Early Malignant Changes Research Articles

A Case of Early Malignant Change from Neurofibroma to Malignant Peripheral Nerve Sheath Tumor

Malignant peripheral nerve sheath tumor (MPNST) is one of the soft tissue sarcoma believed to originate from neural crest cells. The patients with neurofibromatosis type I (NF1) have about 8-13% of the lifetime risk of the malignant transformation. Neurofibroma on patients with NF1 can be surgically resected and has good prognosis if approach to the tumor is possible. We experienced a case of a 50-year-old woman with NF who had incompletely resected neurofibroma, which presented a rapid malignant transformation to MPNST, 3 months after the first surgery. We reported this case with a brief review of literature.

COLPOSCOPY : AN INNOVATIVE DIAGNOSTIC TECHNIQUE FOR ORAL LESIONS

Cancer is one of the leading cause of deaths in public health and is particularly common in developing countries. The inuence of smoking, chewing tobacco and alcohol has usually been considered a relevant confounding factor for oral cancer. Oral cancer is generally preceded by some potentially malignant disorders such as leukoplakia, lichen planus, oral submucous brosis etc. However, even with meticulous follow up, early malignant changes are still overlooked. As the emphasis shifts from damage mitigation to disease prevention, the need for sensitive and accurate detection and diagnostic tools become more important. Many novel and emergent optical diagnostic modalities for the oral cavity are available with a variety of desirable attributes including non-invasiveness, absence of ionising radiation, patient friendliness, repeatability and high resolution surface. One such diagnostic aid is Colposcopy. Because of the rapid pace of innovation in this eld, the cost and ease of use of such modalities is improving rapidly. Hence, early diagnosis is of paramount importance facilitating large scale screening for high risk population. The future is promising for further development and evolution of oral cancer diagnostic aids to enhance the quality of patient care there by reducing the mortality and morbidity.

Estimation of salivary lactate dehydrogenase in oral squamous cell carcinoma, oral leukoplakia, and smokers.

Lactate dehydrogenase (LDH) is an enzyme seen within every cell during their normal metabolic function. It is always confined within the cell cytoplasm and it becomes extracellular only when a cell dies. The extracellular presence of LDH is related to cell necrosis and tissue breakdown. Therefore, we designed a study to estimate and compare LDH levels in the saliva of patients with oral cancer, oral leukoplakia (OL), and smokers without lesions and in controls. A total of 81 subjects of both genders, between the ages of 20 and 70 years, were included in the study. The study group was divided into four: group I-controls (n = 20), Group II-smokers (n = 20), Group III-subjects with OL (n = 20), and Group IV-subjects with oral squamous cell carcinoma (OSCC) (n = 21). Five milliliters of unstimulated salivary sample was collected from each participant, and salivary LDH level was measured. The obtained values were tabulated and statistically analyzed. P < 0.05 was considered to be statistically significant. The difference in LDH levels among the four groups was found to "BE" statistically significant. LDH values showed a marked increase in the leukoplakia group (49.79 ± 19.88 IU/L) and OSCC group (106.97 ± 32.75 IU/L) when compared to controls and smokers. We found that salivary LDH was increased in patients with leukoplakia and OSCC. Smoking alone did not produce any alterations in salivary LDH. It is possible that salivary LDH could be a potential biomarker to identify early premalignant or malignant changes in smokers.

Profiling of Oral Cells Morphology by means of a novel Label-Free Method of Polarization Diffraction Imaging

Currently, all oral leukoplakias, per gold standard, should undergo microscopic examination for diagnosis, which is an invasive procedure, and many patients are resistant to it due to cost, fear, or aversion to pain. We plan to develop a non-invasive assay, by using polarization diffraction imaging flow cytometry (p-DIFC) which is a technique that renders a three-dimensional model of single cells. That acquires a cross-polarized diffraction image pair (p-DI) of the coherent light scattered by a single cell with high image contrast excited by a linearly polarized laser beam. This method of single-cell assay enables extraction of cell morphology related information from the diffraction patterns embedded in the p-DI pair for each individual cell. In addition, the team has developed an optical model of cells based on confocal imaging to simulate the coherent light scattering process of a cell and convert the spatial distribution of scattered light into calculated p-DI pairs. Objectives: We aim to develop a protocol for acquiring oral mucosal cells for confocal imaging and establishing their individual three-dimensional (3D) morphologic profiles in the form of a preliminary database. In Phase 2, we will establish correlations between diffraction patterns from calculated p-DI data and the morphologic features revealed by mi- croscopy. Methods: We are collecting and quantifying individual cells from oral mucosa, in order to set a quantitative 3D morphologic single-cell parameter by confocal microscopy, for modeling study of diffraction patterns. Phase 2 of the study will involve single-cell analysis using p-DIFC for identification of early malignant changes in cytological sampling of mucosal lesions suspicious for malignancy. Conclusions: The results of this ongoing investigation will lay the foundation for future non-invasive, label-free detection of precancerous cells during intraoral examination, by investigating the profiling of cells harvested from patients in our institutions.

Prevalence of precursor lesions (P53 signature, SCOUT, STIL, STIC) in fallopian tubes resected for non-neoplastic causes.

High-grade pelvic serous carcinoma is a common cause of death in women worldwide and India. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis. 1) To study histopathology features of surgically resected specimens of fallopian tubes received with non-neoplastic lesions of the uterus and ovary for the presence of any precursor lesions [secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesion (STIL), p53 signatures, and serous tubal intraepithelial carcinoma (STIC)]. 2) To confirm the findings with immunohistochemistry. 3) To correlate the prevalence of precursor lesions with clinical parameters and benign lesions of the uterus and ovaries. Assessment of histopathological changes in 100 specimens of distal fallopian tubes was done using the sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol. H and E stain followed by immunohistochemistry for Bcl-2, p53, and Ki-67. The statistical significance of the difference in the mean values of precursor areas was evaluated by an unpaired t-test. Among 100 specimens taken on H and E, precursor lesions were suspected in 49% of the cases. SCOUT, suspicious for STIC, suspicious for STIC with areas of SCOUT, and unequivocal for STIC with areas of SCOUT were seen in 8%, 4%, 33%, and 4% of the cases, respectively. However, on IHC, SCOUTS were confirmed in 45% of the cases, p53 signature in 2%, STIL in 9%, and STIC in 4% of the cases. Sectioning and extensive examination of the fimbrial end (SEE-FIM) should be routinely done as it provides the opportunity to detect the early malignant changes. It may help in evolving the strategies for early detection, management, and reducing mortality.

A Case of Facial Discoid Lupus Erythematosus (LE) with Oral Lichen Planus (LP): A Dig into Co-existence and LE-LP Overlap

A distinction between ‘co-existence of Lupus Erythematosus (LE) and Lichen Planus (LP)’ and ‘LE-LP overlap’ bears importance as the criterion for true overlap necessitates histological and immunological features of both LE and LP to be found in the same tissue specimen. However, in the present case report the lesions of LE and LP were present in two different sites. A 51-year-old male presented with a large erythematous scaly atrophic plaque on the right cheek with similar lesions on chin and lips for 10 years. He also had violaceous lesions on the bilateral buccal mucosa and a white lesion over the left buccal mucosa for three years. Discoid Lupus Erythematosus (DLE) and Oral Lichen Planus (OLP) were suspected. Dermoscopy of the facial plaque showed features consistent with DLE. Histopathology of the facial plaque confirmed the diagnosis of DLE, whereas the white plaque on the left buccal mucosa showed features of early invasive squamous cell carcinoma. Violaceous lesion over the right buccal mucosa showed features suggesting OLP. A Direct Immunofluorescence (DI) was also performed for the buccal mucosa to rule out the possibility of DLE with oral involvement, which turned out to be negative. Therefore, a diagnosis of synchronous presentation of DLE and OLP along with Squamous Cell Carcinoma (SCC) of the buccal mucosa was made and patient was treated with topical corticosteroids, systemic hydroxychloroquine and surgical intervention for the squamous cell carcinoma. It is also imperative that not only long standing cutaneous lesions, but also oral lesions like LP should be investigated and kept under observation to look for any early malignant changes.

The absence of early malignant changes in women subjected to Aquafilling breast augmentation on the basis of E-cadherin and N-cadherin immunohistochemical expression

The use of Aquafilling can be associated with a variety of health complications. The filler is an inflammatory process trigger at the site of tissue contact. The aim of this study was to semiquantitatively compare the immunohistochemical expression of E-cadherin and N-cadherin in tissue material from two groups of patients. The first group underwent surgical removal of Aquafilling from the breast, while the second was subjected to breast augmentation with implants or breast lifts (control group). The study group consisted of tissue samples from 16 patients who had Aquafilling removed, while the control group comprised samples from 16 patients who underwent breast augmentation with implants or breast lifts. Histopathology, immunohistochemistry and morphometric analyses were performed, taking into account the number of immunopositive cells and also the immunohistochemical reaction area for E-cadherin and N-cadherin. There were significantly more immunopositive N-cadherin cells in both groups. The immunohistochemical reaction area for N-cadherin did not differ between the two groups. However, the immunohistochemical reaction area for E-cadherin was significantly larger in the test group than in the control group. Moreover, the reaction area for N-cadherin was significantly smaller than that for E-cadherin. In the control group, no significant differences were detected between the immunohistochemical reaction area for N-cadherin and E-cadherin. Immunohistochemical evaluation of N-cadherin and E-cadherin tissue expression may be useful in assessing early cell junction changes. Furthermore, semiquantitative morphometric analysis allows these alterations to be more precisely determined.

SEMINOMA ARISING FROM TESTICULAR AND OVARIAN REMNANTS HERALDS THE EMERGENCE OF A RARE MALE OVOTESTICULAR DISORDER OF SEXUAL DEVELOPMENT

INTRODUCTIONOvotesticular Disorder of Sex Development (OT DSD) or true hermaphroditism is a very rare subset of DSD and accounts for only 5% of cases. It has great phenotypic variability and poses diagnostic challenge to clinicians. It usually presents in childhood with ambiguous genitalia, characterized by histologic demonstration of ovarian and testicular tissues within the same individual. RESULTSWe describe a 22-year-old man with OT DSD complicated by seminoma. He was delivered preterm with ambiguous genitalia and was lost to follow-up. He was raised as a female, at 14 years old, his teachers referred him due to concerns of male phenotype while participating in competitive sports. Phenotypically, he was a developed male with a micropenis, hypospadia, left scrotal cystic structure and empty right scrotum. Chromosomal analysis revealed 46XY and presence of SRY gene. Radiological imaging at age 16 showed fully developed Mullerian structures, with a single cervix and incomplete septate uterus, and an oval structure suggestive of testes at the left hemipelvis. Cysto-genitoscopy demonstrated normal urethra without prostatic urethra, opening at posterodistal bladder neck with blood clots likely representing the vagina. Laparoscopy identified tubulo-nodular structure inside the pelvis suggestive of vas deferens with suspicious early malignant changes. Wolffian remnant and bicornuate uterus were present with a right Fallopian tube with suspicious hydro-corpus. He was advised surgery, however, he defaulted again. He consulted again at age 22 due to pyuria, suprapubic pain and painless cyclical haematuria. Imaging studies demonstrated pyometra, bulky left ovary and bilateral undescended testes suspicious of malignant transformation. Exploratory laparotomy, gonadectomy, subtotal hysterectomy and left orchidectomy were performed. Histopathological examination revealed seminomas arising from testicular and ovarian remnants with suppurative inflammation in the uterus. He was provided testosterone replacement post operatively, and received chemotherapy (etoposide, bleomycin and platinum). CONCLUSIONThe complexity of the case exemplified the pivotal role of multidisciplinary input from various specialties.

Clinical and Immunohistochemical epithelial profile of non-healing chronic traumatic ulcers.

Background Chronic wounds were previously related to cancer. Chronic Traumatic Ulcers (CTU) are lesions caused by chronic mechanical irritation (CMI) frequently diagnosed in Oral Medicine. Although these conditions may reflect a benign nature, some authors have proposed its relationship with malignant transformation. Currently, there are scarce investigations that evaluate biomarkers within CTU. The aim of this study was to evaluate cell differentiation and proliferation biomarkers patterns of CTU and OSCC through recognized markers such as cytokeratin 19 and Ki67 and correlate it with clinical features of both groups of patients. Material and Methods A Cross-sectional study of adult patients (n=79), both sexes, attended at Oral Medicine Department, Facultad de Odontología, Universidad Nacional de Córdoba. The patients were classified into two groups: CTU (n=41), and OSCC (n=38). A subset of specimens were immunolabeled with Ki67 and Ck19. Results The population consisted of 51.9% male and 48.1% female, with an average of 57.0 ± 13.9. years (OSCC group) and 60.9 ± 14.9 years (CTU group). OSCC group presented higher scores for both biomarkers (Ki67 and Ck19), but only there were differences statistically significant for Ki67 (p=0.032). 25% of non-healing CTU were positive with medium scores of Ck19 and showed an immunohistochemical profile similar to OSCC. The lateral tongue was the most frequent site in both groups. Conclusions The altered immunohistochemical pattern found in many specimens of CTU was also observed in OSCC. The tongue border presents physiological conditions that could offer a suitable environment for the development of neoplastic events associated with CMI. Further studies are needed to understand the underlying mechanisms that could link oral non-healing ulcers with early malignant changes. Key words:Ck19, Ki67, Oral Cancer, Chronic Traumatic Ulcer, Chronic Mechanical Irritation.

Efficacy of Fluorescence Technology vs Conventional Oral Examination for the Early Detection of Oral Pre-Malignant Lesions. A Clinical Comparative Study.

Oral cancer is one of the most common malignancies that affect human beings across the world and early detection of oral cancer is believed to reduce the morbidity significantly. Fluorescence diagnosis is emerging as a promising method in the differentiation of cancerous lesions and thus helping in the determination of resolution for the surgical resection of affected area of malignancy very accurately. The aim of this study was to evaluate the usefulness of an autofluorescence hand held device (OralID) to detect oral premalignant lesions. 98 potentially high-risk oral cancer patients were divided into two groups (n=49/group). Both the groups were first examined by conventional oral examination under white light and oral findings were noted. Subjects under group B were further examined under fluorescence light through hand held device, i.e. OralID. After the examinations, a surgical biopsy sample was taken from the suspected lesions under local anaesthesia from both the groups to confirm the diagnosis through histopathological analysis. The positive potential malignant lesions (PMLs) observed in Group A when compared with biopsy reporting was 89.47% true positive while in Group B was 95.24%. The sensitivity reported of Group A was 89.47% and Group B was 97.56%. We observed 8.09% more sensitivity and 11.36% more specificity when we incorporate adjunctive the fluorescence examination using OralID. Results from this study suggests that OralID is a true adjunct to conventional oral examination in detecting early potential malignant changes in subjects visiting for regular dental check-up.

Serum fucose level in oral cancer, leukoplakia, and oral sub mucous fibrosis: A biochemical study.

Aims:To estimate the serum fucose levels in clinically and histopathologically diagnosed oral cancer, oral leukoplakia, and oral submucous fibrosis cases. To compare and correlate the severity of dysplasia or histopathological grading of the premalignant and malignant lesions with serum fucose levels.Objective:To determine the role of serum fucose as a reliable biomarker for early detection of malignant transformation of potentially malignant lesions and conditions and prediction of biologic behavior of the malignant lesions.Material and Method:The intended study shall include 100 participants divided into 4 groups. Groups I, II, and III will include 25 clinically and histological diagnosed cases of oral leukoplakia, oral submucous fibrosis, and oral cancer, and 25 normal control group. Fucose was measured according to the method of Dische and Shettles as adopted by Winzler.Statistical Analysis:Statistical analysis will be done using SPSS statistical software (Version 10), and the levels of significance will be analyzed using the paired and unpaired t-tests.Result:In subjects of 4 groups were age- and gender-matched and comparable thus these may also not influence the study outcome measure (fucose levels). ANOVA revealed significantly different fucose levels among the groups (F = 17.00, P < 0.001). Mean fucose level did not differ (P > 0.05) between oral leukoplakia, oral submucous fibrosis, and oral cancer (84.5%) groups. The increase in mean fucose levels with severity was the highest in the oral cancer group followed by oral submucous fibrosis and oral leukoplakia group. The mean fucose levels did not differ between mild and moderate grades (P > 0.05) in all the 3 groups.Conclusion:The evaluation of serum l-fucose would be of good help in assessing early malignant change in increasing the accuracy of clinical diagnosis and also in assessing the spread and invasiveness of oral cancer, oral submucous fibrosis, and leukoplakia.

Down-regulation of a pro-apoptotic pathway regulated by PCAF/ADA3 in early stage gastric cancer

The loss of p300/CBP-associated protein (PCAF) expression is associated with poor clinical outcome in gastric cancer, and a potential bio-marker for invasive and aggressive tumors. However, the mechanism linking loss of PCAF to the onset of gastric cancer has not been identified. Given that PCAF and its binding partner transcriptional adaptor protein 3 (ADA3) were recently shown to regulate the intrinsic (mitochondrial) pathway to apoptosis via epigenetic regulation of phosphofurin acidic cluster sorting proteins 1 and 2 (PACS1, PACS2), we analyzed PCAF, ADA3, and PACS1/2 expression in 99 patient-matched surgical samples ranging from normal gastric mucosa, through pre-malignant chronic gastritis and intestinal metaplasia to stage I–III invasive cancers. PCAF mRNA levels were not reduced in either pre-malignant state but were significantly down-regulated in all stages of gastric cancer, commencing at AJCC stage I (p < 0.05), thus linking reduced PCAF expression with early malignant change. Furthermore, patients with combined reduction of PCAF and PACS1 had significantly poorer overall survival (p = 0.0257), confirmed in an independent dataset of 359 patients (p = 5.8 × 10e-6). At the protein level, PCAF, ADA3, and PACS1 expression were all significantly down-regulated in intestinal-type gastric cancer, and correlated with reduced progression free survival. We conclude that a pro-apoptotic mechanism centered on the intrinsic (mitochondrial) pathway and regulated by PCAF/ADA3 can influence the progression from premalignant to malignant change, and thus act as a tumor suppression mechanism in gastric cancer.

Salivary micro RNA as a potential biomarker in oral potentially malignant disorders: A systematic review.

Oral potentially malignant disorders (OPMD) are oral mucosal disorders which have a high potential to turn into malignancy. A recent report suggests that 16%–62% of epithelial dysplasia cases of OPMD undergo malignant transformation, showing the need for early detection of malignancy in these disorders. Micro RNA (miRNA) plays an important role in cellular growth, differentiation, apoptosis, and immune response, and hence, deregulation of miRNA is considered a signature of oral carcinogenesis. A search was done using MeSH terms in the PubMed, ScienceDirect databases, hand search, and finally, six studies were included in this systematic review. A total of 167 patients with oral cancer, 78 with OPMDs, 147 healthy controls, and 20 disease controls were analyzed for the expression of salivary miRNAs. Quality assessment based on the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to obtain a risk of bias chart using Revman 5.3 software and it was proved that the study done by Zahran et al. in 2015 had a low risk of bias. The results of this study revealed upregulated miRNA 184 with an area under the curve (AUC) of 0.86 and miRNA 21 with an AUC of 0.73 and downregulated miRNA 145 with an AUC of 0.68, which proved that these miRNAs are significant in detecting early malignancy in OPMD and should be further analyzed in various populations. This systematic review explored the potential of expression of salivary miRNA in OPMD for future studies. This could pave the way to utilize saliva as a surrogate marker in diagnosing early malignant changes in OPMD.

Tu1570 Endoscopic Treatment of Early Malignant Changes in Barrett's Esophagus in More Than 100 Patients: Results of a Swiss Single Center Cohort

Tu1570 Endoscopic Treatment of Early Malignant Changes in Barrett's Esophagus in More Than 100 Patients: Results of a Swiss Single Center Cohort

Pleural effusion with pleural thickening in a patient exposed to zinc chromate paints: A rare case report

A 35-year-old male painter presented with left sided pleuritic chest pain and exertional dyspnea. A chest radiograph revealed left pleural effusion with pleural thickening. This condition is suspected to be caused by chronic exposure to zinc dichromate and history of exposure was >13 years. Pleural effusion with pleural thickening can be both benign and malignant. Biopsy remains gold standard investigation for exclusion. Pleural fluid cytology and pleural biopsy revealed lymphocytic pleural effusion with few macrophages in proteinaceous fluid background and negative for malignant cells, which was suggestive of benign chronic inflammatory reaction and exclude any malignant changes. Pleural fluid drained and symptomatic treatment provided and patient counseled. Further follow-up needed to diagnosis early malignant changes.

Carcinoma Ex Pleomorphic Adenoma, with Particular Emphasis on Early Lesions

Carcinoma ex pleomorphic adenoma (CXPA) is a broad category of carcinomas of the salivary glands which includes at least 2 clinically relevant categories; one is referred here as early CXPA (ECXPA), the other as widely invasive CXPA. The former includes several histological patterns ranging from non-invasive/in situ/intraductal/intratubular, early invasive/extratubular/intracapsular and extracapsular (up to 6 mm). The latter includes any CXPA with invasion of >6 mm. The clinical behaviour of ECXPA is not aggressive and tends to overlap that of a pleomorphic adenoma (PA) which makes the histological report of carcinoma contradictory. These early malignant changes in PA are known since the 1970s but it has been the use of immunohistochemical and molecular genetic analysis for HER-2 and TP53 gene in the last decade that has clarified the genuine malignant nature of the cells. HER-2 and TP53 gene and protein are involved in the early stages of malignant transformation of PA. Moreover the immunohistochemical over-expression HER-2, p53 protein and Mib-1 proliferation marker may be useful markers to identify malignant areas in PA.

Evaluation of Proliferation Activity in Dysplastic and Nondysplastic Oral Lichen Planus Through the Analysis of Argyrophilic Nucleolar Organizer Regions

Lichen planus is a mucocutaneous disease, and its potential for malignant transformation is a subject of controversy. We found dysplastic changes in slide review of about 11% of oral lichen planus (OLP) in our previous research. Dysplastic changes can be an initial phase for carcinogenesis. The question is whether it is possible to detect early malignant changes in OLP through the evaluation of proliferation activity. The aim of this study was to compare the cell proliferation activity in dysplastic and nondysplastic oral lichen planus using the quantitative and qualitative analysis of argyrophilic nucleolar organizer region (AgNOR) and to compare candidal infection in these 2 groups. In this cross-sectional, observational, and analytical study, all 14 cases of confirmed dysplastic OLPs and 17 nondysplastic OLPs were stained with an AgNOR technique. Analysis of argyrophilic nucleolar organizer region dots were counted in 100 cells of basal and parabasal layers, and proliferation index (cells with ≥ 5 dots in nucleus) and variations in size of AgNOR dots were also evaluated. Periodic acid-Schiff staining was performed for detection of candidal infection. Mean AgNOR count in dysplastic OLP (2.39 ± 0.2) was more than nondysplastic OLP (2.27 ± 0.59). Candidiasis was found in 14.3% of dysplastic OLP and in 12.5% of nondysplastic OLP. There was no statistically significant difference between the 2 groups in mean AgNOR count (P = 0.62), variation in size of AgNOR dots (P = 1), proliferation index (P = 0.53), and candidiasis (P = 1). The current study showed slight difference in proliferation rate and candidal infection between dysplastic and nondysplastic OLP.

Abstract 1141: MAb-PAM4 can differentiate between pancreatic ductal adenocarcinoma and chronic pancreatitis.

Abstract Background: Due to the asymptomatic nature of pancreatic ductal adenocarcinoma (PDAC) in its early stages of growth, and its relatively low incidence, screening methods have not received high attention. However, with recent studies providing the ability to identify specific patient groups at high risk for PDAC, a rationale exists for longitudinal surveillance as a means to improve early detection specifically in these high-risk settings. Individuals with a family history of PDAC, those patients with long-standing chronic pancreatitis (CP), patients with new-onset diabetes who meet certain other conditions, or those with FAMMM syndrome, etc., could be evaluated on a long-term basis for the detection of early malignant changes by use of a MAb-PAM4-based immunoassay procedure. Methods: We have developed and validated (in over 600 patient specimens) an enzyme immunoassay (EIA) based upon use of MAb-PAM4 for quantitation of antigen in the serum of patients diagnosed with pancreatic ductal adenocarcinoma. In addition, the antibody has been used for immunohistochemical evaluation of malignant, benign, and normal pancreatic tissues. Results: 71% of patients with confirmed early-stage disease and 91% with advanced disease were positive by EIA for circulating PAM4-antigen. Overall specificity was 81% with respect to benign pancreatic disease. Of 126 patients diagnosed with benign conditions of the pancreas, 24 (19%) were positive for the PAM4-antigen, with the majority of these cases being diagnosed with chronic pancreatitis [18 of 80 positive (23%)], all of whom had surgical resection performed for severity and/or duration of disease activity. ROC curve analyses of PAM4 assays revealed a statistically significant difference between the PDAC and CP groups (P&amp;lt;0.0001), with an area under the curve of 0.84 ± 0.02 (95% CI: 0.79-0.89). The positive likelihood ratio for differentiating PDAC from benign conditions of the pancreas was 4.00, which was significant (P&amp;lt;0.001). It is very important to emphasize that the “true” specificity of this assay is likely underestimated. Immunohistochemistry data have shown the PAM4-biomarker is absent from normal pancreas and benign, non-neoplastic lesions of the pancreas. In over 50 surgical specimens of CP, the PAM4-biomarker was identified only within PanIN lesions that are associated with long-term CP, and not by the inflamed tissue. Conclusions: Our results suggest that PAM4-positive CP patients (and likely other PAM4-positive patients diagnosed with benign conditions of the pancreas) may very likely have pancreatic neoplasia (invasive and/or precursor lesions), and therefore should be followed closely. Indeed, such studies might reveal new cutoff values or kinetic changes that would support early surgical intervention. (Supported in part by NIH grant CA096924.) Citation Format: David V. Gold, Chanjuan Shi, Guy Newsome, David M. Goldenberg. MAb-PAM4 can differentiate between pancreatic ductal adenocarcinoma and chronic pancreatitis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1141. doi:10.1158/1538-7445.AM2013-1141

Medullary thyroid carcinoma in ethnic Chinese with MEN2A: A case report and literature review

Medullary Thyroid Carcinoma (MTC) is the most common cause of death in MEN patients.It is curative by prophylactic total thyroidectomy, but controversies remain as to the optimal timing for prophylactic thyroidectomy. The current recommendation is for prophylactic total thyroidectomy before age 5, but a recent study suggested that in the ethnic Chinese, even “high risk” mutations did not result in early malignant change, and it was suggested that prophylactic thyroidectomy may be performed at a later age. We report a case of an ethnic Chinese girl with MEN2A codon 634 (C634R) mutation, whose operative specimen at prophylactic thyroidectomy at 4years 8months showed MTC. We advocate that management of MEN2A patients should be codon-directed, regardless of ethnicity.

Review of Radiologic and Pathologic Features of Carcinomas and High Risk Lesions Arising from Fibroadenomata: Need for Continued Surveillance for Fibroadenomata and Lessons Learnt from our own Experience

Carcinoma arising within a fibroadenoma is a rare entity. However, fibroadenomas are fairly common, and can arise in young women. A clinical dilemma arises as how to detect early malignant change, with the aim that early detection can result in curative therapy. Most published articles emphasize on pathologic findings, and not radiological findings of this entity. We report a series of four cases of carcinoma and high risk lesions found within fibroadenomas encountered over a five year period, with emphasis on mammographic and ultrasound findings, with pathologic correlation, taken from archived files from a single institution. We aimed to evaluate the radiology features, and determine if there are any unique radiological findings, which are unique to these high risk lesions. There were three cases of ductal carcinoma in situ, one lobular carcinoma in situ with atypical ductal hyperplasia arising within fibroadenomas. A brief literature review on the radiological and pathologic appearances was performed. We found that although some of the lesions may appear mammographically or sonographically suspicious, others may appear benign. Findings that were considered suspicious included large size, indistinct margins, and clustered microcalcifications, which should alert the radiologist of a suspicious finding and prompt a biopsy. When fibroadenomas undergoes malignant change, they behave like any other carcinoma, both radiologically and clinically. Unfortunately, in our review of the literature, there is no early radiologic sign that can predict malignant change. Hence, these should be lifelong follow-up of these lesions, whether clinical or radiologic, as malignant change, though rare, has dire circumstances.