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[Use of quantitative histochemistry in the prognosis of renal cell cancer].

The study was concerned with evaluating the quantitative histochemical and histoenzymatic peculiarities of renal cell carcinoma of various grade of malignancy. It involved measuring levels of lipids, glycogen, protein, nucleic acids and sugar as well as the activities of dehydrogenases, phosphatases, non-specific esterase and lipase in tumor cells. Grade I neoplasms were found to be associated with low proliferative activity matched by relatively high energy production thus causing excessive synthesis of lipids and glycogen to occur. Higher cell proliferative activity in grade II and III tumors accounts for a significantly lower level of lipids and glycogen. Those metabolic peculiarities appeared to correlate with prognosis.

Carcinoma, Renal Cell↗

[Clinico-pathologic differences between bladder neoplasm with low malignant potential and low-grade carcinoma].

OBJECTIVE: To determine if the morphologic subgrouping of grade I bladder tumors between papillary neoplasm of low malignant potential and low grade papillary carcinoma is of clinical and survival value. MATERIAL AND METHODS: All 257 consecutive patients diagnosed of superficial bladder cancer between 1990 and 1995 in HU Reina Sofia of Cordoba were reviewed and further reclassified according to WHO/ISUP consensus classification of urothelial neoplasms of the bladder. Of the tumors 12 were urothelial papilloma, 51 were papillary neoplasm of low malignant potential, 43 were low grade papillary carcinoma Ta, 65 were low grade papillary carcinoma T1 and 37 were high grade papillary carcinoma. Eleven patients were reevaluated as T2 tumors and 38 (14.8%) were lost of control. All patients were reviewed with a follow-up at least of 5 years. We compare the results between groups with Fisher test and the risk factors for recurrence and progression are analyzed by multivariate analysis (Odds ratio). The survival function was calculated using Kaplan-Meier estimates and compared with the log-rank test. RESULTS: There are no differences between groups respect the age or sex distribution. The differences in the multiplicity are not significant and only the mean size is higher in papillary low grade carcinoma. About the risk factors for recurrence and progression of the disease, only is significative the tumor size. Rarely, the use of chemotherapy seems to play a role in the recurrence. There are no differences in recurrence and progression between the groups, although the percentages are always higher in the papillary low grade carcinoma group. CONCLUSIONS: There are enough clinical differences between the two groups and we consider them as distinct pathologic entities. Only the higher tumoral size is prognostic factor in each group. We think that the use of chemotherapy must be avoided in this low grade bladder tumors.

Carcinoma↗

Osteochondromalike parosteal osteosarcoma: a report of six cases of a new entity.

OBJECTIVE: Our purpose was to describe a rare juxtacortical bone sarcoma with deceptively benign, osteochondromalike histologic characteristics. We present criteria by which this low-grade malignant neoplasm can be distinguished from other benign and malignant surface lesions of bone with particular emphasis on the imaging features. MATERIALS AND METHODS: Six cases of a low-grade, chondroossifying parosteal sarcoma of bone were reviewed. Patients included four males and two females 11 months to 66 years old. Histologic findings from initial tumors and from recurrent tumors were reviewed. Two musculoskeletal radiologists analyzed the imaging studies, which included plain films, CT scans, MR images, and a bone scan. RESULTS: Histologically, the lesions were characterized by a thin layer of proliferating, periosteally derived spindle cells overlying a thin, low-grade malignant cartilage cap that underwent calcification, neovascularization, and conversion into benign bone and marrow fat. These lesions were unique in that the malignant elements were only at their periphery. All six cases were initially misdiagnosed as benign lesions on pathologic evaluation. In each patient, imaging revealed a "pasted-on" ossified surface lesion with an intact underlying cortex and no medullary involvement. In three cases, recurrent tumors had histologic appearances consistent with conventional parosteal osteosarcoma. Dedifferentiation, metastases, and death occurred in one of these three cases. CONCLUSION: To our knowledge, this surface lesion of bone has not been specifically described. Whether this tumor constitutes a distinct entity or is a specialized variant of parosteal osteosarcoma is unclear. Precise radiologic-pathologic correlation is essential for appropriate diagnosis and management.

Adolescent↗

Merkel cell tumor of the eyelid. A clinicopathologic case report.

We treated a patient who had clinical and pathological findings of a primary cutaneous tumor of the eyelid with histological and ultrastructural features of a Merkel cell carcinoma. This neoplasm is composed of cells that are thought to be derived from the neural crest and are found normally in the skin. While it may be a low-grade malignant neoplasm, this tumor can grow rapidly and metastasize. Histologically, it can mimic a metastatic undifferentiated small-cell carcinoma from the lung or other primary sites. To our knowledge, this is the first reported case involving an eyelid.

Adenocarcinoma↗

Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.

Ewing's sarcoma, a highly malignant neoplasm, is characterized by an 11;22 translocation [t(11;22) (q24;q12)], resulting in the fusion of genes FLII and EWS. Adamantinoma of extragnathic bones, a low-grade malignant neoplasm with epithelial features, is not typically considered in the differential diagnosis of Ewing's sarcoma. In this study, three osseous Ewing's sarcomas with histological, immunohistochemical, or ultrastructural epithelial features were subjected to reverse transcription-polymerase chain reaction and sequencing studies for the Ewing's sarcoma molecular rearrangement. (Two of the three cases were originally described as adamantinomas or nontypical Ewing's sarcoma before the availability of genetic characterization.) In addition, traditional cytogenetic analysis and a unique combined interphase molecular cytogenetic/ immunocytochemical approach with bicolor 11;22 translocation breakpoint flanking probes (cosmids) and pancytokeratin antibodies were performed on one neoplasm. At(11;22) (q24;q12) was found in one neoplasm and a type II EWS/FLI-1 fusion transcript was detected in all three neoplasms. The combined genetic/immunocytochemical approach revealed the presence of the 11 ;22 translocation in the nuclei of cytokeratin immunoreactive cells. These genotypic and phenotypic findings delineate a novel Ewing's sarcoma histologic variant, "adamantinoma-like Ewing's sarcoma."

Adolescent↗

[Pulmonary carcinoid tumors--ten years experience].

Pulmonary carcinoid tumors are rare, accounting for as many as 2% of all pulmonary neoplasms and for 10% of carcinoid tumors overall. Previously classified as bronchial adenomas, actually are classified as neuroendocrine tumors. They have a subclassification into typical classed as low-grade malignant neoplasm and atypical more aggressive, with more potential to cause local invasion. In this paper, the authors report a retrospective study of 25 patients, who had the diagnosis of pulmonary carcinoid tumors and had been operated between January of 1994 and August of 2004. We conclude that this tumors must be considered malignant in the surgical approach.

Adolescent↗

Preliminary identification of carotenoids in malignant and benign neoplasms of the breast and surrounding fatty tissue.

An attempt has been made to identify the carotenoids present in the tissue of neoplastic tumors and the surrounding fatty tissue taken from women with histologically diagnosed cancer (ca ductale infiltrans, G2,G3; n=20) and those with benign changes (fibroadenoma, n=20). Carotenoid pigments were isolated using column and thin-layer chromatography. Prior to chromatography, the material was homogenized with acetone under nitrogen in dark glass bottles and the extracts kept in a refrigerator until analyzed. In the present study, we isolated 13 carotenoids belonging to provitamin A and nonprovitamin A carotenoids. The total content of carotenoids in microg/g of tissue was slightly lower in cancers and the surrounding fatty tissues in comparison to benign changes, but in general it was higher in the fatty tissue surrounding the tumors, irrespective of their histological structure (the mean values for cancers 20.433+/-10.64 vs fatty tissue 25.361+/-12.025, p<0.01; and the mean values for benign changes 22.889+/-12.011 vs fatty tissue 27.021+/-13.180, p<0.01). Epoxide carotenoids - lutein epoxide and violaxanthin, were predominant in fatty tissue, both in malignant and benign changes; epoxide carotenoids - mutatoxanthin and lutein epoxide and other carotenoids such as zeaxanthin, canthaxanthin, lutein and neoxanthin were predominant in neoplastic material. Beta carotene and lutein epoxide were found in all samples, alpha carotene was found in 50% of them. Antheraxanthin was present in fatty tissue only. Beta carotene, the main provitamin A carotenoid, content in the material examined ranged from 2.43 to 4.33% in tumor tissue and in fatty tissue surrounding the tumors it was twice as higs. Such carotenoids as 3'-lutein, canthaxanthin and astaxanthin were sporadic. No reoccurring carotenoid "sequences" were found despite the same histopathological diagnosis. No relationship was found between the neoplasm histopatological grade, lesion diameter and the occurrence of specific carotenoids.

Adipose Tissue↗

Estrogen and progesterone receptors in breast cancer among women of different racial groups.

No differences in steroid hormone receptor status were detected in premenopausal breast cancer patients of different races. In postmenopausal women, 65% of Whites were found to have tumors positive for cytoplasmic estrogen receptors (CER) compared with 58, 52, and 41% in women of mixed race, Blacks, and Asians, respectively. The proportions of tumors which contained a full complement of receptors (CER, nuclear estrogen receptors, and cytoplasmic progesterone receptors) were similar in Blacks, Whites, and Asians in each menopausal group. In postmenopausal patients, significantly fewer White women had tumors devoid of all receptors, while having a higher incidence of tumors with an abnormal or defective receptor distribution. Neither the stage of the disease nor the degree of nodal involvement appeared to affect receptor status in any population group, but very large tumors had fewer receptors. White patients with large neoplasms had a significantly higher incidence of CER than Blacks or Asians. Similar observations were made for White patients presenting with Stage III disease, whose tumors were greater of histological Grade I tumors were positive for CER, compared with Grade III neoplasms. Indications are that receptor status is inherent to the natural history of the disease and is not influenced by clinical features.

Adult↗

TSH receptor status of thyroid neoplasms--TaqMan RT-PCR analysis of archival material.

Regulation of thyroid follicular cell proliferation and function is mediated by the interaction of TSH with its receptor (TSHr) on the plasma membrane. While it is recognized clinically that responsiveness of thyroid epithelial tumours to TSH varies with the histological type and grade of neoplasm, the level of TSHr expression in these different tumours has not been quantified hitherto. The aim of this study was to provide this information. Total RNA was extracted from 125 samples of formalin-fixed, paraffin-embedded thyroid tissue comprising 48 papillary (PTC), 29 follicular (FTC), eight anaplastic (ATC), and five medullary thyroid carcinomas (MTC), in addition to 35 samples of either follicular adenoma (FA) or normal thyroid tissue. Samples were reverse-transcribed and analysed using TaqMan polymerase chain reaction (PCR). TSHr expression was shown to be similar to normal in FA and inversely related to the grade of the majority of thyroid cancers other than MTC, in which, as expected, there was negligible expression. It is concluded that reduced expression of TSHr implies decreased responsiveness to TSH manipulation and is therefore a clinically important prognostic indicator in thyroid cancers.

Carcinoma↗

Pediatric glial tumors.

Glial neoplasms in children comprise many heterogeneous tumors that include pilocytic and fibrillary astrocytomas, ependymomas, and the diffuse intrinsic pontine gliomas. In contrast to adults, most of whom present with high-grade fibrillary neoplasms, alternate histologies represent most cases seen in the pediatric setting. In addition, although most adult gliomas are supratentorial in location, in pediatrics infratentorial tumors (posterior fossa and brain stem) predominate. We discuss three specific tumors: diffuse intrinsic pontine gliomas; pilocytic astrocytomas; and ependymomas. Maximal surgical resection is the mainstay of therapy for both pilocytic astrocytomas and ependymomas. Failure to achieve an optimal resection often results in progression and the need for further therapy for patients with pilocytic astrocytomas, and is ultimately fatal in most children with subtotally resected ependymomas. Surgical resection has no role in the treatment of pontine gliomas. Focal radiation therapy is included routinely in the treatment of ependymomas, and it has been shown to improve event-free survival. This therapy also is used in the treatment of pontine gliomas because radiation treatment appears to slow inevitable tumor progression. Radiation therapy in pilocytic astrocytomas is generally reserved for patients who progress after an initial surgical resection or for those patients with midline tumors; these patients are poor candidates for aggressive surgical resection. The role of chemotherapy in these tumors is in evolution. Chemotherapy for pilocytic astrocytomas, particularly in young children (for whom radiation therapy is avoided), appears to be effective in the treatment of a subset of patients. Up-front chemotherapy is generally reserved for the youngest children who present with ependymoma. In the recurrence setting, chemotherapy has shown some activity, although this approach is never curative. Despite the application of various chemotherapeutics and other biologic agents, none of these therapies has improved the prognosis for patients with the uniformly lethal pontine glioma.

Antineoplastic Combined Chemotherapy Protocols↗

Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants.

Eighty-one primary pulmonary neuroendocrine neoplasms were assessed by the classification of Gould and associates. The neuroendocrine features of these tumors were studied by a combination of conventional light microscopy, electron microscopy, and immunohistochemical staining for hormonal substances and neuron-specific enolase. In each case, clinical follow-up was obtained to test the prognostic value of this new pathological classification. This study indicated that bronchial carcinoids are very low-grade neuroendocrine neoplasms that are locally invasive and only occasionally metastasize late in their course. Well-differentiated neuroendocrine carcinomas are relatively low-grade carcinomas that either present with or subsequently develop nodal or distant metastases in 73% of patients. Intermediate cell neuroendocrine carcinomas are highly aggressive tumors often mistakenly called "large cell undifferentiated carcinoma." Their clinical course is comparable to that of small cell neuroendocrine carcinomas, which has a mean survival of 9 months. The different clinical courses of these tumors demonstrate the predictive value of the proposed classification. It appears particularly valuable to identify well-differentiated neuroendocrine carcinoma as a low-grade carcinoma, distinct from true bronchial carcinoids. This classification may resolve some discrepancies regarding the therapy for and prognosis of "carcinoids" and their presumed variants.

Biopsy↗

[Barrett's esophagus].

The diagnosis of Barrett's esophagus is rendered based on proof of intestinal metaplasia in the tubular portion of the esophagus. Barrett's develops in a percentage of patients with gastroesophageal reflux disease; risk factors include a long history of the disease, age over 40 years and Caucasian skin. Specifics about a genetic predisposition have not become known to date. Each year, around one out of every 200 patients with Barrett's epithelium develop adenocarcinoma of the esophagus, the incidence of which has risen dramatically over the past two decades. Apart from the early stages, the prognosis for this type of Barrett's carcinoma is extremely unfavorable, even after esophagectomy. It therefore appears sensible to examine patients with a long history of reflux and/or frequently recurrent reflux symptoms and to develop screening strategies for timely detection of persons with Barrett's esophagus along with subsequent monitoring. This would involve regular endoscopic studies accompanied by biopsies aimed at excluding or demonstrating the intraepithelial neoplasms that count as direct precursors to cancer. Treatment of nonneoplastic Barrett's esophagus can be symptomatic. Although theoretically logical, the benefits of normalizing esophageal acid exposure have not been proven. When high-grade intraepithelial neoplasms or mucosal carcinomas have been confirmed, local endoscopical resection and/or ablation appear sufficient, since the risk of lymph node metastasis is extremely low. Previous studies on this subject have been very promising, but should be continued and/or verified. Definitive therapy of more advanced tumor stages is currently given according to multimodal concepts established in an interdisciplinary manner.

Adenocarcinoma↗

Apolipoprotein D expression in primary brain tumors: analysis by quantitative RT-PCR in formalin-fixed, paraffin-embedded tissue.

Apolipoprotein D (apoD) expression has been shown to correlate both with cell cycle arrest and with prognosis in several types of malignancy, including central nervous system astrocytomas and medulloblastomas. ApoD expression was investigated by real-time quantitative RT-PCR using RNA extracted from 68 formalin-fixed, paraffin-embedded brain specimens. Glyceraldehyde phosphate dehydrogenase was used as an internal control. Quantitation was achieved on all specimens. Sixteen poorly infiltrating WHO grade I glial neoplasms (i.e., pilocytic astrocytomas and gangliogliomas) showed an average 20-fold higher apoD expression level compared with the 20 diffusely infiltrating glial neoplasms (i.e., glioblastoma, anaplastic astrocytoma, oligodendrogliomas; p=0.00004). A small number of exceptions (i.e., two high-expressing glioblastomas and three low-expressing gangliogliomas) were identified. Analyzed as individual tumor groups, poorly infiltrating grade I pilocytic astrocytomas and gangliogliomas differed significantly from each tumor type within the diffusely infiltrating higher-grade category (p<0.05 for each comparison) but not from each other (p>0.05). Conversely, each individual tumor type within the diffusely infiltrating category differed significantly from both pilocytic astrocytomas and gangliogliomas (p<0.05) but did not vary from other infiltrating tumors (p>0.05). Ependymomas, non-infiltrating grade II neoplasms, expressed levels of apoD similar to or lower than levels expressed by the diffusely infiltrating gliomas. Ten medulloblastomas with survival longer than 3 years averaged slightly higher apoD expression than four fatal medulloblastomas; however, this result was not statistically significant and individual exceptions were notable. In 17 of the medulloblastomas, MIB-1 proliferation rates quantitated by image cytometry did not correlate with apoD expression. In addition, apoD expression was 5-fold higher in the slowly proliferating grade I glial neoplasms compared with non-proliferating normal brain tissue (p=0.01), suggesting that apoD expression is not simply an inverse measure of proliferation. ApoD expression measured by quantitative RT-PCR may be useful in the differential diagnosis of primary brain tumors, particularly pilocytic astrocytomas and gangliogliomas.

Apolipoproteins↗

Correlation of DNA content and histology in prognosis of astrocytomas.

Thirty-two cases of astrocytoma were analyzed for DNA content and cell-cycle proliferation features by flow cytometry using paraffin-embedded tissue. The findings were correlated with histologic grading and survival. Abnormal DNA (aneuploidy or elevated G2-M fraction greater than or equal to 7%) was present in 18 cases (56%). Glioblastoma multiforme (GBM) had 11 of 16 (69%), anaplastic astrocytomas (ANA) 7 of 11 (64%), and low-grade (LG) neoplasms 0 of 5 cases with abnormal DNA content. Short-term survival (less than or equal to 26 months) occurred in all 16 patients with GBM (100%), 7 of 11 patients with ANA (64%), and 1 of 5 patients with LG neoplasms (20%). Seventeen of 18 patients (94%) with abnormal DNA content were short-term survivors (P less than 0.0002). Abnormal DNA content was found in 17 of 24 short-term survivors (71%), whereas histologic grading identified 16 of 24 such cases (67%). A combination of grading and abnormal DNA content identified 22 of 24 (92%) of the poor survival cases. DNA content was most useful in the anaplastic group. Six of seven cases (86%) with abnormal DNA content had short survival (P less than 0.055), and three of four (75%) with normal DNA content had long survival. DNA analysis combined with histologic grading improves prognosis designation.

Aneuploidy↗

"Atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus: a critique in historical perspective of three concepts flawed fatally.

Our purpose in undertaking this Arbeit was to review all articles published about "atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus, to criticize them in a fashion that illuminates, and to come to conclusions compellingly about those subjects. We found that an overwhelming majority of neoplasms that claimed to be "atypical Spitz's nevus," "metastasizing Spitz's nevus," and "malignant Spitz's nevus" were, in fact, melanomas ( Table 1). Moreover, in our estimation, those designations, and variants of them, like "atypical Spitz's lesion," "atypical dermal melanocytic lesion with features of Spitz's nevus," "atypical Spitzoid melanocytic neoplasm," and "problematic Spitzoid melanocytic lesion," are mere evasions from a diagnosis, straightforwardly, of either Spitz's nevus or melanoma. Diagnoses in pathology equally bogus are "minimal deviation melanoma," "borderline melanoma," "nevoid melanoma," "potentially low-grade melanocytic neoplasm," and "melanocytic lesion of uncertain biologic potential." Rather than admit uncertainty forthrightly, those who employ circumlocutions like those just mentioned resort to linguistic maneuvers that, at first blush, seem to be "academic" and constructed in such a way as to appear to convey confidence, rather than tentativeness, on the part of a histopathologist. On further scrutiny, however, each of those cliches is revealed to be devoid of content. For example, "malignant" Spitz's nevus and "metastasizing" Spitz's nevus not only are contradictions in terms, but they are outrageous violations of fundamental principles of classic Virchowian pathology, and "atypical" Spitz's nevus not only is a redundancy because the neoplasm was so atypical to Spitz, herself, she insisted (from the time she spawned the idea in 194 through 1951 it was a "malignant melanoma," but is abject intellectually, those who invoke it never setting forth, in clear-cut fashion, criteria for what constitutes a "typical" Spitz's nevus in contradistinction to an "atypical" one.

Diagnosis, Differential↗

[Correlation of expression of progesterone receptors with histopathological type and grade of malignancy of cerebral neoplasms].

Steroid receptors play an important role in homeostasis and in proliferation of neoplastic cells as well. Biological effect of steroid hormone on tissues depends on intracellular concentration of its receptor. The binding hormone with its receptor activates adequate genes in cellular nuclei and cell proliferation. The mutation of genes codifying of receptor protein may cause its structural modification or changes in its activity and lead to neoplastic transformation. The aim of our work was the estimation of progesterone receptors (PR) concentration in cerebral neoplasma and correlation with histopathological type and grade of malignancy of cerebral tumours. We examined 89 patients, among them 28 with meningioma, 43 with glioma and 18 with metastatic tumour. The concentration of PR was evaluated using radioreceptor assay. Our results show statistically significant correlation between expression of PR and type and malignancy of neoplastic tumours. It was especially seen in meningioma and the highest concentration of PR were in I grade tumours.

Biomarkers, Tumor↗

Epithelial-myoepithelial carcinoma of the lung. A case report and review of the literature.

Primary lung tumors mimicking the salivary gland-type neoplasms are extremely rare. These types of tumors originate from submucosal bronchial glands. Epithelial-myoepithelial carcinoma is an uncommon tumor in this group, and only 7 cases have been reported. It is considered to be a low-grade malignant neoplasm. We report a case of epithelial-myoepithelial carcinoma of bronchial gland origin in a 73-year-old man who presented with coughing and dyspnea. The bronchus of the left lower lobe contained a tumor mass that had a polypoid growth pattern. The tumor also extended into the pulmonary parenchyma, forming a well-circumscribed mass with a pushing margin. The tumor consisted of epithelial and myoepithelial cells. The epithelial cells were positive for cytokeratins and epithelial membrane antigen, while the myoepithelial cells were positive for S100 protein and muscle-specific actin. According to these findings, we diagnosed epithelial-myoepithelial carcinoma. After undergoing pneumonectomy, the patient has been disease free for 34 months.

Aged↗

[Proliferative activity of ependymomas. (Quantitative analysis of the expression of Ki67 and AgNOR)].

One of the problems connected to the anatomo-clinical evaluation of ependymomas consist in the difficulty of precisely grading these neoplasms and of making a prognosis. Traditional histopathologic procedures have proven themselves unsuitable to solve these biological problems of neoplastic growth: their solution requires the identification and responsiveness of molecules that are part of cellular kinetic processes such as antigen Ki67 and the granules of AgNOR as indexes of the rDNA transcriptional activity. With the aim of contributing to the knowledge of ependymomas' grading, the Authors performed qualitative and quantitative assays on 35 cases of benign ependymomas (by means of an image analyzer) using the nuclear antigen Ki67 and the AgNOR nucleolar areas. The results thus obtained allow to draw the following conclusions: 1) The biological validity of the labeling of antigen Ki67 and the quantification of argentophilic granules in the NOR areas has once more been confirmed. 2) The expressiveness and biological significance of antigen Ki67 is finer than what can be derived from the count of AgNOR granules. 3) The level of diagnostic reliability for the differentiation between and the corresponding malignant forms is optimal; such a level falls considerably when one wishes to grade levels of benignity of malignity. 4) Such drawbacks are likely to be due to the action of heterogeneous factors which are often unrelated to the neoplasm, such as poor oxygenation, blood stream alterations, necrosis, phlogosis, nutritional conditions of the cell populations etc.

Adolescent↗