RESUMO
AIMS: Familial partial lipodystrophy, Dunnigan variety (FPLD), is an autosomal dominant disorder due to missense mutations in the lamin A/C gene and is characterized by gradual loss of subcutaneous fat from the extremities and trunk, fat accumulation in the head, neck and intra-abdominal areas, insulin resistance and its metabolic complications. We studied autopsy findings in two patients with FPLD to determine fat distribution and organ involvement. RESULTS: Patient 1, a 66-year-old woman with the R482Q mutation, had diabetes mellitus, dyslipidaemia, and coronary artery disease and died suddenly. Autopsy confirmed the typical body fat distribution and further revealed excess fat deposition in the subpectoral regions extending to the axillae, in the axillary lymph nodes and in the retroperitoneum. Atherosclerotic vascular disease including old infarcts of the myocardium, temporal lobe and kidneys were noted. Severe amyloidosis of the pancreatic islets and grouped muscle atrophy of the quadriceps and diaphragmatic muscles were present. Patient 2, a 29-year-old woman belonging to a pedigree with the R62G mutation, died of hyperlipidaemia-induced acute pancreatitis. Autopsy of patient 2 revealed extensive pancreatitis, hepatic steatosis and polycystic ovaries. CONCLUSIONS: Our study confirms typical body fat distribution and describes new sites of excess fat deposition. Our data show predisposition to atherosclerosis and polycystic ovaries and suggest that pancreatic amyloidosis may underlie development of hyperglycaemia in FPLD patients.
Assuntos
Doenças Cardiovasculares/patologia , Hiperglicemia/patologia , Lipodistrofia/patologia , Tecido Adiposo/patologia , Adulto , Idoso , Autopsia , Composição Corporal , Morte Súbita , Evolução Fatal , Feminino , Humanos , Lipodistrofia/genéticaRESUMO
Hyalinizing clear-cell carcinoma (HCCC) is a recently described distinctive salivary gland neoplasm. Because of its cytoplasmic clearing and the bland nuclear features, HCCC resembles other tumors. The authors describe the cytomorphologic features of four cases of HCCC in fine-needle aspirates (FNA) and discuss the differential diagnosis. Fine-needle aspirates from 4 patients with primary HCCC of minor salivary glands were reviewed. Smears were stained with Diff-Quik and Papanicolaou stains. The cytologic features of the epithelial and the stromal components were analyzed. Cell blocks were prepared, and findings were correlated with prior or subsequent surgical specimens in each case. The smears contained numerous cohesive small and large epithelial cell groups and sheets which had sharp outlines and showed focal nuclear overlapping. The cells had uniform round to ovoid nuclei, granular chromatin, and small nucleoli. The abundant, well-defined cytoplasm was clear in many cells but denser in others. No myoepithelial cells or hyaline globules were identified. HCCC seems to have characteristic cytomorphologic findings on FNA smears. Because these cytologic features are not specific, and overlap with those of a number of salivary gland neoplasms that contain clear cells, a high level of suspicion, clinico-pathologic correlation, and examination of cell blocks are necessary to suggest the diagnosis. A diagnosis of HCCC by FNA was suspected in 3 of the 4 cases reported here.
Assuntos
Adenocarcinoma de Células Claras/patologia , Biópsia por Agulha , Neoplasias das Glândulas Salivares/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Castleman's disease of the hyaline vascular subtype is an uncommon lesion; experience with fine-needle aspiration (FNA) of this tumor is limited to rare case reports. We describe the cytologic, flow cytometric, and immunohistochemical findings in two cases initially sampled by FNA. Two females, aged 40 and 26 yr, were found incidentally to have an oropharyngeal and a mediastinal mass, respectively. Neither complained of systemic symptoms, and both had a normal routine laboratory workup. FNA followed by surgical excision in both cases was consistent with Castleman's disease of the hyaline vascular type. In the appropriate clinical context, a mature small lymphoid population associated with larger atypical cells, which are consistent with follicular dendritic cells, can be suggestive of Castleman's disease. Confirmation of a polytypic B-cell population by flow cytometry, supported by immunohistochemistry, is very helpful. However, definitive distinction from Hodgkin's lymphoma on FNA is probably not possible.
Assuntos
Hiperplasia do Linfonodo Gigante/patologia , Adulto , Biópsia por Agulha , Hiperplasia do Linfonodo Gigante/imunologia , Feminino , Citometria de Fluxo , HumanosRESUMO
BACKGROUND: Polymorphous low grade adenocarcinoma of the salivary glands (PLAC) is a low grade neoplasm that predominantly occurs in the minor salivary glands. In this site it is amenable to biopsy and histologic diagnosis. However, experience with fine-needle aspiration (FNA) biopsy findings in these tumors is limited. The authors describe the FNA cytology of this entity. METHODS: Fine-needle aspirates from two primary parotid and three metastatic PLACs were reviewed and correlated with their histology. RESULTS: All aspirates showed similar cytologic features, with hypercellular smears showing branching papillae, sheets and clusters composed of bland uniform cells with round-to-oval nuclei, dispersed chromatin, and absent or inconspicuous nucleoli. The cells generally had a scant-to-moderate amount of eosinophilic cytoplasm. Mitoses and nuclear pleomorphism were absent. These cells formed tubular structures containing hyaline globules in all cases and often a dispersed myxohyaline stroma. Bare nuclei also frequently appeared in the background. Two cases, which had prior histologic diagnoses, were diagnosed on FNA as metastatic PLAC. One metastatic case was diagnosed as benign metastasizing pleomorphic adenoma. One primary case was diagnosed as adenoid cystic carcinoma and one case as PLAC on FNA. CONCLUSIONS: The cytologic differential diagnosis of PLAC includes adenoid cystic carcinoma, pleomorphic adenoma, and monomorphic adenoma. PLAC should be considered in the differential diagnosis of head and neck masses, where the cytology suggests one of these tumors, even when the clinical context (involvement of a major salivary gland, lymph node metastasis) is not typical of PLAC.
Assuntos
Adenocarcinoma/secundário , Neoplasias Parotídeas/patologia , Glândulas Salivares Menores/patologia , Adenoma Pleomorfo/patologia , Adulto , Idoso , Biópsia por Agulha , Carcinoma Adenoide Cístico/patologia , Diagnóstico Diferencial , Humanos , Metástase Linfática/patologiaRESUMO
Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions. In contrast, four of the five clear cell adenocarcinomas contained prominent areas with clear cells. Nephrogenic adenomas generally showed only mild cytologic atypia, whereas four of the five clear cell adenocarcinomas showed severe atypia. A single mitotic figure was identified in only two of the nephrogenic adenomas, whereas the mitotic rate in the clear cell adenocarcinomas ranged from 2 to 14 per 10 high-power fields. None of the nephrogenic adenomas showed evidence of necrosis, but focal necrosis was noted in four of the five clear cell adenocarcinomas. In general, the nephrogenic adenomas and clear cell adenocarcinomas showed negative to weak staining with CK903 but strong staining with AE1, AE3, and Cam 5.2. Variable staining was observed with Brst-3 and antibodies to S-100, CEA (monoclonal and polyclonal), LeuM-1, and CA19.9. Nephrogenic adenomas and clear cell adenocarcinomas were all negative for prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and estrogen and progesterone receptors (except for two nephrogenic adenomas, which showed only focal weak staining for estrogen receptor). Neither bcl-2 nor c-erbB-2 staining was able to discriminate between the tumors. However, strong staining for p53 was noted in each clear cell adenocarcinoma and in none of the nephrogenic adenomas. MIB-1 positivity in nephrogenic adenomas ranged from 0 to 13 (average of 5.5) per 200 cells, whereas the positive range for clear cell adenocarcinomas was 33 to 70 (average of 47) per 200 cells. In summary, histopathologic features that favor clear cell adenocarcinoma over nephrogenic adenoma include a predominance of clear cells, severe cytological atypia, high mitotic rate, necrosis, high MIB-1 positivity, and strong staining for p53.
Assuntos
Adenocarcinoma de Células Claras/patologia , Adenoma/patologia , Neoplasias Uretrais/patologia , Neoplasias da Bexiga Urinária/patologia , Adenocarcinoma de Células Claras/metabolismo , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Nucleares , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-67 , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Necrose , Proteínas Nucleares/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Uretrais/metabolismo , Neoplasias da Bexiga Urinária/metabolismoRESUMO
OBJECTIVES: The identification of reliable prognostic factors to guide the selection of patients at high risk of harboring subclinical metastases in penile cancer is important. We evaluated traditional pathologic variables and deoxyribonucleic acid (DNA) flow cytometry to determine the prognostic significance of these variables for the subsequent development of lymph node metastases. METHODS: Clinical data and pathologic specimens were retrospectively reviewed from patients treated surgically at university-affiliated hospitals from 1958 to 1987. Pathologic analysis (grade, depth of invasion, and pathologic stage) and DNA flow cytometry were performed on specimens from 46 patients with invasive penile carcinoma and complete medical records. Pathologic variables were compared with DNA flow cytometry results in patients who never developed lymph node metastasis (32 patients, median follow-up 121 months) and in those who presented with or developed proved lymph node metastases (14 patients, median follow-up 18 months). RESULTS: The distributions of diploid and nondiploid tumors were similar in patients with or without lymph node metastasis. In addition, there was no significant difference in the grade distributions of tumors with respect to lymph node status. Patients with positive nodes more commonly had tumors that invaded greater than 0.5 cm or that exhibited pathologic Stage T2 or greater (deep invasion). All 14 patients who presented with or subsequently developed metastasis had deep primary tumors. Thirteen of 36 patients with clinically negative nodes had superficially invasive tumors (pathologic Stage T1 and depth of invasion 0.5 cm or less), and none developed metastasis (median follow-up 124 months [range 58 to 240]). Tumor grade was significantly related to the likelihood of deep invasion but was not an independent prognostic factor for metastasis. CONCLUSIONS: DNA flow cytometry does not add prognostic information to that obtained by pathologic assessment in patients with invasive penile carcinoma. The presence of pathologic Stage T2 or greater or depth of invasion greater than 0.5 cm defines a group of patients at high risk of inguinal node metastasis. A novel finding was that patients with minimally invasive lesions (0.5 cm or less) and no evidence of corporal invasion (pathologic Stage T1) have little risk of inguinal node metastasis. Close observation of reliable patients meeting these criteria may be a safe alternative to prophylactic lymphadenectomy.
Assuntos
Neoplasias Penianas/genética , Neoplasias Penianas/patologia , DNA de Neoplasias/análise , Citometria de Fluxo , Seguimentos , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , PrognósticoRESUMO
Where and how frequently p53 abnormalities are involved in the development of pleomorphic adenoma (PA) and its malignant progression to carcinoma was investigated. The presence of p53 gene abnormalities was analyzed in eight patients with carcinoma in pleomorphic adenoma (CPA) by polymerase chain reaction (PCR)-based assays and immunohistochemistry. Normal salivary gland tissue, adenomatous, transitional and carcinomatous areas were microdissected from archival microslides and analyzed for allelic deletions of the p53 gene using two microsatellite markers at the p53 locus; dinucleotide (CA)n repeat and pentanucleotide (AAAAT)n repeat. Loss of heterozygosity (LOH) of the p53 gene was detected in 57% of adenomas, 86% of transitional lesions and 86% of carcinomas. In contrast, overexpression of p53 oncoprotein was noted immunohistochemically in 13% of adenomas, 50% of transitional areas and 75% of carcinomas. All of the tumors with immunoreactivity for p53 oncoprotein demonstrated LOH. Moreover, when LOH was present in adenomatous or transitional areas, the identical LOH was always detected in the corresponding carcinomatous areas in the same CPA tumors. These findings indicate that p53 gene mutation is an early event and occurs frequently at an early stage of precancerous lesions and may be responsible for most cases of malignant transformation of PA.
Assuntos
Adenoma Pleomorfo/genética , Carcinoma/genética , Transformação Celular Neoplásica/genética , DNA de Neoplasias/análise , Genes p53/genética , Neoplasias das Glândulas Salivares/genética , Adenoma Pleomorfo/metabolismo , Carcinoma/metabolismo , Transformação Celular Neoplásica/metabolismo , Humanos , Técnicas Imunoenzimáticas , Perda de Heterozigosidade , Neoplasias das Glândulas Salivares/metabolismo , Proteína Supressora de Tumor p53/biossínteseRESUMO
Abnormalities of the p53 tumor suppressor gene were investigated in 22 foci from 14 adenoid cystic carcinomas (ACC) by polymerase chain reaction (PCR)-based assays for dinucleotide (CA)n and pentanucleotide (AAAAT)n repeat polymorphisms and by immunohistochemical staining for oncoprotein expression. Adenoid cystic carcinomas were divided into lower grade (tubular and cribriform) subtypes and higher grade (trabecular and solid) subtypes. Histologically identified tumor cells were precisely microdissected from archival microslides and were used for molecular analysis. The overall frequency of p53 gene mutations detected by PCR-loss-of-heterozygosity (LOH) analysis was 57% and was higher than the frequency of over-expression of p53 oncoprotein detected by immunostaining (43%). In the molecular analysis of individual histological subtype foci, the number of foci with p53 gene mutation was significantly greater in the higher grade subtype foci than in the lower grade subtype foci and was greatest in solid-type foci (100%). In all six tumors in which histologically different foci were present in the same tumors, mutations of the p53 gene were detected. When tumor heterogeneity of the p53 gene was present among different histological foci in the same tumors, the mutations were always detected in the higher grade foci. When lower and higher grade foci were present in the same tumors, the identical mutations detected in the lower grade foci were present in the corresponding higher grade foci. These findings indicate that abnormalities of the p53 gene are involved in carcinogenesis and/or progression of this tumor and, furthermore, suggest that molecular analyses of ACC may provide information of prognostic importance.
Assuntos
Carcinoma Adenoide Cístico/genética , DNA de Neoplasias/análise , Genes p53/genética , Carcinoma Adenoide Cístico/metabolismo , Humanos , Imuno-Histoquímica , Perda de Heterozigosidade , Mutação , Reação em Cadeia da Polimerase , Proteína Supressora de Tumor p53/biossínteseRESUMO
Dermoid cysts of the head and neck are rare lesions comprised of epidermal and mesodermal elements. We report a dermoid cyst presenting in the middle ear of the youngest patient reported to date. Structures of endodermal descent were also identified, but, given that the entire middle ear mucosa is of endodermal origin, specific classification as a teratoma would be imprecise. This lesion is interesting in that it did not directly involve the mastoid. Possible embryologic sites of origin are discussed.
RESUMO
BACKGROUND: The macrofollicular variant of papillary thyroid carcinoma that is the subject of this study has only recently been characterized. Information about its morphologic spectrum and biologic behavior is limited. METHODS: The authors reviewed 29 examples, including 17 previously reported cases. The clinical and pathologic features of five patients who had the macrofollicular variant of papillary thyroid carcinoma with a minor insular component were analyzed in detail. The insular component in thyroid carcinomas has been associated with aggressive clinical behavior. RESULTS: The ages of the 5 patients ranged from 31 to 70 years; the mean age was 40 years. Three patients presented with a palpable thyroid nodule and two with a large thyroid mass of long duration. The latter two tumors, which metastasized, were the largest (8 and 11 cm) and showed extrathyroidal and blood vessel invasion. All five tumors were composed predominantly of macrofollicles (>50%) and had a minor insular component that comprised less than 5% of the tumor mass. In most tumors, the macrofollicles were lined by cells with large, clear, grooved nuclei, and all five contained areas of conventional follicular variant of papillary thyroid carcinoma. In the two that metastasized, however, the lining of many macrofollicles consisted of cuboidal cells with small, hyperchromatic, follicular-type nuclei. Only the macrofollicular component was identified in the metastatic deposits in these two patients. All five patients were alive at last follow-up, two with metastases; but follow-up for this study is limited. CONCLUSIONS: A minor insular component is an additional feature of the macrofollicular variant of papillary thyroid carcinoma that may aid in diagnosis and does not appear to have an adverse effect on the excellent prognosis of patients with these tumors.
Assuntos
Carcinoma Papilar, Variante Folicular/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-IdadeRESUMO
The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when combined with standard, curative-intent radiation therapy (RT) for previously untreated, locally advanced non-small cell lung cancers. Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell cancer ineligible for potentially curative surgical resection, a good performance status, adequate hematologic, hepatic, and renal functions, and no distant metastases. All patients receive a total tumor dose of 64.8 Gy megavoltage RT in 7 weeks at 1.8 Gy once daily, 5 d/wk. Paclitaxel is delivered by continuous intravenous infusion starting 48 hours before RT and continuing for its duration. The dose of paclitaxel is escalated in cohorts of three patients in a standard phase I design. To date, 16 patients have entered the trial, and 15 are evaluable for toxicity in this ongoing study. Paclitaxel dose is currently at a 6.5 mg/m2/d dose level, with no dose-limiting toxicity recorded thus far. One patient at the highest dose level has had grade 2 pneumonitis. With the exception of anemia, toxicities are those that would be expected from RT alone. A slowly progressive normocytic anemia with no renal dysfunction was found to be associated with an acquired hypoerythropoietin state. These findings indicate that this therapy is feasible and well tolerated through current dose levels, with no dose-limiting toxicity. Dose escalation is ongoing.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Paclitaxel/uso terapêutico , Radiossensibilizantes/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacocinética , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Masculino , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/farmacocinética , Radioterapia de Alta EnergiaRESUMO
Our understanding of the molecular genetic changes in lung cancer pathogenesis is advancing rapidly with several specific genes and chromosomal regions having been identified. As the biochemical functions of the proteins encoded by these genes are discovered, they appear to fall into several growth regulatory pathways. The large number of genetic lesions in clinically evident lung cancer has prompted searching for mutations in preneoplastic lung tissue before the pathologic evidence of cancer as a tool for early molecular diagnosis. In addition, these markers need to be rigorously assessed for their prognostic importance. Finally, understanding the molecular basis of lung cancer should allow "translation" of these findings from the bench to the bedside. These include very early molecular diagnosis, identification of persons at highest risk of developing lung cancer to allow for more effective smoking cessation strategies, chemoprevention, and very early treatment studies (clinical studies beginning); rational development of novel therapies such as immunization against tumor-specific mutant peptides (clinical studies ongoing); blocking the expression of activated oncogenes (such as with antisense or triple helix agents); and replacing defective tumor suppressor genes (clinical studies ongoing).
Assuntos
Tumor Carcinoide/genética , Carcinoma de Células Grandes/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Pequenas/genética , Neoplasias Pulmonares/genética , Tumor Carcinoide/patologia , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Genes Supressores de Tumor/genética , Humanos , Neoplasias Pulmonares/patologia , Biologia Molecular , Oncogenes/genéticaRESUMO
Patients with locally advanced solid tumors of the lung, head and neck, and malignant astrocytomas usually succumb to their disease despite aggressive standard therapy. Laboratory data suggest that the addition of 1.0 to 10 nmol/L paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a microtubule stabilizing drug, to radiation therapy may result in significant radiation sensitization, perhaps due to accumulation of cells at G2/M. Relatively low concentrations (1.0 to 10 nmol/L) appear to be optimal for direct cytotoxicity and radiosensitization in vitro. Within this dose range, more prolonged exposure seems to result in higher response rates. The phase I trials reported here are designed to test the combination of paclitaxel, administered by continuous intravenous infusion (24 hours a day, 7 days a week), and standard, curative-intent radiation therapy. The ultimate goal of this study is to improve local and systemic control and survival for patients with these three tumor types. To date, 39 evaluable patients are enrolled in this study; there has been no dose-limiting toxicity up to 6.5 mg/m2/d. Observed toxicities include anemia, lymphopenia, mucositis, and cutaneous toxicities.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Radiossensibilizantes/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/radioterapia , Paclitaxel/administração & dosagem , Radiossensibilizantes/administração & dosagem , Radioterapia Adjuvante , Análise de SobrevidaRESUMO
The complications of posterior fossa surgery continue to decrease in incidence as our collective experience broadens. Most complications are seen in the immediate postoperative period and the minimized by careful attentiveness to subtle changes in mental status, vital signs, and cranial nerve examination. Long-term follow-up is necessary to identify tumor recurrence, but strict imaging protocols as yet do not exist to facilitate the early identification of recurrent disease, as recurrence is very rare. We report the first case of secondary mucocele formation in the middle ear cleft following translabyrinthine excision of an intracanalicular acoustic neuroma. This complication was found in the fourth postoperative year on routine magnetic resonance imaging, which itself followed previously normal contrasted magnetic resonance imaging in the second postoperative year. The genesis of this complication and possible treatment options are discussed.
RESUMO
BACKGROUND: Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant cells and is inactive in most normal somatic cells, with the excitation of proliferative stem cells, male germ cells, and activated lymphocytes. The measurement of telomerase activity in clinically obtained tissue samples may provide useful information as both a diagnostic and prognostic marker. In this study, we sought to determine whether telomerase activity might prove helpful in the assessment of benign and malignant thyroid tumors. METHODS: A modified, semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol assay was used for detection of telomerase activity in 59 samples obtained at thyroidectomy, including 15 thyroid cancers, 22 benign thyroid diseases, and 22 adjacent normal thyroid tissues. RESULTS: Four of 13 differentiated thyroid carcinomas (30%) and 2 of 2 medullary carcinomas (100%) expressed telomerase activity. Unexpectedly, we also detected activity in 3 of 22 (14%) adjacent normal thyroid tissues and 6 of 22 (28%) benign thyroid diseases. Pathologic review of the telomerase-positive benign specimens revealed that many contained extensive lymphoid infiltrates with germinal centers (six of nine, 67%), as did two of four telomerase-positive papillary carcinomas. CONCLUSIONS: In contradistinction to other epithelial carcinomas, telomerase does not appear to be frequently reactivated in differentiated thyroid carcinomas.
Assuntos
Telomerase/metabolismo , Doenças da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/enzimologia , Adulto , Idoso , Ativação Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7-week total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with standard curative radiotherapy (RT) for previously untreated, locally advanced head and neck squamous cell cancers. Eligible patients have squamous cell cancers of the head and neck with expected 5-year survival rates of < or =25%; a good performance status; adequate hematologic, hepatic, and renal functions; and no distant metastases. All patients receive 70 Gy megavoltage RT in 7 weeks (2 Gy/d x 5 d/wk). Paclitaxel is delivered by protracted venous infusion starting 48 hours before RT and continuing for its duration. Biopsies for cell-cycle distribution analyses and paclitaxel tissue levels are obtained, if possible, before beginning paclitaxel and after 48 hours just before RT begins. The dose of paclitaxel is escalated in cohorts of three patients. Eighteen patients are evaluable for toxicity. Treatment has been completed through the 6.5 mg/m2/d dose level and is ongoing at 10.5 mg/m2/d. There has been no dose-limiting toxicity thus far. With the exception of anemia, toxicity is commensurate with what would be expected from RT alone. A slowly progressive normocytic anemia with no renal dysfunction was found to be associated with an acquired hypoerythropoietin state. Tumor biopsies have suggested the possibility of paclitaxel-induced mitotic arrest. This therapy is feasible and has been well tolerated through current dose levels with no dose-limiting toxicity. There is a suggestion of biologic activity evidenced by the anemia and the possibility of alteration in cell-cycle distributions. Dose escalation is ongoing.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Paclitaxel/administração & dosagem , Antineoplásicos Fitogênicos/sangue , Terapia Combinada , Eritropoetina/sangue , Feminino , Hemoglobinometria , Humanos , Infusões Intravenosas , Masculino , Paclitaxel/sangueRESUMO
Adenoid cystic carcinomas (ACC) constitute approximately 20% of malignant salivary gland tumors. Several histological types of ACC are recognized and may coexist in a single tumor. The authors divided ACC into lower grade (tubular and cribriform subtypes) and higher grade (trabecular and solid) subtypes. A preliminary analysis of 10 ACCs showed a relatively high incidence of loss of heterozygosity (LOH) at the p53 and RB genes and low or absent K-ras mutations and LOH at chromosomal loci 3p, 5q, 8p, and 9p. From 21 tumors, the authors carefully microdissected and analyzed 36 subtype foci. Three interrelated pieces of evidence indicate that the relatively poor prognosis higher grade subtype arises from one or more of the lower grade subtypes via progression events associated with mutations in the p53 or RB genes. First, the number of mutations (both LOH and microsatellite alterations) at either gene is greater in higher grade foci than in lower grade foci; second, multiple mutations (two and occasionally three) are present in only higher grade foci; and third, when lower and higher grade foci are present in the same tumors, identical mutations plus other mutations are present in the corresponding higher grade foci. These findings suggest that molecular analyses of ACCs may provide information of prognostic importance.
Assuntos
Carcinoma Adenoide Cístico/patologia , Genes do Retinoblastoma/genética , Genes p53/genética , Heterozigoto , Repetições de Microssatélites/genética , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/genética , Humanos , Mutação , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/genéticaRESUMO
Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. Carcinomas in pleomorphic adenomas (CPAs) may arise by malignant transformation of the epithelial components of PAs. Occasionally, transitional zones containing cells with histological features intermediate between those of the benign PA and carcinomatous components of CPA are identified. After careful microdissection of archival microslides, the authors studied 12 cases of CPAs and their attendant adenomatous and transitional areas for mutations in the p53, RB, and K-ras genes, and at chromosomal loci 5q and 9p. The authors failed to find mutations in the K-ras gene or 9p locus. A relatively high rate of mutations (loss of heterozygosity [LOH] and microsatellite alterations) at the p53 gene were detected in CPAs (58%), and at somewhat lower frequencies at the RB gene (33%) and chromosomal location 5q (17%). Mutational frequency in the associated transitional and adenomatous areas were slightly lower than in the corresponding CPAs. No mutations were detected in adenomatous or transitional areas unless they also were present in the corresponding CPAs. Mutations of these three genes were absent in four cases of CPA, and in seven PAs without malignant change. These findings indicate that most CPAs arise from adenomas as the result of mutations in the three genes, especially p53. In addition, other, as yet unidentified genes may also be involved both in the development of PA and in its malignant progression to CPA. Mutational analysis of PAs may provide information of prognostic importance.
Assuntos
Adenocarcinoma/genética , Adenoma Pleomorfo/genética , Carcinoma/genética , Mutação , Neoplasias das Glândulas Salivares/genética , Adenocarcinoma/patologia , Adenoma Pleomorfo/patologia , Cromossomos Humanos Par 5 , Genes do Retinoblastoma , Genes p53 , Heterozigoto , Humanos , Neoplasias das Glândulas Salivares/patologiaRESUMO
OBJECTIVE: Islet amyloidosis may be one mechanism for pancreatic islet beta-cell loss that is associated with the development of NIDDM. However, the question remains whether chronic overstimulation of insulin and islet amyloid polypeptide (IAPP) secretion in states of insulin resistance could lead to formation of islet amyloidosis and hence NIDDM in some patients. We studied pancreatic islet pathology in congenital generalized lipodystrophy, a genetic syndrome of extreme insulin resistance that may provide some clues. RESEARCH DESIGN AND METHODS: Our patient was a 24-year-old African-American woman with congenital generalized lipodystrophy. Severe acanthosis nigricans was noted in her since age 6. At ages 12 and 16, normal and impaired glucose tolerances, respectively, were noted on oral glucose tolerance tests but were accompanied by extreme fasting and post-prandial hyperinsulnemia. Overt diabetes developed at age 18 and she required approximately 180 U of insulin daily. Immediately after an accidental death at age 24, an autopsy was performed. Pancreatic histology was studied in detail using routine methods and immunohistochemical techniques. RESULTS: Some scarring of the pancreas as a result of previous episodes of acute pancreatitis was observed. Severe amyloidosis was noted in 89% of the islets, sparing those that were rich in pancreatic polypeptide-secreting cells. Amyloid deposits stained intensely on immunostaining with antibodies against amylin. Marked paucity of beta-cells was evident. The ratio of beta- to alpha-cells was reduced to 1:1 (normal ratio approximately 4:1). CONCLUSIONS: These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as beta-cell atrophy.
Assuntos
Amiloidose/patologia , Ilhotas Pancreáticas/patologia , Lipodistrofia/patologia , Pancreatopatias/patologia , Adulto , Amiloidose/sangue , Amiloidose/complicações , Glicemia/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Lipodistrofia/sangue , Lipodistrofia/complicações , Pancreatopatias/sangue , Pancreatopatias/complicaçõesRESUMO
According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bronchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-stained sections using a high-performance digitised image analyser. Archival material from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected, including 16 central tumours (mainly squamous cell carcinomas) and 19 peripheral tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour from extrathoracic primary sites. Of the NSCLCs, 31/35 (89%) were aneuploid, as were 60% of the metastases from extrathoracic sites. Multiple, focal areas of preneoplasia or preinvasive carcinoma were present in the selected cases. The lesions ranged in severity from hyperplasia through metaplasia and dysplasia to carcinoma in situ. Aneuploid preinvasive lesions were not noted in association with the four diploid tumours but were present only when the accompanying NSCLC was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic lesions were more frequent in the peripheral parts of the lung (bronchioles or alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy increased with progressive severity of morphological change. Aneuploidy was not found in preinvasive lesions accompanying the five metastatic cases. Our findings provide strong support for the concept of field cancerisation.