Frequency Of Malignant Transformation Research Articles

Immunohistochemical Glutamine Synthetase As a Surrogate Marker for Beta Catenin (Exon 3 Deletion) in a Rare Case of Hepatic Adenomatosis with Early Malignant Transformation to Well Differentiated Hepatocellular Carcinoma

Abstract Introduction/Objective Hepatic adenomatosis (HA) is a rare entity defined by ≥ 10 hepatocellular adenomas (HCAs). About half of HA cases are asymptomatic and incidentally found. Compared to individual HCAs, HA carries a higher risk of complications including: tumor rupture, bleeding, and an approximate 4.2% overall frequency of malignant transformation. Methods/Case Report A 29-year-old woman presented to the emergency department (ED) requesting a CT scan. She was seen by a gastroenterologist days prior to her ED visit for ongoing sharp rectal pain for 2-3 months. After a recent rectal exam, she was recommended to have a CT abdomen/pelvis to rule out a potential abscess. CT did not show a perianal or perirectal abscess but instead identified a 9.1 cm right hepatic lobe mass. A liver MRI showed a 6.4 x 8.5 cm mass with arterial enhancement. The patient had a prior history of OCP use. She underwent robotic wedge resection of liver segment 6 with cholecystectomy. Gross examination showed a 6 cm tumor with many smaller nodules ranging in size from 0.5-2.2 cm. Our case was submitted entirely for histologic examination. Microscopy demonstrated well differentiated hepatocellular carcinoma (WDHCC) confirmed with positive immunohistochemical (IHC) staining for HepPar1 and Arginase. Tumor cells showed mild patchy cytological atypia, occasional pseudoglands, and architectural atypia with “nodule in nodule growth.” There was reticulin loss in multiple areas and CD34 showed strong diffuse sinusoidal staining. Glypican 3, CRP, and HAA were negative. Low Ki-67, LFABP retention, and absent nuclear staining of beta catenin (BC) were noted. Glutamine synthetase (GS) was diffuse and homogeneous. The gallbladder was unremarkable. Results (if a Case Study enter NA) NA Conclusion This case emphasizes that, despite negative nuclear BC staining, diffuse homogenous staining of GS is a quality surrogate marker for BC mutations (ex. exon 3 deletions). Thorough gross, microscopic, and molecular examination in HA cases is essential for identifying transformation to WDHCC.

LGG-03. INCIDENCE AND OUTCOME OF PEDIATRIC IDH-MUTANT GLIOMA

INTRODUCTIONThe incidence of IDH mutations in pediatric glioma is unclear. Recent publications suggest rates ranging between 0–20%. Therapy poses challenges as it is unclear if the biology and prognosis of pediatric IDH-mutant gliomas are identical to adults.METHODSWe performed an IRB approved, systematic retrospective search for IDH-mutant gliomas in the Dana-Farber Cancer Institute/Boston Children’s Hospital database between 2009–2018, analyzing incidence, demographics, histology, co-occurring genetic alterations and outcome.RESULTSWe identified 575 patients with glioma, ages 0–21 years. Of these, 394 underwent biopsy/resection (0–9 years:n=204; 10–21 years:n=190), with 294 genetic testing. Fifteen of 294 tumors (5%) were IDH1-mutant. Among patients 0–9 years and 10–21 years, 1/156 (0.6%) and 14/138 (10%) had IDH1-mutant tumors, respectively. Among patients 10–21 year old, 13/115 low-grade gliomas were IDH1-mutant (11%). High-grade gliomas accounted for the remaining 23, with one IDH1-mutant glioma (4%). Most common co-occurring genetic alterations for diffuse astrocytoma (n=12) were TP53 (n=9) and ATRX (n=2). Three patients with IDH1-mutant oligodendrogliomas had 1p/19q deletion. Eleven IDH1-mutant patients were evaluable for outcomes with median follow-up of five years. Five-year radiation-free, progression-free and overall survival for patients with low-grade histology were 76% and 100%, respectively. One patient with high-grade glioma recurred 1.2 years after upfront chemo-radiation and died soon after recurrence.CONCLUSION IDH-mutant gliomas comprise a small proportion of pediatric gliomas. Incidence rate is higher in the second decade of life. Comparative analyses between pediatric IDH-mutant gliomas and adult historical cohorts are currently underway, evaluating outcomes, radiation therapy and frequency of malignant transformation.

Doughnut-like hyperintense nodules on hepatobiliary phase without arterial-phase hyperenhancement in cirrhotic liver: imaging and clinicopathological features.

To determine the imaging and clinicopathological features of MRI doughnut-like nodules (HBP-doughnut nodules), hyperintense at the hepatobiliary phase (HBP) after injection of gadoxetic acid (EOB) and without arterial-phase hyperenhancement (APHE) in cirrhotic liver. The Institutional Review Board approved this retrospective study and informed consent was waived. We enrolled 309 consecutive patients with liver cirrhosis who were examined by EOB-MRI, dynamic CT, and angiography-assisted CT between 2008 and 2012 and searched for HBP-doughnut nodules. We evaluated imaging characteristics including haemodynamics and signal intensity of MRI, pathological findings, and frequency of malignant transformation. One hundred and one HBP-doughnut nodules without APHE were identified in 18 patients (6%), including seven of 59 (12%) patients with hepatitis-B-virus-related, nine of 230 (3.9%) with hepatitis-C-virus-related, and two of 33 (6.1%) with alcoholic cirrhosis. All nodules showed enhancement peaks in the portal phase, the same or increased intranodular portal supply on CT during arterial portography, and the same or decreased intranodular arterial supply on CT during hepatic arteriography. On T2-weighted and diffusion-weighted images, 37 (36%) and 24 (24%) nodules, respectively, showed hyperintensity predominantly in the central area. Three nodules were diagnosed by fine needle biopsy as non-neoplastic hepatic nodules. Ninety-three of 101 (92%) nodules in 16 patients were followed up during an observation period of 1163 ± 902days (range 57-2920days), and none showed malignant transformation. HBP-doughnut nodules without APHE in cirrhotic liver were not infrequent. None became malignant. We propose calling them 'multiacinar cirrhotic nodules' based on the classification by an International Working Party. • HBP-doughnut nodules without APHE were seen in 6% of patients with liver cirrhosis. • The enhancement peak of HBP-doughnut nodules without APHE was in the portal phase, which reflected the fact that they were supplied predominantly by the portal vein, based on angiography-assisted CT findings. • None of the HBP-doughnut nodules without APHE in cirrhotic liver became malignant, and in conjunction with limited pathological features, they may be corresponding to multiacinar cirrhotic nodules in the International Working Party classification.

The Dynamics of Oral Lichen Planus: A Retrospective Clinicopathological Study

To evaluate disease dynamics, treatment results, and frequency of malignant transformation. Ten-year single center retrospective study. The study included 171 patients, 28-99 years old. Follow-up was 1-16 years. 49.5% exhibited changes in clinical presentation, with 19% yearly increase of probability for type shift. Index of extent (number of oral locations) showed a mean 40% decrease and 94.1% reported improvement. There were significant differences between treated and untreated patients (P=0.012). Patients with or without systemic diseases had identical treatment requirements for oral lesions. The prevalence of SCC was 5.8%. Oral lichen planus constantly changes presentation and extent of involvement. The effect of systemic diseases was insignificant in the present study. There is a clear value for treatment to reduce the extent of lesions. The results indicate that all clinical forms of the disease need to be equally followed since the clinical presentation typically changes over time, while malignant transformation can occur in all forms.

Malignant transformation of vaginal endometriosis treated with neoadjuvant chemotherapy and surgery

Malignant transformation of extragonadal endometriosis is a described. A 40-year-old multiparous woman presented with dyspareunia and dysmenorrhea. Physical examination revealed a 3 x 3.5 cm vaginal nodule. The histological examination of a bioptic sample revealed a moderately differentiated endometrioid adenocarcinoma. The patient was treated with neoadjuvant chemotherapy followed by surgery and is free from disease after 24 months. The frequency of malignant transformation of vaginal endometriosis is unknown. Obesity, hyperestrogenism, and exposure to unopposed estrogen are known risk factors, but were not present in the medical history of the present patient. In our case, preoperative chemotherapy allowed a complete resection without a vaginal demolitive surgery. This therapeutic option may be considered in order to reduce surgical resection and to preserve sexual function. However, because of the rarity of this disease, it is difficult to establish a standard treatment.

Experience of diagnosis and treatment of carcinoma arising from congenital biliary duct cyst

To summarize the experience in diagnosis, prevention and treatment of carcinoma arising from congenital biliary duct cyst. The clinical and pathological data of 185 patients with congenital biliary duct cyst admitted to Chinese PLA General Hospital were analyzed retrospectively. Among 185 patients, twenty-seven cases had carcinomas arising from congenital biliary duct cyst, and the frequency of malignant transformation was 14.6%, which closely related to the age (P < 0.001). The incidences of malignancy for different age groups were: 0 for 0-9 age group, 5.1% for 0-19, 9.1% for 20-29, 16.2% for 30-39, 26.7% for 40-49, 33.3% for 50-59, and 50% for over 60, respectively. Six patients had the history of cyst-enterostomy. Abdominal pain, fever, jaundice and weight loss were the main clinical manifestations. Abdominal ultrasonography, CT, MRI or magnetic resonance cholangiopancreatography, MRCP and endoscopic retrograde choledochopancreatography (ERCP) were the main diagnostic methods. For twenty patients (74.1%), a definite diagnosis was made preoperatively, but it's hard to make an early diagnosis. Nine patients (33.3%) underwent curative resection. Congenital biliary duct cyst is a premalignant lesion, and the incidence of carcinogenesis increases remarkably with age. The most effective method for prevention of carcinogenesis in choledochal cyst is complete excision of choledochal cyst during childhood, and the prognosis is poor for patients with biliary malignancy.

A Case of Malignant Transformation of Sertoli-Leydig Cell Tumor of Both Ovary

The Sertoli-Leydig cell tumor is a rare sex cord stromal tumor that has low grade malignancy and low bilateral occurrence rate. About two third of recurrence appears within 1 year after the initial treatment and most common recurrence sites are intraperitoneal cavity and retroperitoneal lymph nodes. The frequency of malignant transformation is high in the poor differentiated cell type, retiform pattern, and tumor rupture. In young women with stage I, unilateral salpingo-oophorectomy is performed to preserve uterus and reproductive function. In more advanced stages, hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection are performed and occasionally chemotherapy can be combined. We experienced a rare case of malignant metastasis in Sertoli-Leydig cell tumor, and presented with a brief review of literature.

Effects of fluence fractionation on UV-induced malignant transformation and cell killing in non-cycling plateau phase mouse cells.

AbstractPlateau phase C3H 10T 1/2 mouse cells were used to measure the response to split fluence UV light irradiation in the absence of any cell cycle effects. It was found that fluence fractionation with up to 24 h between the fluences resulted in no survival enhancement. The frequency of malignant transformation was potentiated 2.5‐fold when the time interval between the fluences was greater than 4h. This potentiation of transformation was attributed to plateau phase holding rather than to fluence fractionation per se.

Induction of Chromosome Aberrations and Sister Chromatid Exchanges by X Rays in Density-Inhibited Cultures of Mouse 10T 1/2 Cells

The frequency of gross chromosomal aberrations (CA) and of sister chromatid exchanges (SCE) was measured in cells X-irradiated while in the density-inhibited plateau phase of growth. When the cells were subcultured immediately after irradiation with 0 to 800 rad, CA increased exponentially with dose, whereas SCE increased about twofold with doses up to 100 rad but declined with higher doses (200-400 rad). When subculture was delayed to facilitate repair, CA declined and reached a minimum level after 4-6 hr of repair time. Delayed subculture during this interval led to an enhancement in SCE; with longer repair times, SCE declined and reached spontaneous levels by 12-24 hr. CA appear to be related to cell killing, whereas SCE correlate more closely with changes in the frequency of malignant transformation induced under similar conditions by X irradiation.

Nonimmunogenic sarcomas induced by 3-methylcholanthrene treatment of murine fibroblasts in diffusion chambers.

A 30-mug dose of 3-methylcholanthrene (MCA) was applied for 1 week to normal BALB/c fibroblasts in cell-impermeable diffusion chambers (DC) in the peritoneal cavities of BALB/c micemtwo groups of DC cultures, in which the carcinogen was given during weeks 1 and 5 of cultivation, respectively, were compared for the frequency of malignant transformation and for the immunogenicity of the resulting neoplasms. The cells from each DC were transplanted sc into immunodepressed semisyngeneic mice for assay of their tumorigenicity. Although tumor yield was similar in the 2 groups (25 and 22%, respectively), there was clear difference in immunogenicity; 10 of 16 sarcomas from fibroblasts treated during week 1 of culture were nonimmunogenic, whereas 8 of 9 tumors from the older cultures were immunogenic (P less than 0.02). A kinetic study of normal fibroblasts in DC revealed that cells proliferated rapidly, with a peak at day 4 after seeding, then grew progressively more slowly and ceased to replicate between 14 and 28 days of culture. Thus there was a notable difference at the moment of MCA application in the growth phase of the target cell population of the first as compared with the fifth week of culture, possible related to the different expression of tumor-associated transplantation antigens in the resulting neoplasms.