High Incidence Of Malignant Transformation Research Articles

Primary Melanocytic Tumors of the Central Nervous System in Children: Imaging Features with Pathologic Correlation

Primary melanocytic tumors of the central nervous system are rare neoplasms arising from proliferation of multipotent melanin-containing neural crest cells found in the leptomeninges. This review describes the imaging appearance of the entire spectrum of primary melanocytic tumors of the brain and spine in the pediatric population, in correlation with histopathology, clinical features, and prognosis, using sample cases from our institution. These tumors are subclassified by the World Health Organization on the basis of disease distribution and pathologic aggressiveness into the following 4 subtypes: meningeal melanocytoma, meningeal melanoma, meningeal melanocytosis, and meningeal melanomatosis. They can occur in any age group, though the diffuse form of the disease is more prevalent in children and has an association with giant cutaneous melanocytic nevi. Imaging is characterized by hyperattenuation on CT and intrinsic T1 hyperintensity on MR imaging from the presence of melanin and/or hemorrhage. The focal forms usually manifest as dural-based hemorrhagic masses, and the diffuse forms demonstrate dural thickening and enhancement, with or without hydrocephalus. There is a predilection for the medial temporal lobes, posterior fossa, and upper cervical spine. The prognosis is often poor, with a high incidence of malignant transformation of benign disease.Learning Objective: To describe the imaging appearance of the spectrum of primary melanocytic tumors of the brain and spine in the pediatric population and to review the histopathology, clinical, and prognostic data available

Intrathoracic Liver Heterotopia: An Incidental Finding at Autopsy

AbstractHeterotopia is the presence of a particular tissue at a nonphysiological site. The most common sites are gastric, pancreatic, and splenic heterotopias. While liver heterotopias are rare, intrathoracic heterotopias are much more limited. It is usually reported incidentally on imaging investigations or at autopsy. There is a high incidence of malignant transformation of heterotopic livers, and hence resection is always recommended. Here we report a case of heterotopic liver tissue in the right lung in a 42-year-old male, incidentally found at the gross examination of autopsy specimen of the lung.

Growth-regulated oncogene-α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells.

Oral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous lesions with high incidence of malignant transformation. In addition to cancer cells, cancer-associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth-regulated oncogene-α (GRO-α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO-α from OSF-associated fibroblasts in oral cancer progression. We isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST-1 cell proliferation assay, rhodamine-phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO-α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage-independent growth. GRO-α was identified to be increased in conditioned media of OSF-associated fibroblasts. GRO-α promotes DOK cells proliferation, migration, and anchorage-independent growth through enhancing the EGFR/ERK signaling pathway, F-actin rearrangement, and stemness properties, respectively. Moreover, GRO-α neutralizing antibodies downregulated the conditioned medium-induced cell proliferation and migration of DOK. GRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.

Oral Submucous Fibrosis as an Overhealing Wound: Implications in Malignant Transformation.

Oral submucous fibrosis is an oral potentially malignant disorder with high incidence of malignant transformation and rising global prevalence. However, the genesis of oral submucous fibrosis is still unclear despite superfluity of literature. In the background of ineffective treatment, it is necessary to decode its onset and progression before designing customized treatment regimens. The objective of this article is to decipher the pathogenesis of oral submucous fibrosis in order to identify novel drug targets. A thorough literature review based on oral submucous fibrosis being an overhealing wound was conducted; several related patents were identified and herewith reviewed. Necessary pathways were elaborated and deliberated in the manuscript in the form of schemas, keeping our hypothesis in mind. Several novel molecular targets were identified and discussed in detail. Several patents demonstrating inhibition of fibrosis via chemokine ligand mimetics, anticonnexon antibodies, stem cell therapy, fibronectin blocking peptides, HIF inhibitors, recombinant erythropoietin, xanthine oxidase inhibitors, long non-coding RNAs, targeting inflammation, increasing TH-1/TH-2 cytokine ratio, t-box protein 4, chromium containing compositions, Iron-based nanocomposites, Lactate Dehydrogenase-5 inhibitors, Carbonic Anhdrase-9 inhibitors, proton pump inhibitors, liposomal encapsulated glutathione, monocarboxylate-4 inhibitors, autophagy inhibitors, Submucosal anti-IL-6 antibodies, fibrin degradation products for monitoring of malignancy and fibrosis, small molecule antagonists like vorapaxar, tiplaxtinin, and TM-5275, TGF-β signalling inhibitors were identified as future therapeutic avenues. Considering, oral submucous fibrosis as an overhealing wound explains both pathogenesis and malignant transformation. Certainly, abnormalities in coagulation and fibrinolytic system are a common denominator in the profibrotic milieu and associated malignancy.

Optimization of CSF3R Mutation Detection in Severe Congenital Neutropenia and Cyclic Neutropenia Patients for Routine Diagnostics Using Next Generation Sequencing

Severe congenital neutropenia (CN) is a group of bone marrow failure syndromes characterized by absolute neutrophil counts below 0.5x109/L, susceptibility to bacterial infections and frequently associated with maturation arrest at promyelocyte stage in the bone marrow (BM).There is a high incidence of malignant transformation among CN patients with a cumulative rate of MDS/AML 22 % after 15 years of G-CSF treatment. The acquisition of G-CSFR truncating mutations is a risk factor for leukemic transformation in CN patients. Therefore, annual monitoring of CSF3Rmutations by means of next generation sequencing (NGS) is required for identification of CN patients with high risk of MDS/AML development.Since CSF3R mutations usually occur at low frequency without additional clinical features, it is important to carefully select suitable clinical sample type and methods for mutation detection. Next, it remains to be evaluated which CN genetic subgroups should be considered for annual screening of CSF3Rmutations.We performed CSF3R mutational screening in DNA and/or cDNA in 101 patients (ELANE, n = 42; HAX1, n = 16; G6PC3, n = 7; JAGN1, n = 2; WASP, n = 1; digenic ELANE, HAX1, n =1; digenic HAX1 and G6PC3, n =1; inherited mutations in CSF3R, n = 2; genetically unclassified CN, n = 9; cyclic neutropenia (CyN), n = 20) from the European Branch of the Severe Congenital Neutropenia Registry (SCNIR).Using DNA deep sequencing we screened 63 of 81 CN-patients and 20 CyN patients. Using this method, we identified CSF3R mutations in 22.2% (14/63) of CN patients and 10% (2/20) of CyN patients. The frequency of CSF3R mutations in CN patients with known inherited mutations was 20% (11/55): 30 % (3/10) in CN-HAX1 patients, and 22.9 % (8/35) in CN-ELANE patients. Interestingly, 3/8 (37.5 %) patients harbouring CSF3R mutations were observed in genetically unclassified CN. We did not detect any acquired CSF3R mutations in the small groups of CN patients (n=10) harbouring inherited G6PC3, JAGN1, CSF3Ror digenic mutations.In order to increase the sensitivity of mutation detection we performed cDNA deep sequencing of the critical region of G-CSFR. We sequenced 38 CN patients (ELANE, n = 15; HAX1, n = 11; JAGN1, n = 2; G6PC3, n = 2; WASP, n = 1; germline CSF3R, n = 1; genetically unclassified, n = 6). We found 13% (2/15) CN-ELANE, 27% (3/11) CN-HAX1 and 33% (2/6) genetically unclassified CN patients to be positive for acquired mutations in the critical region of G-CSFR. One CN patient with WASP mutation also acquired CSF3R mutation. Based on our sequencing data we would suggest CSF3Rmutation sequencing in all studied groups of patients regardless of mutations in ELANE and HAX1 genes.Intriguingly, 3 out of 5 CN patients with CSF3R mutations detected by cDNA deep sequencing were negative based on results of previous DNA deep sequencing. All of them were found to acquire low frequency CSF3R mutant clones (ELANE pos. patient with 0.3% of p.Q739* clone; genetically unclassified CN patient with 2% of p.Q749*clone; HAX1pos. patient with 0.9% of p.Q749* clone) in cDNA deep sequencing.In 2 patients (one CyN-ELANE and one CN-HAX1) with multiple acquired CSF3R mutations we compared mutant clone enrichment in different cell types (BM MNC; BM PMN; PB MNC and PB PMN) by means of cDNA and DNA deep sequencing. In the CyN-ELANE patient with 2 CSF3R mutant clones, the highest mutant allele frequency (MAF) was detected in the cDNA sample of PB PMN (11% of p.Q749* clone and 0.44% of p.Q739* clone), whereas in the PB MNC cDNA sample clone p.Q749* had only 2.5% MAF and clone P.Q739 was not detectable. Similar to that, in the CN-HAX1 patient the highest MAFs for all 3 CSF3R mutant clones were in PB PMN cDNA and the lowest in PB MNC DNA sample. Frequency of mutated CSF3Rclones in BM PMNs of both patients was comparable to PB PMN samples.Taken together, sequencing of cDNA extracted from peripheral blood or bone marrow PMN samples may provide better results than from MNC in terms of frequency of CSF3R mutation detection in CN and CyN patients. Sequencing of cDNA extracted from BM or PB samples allows enrichment of G-CSFR expressing mutant cells, but due to intrinsic low fidelity of reverse transcriptase the threshold level for positive calls could not be improved significantly (current threshold for candidate calls is 0.2-0.5%).We would suggest CSF3R mutation screening using deep-sequencing of cDNA from peripheral blood PMN in all patient groups (CN and CyN) for routine diagnostics. DisclosuresNo relevant conflicts of interest to declare.

ED-24 * GANGLIOGLIOMAS IN CHILDREN- THE MD ANDERSON CANCER CENTER EXPERIENCE

BACKGROUND: Ganglioglioma (GG) are rare mixed glial-neuronal neoplasms of the central nervous system. METHODS: Retrospective review of 57 patients below 21 years diagnosed with GG at MD Anderson Cancer Center, Houston from 1992 to 2012 was performed. Patient demographics, clinical history, radiological features and treatment data were collected and analyzed. Kaplan-Meier and Cox-regression analysis were used to assess disease progression free survival (PFS) and symptom free survival (SFS) time after surgery. RESULTS: Median follow-up period was 6.08 years with mean age at presentation as 10.89 years. 3 patients had tumor recurrence after gross total resection (GTR) and 16 patients had sub-total resection (STR). Patients with GTR had a longer PFS time compared to patients with STR (5-year PFS 89% vs. 13%; p < 0.0001). Tumor type (cystic versus mixed cystic/solid) and location (supra-tentorial vs. infra-tentorial) of tumors correlated significantly with prolonged PFS (p = 0.014, p < 0.0001). Children 14 years or older were noted to have longer PFS than younger ages (p = 0.0053). Both PFS and SFS worsened with the adjuvant therapy use (p = <0.0001, p = 0.0027). 2 of the 4 patients had malignant transformation following radiation therapy. One patient was diagnosed with grade IV anaplastic GG and 4 patients died due to progressive tumor. Based on multivariate analyses, PFS and SFS correlated significantly with the surgery type (GTR vs. STR; HR = 0.185, p = 0.0262) and adjuvant therapy (Yes vs. No; HR = 0.222, p = 0.044). CONCLUSION: We present one of the largest retrospective reviews of pediatric gangliogliomas. High incidence of malignant transformation (15.38%) following radiation was noted in STR tumors. Extent of surgery, adjuvant treatment, location and radiological feature of the tumor correlated significantly with PFS, whereas age and adjuvant treatment with SFS. Larger prospective studies are warranted to better understand the molecular signature including targetable mutations of this rare tumor, and evaluate the need and define an optimal adjuvant therapy.

Management of Hepatocellular Adenoma: Recent Advances

Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the β-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-1α-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of HCA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended.

Gastric outlet obstruction due to a giant antral polyp which have malignant transformation

Introduction: Gastric polyps are seen 2–3% in all gastrointestinal endoscopic examinations. Hyperplastic polyps, the most common type of gastric polyps, are present 85–90% of cases. Giant villous tumors of the stomach are somewhat rare and the high incidence of malignant transformation of them requires prompt diagnosis. Giant gastric polyps can also cause gastrointestinal bleeding that leads to iron deficiency anemia or partial gastric outlet obstruction. All giant polyps must be resected endoscopically or surgically and still there are no marked

Endoscopic Multiple Gastric Polypectomy in Two Phage of the Same Patient - A Case Report and Discussion

A POLYP is defined as a proliferative or neoplastic of gastrointestinal mucosal layer. It is a lesion which appeared at endoscopy, protruding into the lumen of digestive tract as discrete projection above the adjacent mucosal surface. In most cases, polyps are incidental findings during routine endoscopy, also they are typically found incidentally when upper gastrointestinal endoscopy is performed for an unrelated indication. These lesions have previously been accepted as completely benign but Gastric adenomas have a higher incidence of malignant transformation than adenomatous polyps in colon. Though polypectomy has various immediate and delayed complications, Specially in case of multiple polypectomy. Multiple polypectomy has been advised and applied in several phages for the achievement of complete removal of polypoid lesions in same patient. In the aim to reduce the frequency of this invasive procedure and to achieve a probable safe limit in a single phase we performed an evaluatory multiple endoscopic gastric polypectomy under extensive precaution and close supervision in two phages of a same patient. To avoid possible hazards and to minimize the complication as possible we choose a non-diabetic, non-hypertensive patient with no established cardiovascular disorder. In first phage a number of thirty two and in second phage twenty nine gastric polyps had been success fully removed by electro coagulation without any immediate or delayed complications.

PITX1 is a reliable biomarker for predicting prognosis in patients with oral epithelial dysplasia

Paired-like homeodomain 1 (PITX1) genes are essential in human development. In the present study, PITX1 protein expression was evaluated in human normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC), with the aim of examining the expression patterns of these critical genes during the multi-stage transformation of oral epithelial dysplasia to OSCC. PITX1 and Ki-67 expression were assessed by immunohistochemistry in 26 individuals with normal oral mucosa, 106 patients with oral epithelial dysplasia and 97 OSCC patients. The labeling indices (LIs) of PITX1 and Ki-67 were calculated and their correlation with the incidence of malignancy was evaluated. The PITX1 LI of the dysplasia specimens was significantly lower than that of the normal oral mucosa samples, but significantly higher than that of the OSCC samples. The oral epithelial dysplasia patients that exhibited low PITX1 expression showed a significantly higher incidence of malignant transformation than those exhibiting high PITX1 expression, regardless of the histological grades of their oral epithelial dysplasias. On the other hand, no correlation was observed between the Ki-67 LI and the incidence of malignancy. These results suggested that PITX1 suppression is associated with malignant transformation in the oral epithelium and that PITX1 expression may serve as a novel biomarker for predicting prognosis in oral epithelial dysplasia.

Human papillomavirus–related genital disease in the immunocompromised host

Human papillomavirus is responsible for common condyloma acuminata and a number of premalignant and malignant anogenital lesions. The immunocompromised population is at particular risk because of a higher incidence of malignant transformation. Lesions in this population may prove refractory to standard treatment. This is part II of a two-part review that will discuss the treatment of condyloma acuminata and vaginal, vulvar, penile, and anal intraepithelial neoplasias. This article will provide an updated review of available treatments, with a focus on recent advances and the challenges faced in successfully treating human papillomavirus lesions in the immunocompromised host.

Mean Corpuscular Volume as An Early Predictor of Malignant Evolution of Monoclonal Gammopathy of Undetermined Significance

AbstractAbstract 1925 Introduction:Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant clonal plasma cell proliferative disorder. It occurs in over 3 percent of the general population over the age of 50. MGUS can progress to multiple myeloma (MM) or related cancers at a rate of about 1.0 to 1.5 percent per year. There are no findings at diagnosis of MGUS that reliably distinguish patients who will remain stable from those who will progress to a malignant disease. Size and type of serum monoclonal protein, as well as serum free light chain ratio have been suggested in some studies as independent risk factors for disease progression. In this study, we tried to analyze the relationship between Mean Corpuscular Volume (MCV) and the risk of progression of MGUS into a malignant lymphoproliferative condition. Methods:A total of 1744 patients, from a single institution, with a first diagnosis of MGUS from April 18th, 1995 till June 24th, 2010 were included in this study. Patients analyzed were divided into two groups. Group 1 consisted of 345 patients with an elevated MCV (>100fL/red cell) and group 2 consisted of 1399 patients with a normal MCV (between 80fL/red cell and 100fL/red cell). Patients with short follow up (<3 months), low B12/folate levels, hypothyroidism, liver disease or a serum monoclonal protein >1.5g/dL were excluded. The Chi-square test was used to compare the proportion of patients who progressed in group 1 relative to group 2. Results:After a median follow up of 51 and 58 months for the high MCV and normal MCV respectively, there were 78 progressions (22.6%) versus 267 non-progressions (77.4%) among the high MCV patients (Group1) and 110 progressions (7.9%) versus 1289 non-progressions (92.1%) among the normal MCV patients (Group 2). The difference in progression between the two groups was statistically significant (Chi-square test p-value < 0.001). The odds ratio for the progression comparison of the high versus normal MCV groups was 3.4 with a 95% confidence interval of 2.5 to 4.7. Conclusion:In our single institution, retrospective study, there seems to be a higher incidence of malignant transformation in the subset of patients with MGUS having an elevated MCV. MCV is a cost effective method that might help identify, at presentation, patients with benign monoclonal gammopathies requiring stricter monitoring. Disclosures:No relevant conflicts of interest to declare.

High Incidence of Malignant Transformation of Laryngeal Papilloma in Taiwan

Papillomas of the larynx include solitary laryngeal papilloma and recurrent respiratory papillomatosis. This study investigated the incidence of malignant transformation and assessed possible risk factors for laryngeal papillomas. A prospective, longitudinal study. Twenty-six consecutive laryngeal papilloma patients were prospectively studied for 5 or more years, and each patient was periodically examined at 3 to 6 month intervals. A detailed epidemiologic questionnaire was administered at the initial visit. After enrollment, tissue obtained during each laryngeal surgery was examined by polymerase chain reaction assay for human papilloma virus (HPV) and typing. During 237 person-years of follow-up, six new, pathologically confirmed cases of laryngeal carcinoma were ascertained (incidence 2.5/100 person-years), and all were associated with HPV-6 or HPV-11. Malignant transformation revealed no correlation with the following: age less than 3 years at diagnosis, sex, history of tobacco use, history of alcohol consumption, family history of laryngeal cancer, or type of laryngeal papilloma. Laryngeal papilloma without demonstrable HPV DNA was the only significant risk factor for malignant transformation (P < .05). The cumulative risk of malignant transformation in subjects without demonstrable HPV DNA was significantly higher than that in HPV-positive patients (relative risk, 8.0; 95% confidence interval, 1.1-60.3; P = .05). A relatively high incidence of malignant transformation of laryngeal papilloma was noted in Taiwanese patients. Patients without demonstrable HPV DNA require more frequent follow-up and may benefit from anti-HPV vaccinations.

Oral Leukoplakia Related to Malignant Transformation

Oral leukoplakia and its malignant transformation are reviewed in this article. Oral leukoplakia is defined as a predominantly white lesion of the oral mucosa that can not be characterized as any other definable lesion; however, the lesion must be confirmed histopathologically by biopsy in order to discuss malignant transformation of oral leukoplakia. Malignant transformation rates of oral leukoplakia range from 0.13 to 17.5%, while the rates of five-year cumulative malignant transformation range from 1.2 to 14.5%. Some reports found a high incidence of malignant transformation in older patients. Chewing tobacco and smoking are distinct risk factors particularly among males in certain countries; however, other countries have noted that females or non-smokers may be at risk of malignant transformation. HPV has been detected in oral dysplasia lesions and cancer in non-smokers. Conflicting reports have been presented regarding the malignant transformation of oral leukoplakia with epithelial dysplasia; however, we and some authors believe that epithelial dysplasia is an important factor in the malignant transformation of oral leukoplakia. The majority of researchers showed non-homogenous leukoplakia as a risk factor, although different terms have been used to describe these lesions. There may be several routes to malignant transformation of oral leukoplakia, including transformations induced by carcinogenesis due to betel quid chewing or smoking, or by HPV infection. While no definite treatment modalities for oral leukoplakia have been established, we suggest surgical therapy with an adequate safety-margin and well-timed evaluation as an appropriate treatment in preventing malignant transformation.

Use of Interferon-Alpha in Recurrent Respiratory Papillomatosis: 20-Year Follow-up

The aim of this study was analysis of the results of use of interferon-alpha (IFN-alpha) in patients with recurrent respiratory papillomatosis (RRP) and correlation of the results with human papillomavirus (HPV) type. A multicenter prospective series (42 patients from 22 hospitals) yielded 20 years of follow-up of patients with RRP and HPV typing who were treated with IFN-alpha in doses of 3 MU/m2 3 times per week. During long-term follow-up (mean +/- SD, 172 +/- 36.8 months), the rate of event-free survival evaluated by Kaplan-Meier analysis was 42.8%, and the overall survival rate was 82.6%. The HPV typing revealed an association of HPV 11 with a more aggressive disease course (64% of HPV 11 patients versus 24% of HPV 6 patients), a lower incidence of long-term response to IFN-alpha therapy (14% of HPV 11 patients versus 64% of HPV 6 patients), and a higher incidence of malignant transformation and mortality during follow-up (36% and 24%, respectively, of HPV 11 patients versus 0% of HPV 6 patients). The obtained results revealed maximal effectiveness of IFN-alpha therapy in RRP patients with HPV 6 as compared with HPV 11. The association of HPV 11 with a worse long-term response to IFN-alpha therapy and a higher incidence of malignant transformation and mortality is clinically important and indicates the necessity of HPV typing in RRP patients after the first biopsy.

Long term follow-up study of laryngeal precancer

The goal of this study was to determine subsequent malignancy on a discrete group of precancerous laryngeal lesions, and to assess the mortality. In a series of 227 patients, average age 51.8 years (ranging from 13 to 80 years). The changes were followed-up for 12.3 years (minimum of 5 years and maximum of 40 years). 58% are living without any sign of premalignant laryngeal mucosal disease, 13% with controlled precancer, and 3% in remission after surgery for carcinoma. 11% died (9% due to cause unrelated to the cancer) and 15% were lost for follow-up. 17% of the group with mucosal hyper- or metaplasia progressed to mild dysplasia, but none progressed to carcinoma. Reinke's oedema recurred in 4%, no malignancy was observed. Carcinoma developed in 16% of laryngeal papilloma (8% in situ and 8% invasive). 15% of mild dysplasia progressed in severity, but none transformed to malignancy. Moderate dysplasia progressed to severe dysplasia in 12%, carcinoma in situ in 4%. Of cases with severe dysplasia 13% developed in situ carcinoma while 43% progressed to invasive cancer. In the whole series progression to severe grade was seen in 7.1%, and malignant transformation in 4.4%. Three patients (1.3%) died due to subsequent carcinoma. Our results agree with some authors; but the majority of them reports higher incidence of malignant transformation. Invasive carcinoma was diagnosed in the follow-up in seven patients. Those represent only 3% of all laryngeal carcinomas diagnosed in our department in the same period of time. Based on the data we have evaluated the intensity of follow-up in patients with hyperplasia, metaplasia, keratosis and mild dysplasia.

A CASE OF SYNCHRONOUS MULTIPLE CARCINOMA OF THE COLON -MUCOSAL CARCINOMA IN THE THREE NOUDLE-AGGREGATING LESIONS ACCOMPANIED BY A TYPE 2 CARCINOMA-

An 80-year-old woman with loss of appetite was admitted to the hospital for evaluation and treatment of a tumor in the colon, which was found by barium enema examination. By colonofiberscopy, three flat elevated noudle-aggregating lesions were detected in the ascending colon, hepatic flexure of the transverse colon and descending colon. Further a type 2 tumor was detected in the hepatic flexure. Under the diagnosis of carcinoma in two lesions confirmed by histological examination, and taking a high incidence of malignant transformation of the adenoma into consideration, a right hemicolectomy and a partial resection of the descending colon were performed on May 15, 1997. In all of the noudle-aggregating lesions, well differentiated adenocarcinomas, limiting within the mucosa were confirmed by histological examination of the resectd spacimen. And these lesions were considered carcinoma in adenoma by the histological formation. The type 2 tumor was also confirmed as moderately differentiated adenocarcinoma, invading the proper muscle layer.

Prognostic factors in well-differentiated cerebral astrocytomas in the adult.

Eighty-five "well-differentiated" astrocytomas in adults (age, greater than or equal to 18 years), operated on between 1950 and 1982, were retrospectively reviewed. The pilocytic variant was not included. Twenty-four clinical and 8 histological factors were analyzed to investigate their importance in predicting length of survival. Multivariate analysis showed that the following variables were correlated with survival time (P less than 0.01): extent of surgical removal, altered consciousness during preoperative examination, focal deficit as presenting symptom, performance status (Karnofsky rating) after surgery, and vessel size in the surgical specimen. Total removal of the tumor was related to a higher 5-year survival rate (51%) than subtotal removal (23.5%), and none of the patients with partial removal survived more than 5 years. Postoperative radiotherapy (40-55 Gy) improved only the 1- and 3-year survival rates. Based on the significant factors provided by multivariate analysis, a score was developed to detect subgroups with different prognoses. Median survival time ranged from 383 days for patients with a score greater than or equal to 2.5 to 1,533 days for those with a score less than 0.5; no patient with a score greater than or equal to 1.5 survived more than 10 years. The percentage of recurring astrocytomas that showed anaplastic areas in the second biopsy specimen was 79%. Total surgical removal is the most important factor in the management of well-differentiated astrocytomas, whereas the efficacy of postoperative radiotherapy still needs to be confirmed by prospective and randomized studies. The rationale for treating incompletely resected astrocytomas with radiation therapy could lie in the high incidence of malignant transformation.

Invasive squamous cell carcinoma of the carpus: Malignant transformation of epidermis dysplasia verruciformis

Epidermodysplasia verruciformis is a rare disease that is characterized by the eruption of wartlike skin lesions. There is a high incidence of malignant transformation of these lesions, especially in areas exposed to the sun, such as the face or the dorsum of the hands. We present a case that demonstrates many aspects of this disease entity, which ultimately required amputation of the hand because of invasive squamous cell carcinoma of the carpal bones.

Melanocytic and nevocytic malignant melanomas.Cellular and subcellular differentiation

Two biologically and clinically different malignant melanomas are found in man. As compared to the malignant melanoma developed from junction nevus, the melanoma developed from Dubreuilh's precancerous melanosis has a slower rate of growth, metastasis and invasiveness. Furthermore, in contrast to melanoma of junction nevus origin, melanoma from Dubreuilh's melanosis is radiosensitive and does not assume the amelanotic form. Not only the malignant melanomas but also the premalignant stages exhibit differences. Dubreuilh's precancerous melanosis, in contrast to junction nevus, is a condition which occurs during later life in exposed areas, is radiosensitive and has a high incidence of malignant transformation. Cellular and subcellular differential characteristics expressing enzymic and ontogenic differences of these two melanomas are described. The author proposes that in the future we consider human malignant melanoma to be not one but two diseases—melanocytic malignant melanoma and nevocytic malignant melanoma. These may be called malignant melanocytoma and malignant nevocytoma, respectively.