WHO Histological Classification Research Articles

The correlation of morphological features of chest computed tomographic scans with clinical characteristics of thymoma.

Chest computed tomography (CT) scanning has been widely utilized in thymoma identification and staging as well as in follow-up monitoring for recurrence. However, the relationship between some CT imaging features and pathological types, clinical stage, completeness of resection, or prognosis in thymoma has not been well explored. We retrospectively reviewed preoperative CT imaging for 238 thymoma patients, who had undergone thymectomy from October 2007 to December 2011. All CT parameters were assessed in each case based on clinical and pathological data. Survival analysis was performed by using the Kaplan-Meier and log-rank tests. Tumour contours (P = 0.008), homogeneity (P = 0.009), degree of enhancement (P = 0.013), fat plane obliteration with adjacent structures (P < 0.001), the presence of mediastinal lymphadenopathy (P = 0.010), irregular infiltration into the lung (P = 0.012) and tumour shape (P = 0.007) were associated with the World Health Organization (WHO) histological classification. Lobulated or irregular tumour contours (P < 0.001), presence of calcifications (P = 0.002), infiltration of surrounding fat (P < 0.001), irregular infiltration into the lung (P < 0.001), irregular infiltration into vascular (P < 0.001), more abutment of vessels (P < 0.001) and pulmonary changes adjacent to the tumour (P < 0.001) were associated with the more advanced Masaoka-Koga clinical stage. Tumour contours (P < 0.001), infiltration of surrounding fat (P = 0.008), irregular infiltration into the lung (P < 0.001) and degree of abutment of vessel circumference (P = 0.001) were associated with completeness of resection. With multivariate analysis, no CT image features could reliably predict on the overall or disease-free survival rate. CT imaging does have some features, which are significantly correlated with the WHO classification, the Masaoka-Koga clinical staging and the completeness of resection, although it has no definite role to evaluate preoperatively the survival rate of thymoma patients.

Does the World Health Organization histological classification predict outcomes after thymomectomy? Results of a multicentre study on 750 patients.

The World Health Organization (WHO) thymoma histological classification clinical value remains a controversy. In this study, we evaluated its prognostic significance in patients with thymoma treated with radical intent. Six high-volume Italian Thoracic Surgery Institutions collaborated with their own retrospective anonymized datasets. Demographic, clinical, pathological and treatment data were examined. A WHO histological classification (WHO-HC) collapsed scheme (A/AB and B1/B2 types merged) was proposed and compared with the traditional one. Predictors of survival were assessed using a Cox model with shared frailty. Competing-risk regression models were performed to identify the association between individual factors and freedom from recurrence. Between 1990 and 2011, 750 thymomas were operated on in participating centres. Myasthenia gravis was observed in 363 (48%) patients. A complete resection was achieved in 676 (91%) cases. One hundred and nine patients (15%) had a WHO-HC A type, 166 (22%) AB, 179 (24%) B1, 158 (21%) B2 and 135 (18%) B3. The rate of 5-year OS and cumulative incidence of recurrence for all cases was 91% and 0.11, respectively. Five-year survival rates by WHO-HC in the collapsed scheme were A/AB 93%, early-B 90% and advanced-B 85%. Masaoka stage only was demonstrated to be an independent predictor for survival and recurrence. The WHO-collapsed scheme showed a trend in influencing recurrence overall survival development (hazard ratio: 1.32; P = 0.16). Our results show evidence of lack of significance by WHO-HC in influencing prognosis, even though the proposed collapsed scheme revealed a fair stratification of risk to relapses and better correlation with patients' clinical characteristics.

ITMIG Consensus Statement on the Use of the WHO Histological Classification of Thymoma and Thymic Carcinoma: Refined Definitions, Histological Criteria, and Reporting

The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.

Carcinoma of Exocrine Pancreas – A mortal enigma

Background and Objective: Exocrine pancreatic cancer is a highly malignant neoplasm with ductal adenocarcinoma being the most frequent type. The objective of this study is to understand the morphological spectrum of exocrine pancreatic tumors with their clinical aspect. Methods: This is a retrospective histopathological evaluation of 15 cases from 2006-2011 of exocrine pancreatic tumoursstudied light microscopically on Hematoxylin and Eosin stained paraffin sections and categorized according to the WHO Histological Classification of Tumors of Exocrine Pancreas (2000). Results: Periampullary adenocarcinoma formed the majority of malignant tumors accounting for 7 cases with age ranging from 45 to 88 years with male predominance followed by 5 cases of ductal adenocarcinomas,all found in females, age ranging from 45 to 67 years.There was one case each of Pancreatoblastoma (1year old boy), solid pseudopapillaryneoplasm of uncertain malignant potential (16 year old girl)and mucinous cystadenoma in the body and tail (32 year old lady). Conclusion: Malignant tumors were more common than benign tumors (93 %). Periampullary adenocarcinomas constituted the majority (47 %) with male predominance. Ductal adenocarcinomas were all found in females and the common site was head of the pancreas (80 %).Pancreatoblastoma, mucinous cystadenoma and solid pseudopapillary neoplasms are not uncommon. Body and tail of pancreas was the least common site of tumors (13 %). All periampullary and ductal adenocarcinomas were found in patients above 45 years of age.

Prognostic Value of Volume-Based Metabolic Parameters Measured by (18)F-FDG PET/CT of Pancreatic Neuroendocrine Tumors.

To date, the prognostic value of (18)F-FDG PET/CT for patients with pancreatic neuroendocrine tumors (PNETs) has not been well characterized. We investigated the prognostic value of volumetric parameters using (18)F-FDG PET/CT in this patient population. We retrospectively reviewed 20 cases of pathologically proven PNET in patients who had undergone pre-therapeutic (18)F-FDG PET/CT. PET parameters including maximum and average standardized uptake values (SUVmax, SUVave), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using a threshold SUV to determine the boundaries of the tumors. Univariate and multivariate survival analyses were performed with adjustments for PET parameters and other clinical values. The median clinical follow-up was 22.3 (range, 1.2-95.4)months. Cancer-related death occurred in 5 of 20 patients (25%). Patients had clinical or pathological stages of I in seven patients, II in six patients, III in three patient, and IV in four patients. According to the WHO histological classification of subtypes, 3 patients exhibited well-differentiated PNETs, 13 patients had well-differentiated endocrine carcinomas, and 4 had poorly differentiatedendocrine carcinomas. Univariate analysis showed that tumor size (p = 0.028), AJCC stage (p = 0.009), T stage (p = 0.028), M stage (p = 0.029), treatment modality (p = 0.045), MTV (p = 0.003) and TLG (p = 0.027) were significant predictors of overall survival. On multivariate analysis, MTV (HR = 10.859, p = 0.031) was a significant independent predictor of overall survival along with the AJCC stage (HR = 11.556, p = 0.027). In patients with PNETs, the MTV of the primary tumor as measured by (18)F-FDG PET/CT along with the AJCC stage may be a significant independent prognostic factor for overall survival.

Histopathological Patterns of Thyroid Neoplasms in Ibadan Nigeria: A Twenty Year Retrospective Study

Background: The thyroid gland is an endocrine organ which has an important function in regulation of physiological functions of normal body metabolism. Thyroid neoplasms are usually presented with palpable solitary or multiple nodules. This retrospective study aimed at describing the histopathological patterns of various thyroid neoplasms at the Pathology Department, University College Hospital (UCH), Ibadan between 1987 and 2006. Methods: We reviewed 174 cases with thyroidectomy and diagnosed thyroid neoplasm. We evaluated heamatoxilin and eosin stained slides retrieved from the records of the department and the population based cancer registry and where necessary the paraffin blocks were recut and stained. The World Health Organization Histological Classification of Thyroid tumour (2004) was used in this study. Results: A total 74,202 biopsies were received in the department over the study period. 1,207 cases were thyroidectomy specimens constituting 1.6% of all biopsies in the study period. 174 cases (14.4%) were thyroid gland neoplasms 122 (70.1%) of which were Research article a Article International Journal of TROPICAL DISEASE & Health, 3(2): 148-156, 2013 149 females and 52 of which (29.9%) were males. The ratio of female to male is 2.3:1. Seventy six (43.7%) cases were benign and 98 (56.3%) cases were malignant. Follicular adenoma accounted for 89.5% of benign thyroid neoplasms which makes a peak in the 5th decade. Papillary carcinoma was the most common malignant thyroid neoplasm in this study with a peak in the 3rd decade. Conclusion: This study showed that thyroid neoplasms were showing female predominance. The most common benign neoplasm was follicular adenoma and the malignant neoplasm was papillary carcinoma.

Thymic Epithelial Neoplasms: A 12-Year Canadian Regional Cancer Program Experience

BackgroundThymic epithelial neoplasms are rare, with little prospective research to guide management. Surgery is the primary treatment modality for localized disease, but chemotherapy may be indicated in advanced disease. We performed a retrospective chart review of all cases over a 12-year period at our institution. Patients and MethodsWith ethics approval, data collected included patient characteristics, histologic type (World Health Organization [WHO] criteria), staging (Masaoka system), paraneoplastic syndromes, treatment details, and outcomes. The primary analysis is descriptive. ResultsThymic epithelial neoplasms were identified in 76 patients: 46% women with a median age 60 years (range, 25-89 years), 93% with Eastern Cooperative Oncology Group performance status of 0 to 1. Myasthenia gravis was present in 21%. The distribution by WHO histologic classification was A, 15%; AB, 30%; B1, 16%; B2, 13%; B3, 17%; C, 7%; neuroendocrine thymic tumor (NETT), 1%; and unclassified, 1%. Of 64 patients who underwent operation, 53 underwent R0 resection. Eleven surgical patients received chemotherapy (induction, n = 6; adjuvant, n = 4; both, n = 1) and 27 received radiotherapy (induction, n = 2; adjuvant, n = 25). Twelve patients were not considered for surgery, and 3 patients received no therapy at all. Chemotherapy was received at some point in the disease course in 14 patients. Common first-line regimens were platinum/etoposide (n = 8), carboplatin/paclitaxel (n = 3), and CAP (cyclophosphamide, doxorubicin [Adriamycin], cisplatin [n = 2]). The first-line response rate (Response Evaluation in Solid Tumors [RECIST]) was 55%. After a median follow-up of 45 months, 59 (78%) patients remain alive. Thymoma was associated with superior overall survival compared with thymic carcinoma (P < .0001). ConclusionAlthough surgical resection is the mainstay of treatment for thymic epithelial neoplasms, it remains clear that these are chemosensitive diseases.

Radikale Pleurektomie und hypertherme intrathorakale Chemotherapie zur Behandlung pleural metastasierter Thymome

Patients with pleural thymoma spread (Masaoka stage IV a) should be treated within a multimodal treatment regime. However, the extent of local surgical resection to achieve optimal tumour control remains controversial. Prospective analysis between September 2008 and April 2013 of all patients with a Masaoka stage IV a thymoma, who underwent radical pleurectomy/decortication (P/D) followed by hyperthermic intrathoracic chemotherapy (HITHOC). A total of 11 patients (male n = 7; mean age 46.5 ± 11.4 years) with a primary stage IV a thymoma (n = 3) or thymoma with pleural relapse (n = 8) were included after successful transsternal thymoma resection. WHO histological classification was: B1 n = 1, B2 n = 6, B3 n = 3 and C n = 1. A radical P/D (5/11; 45 %) was extended with resection of the pericardium and diaphragm in 6/11 (55 %) patients. After surgical resection (91 % complete macroscopic R0/R1-resection) the HITHOC with cisplatin (100 mg/m2 body surface area (BSA) n = 7; 150 mg/m2 BSA n = 4) was performed for one hour at 42 °C. Operative revision was necessary in two patients (chylo- and hematothorax) with one patient also requiring temporary renal replacement therapy due acute renal failure (cisplatin 150 mg/m2 BSA). 30-day mortality was 0 %. Local recurrence (pulmonary n = 1, paravertebral n = 2) was documented in 3/10 (30 %) patients after R0/R1 resection. After a mean follow-up of 23 months the overall median survival was 27 months and 82 % (9/11) patients are still alive at the end of the study period. Masaoka stage IV a thymoma could be safely treated with lung-sparing radical P/D and HITHOC with cisplatin in a multimodality treatment regime. Early results with respect to recurrence and survival are encouraging, but further studies are warranted and we have to await long-term results.

Caractère potentiellement malin du lichen plan buccal et des lésions lichénoïdes

Many authors have reported the possible malignant transformation of oral lichen. The incidence of this event remains controversial. Many authors make a distinction between the "true" oral lichen planus (OLP) and lichenoid lesions (LL) according to the WHO clinical and histological classification. For these authors an increased risk of development of oral cancer could occur only on LL. Our aim was to check this hypothesis on a cohort followed for 10 years. We included patients who were referred to our team for the first time between 1995 and 1997, still followed in 2010, with a histological diagnosis of buccal lichen planus. We classified lesions as OLP or LL according to the WHO clinical and histological classification: the two clinical criteria for OLP were a reticulated aspect and bilateral and symmetric lesions. Three histological criteria were necessary for the diagnosis: dense inflammatory infiltrate in the upper lamina propria, liquefaction degeneration of basal keratinocytes, and no signs of dysplasia. The final diagnosis was OLP, when all clinical ad histological criteria were met otherwise it was LL. We studied the patient's outcome between their first consultations and May 2010. Thirty-two patients, whose data was available, met inclusion criteria. Eight were diagnosed with OLP and 24 with LL. The mean follow-up was 164 months [154-183]. No oral cancer was observed in the OLP group. Two patients in the LL group presented with oral cancer after 45 and 143 months of follow-up. Malignant transformations were observed only in the LL group. Our results correlate with those of Van Der Meij et al. published in 2006. The strict use of the WHO diagnostic criteria seems to allow identifying patients at risk of developing oral cancer (LL) and others with only a benign course of this chronic oral mucosal disease. These results need to be confirmed by prospective multicentric studies.

Prognosis based on the revised histological classification by the World Health Organization (2010) for pancreatic neuroendocrine tumors

Background/aim: Pancreatic neuroendocrine tumors (PNETs) are a rare subgroup of tumors, for which the factors predictive of survival and prognosis are not well known. Recently, the European Neuroendocrine Tumors Society (ENETS) proposed the TNM staging and the World Health Organization (WHO) revised its histological classification in 2010. This study aimed to evaluate whether the ENETS staging and the revised WHO classification can predict survival after surgical resection of PNETs. Methods: Twenty consecutive curative resections for PNETs were performed at our institute from 1998 to 2012. The prognostic factors based on the revised WHO histological classification (2010) for survival were retrospectively evaluated using the Kaplan–Meier method. Results: The mean patient age was 60.3 10.9 years. Twelve patients (60%) were diagnosed with functioning tumors and 8 (40%) with nonfunctioning tumors. Surgical methods comprised pancreatoduodenectomy (n 1⁄4 3), distal pancreatectomy (n 1⁄4 5), enucleation (n 1⁄4 9), and central pancreatectomy (n 1⁄4 3). Hepatectomy was performed for 2 patients with synchronous liver metastasis. According to the ENETS staging, 14 (70%), 2 (10%), 2 (10%), and 2 (10%) had stage I, II, III, and IV tumors, respectively. According to the revised WHO histological classification (2010), 13 (65%), 5 (25%), 1 (5%), and 1 (5%) patient was diagnosed with neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC), and mixed adenoneuroendocrine carcinoma (MANEC), respectively. Univariate analysis revealed that both the ENETS staging and the revised WHO histological classification (2010) significantly predicted survival after surgical resection for PNETs. Conclusions: The ENETS staging and the revised WHO histological classification (2010) may be useful to predict survival in PNETs. However, because PNETs represent a rare tumor subgroup, more time and a sufficient number of cases are required to confirm its prognostic reliability.

Gallbladder carcinoma: An attempt of WHO histological classification on fine needle aspiration material

Background:Carcinoma of the gallbladder (CaGB) is common in India and its prognosis depends primarily on the extent of the disease and histological type. We aim to study the role of guided fine needle aspiration cytology (FNAC) for diagnosis of CaGB and to evaluate the feasibility of applying world health organization (WHO) classification on fine needle aspiration (FNA) material to predict the outcome of the tumor.Materials and Methods:Retrospective cytomorphologic analysis was performed in all cases of CaGB diagnosed by ultrasound (US) guided FNAC over a period of 2 years. A specific subtype was assigned according to WHO classification based on characteristic cytologic features. These included papillary or acinar arrangement, intra and extracellular mucin, keratin, rosettes and columnar, signet ring, atypical squamous, small, clear, spindle and giant cells. Correlation with histopathology was performed when available.Results:A total of 541 aspirations with clinical or radiological suspicion of primary CaGB were studied. Of these, 54 aspirates were unsatisfactory. Fifty cases were negative for malignancy. Remaining 437 aspirates were positive for carcinoma. Histopathologic diagnosis was available in 32 cases. Adenocarcinoma was the most frequent diagnosis in 86.7% of cases. Mucinous, signet ring, adenosquamous, squamous, small cell, mixed adenoneuroendocrine and undifferentiated carcinoma including spindle and giant cell subtypes were diagnosed identifying specific features on FNAC. Correlation with histopathology was present in all, but one case giving rise to sensitivity of 96.8%. No post-FNA complications were recorded.Conclusions:US guided FNAC is a safe and effective method to diagnose CaGB. Although, rare, clinically and prognostically significant variants described in WHO classification can be detected on cytology.

Extended Surgical Resections of Advanced Thymoma Masaoka Stages III and IVa Facilitate Outcome

Extended thymoma resections including adjacent structures and pleurectomy/decortication (P/D) with hyperthermic intrathoracic chemotherapy (HITHOC) perfusion were performed in a multidisciplinary treatment regime. Between July 2000 and February 2012, 22 patients with Masaoka stage III (n = 9; 41%) and Masaoka stage IVa (n = 13; 59%) thymic tumors were included. Mean age was 55 years (25-84 years) and 50% (11 out of 22) of patients were female. World Health Organization histological classification was as follows: B2 (n = 15), A (n = 1), B1 (n = 1), B3 (n = 2), and thymic carcinoma (C; n = 3). Radical thymectomy and partial resection of the mediastinal pleura and pericardium were performed. Of the 13, 9 patients with pleural involvement (stage IVa) received radical P/D followed by HITHOC (cisplatin). Macroscopic complete resection (R0/R1) was achieved in 19 (86%) patients. All patients received multimodality treatment depending on tumor stage, histology, and completeness of resection. Thirty-day mortality was 0% and three (13.6%) patients needed operative revision. Recurrence of thymoma was documented in five (22.7%) patients (stage III, n = 1; stage IVa, n = 4). Mean disease-free interval of patients with complete resection (n = 14 out of 22) was 30.2 months. After a mean follow-up of 29 months, 18 out of the 22 (82%) patients are alive. After P/D and HITHOC, 89% (8 out of 9 patients) are alive (current median survival is 25 months) without recurrence. Extended surgical resection of advanced thymic tumors infiltrating adjacent structures (stage III) or with pleural metastases (stage IVa) is safe and feasible. It provides a low recurrence rate and an acceptable survival. Additional HITHOC in patients with pleural thymoma spread seems to offer a better local tumor control.

Analysis of surgical strategy of treating thymomas: A single center experience.

e18519 Background: Thymomas are epithelial thymic tumors, generally considered to have an indolent growth pattern but are malignant. 20-40% of patients with thymomas have paraneoplastic syndromes,including myasthenia gravis(MG). The objective of this study is to evaluate outcome of surgical treatment to thymoma and determine whether the different pathological and clinical characteristics of thymomas influences the prognosis in thymoma patients. Methods: We retrospectively studied data from 228 consecutive patients operated on from1992 to 2007. All thymic epithelial tumors were reclassified according to the WHO histologic classification, and the Masaoka clinical staging system. Patients with type A and stage I thymoma had no adjuvant therapy. Most patients with types AB and B1 thymomas had radiotherapy postoperatively. Patients (stageII, III) were treated with adjuvant mediastinal radiation therapy, and both adjuvant radiation therapy and chemotherapy was administered to stage IV and type C one month after operation. For patients with tumor nodules found on the pleural surface, cytoreductive surgery was performed. After that, patients had both adjuvant radiation therapy and chemotherapy. Results: There were no peri-operative deaths. 19 cases were inoperable. 16.2% patients had postoperative complications: The proportions of type A, AB, B1, B2, B3, and C thymoma in this data were 0%, 22.4%, 26.4%, 30.4%, 20.8%, and 0% respectively in patients with MG. Microthymoma was identified in the paraneoplastic thymus of 3 patients. There were 198 patients followed up. There was no recurrence in patients with type A and a few patients with type AB, B1, B2, B3 and C recurred. The actuarial 5- and 10-year survival rates were 89.6% and 80.5% respectively. Within 5 years postoperatively, 6 of 16 deaths died of myasthenia crisis, 6 were attributable to inoperable tumors (stageIV) and type C thymoma. Conclusions: Surgical treatment to thymoma has a sound prognosis. Multimodality treatment of stage III or IV thymomas may be critical to improve the 5-year survival rate. MG seldom occurs in type A and C thymoma. The main cause of death is myasthenia crisis for thymoma patients with MG and stage IV and /or type C for thymoma patients without MG.

Did the 2004 World Health Organization (WHO) histologic classification result in better prognostic categories for resected thymomas as compared to 1999 WHO classification scheme?

e18552 Background: The classification of thymic epithelial neoplasms is subject of controversy. The purpose of our investigation is to see whether the 2004 histologic classification results in better prognostic categories than that of the 1999 classification. Methods: The SEER 18 database was used to investigate incidence and overall survival/cause-specific survival (OS/CSS) of resected thymomas during 2000-2009. Incidence was examined by frequency and trend analyses. Patients diagnosed with first primary localized thymoma/thymic carcinoma were selected in two time periods (2000-2003: N=201; 2005-2009: N = 497). The median follow up is 79 months and 27 months respectively. OS/CSS in two patients group were analyzed by Kaplan-Meier estimation, log-rank tests, and multivariate proportional hazards modeling. Results: The proportion of six histology categories (A, AB, B1-B3,C) did not change significantly during the two time periods. Compared to patients diagnosed in 2000-2003, OS was not significantly different in patients diagnosed in 2005-2009 in the log rank tests or multivariate analysis after accounting for treatment, tumor factors, and patient characteristics (OS, HR=0.737, p=0.1580; CSS, HR=0.731, p=0.3711). Histology as 6 categories is a significant predictor for OS in the multivariate analysis in 2005-2009, but not in 2000-2003. However, the predictive role of histology is similar in both time periods in the multivariate analysis of CSS. Complete resection, classification C, and tumor stage are significantly linked to OS and CSS. Conclusions: Patients diagnosed after 2004 did not have better survival outcomes than earlier patients. The WHO classification of 2004 may be a better predictor of OS than that of 1999 as shown by the wide-spectrum of pathologists reporting to SEER.

STAT3 expression correlates with prognosis of thymic epithelial tumors

BackgroundMore and more evidences demonstrate the significance of Signal transducers and activators of transcription 3(STAT3) in oncogenesis and tumor development. However, little systematic researches have been reported on the correlation between STAT3 and thymic epithelial tumor (TET).MethodsExpression of STAT3 protein in 80 thymic epithelial tumors was detected by immunohistochemistry (IHC). The difference of STAT3 expression was compared by the χ2 test. Estimation of survival was calculated using the Kaplan-Meier method, and the statistical differences were analyzed using the Log-rank test.ResultsPositive expression of STAT3 protein was significantly associated with Masaoka staging and WHO histological classification (P < 0.05), but not with age, gender, or tumor size. The rate of postoperative recurrence/metastasis was 33.33% in STAT3-positive tumors, compared with 4.55% in negative ones (P < 0.05). 5-year survival was significantly lower in STAT3-positive subjects (61.11%) than in negative ones (97.73%) (P < 0.01); In patients in Masaoka stage III or IV and WHO B3 or C, 5-year survival rate of subjects positive in STAT3 (35.00%, 35.00%) was statistically lower than that of the negative ones (92.31%, 91.67%). Cox regression analysis revealed that positive expression of STAT3 protein was an independent prognostic factor of thymic epithelial tumors (HR = 9.325, P = 0.044).ConclusionPositive expression of STAT3 protein increases along with the rising malignant degree of thymic epithelial tumors. It may be considered as an independent prognostic parameter with good prognostic value to evaluate the possibility of recurrence/metastasis in patients with thymic epithelial tumor.

Tumeurs épithéliales thymiques : actualités dans la prise en charge en France

Thymic epithelial neoplasms are rare malignancies with about 250 new incident cases in France every year. The WHO histologic classification distinguishes thymoma and thymic carcinoma which are tumors with different biological and clinical behaviors and outcomes. The Masaoka-Koga staging system is considered as a reference and is also of prognosis value. Diagnosis, multimodal treatment and follow-up of thymic epithelial neoplasms require a multidisciplinary approach where surgery is the cornerstone treatment. A national expert center coordinates thymic epithelial neoplasms management with 12 other regional expert centers through the French organization named RYTHMIC (www.rythmic.org). Patient's files have to be discussed at regional or national multidisciplinary staff. A group of expert pathologists will centrally review tumors when the diagnosis or classification is a matter of controversy. Among its objectives, RYHTMIC has to promote medical education, patient's information and research. This review focuses on RYTHMIC guidelines and data regarding multimodal management and targeted therapies in epithelial thymic neoplasms.

P2-023 - Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography for Distinguishing between the Histologic Types of Early Stage Thymic Epithelial Tumors

ABSTRACT Objectives Recent studies have shown the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiatingbetween World Health Organization (WHO) histological subgroups of thymic epithelial tumours. However, these reports may have includedmany advanced cases of these lesions (Masaoka stage III or IV) of high-risk subtypes. The objective of our present study was to assess the usefulnessof FDG-PET for distinguishing the histological subtypes of early stage thymic epithelial tumours (Masaoka stage I or II). Methods Twenty patients who had undergone an FDG-PET examination before treatment and had been diagnosed with an earlystage thymic epithelial tumour between July 2005 and July 2011 were enrolled in the present study. All patients underwent a total thymectomy.This cohort was divided into two groups according to the WHO histological classification of their lesion, i.e. low-risk tumours (types A, AB or B1) in one group and high-risk tumours (types B2, B3 or thymic carcinoma) in the other. Focal FDG accumulation was evaluated by determining the maximum standardized uptake value (SUV-max). Results The patient cohort for this study included 13 men and 7 women ranging in age from 26 to 70 years (mean 55 years). The low-risk group included seven cases (type A, 0; type AB, 7; type B1, 0), and the high-risk group comprised 13 cases (type B2, 7; type B3, 3; thymic carcinoma, 3). The SUV-max values of the low- and high-risk tumours were 3.09 ± 0.51 and 6.19 ± 3.13, respectively, and this was a significant difference. For the differential diagnosis of low- and high-risk tumours, sensitivity and specificity were 92.3 and 83.3%, respectively, when an SUV-max of 3.5 was used as a cutoff. Conclusions FDG-PET is a useful method for distinguishing histological types of early-stage thymic epithelial tumours.

Perspectives for Improved and More Accurate Classification of Canine Mammary Gland Neoplasms

We read with particular interest the article by Dr Goldschmidt and colleagues entitled ‘‘Classification and Grading of Canine Mammary Tumors,’’ which was published in Veterinary Pathology. It was a very interesting subject since mammary neoplasms are very important tumors in veterinary medicine because they are the most common neoplasms of intact adult female dogs and have high importance in countries in which dogs are not routinely spayed, such as many European and South American countries. We know that histologic examination of canine mammary gland nodules is the current standard to distinguish benign from malignant epithelial or complex tumors and to classify histologic subtypes, making new data regarding such features such as those provided in Dr Goldschmidt and colleagues’ article very useful. However, there are still some histotypes that are currently recognized in the literature that were not discussed in such article. The morphologic spectrum of mammary neoplasms in canine species is generally quite different from that seen in humans. However, the increase in reports regarding histologic types of mammary tumors occurring in dogs with a striking similarity with their human counterpart has been raising the interest of veterinary pathologists and clinicians about the possibility of facing distinct subtypes with particular and/or aggressive behavior. In our diagnostic services, we have frequently observed certain discrepancies between the last World Health Organization histologic classification for canine mammary neoplasms (CMNs) by Misdorp and colleagues, particularly regarding the so-called rare histotypes, which are not discussed. Classifying conventional CNMs such as papillary and tubular types poses no difficulty, as those morphologic variants are widely recognized in both mammary and other epithelial tumors. However, diagnosing rare histotypes that are not commonly discussed in the veterinary literature many times requires knowledge usually gained by systematically evaluating women’s breast neoplasms, which have a more recent histologic classification that discusses some rare histotypes that can be also observed in dogs. Since histologic evaluation is still the main diagnostic criterion for CMNs and is performed before chemotherapy institution, a new histologic classification is highly desirable, particularly because more than 10 years have passed since its publication and many new data regarding CNMs have been documented in the veterinary literature. Different neoplasms that were not discussed by Misdorp and colleagues’ classification are being more and more published in the veterinary literature, such as micropapillary carcinomas, mammary neoplasms with sebaceous differentiation, lobular carcinomas of the mammary gland, and pleomorphic lobular carcinomas. Important information regarding those tumors were recently published in an useful review. Rare histotypes of CMNs usually have different behavior from the tumors discussed in the Misdorp and colleagues classification, which makes the proposition of a new classification scheme even more important since veterinary pathologists can provide valuable information for practitioners by making a more accurate diagnosis. Given this scenario, a question arises: Isn’t it time to review the canine mammary tumors’ histologic classification? To address this issue, it is necessary to establish guidelines for the diagnosis of canine mammary tumors. Articles such as the one written by Webster and colleagues are good models. These articles represent a consensus statement in veterinary oncology made by veterinary pathologists and oncologists from around the world and constitute an important basis for producing relevant new material regarding canine mammary tumor classification.

1541 - Expression oF C-KIT (CD 117) in Epithelial Thymic Malignancies

ABSTRACT Study objectives The expression of c-kit (CD117) was investigated to evaluate its usefulness as a marker supporting differential diagnosis and choice of therapy. In thymic epithelial tumors the expression of c-kit may explain a new model of tumor biology, and support the use of determinate target therapy as a new optional approach. Methods We examined the immunohistochemical expression of c-kit in 28 cases of thymic epithelial tumors diagnosed in our department between 2003-2010, that had been classified on the basis of the World Health Organization histologic classification system: 24 thymoma and 4 thymic carcinoma (1 type A, 4 type AB, 1 type B1, 12 type B2, 6 type B3 and 4 type C). Results c-kit expression showed immunoreactivity positive in 18% of the all cases (5 patients). In this subgroup, 1 type B2, 1 type B3 and 3 type C. In contrast no immunoreactivity was found in the thymoma cases (types A, AB and B1). No differences were found in the c-kit expressing group between the genders (12 females, 16 males). All c-kit expressing cases were older than 61 years old. Conclusion Expression of c-kit is an immunohistochemical marker for the diagnosis of thymic carcinoma, and represent a new model of tumor biology with potential development of new targeted therapies as an option for the treatment of thymic carcinoma on the basis of the kit pathways. Clinical trials are necessary to demonstrate the efficacy of these new theoretical strategies. Disclosure All authors have declared no conflicts of interest.

1536P - Multicenter Institutional Experience of Surgically Resected Thymic Epithelial Tumors (TETS): an Observational Report on Behalf of F.O.N.I.C.A.P. (Forza Operativa Nazionale Interdisciplinare Contro Il Cancro Del Polmone)

ABSTRACT Purpose thymic epithelial tumors (TETs) are a rare neoplasms. Due to their rarity, large-scale prospective trials are lacking. The present retrospective multicenter analysis aimed to evaluate clinical outcome and clinical-pathological features of TETs after complete surgical resection and adjuvant treatments (Adj) such as chemotherapy (CHT) or radiotherapy (RT). Patients and methods Patients who underwent a complete surgical resections for TETs between 2000 and 2007 were reviewed. WHO histological classification criteria and Masaoka staging system were used. Adj were: anthracycline- and platin-based CHT, RT on irradiation fields covering the primary tumor bed. Overall survival (OS) was calculated from the date of diagnosis until patient death or last follow-up visit. Disease free-survival (DFS) was defined as the interval between surgery and date of first documentation of recurrence. OS, DFS and 95% Confidence Interval (95% CI) were estimated by Kaplan-Meier method. Results 62 patients were analyzed: 30 patients (48%) male and 32 (52%) female. Median age was 60 years (range: 33 - 86). At the beginning of their cancer history 20 (32%) patients had myasthenia. Clinical staging showed: 31 (50%) stage I disease, 19 (30%) stage II, 5 (8%) stage III, 2 (4%) stage IVa, 5 (8%) stage IVb. Histologies were: 11 (19%) A tumor type, 18 (29%) AB type, 7 (12%) B1 type, 11 (17%) B2 type, 11 (17%) B3 type and 3 (6%) C type. Pathological staging were: 30 (48%) stage I, 22 (35%) stage II, 3 (6%) stage III, 2 (3%) stage IVa, 5 (8%) stage IVb. 3 (5%) patients received Adj-CHT and 16 (26%) Adj-RT. Median follow-up was 71 months (range 1-145), DFS and OS are the following: % DFS (95% CI) % OS (95% CI) Events 48 mo 60 o0 72 mo Events 48 mo 60 mo 72 mo 9 89 (80-97) 89 (80-97) 86 (76-96) 7 97 (92-100) 95 (88-100) 92 (85-100) mo, months. Conclusions TETs are rare and indolent tumors. Surgery offers good results which can be further improved by Adj such as CHT and/or RT. Supported by GIPO. Disclosure All authors have declared no conflicts of interest.