology , Laryngeal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasms, Second Primary/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/therapy , Cause of Death , Female , Follow-Up Studies , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/therapy , Hypopharynx/pathology , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/therapy , Larynx/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Neoplasms, Second Primary/mortality , Neoplasms, Second Primary/therapy , Retrospective Studies , Salvage Therapy , Survival Rate
5.
Mod Pathol ; 13(8): 914-8, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10955460

ABSTRACT

Squamous papillomas of the lung are an uncommon feature of recurrent respiratory papillomatosis, occurring in fewer than 1% of cases. We describe a 23-year-old patient with pulmonary papillomas who developed a fatal squamous cell carcinoma of the lung. PCR-based human papillomavirus (HPV) typing showed the presence of HPV 11 DNA in both benign papillomas and invasive carcinoma. A review of the literature reveals four reports of malignant transformation of juvenile-onset recurrent respiratory papillomatosis in which HPV typing was performed. Similar clinical features are noted in all of the reports; specifically, each case has arisen in a young adult man with a history of papillomatosis since childhood. In each of the cases, HPV 11 was identified in association with the squamous cell carcinoma. Although HPV 11 is uncommonly associated with the development of invasive carcinoma at other sites, these findings suggest that it is correlated with malignant transformation in the setting of juvenile-onset recurrent respiratory papillomatosis.


Subject(s)
Carcinoma, Squamous Cell/pathology , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasms, Second Primary/pathology , Papilloma/pathology , Papillomaviridae/isolation & purification , Papillomavirus Infections/pathology , Tumor Virus Infections/pathology , Adult , Carcinoma, Squamous Cell/virology , DNA Primers/chemistry , DNA, Viral/analysis , Fatal Outcome , Humans , Lung Neoplasms/virology , Male , Neoplasm Recurrence, Local/virology , Neoplasms, Second Primary/virology , Papilloma/virology , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomavirus Infections/complications , Polymerase Chain Reaction , Sequence Analysis, DNA , Tumor Virus Infections/complications
6.
Ann Otol Rhinol Laryngol ; 109(3): 281-6, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10737312

ABSTRACT

Blastomycosis is a relatively uncommon fungal disease that most commonly affects the lungs. Other organs may be involved, usually secondary to dissemination of the organism. Laryngeal blastomycosis may occur in isolation from active pulmonary disease. The signs, symptoms, clinical features, and pathological findings of laryngeal blastomycosis mimic those of squamous cell carcinoma. Misdiagnosis may result in inappropriate treatment with potential morbidity. Proper understanding of the clinical presentation and familiarity with the histopathologic features of this disease are therefore imperative. In this paper, we report 2 cases of laryngeal blastomycosis, 1 of which was misdiagnosed as squamous cell carcinoma, clinically and microscopically, with consequent radiotherapy and laryngectomy. In the other case, a clinical diagnosis of glottic squamous cell carcinoma was rendered. However, blastomycosis was identified in a biopsy specimen. We also review cases of isolated laryngeal blastomycosis that have been reported in the English-language literature during the last 80 years. A number of those cases were misdiagnosed clinically and microscopically as squamous cell carcinoma.


Subject(s)
Blastomycosis/diagnosis , Laryngitis/diagnosis , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Blastomyces/cytology , Blastomycosis/complications , Blastomycosis/drug therapy , Carcinoma, Squamous Cell/diagnosis , Diagnosis, Differential , Diagnostic Errors , Female , Humans , Laryngeal Neoplasms/diagnosis , Laryngitis/drug therapy , Laryngitis/microbiology , Male , Middle Aged
8.
Semin Diagn Pathol ; 16(4): 302-7, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10587273

ABSTRACT

Cementum is a calcified dental tissue that covers the roots of teeth and is part of the periodontium. Its function is to help anchor the teeth in their sockets within the alveolar bone of the jaws. Two benign mesenchymal odontogenic tumors are uniquely distinguished by elaboration of cementum or cementum-like material: cemento-ossifying fibroma and benign cementoblastoma (true cementoma). Cemento-ossifying fibroma, which is also termed periodontoma, is characterized by production of cementum and bone in a fibrous stroma. It is a painless, slow-growing tumor usually detected in the third and fourth decade of life and is more common in women. The mandible is its site of predilection. Benign cementoblastoma is intimately associated with the roots of teeth, most commonly mandibular molars. It affects young patients, usually under the age of 20 years. Pain is a common symptom in addition to bone expansion. Benign cementoblastoma bears considerable histologic resemblance to osteoblastoma.


Subject(s)
Dental Cementum , Fibroma, Ossifying/pathology , Jaw Neoplasms/pathology , Odontogenic Tumors/pathology , Adolescent , Adult , Dental Cementum/metabolism , Female , Fibroma, Ossifying/metabolism , Fibroma, Ossifying/surgery , Humans , Jaw Neoplasms/metabolism , Jaw Neoplasms/surgery , Male , Odontogenic Tumors/metabolism , Odontogenic Tumors/surgery
9.
Oncogene ; 18(16): 2651-5, 1999 Apr 22.
Article in English | MEDLINE | ID: mdl-10353609

ABSTRACT

Several regions of chromosome arm 8p are frequently deleted in a variety of human malignancies including those of the prostate, head and neck, lung, and colon, suggesting that there is more than one tumor suppressor gene on this chromosome arm. Both laryngeal and oral squamous cell carcinomas exhibit three distinct and nonoverlapping regions of deletion on 8p. We have further refined the localization of the putative suppressor in 8p23 by using eight microsatellite loci to create a high resolution deletion map of 150 squamous cell carcinomas of the larynx and oral cavity. These new data demonstrate that there are two distinct classes of deletion within this relatively small region of the chromosome and suggest two possible locations for the gene within the D8S264 to D8S1788 interval. We also determined that there is little difference between the allelic loss frequencies of microsatellites mapping near the telomeric ends of other chromosome arms and loci mapping to more centromere proximal regions of the same arm. These data suggest that the high allelic loss frequencies seen at 8p23 loci are not the result of a generalized instability of chromosome ends and are instead consistent with the activation of a specific suppressor gene.


Subject(s)
Carcinoma, Squamous Cell/genetics , Chromosomes, Human, Pair 8 , Genes, Tumor Suppressor , Head and Neck Neoplasms/genetics , Loss of Heterozygosity , Chromosome Mapping , Gene Frequency , Humans , Laryngeal Neoplasms/genetics , Mouth Neoplasms/genetics , Sequence Deletion , Telomere/genetics
10.
Article in English | MEDLINE | ID: mdl-9574952

ABSTRACT

Tubulopapillary hidradenoma is a benign sweat gland tumor that appears as a well-defined, superficially located dermal nodule. It combines ductal as well as apocrine and eccrine glandular differentiation. Microscopically, the tumor is composed of tubular structures that characteristically show intraluminal non-villous papillary projections and a peripheral myoepithelial cell layer. A tumor that is histologically and immunohistochemically identical to tubulopapillary hidradenoma occurred in the mandible of a 73-year-old man and resulted in considerable diagnostic difficulty. The neoplasm developed in a mandibular cyst and recurred 5 years after initial enucleation. This is the first report of a central (intraosseous) sweat gland adenoma of the mandible. The differential diagnosis and possible histogenesis are discussed.


Subject(s)
Adenoma, Sweat Gland/pathology , Mandibular Neoplasms/pathology , Actins/analysis , Adenoma, Sweat Gland/etiology , Aged , Apocrine Glands/pathology , Bone Cysts/pathology , Cell Nucleolus/ultrastructure , Cell Nucleus/ultrastructure , Cell Transformation, Neoplastic/pathology , Cytoplasm/ultrastructure , Diagnosis, Differential , Eccrine Glands/pathology , Epithelial Cells/pathology , Follow-Up Studies , Humans , Keratins/analysis , Male , Mandibular Neoplasms/etiology , Muscle, Smooth/pathology , Neoplasm Recurrence, Local/pathology , Vimentin/analysis
11.
Otolaryngol Head Neck Surg ; 118(3 Pt 1): 363-70, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9527118

ABSTRACT

Frequent allelic loss at a genetically polymorphic locus in tumors is an established marker for the presence of a tumor suppressor gene in the neighboring chromosomal region. This technique can be used to identify novel tumor suppressor genes and to monitor their status before the cloning of the gene itself. We have used the polymerase chain reaction and microsatellite loci on all 39 nonacrocentric autosomal chromosomal arms to identify sites of frequent allelic loss in squamous cell carcinomas of the supraglottic larynx. Our allelotype identified seven chromosomal arms (3p, 5q, 8p, 9p, 9q, 13q, and 17p) likely to contain tumor suppressor genes frequently inactivated during squamous tumorigenesis in the larynx. We tested for associations between allelic losses on these chromosomal arms and the clinical and histopathologic features of these tumors. There were no correlations with either T or N classifications. Allelic loss on chromosomal arm 13q is significantly associated with a number of histopathologic features characteristic of poorly differentiated or histologically aggressive tumors. Allelic loss on this arm also exhibits statistical trends toward association with early tumor recurrence and poor survival. The association with survival was substantiated by a multivariate Cox proportional hazards model.


Subject(s)
Alleles , Carcinoma, Squamous Cell/genetics , Glottis , Laryngeal Neoplasms/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Genes, Tumor Suppressor/physiology , Glottis/pathology , Humans , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Microsatellite Repeats , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Statistics as Topic
12.
Article in English | MEDLINE | ID: mdl-9195625

ABSTRACT

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.


Subject(s)
Adenocarcinoma/pathology , Biomarkers, Tumor/analysis , Glial Fibrillary Acidic Protein/analysis , Salivary Gland Neoplasms/pathology , Adenocarcinoma/chemistry , Adenoma, Pleomorphic/chemistry , Adenoma, Pleomorphic/pathology , Diagnosis, Differential , Histocytochemistry , Humans , Salivary Gland Neoplasms/chemistry , Salivary Glands, Minor/chemistry , Salivary Glands, Minor/pathology
13.
Pathol Res Pract ; 193(11-12): 791-6; discussion 797-9, 1997.
Article in English | MEDLINE | ID: mdl-9521512

ABSTRACT

A case of primary intrathyroidal paraganglioma is reported, and the light microscopic and immunohistochemical findings are described. Primary paragangliomas of the thyroid region are extremely uncommon and are therefore often confused clinically and histopathologically with more common intrathyroidal mass lesions. The diagnostic difficulties are underscored by the present case, which was misdiagnosed twice, firstly as a medullary thyroid carcinoma and secondly as a follicular thyroid carcinoma. Immunohistochemistry may be very helpful in arriving at the correct diagnosis. The case was further complicated by a second neck mass contralateral to the original thyroid nodule, which was interpreted as consistent with metastasis. The second lesions was proved angiographically and histologically to be a carotid body paraganglioma.


Subject(s)
Carotid Body Tumor/secondary , Paraganglioma/pathology , Thyroid Neoplasms/pathology , Adult , Female , Humans , Immunohistochemistry , Paraganglioma/chemistry , S100 Proteins/analysis , Thyroid Neoplasms/chemistry
14.
J Natl Cancer Inst ; 88(22): 1676-82, 1996 Nov 20.
Article in English | MEDLINE | ID: mdl-8931613

ABSTRACT

BACKGROUND: Loss of genetic heterogeneity (allelic loss or loss of heterozygosity) on chromosome arm 8p is frequent in squamous cell carcinomas of the head and neck and has been associated with poor prognosis. We have previously demonstrated that there are three minimal regions of allelic loss on this chromosome arm. The location of each region is marked by a microsatellite locus: D8S264 (8p23), D8S552 (8p23-p22), and D8S133 (8p21). These findings imply the existence of at least three putative tumor suppressor genes on this chromosome arm that may become inactivated during the progression of squamous cell carcinoma. PURPOSE: We used allelic loss data from these three loci to determine if inactivation of these putative suppressors is associated with poor prognosis for patients with squamous cell carcinoma of the supraglottic larynx. We also used multivariate statistics to compare the prognostic power of allelic loss at these genetic markers with that of demographic, clinical, and histopathologic parameters. METHODS: We examined the D8S264, D8S552, and D8S133 microsatellites in tumors from a retrospective population of 59 patients. All patients had histologically confirmed squamous cell carcinoma of the supraglottic larynx and had been treated surgically. DNA was extracted from matched sets of normal and microdissected tumor tissue and used for polymerase chain reaction amplification of the microsatellite markers. Reaction products were separated by denaturing gel electrophoresis and visualized by autoradiography. Patient data were obtained from the original pathology report and from the tumor registry of the Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO. Histopathologic data were obtained by reviewing the portion of the resection specimen used for DNA extraction. Parameters whose association with reduced disease-free interval and reduced disease-specific survival was statistically significant were identified by use of the Kaplan-Meier method and the logrank statistic. Multivariate Cox proportional hazards models were used to identify independent predictors of poor prognosis. All statistical tests were two-sided. RESULTS: In this patient population, allelic loss at the D8S264 locus was associated with both shorter disease-free interval (logrank P = .028) and reduced disease-specific survival (logrank P = .004). Allelic loss at the next most centromeric locus, D8S552, had a statistically significant association with only reduced disease-specific survival (logrank P = .034), whereas allelic loss at the most centromeric region, D8S133, showed no statistically significant association with reductions in either interval. Multivariate Cox models suggested that D8S264 was the only 8p marker of the three microsatellites with a statistically significant and independent association with shortened disease-free interval (relative risk [RR] = 3.38; P = .0107) and reduced disease-specific survival (RR = 3.41; P = .0105). CONCLUSIONS: Allelic loss in the p23 region of chromosome 8 appears to be a statistically significant, independent predictor of poor prognosis in patients with supraglottic squamous cell carcinoma.


Subject(s)
Carcinoma, Squamous Cell/genetics , Chromosome Deletion , Chromosomes, Human, Pair 8 , Laryngeal Neoplasms/genetics , Alleles , Carcinoma, Squamous Cell/pathology , DNA, Neoplasm/genetics , Disease-Free Survival , Female , Glottis , Heterozygote , Humans , Laryngeal Neoplasms/pathology , Male , Microsatellite Repeats , Middle Aged , Multivariate Analysis , Polymorphism, Genetic , Predictive Value of Tests , Prognosis , Proportional Hazards Models
15.
Cancer ; 78(8): 1693-700, 1996 Oct 15.
Article in English | MEDLINE | ID: mdl-8859182

ABSTRACT

BACKGROUND: Numerous clinical parameters have been suggested as predictors of outcome for patients with head and neck carcinoma treated with radiation therapy, but their applicability remains controversial. Inactivation of the p53 tumor suppressor results in radioresistance in experimental systems and might predict treatment failure in human patients. We have tested this hypothesis by comparing the predictive power of nuclear accumulation of p53 protein with that of clinical and histopathologic markers in patients with glottic carcinoma treated with primary radiotherapy. METHODS: Clinical charts were reviewed for 165 patients with glottic squamous cell carcinoma treated with radiation therapy. One hundred and twenty-one patients with T1 or T2 classified tumors were determined to have received adequate treatment and to have adequate follow-up data for further study. Archival pretreatment tumor biopsies from a subpopulation of patients were examined for p53 protein by immunohistochemistry. The influence of clinical and histopathologic variables and p53 nuclear protein on tumor recurrence was studied by bivariate and multivariate analysis. RESULTS: The recurrence rate was lowest for patients with moderately to poorly differentiated tumors (P < 0.05). This was the only significant predictor of outcome in this patient population. The presence of immunohistochemically detectable p53 antigen was not predictive of tumor recurrence in 70 patients for whom there was both p53 and sufficient follow-up data. CONCLUSIONS: Histologic differentiation was prognostic for tumor recurrence in this population of patients with glottic carcinoma treated with radiation therapy. In contrast, nuclear accumulation of p53 protein was not predictive of tumor response or recurrence in this population.


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Laryngeal Neoplasms/radiotherapy , Tumor Suppressor Protein p53/analysis , Aged , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/pathology , Female , Humans , Laryngeal Neoplasms/chemistry , Laryngeal Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local , Predictive Value of Tests , Prognosis
16.
Pediatr Pathol Lab Med ; 16(1): 89-98, 1996.
Article in English | MEDLINE | ID: mdl-8963634

ABSTRACT

Primary epithelial neoplasms of the salivary gland in children are uncommon but are well recognized and occur principally in the major salivary glands. The purpose of this report is to document our experience with an adenocarcinoma of the buccal submucosa (one of several sites of minor salivary gland tissue) that metastasized to multiple bones as the initial sites of distant disease after a local recurrence. The clinical history, imaging studies, and microscopic sections including immunoperoxidase studies were evaluated from the primary tumor, local recurrence, and a metastatic lesion from the femur. The histopathologic features and immunohistochemical phenotype of the adenocarcinoma in the buccal submucosa supported its salivary gland origin. This case of adenocarcinoma of the intraoral buccal tissues independent of the parotid gland in a 12-year-old female is an unusual clinical presentation of a salivary gland neoplasm in childhood, and its ability to metastasize to distant skeletal sites is also remarkable in terms of a primary salivary gland carcinoma regardless of age at diagnosis.


Subject(s)
Adenocarcinoma/pathology , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Salivary Gland Neoplasms/pathology , Salivary Glands, Minor/pathology , Child , Female , Humans , Immunoenzyme Techniques , Staining and Labeling
17.
Genes Chromosomes Cancer ; 14(2): 145-8, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8527396

ABSTRACT

The mutational inactivation of suppressor genes, a process required for cancer progression, generates new genetic subclones within a tumor. The allelic losses that frequently unmask these mutations serve not only as markers of the chromosomal locations of these genes but also as clonal fingerprints of the shifting relationships between these genetically heterogeneous cell populations. The rise of the metastasis-competent subclone to dominance within the primary tumor should be reflected in the similarity of the genetic fingerprints of the primary tumor and its resultant metastases. We have tested this hypothesis by comparing the patterns of allelic loss of individual primary laryngeal squamous cell carcinomas and their resultant cervical lymph node metastases at 16 different genetically polymorphic loci on 15 chromosome arms. Although primary tumors and metastases both frequently lose heterozygosity on the same chromosome arms (3p, 9p, 9q, 13q, and 17p), five of the 12 metastases differed from their primary tumors at one or two of the loci examined. Discordance between the two tumor cell populations from the same patient is suggestive of either subclone heterogeneity within the primary tumor at the time of establishment of the metastasis or further clonal evolution of both tumors after metastasis.


Subject(s)
Carcinoma, Squamous Cell/genetics , Chromosome Deletion , Chromosomes, Human , Gene Deletion , Genes, Tumor Suppressor , Laryngeal Neoplasms/genetics , Lymphatic Metastasis/genetics , Neoplasm Metastasis/genetics , Alleles , Carcinoma, Squamous Cell/pathology , Chromosome Mapping , DNA, Neoplasm/analysis , Humans , Laryngeal Neoplasms/pathology , Polymerase Chain Reaction
18.
Cancer ; 73(10): 2472-80, 1994 May 15.
Article in English | MEDLINE | ID: mdl-8174043

ABSTRACT

BACKGROUND: The inactivation of some tumor suppressor genes classically manifests itself through the loss of heterozygosity at nearby genetic mapping markers. Inactivation of these genes appears to have diagnostic/prognostic significance in some types of tumors. Molecular genetic tools based on suppressor inactivation might, therefore, have great utility in treatment planning. METHODS: The polymerase chain reaction and highly informative microsatellite markers were used to compare DNA derived from matched sets of tumor and normal tissue samples from 37 supraglottic laryngeal squamous cell carcinomas. Tumor samples were microdissected free of contaminating normal tissue to maximize the detection of allelic loss. Polymerase chain reaction products were fractionated by denaturing gel electrophoresis and were visualized by autoradiography. RESULTS: Allelic losses were frequent at TP53 (56% of the tumors), the retinoblastoma gene (Rb, 59%), and the p13-14 region of chromosome 3 (64%). In contrast, the putative metastasis suppressor, NME1 (also known as NM23), was lost infrequently (7%). NME1 allelic loss did not correlate with the presence of lymph node metastases in these patients. CONCLUSIONS: The high frequencies of allelic loss at TP53, Rb, and 3p13-14 suggest that these suppressors play a major role in laryngeal carcinogenesis. In sharp contrast, the low frequency of loss at NME1 and its equal distribution in nodal metastasis-positive and -negative patients suggests that inactivation of this gene by allelic loss probably does not play a role in the development of regional metastases from these tumors. Allelic loss in 3p13-14 was found in tumors of all histopathologic grades.


Subject(s)
Carcinoma, Squamous Cell/genetics , Chromosomes, Human, Pair 3 , Genes, Retinoblastoma , Genes, p53 , Laryngeal Neoplasms/genetics , Monomeric GTP-Binding Proteins , Nucleoside-Diphosphate Kinase , Transcription Factors/analysis , Base Sequence , Carcinoma, Squamous Cell/pathology , Chromosome Mapping , DNA, Neoplasm/analysis , Heterozygote , Humans , Laryngeal Neoplasms/pathology , Molecular Sequence Data , NM23 Nucleoside Diphosphate Kinases , Polymerase Chain Reaction
20.
Oral Surg Oral Med Oral Pathol ; 75(6): 716-22, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8515985

ABSTRACT

Eosinophilic ulcer of the oral mucosa (traumatic eosinophilic granuloma) mimics oral cancer clinically and is occasionally misdiagnosed as lymphoma on microscopic examination. Trauma is believed to play a role in its development, but its exact pathogenesis is not known. The demographic, clinical, and histologic features of 38 previously unreported cases of eosinophilic ulcer of the oral mucosa are reviewed. Nine representative cases were studied immunohistochemically. Microscopically, the lesions contained a polymorphic inflammatory infiltrate extending deep into the submucosa, underlying muscle, and salivary glands. Numerous eosinophils and large mononuclear cells with pale nuclei and frequent mitoses were seen in all lesions. Lymphocytes, histiocytes, plasma cells, granulocytes, and mast cells were also present. Immunohistochemical stains showed that the lymphocytic infiltrate was composed predominantly of T cells. T-cell-specific antigen-presenting cells were more numerous than the non-antigen-presenting cell type. The large cells with pale nuclei stained positively only for vimentin; the possible myofibroblastic nature of these cells is discussed. Although trauma might have an etiologic role, the pathogenesis of eosinophilic ulcer of the oral mucosa is probably T cell mediated.


Subject(s)
Eosinophilic Granuloma/pathology , Mouth Diseases/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Eosinophilic Granuloma/immunology , Female , Humans , Langerhans Cells/chemistry , Male , Middle Aged , Monocytes/chemistry , Mouth Diseases/immunology , Mouth Mucosa/pathology , Retrospective Studies , S100 Proteins/analysis , T-Lymphocytes/chemistry , Vimentin/analysis
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