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PubMed2001

The association between tumour progression and vascularity in myxofibrosarcoma and myxoid/round cell liposarcoma.

Angiogenesis is an important factor in the morphological progression and metastasis of many solid tumours. We studied two homogeneous series of myxofibrosarcoma (MFS) and myxoid/round liposarcoma (MRLS), characterised by distinct vascular patterns and correlated the intratumoral microvessel density (IMD) with morphologic progression in both types of sarcoma. In our study, 43 cases of MFS and 42 cases of MRLS were graded according to established diagnostic criteria. For evaluation of IMD, representative sections were stained immunohistochemically for CD31. After selection of "neovascular hot spots", IMD was calculated by measuring the endothelial surface within twenty 200x fields in relation to the total analysed area. In addition to the correlation of IMD with histological grades of malignancy, a correlation of IMD with the inflammatory infiltrate in MFS was done. To determine whether vascular endothelial growth factor (VEGF) and its receptors, KDR and flt-1, may play a role in the progression of both types of sarcomas, we used mRNA in situ hybridisation (ISH) to study VEGF, KDR and flt-1 expression in selected cases. In addition, the expression of thrombospondin-1, which has been reported to inhibit angiogenesis, and of collagen type I was studied using mRNA ISH. Cases of MFS varied histologically from hypocellular, mainly myxoid, neoplasms (low-grade malignant, 18 cases) to intermediate-grade malignant lesions with increased cellularity and mitotic activity (13 cases), and high-grade malignant cases with marked pleomorphism, high proliferative activity and areas of necrosis in many cases (12 cases). Cases of purely low-grade myxoid liposarcoma (16 cases) were characterised by low-cellularity, mucin pooling and plexiform vasculature. In combined MRLS, these hypocellular areas were admixed with hypercellular, round cell areas (5-80% of the analysed tumour area; 23 cases), and in round cell liposarcoma (three cases) rounded tumour cells predominated (>80% of the analysed tumour area). The average IMD in intermediate and high-grade malignant MFS (4.03 and 4.09, respectively) was significantly higher than in low-grade malignant MFS (2.73). Correlation of vascularity with the inflammatory infiltrate in MFS showed increased IMD only in cases with abundant neutrophils; most of these cases were high-grade malignant neoplasms. In contrast, no statistical correlation between morphological progression and IMD was seen in myxoid liposarcoma (6.08), MRLS (6.57) and round cell liposarcoma (4.07). VEGF mRNA was expressed by tumour cells in all histological grades of MFS and MRLS. VEGF receptor mRNA was weakly expressed by endothelia of newly formed blood vessels in both entities. Interestingly, tumour cells of all analysed cases of MFS strongly expressed collagen type I and thrombospondin-1, while these proteins were not detected in tumour cells of MRLS. In conclusion, morphologic tumour progression in MFS is associated with increased IMD, whereas, in MRLS, no such correlation is seen. Whereas VEGF and VEGF receptor mRNA were expressed in both entities, a characteristic expression profile of collagen type I and thrombospondin-1 in MFS emerged. Further studies are necessary to correlate vascularity and clinical course in MFS and MRLS.

Adolescent↗
PubMed2006

A study of the utility of silver nucleolar organizer regions in categorization and prognosis of salivary gland tumors.

BACKGROUND: this study aimed at assessing the utility of silver nucleolar organizer region (AgNOR) staining in categorization and prognostication of salivary gland tumors. METHODS: Twenty-seven malignant salivary gland tumors, 16 benign neoplasms, and 6 chronic sialadenitis lesions were stained using the technique described by Ploton et al. (1986). RESULTS: The mean AgNOR counts for inflammatory lesions (1.67 +/- 0.19) and benign neoplasms (1.67 +/- 0.11), were less than for malignant neoplasms (3.59 +/- 0.55), P < .05. There was no significant difference between the mean AgNOR counts of different specific histological types and grades of malignant neoplasms. In addition, no correlation was found between mean AgNOR counts and the clinical course of malignant or benign salivary gland neoplasms. CONCLUSION: Our results suggest that AgNOR staining is useful for distinguishing benign from malignant lesions, but is neither helpful for discriminating between histological types and grades of malignant neoplasms, nor prognostication of malignant salivary gland neoplasms.

Adenocarcinoma↗
PubMed2000

Expression of DNA topoisomerase I in neoplasms of the kidney: correlation with histological grade, proliferation, and patient survival.

Renal cell carcinoma is an inherently chemotherapeutically resistant neoplasm. Because of this, new drugs targeting this tumor are needed. One class of new anticancer drug targets the enzyme DNA topoisomerase I. Laboratory data indicate that cells sensitive to topo I targeting drugs contain high topo I levels. To determine whether some renal cell carcinomas contain elevated topo I and might therefore be targets of topo I active antitumor agents, we used a new immunohistochemical stain for topo I to determine the expression of the enzyme in 51 tumors of the kidney. Increased topo I expression was found in 4 of 11 (36%) grade 3 renal cell carcinomas and in 8 of 8 (100%) grade 4 renal cell carcinomas. Normal topo I expression was observed in all adenomas, oncocytomas, and grade 1 and grade 2 renal cell carcinomas. Because topo I targeted anticancer drugs are S-phase specific, topo II-alpha and MIB-1 proliferation indices also were performed. Topo II-alpha correlates well with MIB-1 (correlation coefficient = 0.96). Of the 12 tumors with elevated topo I, only 3 had topo II-alpha proliferation indices greater than 40, indicating a tumor with elevated topo I expression and a large growth fraction. We hypothesize that these tumors might be susceptible to topo I anticancer drug therapy. In addition, we found that the average topo II-alpha proliferation index of tumors from patients who died of disease was 27.4 +/- 19.8, which was statistically different from the average topo II-alpha index of 5.8 +/- 6.5 observed in tumors from patients who remained alive during our follow-up.

Adenoma↗
PubMed1988

[Conservative treatment of grade 3 intra-epithelial cervical neoplasms. Comparative study of CO2 laser vaporization, laser conization and cold scalpel conization].

Carbon dioxide laser was used in 79% of the 141 conservative treatments carried out for grade 3 cervical intra-epithelial neoplasia (CIN III) between the years 1982 and 1986 (41% vaporized and 38% coned out by using the laser as against 21% that were treated by scalpel conisation. The mean age of the women treated in this way by the laser was low (28.5 years of age and 32.5 years as against 38.1). Their parity was also low (0.8 and 1.2 as against 2.2). The lesions were very often spread out on the ectocervix and sometimes going into the vagina (26 and 9% as against 26%) or associated with koilocytosis (65.5 and 47.2% as against 41.3%). In one out of two cases vaporisation of the lesion is contra-indicated and the three diagnostic methods that are used (an ecto and endocervical smear, colposcopy and multiple directed small biopsies) do not make it certain that there is no underlying invasion of the tissues. Vaporisation and conisation are easily carried out under colposcopic control and are associated with widespread lesions at the squamo-columnar junction. These treatments sometimes have to be repeated; then they give a cure rate of 92-96% as against 96%. They are more reliable than conventional surgery for widespread lesions and they do make it possible to keep to the morphology of the cervix and thus make it possible for the cervix that is treated to behave more physiologically. It is also much easier and more reliable in these cases to carry out follow-up for carcinoma. This follow-up should be carried out on two occasions. The triple diagnostic method should be carried out again at the third month (2 smears, colposcopy and colposcopically directed small biopsies). This makes it possible to diagnose and treat early the cases where there has been failure of the original treatment. Then ecto and endocervical smears should be repeated at 3-monthly intervals, then at 6-monthly intervals and finally annually to screen for recurrences of these neoplastic conditions, and for koilocytosis which sometimes repeat themselves in an extensive manner.

Adult↗
PubMedDate not supplied

Stereotactic radioisotope implantations in the treatment of inoperable low malignancy neoplasms.

The authors report their experience of 53 patients with low grade malignancy cerebral neoplasms treated by means of stereotactic 125-I permanent interstitial radiotherapy. The method has been employed from 1981 to date. The authors confirm the validity of the technique in this brief report, and stress the greater efficacy of this treatment in young patients (less than 40 y/o) than in adults.

Adult↗
PubMed1994

Gastrointestinal autonomic nerve tumor presenting as high-grade sarcoma. Case report and review of the literature.

Gastrointestinal autonomic nerve (GAN) tumors, also known as plexosarcomas, are a rare distinct subtype of the gastrointestinal stromal tumors. These tumors are usually histologically low-grade, epithelioid or spindle-cell neoplasms that can be distinguished from the other gastrointestinal stromal tumors on the basis of their unique ultrastructural features. A 66-year-old female presented with a histologically high-grade sarcoma of the small bowel. Ultrastructural studies showed features of a GAN tumor. The light microscopic and ultrastructural features are described. The tumor cells gave strong, diffuse staining for vimentin and synaptophysin, and weak focal staining for neuron-specific enolase and S100. While usually presenting as low-grade neoplasms on histologic examination, this case demonstrates that GAN tumors should be considered in the differential diagnosis of a histologically high-grade sarcoma of the gastrointestinal tract, especially when evidence of smooth muscle, peripheral nerve sheath, or neuroblastic origin is not forthcoming.

Aged↗
PubMed2004

Fine-needle aspiration of primary and recurrent benign fibrous histiocytoma: classic, aneurysmal, and myxoid variants.

There is a limited number of correlative cytopathological studies of fibrous histiocytoma (FHC). To better define cytopathological criteria of diagnosis, we have reviewed fine-needle aspirates (FNA) from 36 FHCs (32 classical, 1 myxoid, and 3 aneurysmal variants on corresponding histological sections). Original cytological diagnoses were benign in 33 (91.7%) cases (22 accurate) and false positive in 3 (8.3%) cases. All smears were surprisingly homogenous and composed of histiocytic cells with finely vacuolated cytoplasm in 27 (75%) cases, small regular spindle cells in 25 (69%) cases, and giant cells in 17 (47%) cases. Histiocytic cells were attached to vascular structures in 9 (25%) cases. Slight cytonuclear atypia was seen in five (14%) cases. Three (8.3%) cases showed numerous siderophages. In two (5.6%) cases, there were abundant inflammatory backgrounds and in one (3%) case there was a scant myxoid background. Storiform patterns, round cells, prominent atypia, necroses, or mitotic figures were not seen. FHC should be differentiated from other benign, low- and intermediate-grade spindle-cell neoplasms such as low-grade fibrosarcoma, dermatofibrosarcoma protuberans, nodular fasciitis, spindle-cell malignant melanoma, and monophasic synovial sarcoma. Some cases may be misinterpreted as malignant, especially in cases of recurrence or in patients with a cancer history.

Adolescent↗
PubMed1996

Loss of adipocyte-type fatty acid binding protein and other protein biomarkers is associated with progression of human bladder transitional cell carcinomas.

Multifocal recurrent papillary tumors provide a unique model system to study the molecular mechanisms underlying the steps involved in transitional cell carcinoma progression and offer a valuable source of material to search for biomarkers that may form the basis for diagnosis, prognosis, and treatment. We have examined the protein expression profiles of normal bladder urothelium and of 63 transitional cell carcinomas of various histopathological grades and T stages using high-resolution, two-dimensional gel electrophoresis, microsequencing, mass spectrometry, and a two-dimensional gel protein database approach for polypeptide identification (http://biobase.dk/cgi-bin/celis). In general, the results revealed a striking similarity between the overall qualitative expression patterns of papillary tumors of all grades, as well as of papillary and solid tumors of grade III. With few exceptions, tumors of grades I-III expressed, albeit at different levels, all of the keratins (7, 8, 13, 17, 18, 19, and 20) found in the normal urothelium. Grade IV tumors lacked or expressed reduced levels of keratin 13 but most resembled low-grade tumors. One invasive grade IV tumor, however, expressed a fibroblast-like protein phenotype. Four proteins that were expressed by normal urothelium and were lost at various stages of progression were identified as glutathione S-transferase mu, prostaglandin dehydrogenase (PGDH), a fatty acid binding protein with homology to the adipocyte isoform (A-FABP), and keratin 13. The percentage of tumors expressing A-FABP was very high in low-grade lesions but decreased drastically (P = 0.0006) in grade III and IV neoplasms. In addition, low-grade tumors contained more A-FABP than their high-grade counterparts. The stage of the disease was also statistically (P = 0.0269) related to the presence or absence of A-FABP in grade III tumors. Similar analysis of glutathione S-transferase mu and PGDH showed a statistically significant decrease of these proteins in high-grade (grades III and IV) tumors (P = 0.0026 and P = 0.0044, respectively). Only PGDH showed a suggestive correlation (P = 0.0775) with the stage of the disease in grade III tumors. Keratin 13 showed a drastic decrease in grade IV tumors. In addition to identifying biomarkers that may have prognostic value, our studies have suggested that A-FABP is an important component of the pathway(s) leading to bladder cancer development.

Biomarkers, Tumor↗
PubMed2005

High-grade trichoblastic carcinoma arising in trichoblastoma: a rare adnexal neoplasm often showing metastatic spread.

It has been debated whether malignant transformation of trichoblastoma occurs. The concept was recently forwarded that basal cell carcinoma is as a malignant neoplasm of follicular germinative cells and should be named trichoblastic carcinoma to show its relationship to trichoblastoma. Almost all basal cell carcinomas are low-grade malignant neoplasms and develop metastases only very rarely, and if so, only after very long duration and untreated growth. Only rare basal cell carcinomas arise in trichoblastomas. Up to now there have only been two reports of high-grade trichoblastic carcinoma arising in trichoblastoma, showing systemic metastatic spread and death. We add two further cases of trichoblastic carcinoma with anaplastic nuclei, arising in trichoblastoma. One of the tumors arose in a small nodular trichoblastoma on the right forearm of an 84-year-old male patient. The other one was a trichoblastic carcinoma at the base of a trichoepithelioma on the right thigh of an 87-year-old woman with Brooke-Spiegler syndrome. Our cases emphasize that high-grade trichoblastic carcinoma develops via malignant transformation of trichoblastoma, and is very rare.

Aged↗
PubMed1978

The role of exfoliative cytology in the management of bladder carcinoma.

Cytological analyses of bladder washings from 974 patients with disorders of the urinary tract are reported. The cytological findings were compared with the clinical and histological diagnoses. The histological grading of bladder tumours was based on the classification proposed by Bergkvist et al. No false positive diagnosis of malignancy was made in the 320 patients without tumour growth. The five cases with positive cytology had histologically verified carcinoma in situ. The frequency of cytological diagnosis of cancer increased with the histological grade of malignancy in the 428 patients with bladder neoplasm. Carcinoma was graded in smears according mainly to the degree of epithelial atypia. A comparison with the histological grading was attempted. Of 226 cases of bladder carcinoma treated with supervoltage irradiation, 108 had persistence or recurrence of carcinoma. The clinical diagnosis was cytologically confirmed in 92 per cent of these cases.

Carcinoma in Situ↗
PubMed1996

Additional neoplasms and HCV infection in low-grade lymphoma of MALT type.

Several chronic inflammatory conditions and genetic alterations are likely to be involved in the pathogenesis of low-grade lymphoma of MALT type. In a well-characterized series of 27 patients with low-grade lymphoma of MALT type, we studied: (1) the incidence of other neoplasms, which might be indicative of genetic instability, apparently a characteristic of this disease; (2) the prevalence of serologic and molecular markers of HCV infection, which has been found in association with other lymphoproliferative disorders. Three patients had one or more additional cancers; a total of eight tumours, five of which occurred in the same patient, suggests the presence of some genetic instability in at least some cases of the disease. Rather unexpectedly, anti-HCV antibodies and HCV RNA sequences were documented in 50% of the patients examined, without elevation of serum transaminases. Of interest, the two patients with parotid and conjunctival MALT lymphomas, respectively, with a previous history of Sjögren's syndrome, were HCV positive. We suggest, for the first time, that HCV may be considered, in addition to Helicobacter pylori, as another potential infectious co-factor in the multistep pathogenesis of low-grade lymphomas of MALT type.

Adult↗
PubMedDate not supplied

[The reliability of biopsy-determined grading in laryngeal squamous cell carcinoma].

Grading evaluation is becoming increasingly more important in establishing a valid prognosis and in the choice of therapeutical strategies in dealing with squamous laryngeal cancer. It follows, therefore, that grading of bioptic tissue, made before therapy planning, must offer reliable data and correspond to data gathered through grading of the entire neoplasm. Thus the aim of our study carried out on 267 cases was to verify if grading of bioptic tissue corresponds to that of the operatory specimen. In 7% of the cases (19 in 267) bioptic grading overestimated the neoplasm in that post-operatory grading revealed a less differentiated form. On the contrary, in 16% of the cases (43 in 267) bioptic grading underestimated the form since as post-operatory grading showed a more highly differentiated form. It appears clear that these values depend on the clinical extension of the neoplasm in that the difference was inferior in the case of limited neoplasms and greater in that more largely extended ones. Generally speaking then, the less extended the neoplasm (the most frequently observed clinical form), the more coinciding the bioptic evaluation indicating good differentiation with the post-operatory evaluation. On the other hand, bioptic evaluation indicating moderate or poor differentiation is less reliable since it does not coincide with findings in approximately 16% of the neoplasms, above all those most limited (12%). This means that any reductive adoption of therapy planning made on the basis of the degree of differentiation revealed upon bioptic examination is possible only in the case of those forms more advanced with regard to extension.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed2004

Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas.

PURPOSE: The purpose of this study was to determine the extent of p63 immunoreactivity in the malignant salivary gland neoplasms adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare this to the expression of this marker in the benign salivary gland tumors canalicular adenoma and basal cell adenoma. Few studies on the expression of p63 in head and neck salivary gland tumors have been published to date. P63, a selective immunohistochemical marker of basal/stem cells of stratified epithelium and of myoepithelial cells, is a p53 homologue that plays an essential role in both morphogenesis of epidermis and limb development. P63 immunoreactivity has been demonstrated in squamous cell and urothelial carcinomas. It is generally absent in most nonsquamous cell carcinomas. Study design Formalin-fixed paraffin-embedded sections from 49 salivary gland neoplasms, representing 6 canalicular adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to 2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY, were stained with an anti-p63 monoclonal antibody. RESULTS: Nuclear p63 reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was also identified in the majority of cases of ACC (13/15, 87%), primarily in the nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of parotid origin stained strongly for p63, with staining localized to the peripheral tumor cells situated adjacent to the connective tissue stroma. None of the basal cell adenomas originating in the upper lip stained with p63. In native adjacent salivary gland tissue, p63 reactivity was identified focally in the nuclei of myoepithelial and basal duct cells. CONCLUSIONS: P63 is strongly expressed in basal cell adenoma of parotid origin, and in ACC and PLGA. Canalicular adenoma did not demonstrate p63 staining, consistent with this tumor's putative luminal ductal cell differentiation. Our results suggest that the neoplastic cells in PLGA may represent either a population of p63-positive epithelial stem/reserve cells similar to the basal cells of stratified epithelium, or modified myoepithelial cells. Given the staining pattern of the tumors examined, p63 does not appear to be an ideal marker for distinguishing between ACC, PLGA, and basal cell adenoma.

Adenocarcinoma↗
PubMed1980

Bronchial adenoma. Clinicopathologic study and results of treatment.

Among 1,700 primary tumors of the lung, there were 53 cases of bronchial adenoma (3.1 percent); 38 (72 percent) of the 53 were typical carcinoids, and the remaining 15 were of a higher grade of malignant neoplasm. There was a slight predominance of female patients, and the age of greatest incidence was between 30 and 50 years (31/53; 58 percent). The most frequent localization was in the main bronchi and in the left bronchial tree. In cases of higher grades of malignant neoplasm, extensive bronchopulmonary resections were performed, while in the less active and less metastatic carcinoids, partial resections were generally performed, using bronchoplastic techniques, sleeve resections, and grafts, except in those cases in which bronchial obstruction had produced extensive and irreversible lesions. Survival at five and ten years after surgery is presented.

Adenocarcinoma↗
PubMed1990

[The reliability of the grading assessment of the biopsy samples in malignant colorectal neoplasms].

The authors evaluate the results of preoperative bioptic grading compared with those obtained from postoperative specimens. Altogether, there was nonagreement in 45% of cases; therefore there is the risk of underestimating the biological aggressiveness of the disease. In fact, 68% of patients who were assessed as G1 in preoperative staging were found to have a higher degree of neoplastic dedifferentiation.

Adult↗
PubMed2005

Matrix metalloproteinase expression is related to angiogenesis and histologic grade in spindle cell soft tissue neoplasms of the extremities.

We defined the immunocytochemical expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in benign soft tissue neoplasms, fibromatoses, and sarcomas, together with the activity of gelatinase MMPs and TIMPs measured by zymography and reverse zymography in a subset of cases. The most strongly expressed MMP in all tumors was MMP-1, with weaker expression of MMP-10, MMP-11, and MMP-14 in most tumors. Nuclear expression of MMP-1, MMP-8, and MMP-13 was an unusual feature. TIMP-2 was expressed in all tumors, with stronger expression in fibromatoses than in sarcomas. Fibromatoses and high-grade sarcomas showed greater MMP-1 expression than other groups, and endothelial MMP-2 expression was more extensive in sarcomas. Differences in MMP and TIMP expression might be linked to the biologic behavior of soft tissue neoplasms. The activation of endothelial MMP-2 linked to widespread MMP-14 expression provides a mechanism for sarcomas to modulate their matrix and facilitate angiogenesis.

Adolescent↗
PubMed2002

The WHO/ISUP 1998 and WHO 1999 systems for malignancy grading of bladder cancer. Scientific foundation and translation to one another and previous systems.

Recently, two new classification systems for grading of urothelial neoplasms have been published. The objective of both was to avoid the overdiagnosis of cancer and to create better criteria for the grades. The WHO/ISUP classification of 1998 distinguishes papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), low and high grade carcinomas, whereas the WHO 1999 system subdivides the high grade into grades II and III, and is otherwise identical. This note summarizes studies supporting the rationale of the two new systems, describes pattern recognition criteria for the grades, and highlights the homology between them.

Carcinoma↗