Review of the literature about Thymic Carcinomas

Background: Thymic carcinomas (TC) are rare tumors with challenging diagnosis and management. We aimed to describe the clinical and microscopic characteristics of TC through a literature review. Results: 82 articles and abstracts were retained about 2913 TC. Our study contained 1760 men and 1153 women with a mean age of 55.32 years. The delay of diagnosis was specifi ed in 10 cases and varied between 8 months and 2 years. Symptoms consisted mainly in chest pain and dyspnea. The Computed Tomography-scan (CT-scan) fi ndings were specifi ed in 63 cases. Microscopic fi ndings were noticed in 1766 cases. They consisted mainly in squamous cell carcinoma in 1297 cases and undifferentiated carcinoma in 239 cases. The patients presented stage 1 tumors in 165 cases, stage II in 362 cases, stage III in 1011 cases and stage IV in 1166 cases. The treatment modalities were noticed in 2803 cases. There was no consensus of the regimen of chemotherapy or the place of the radiation therapy but all studies highlighted the key role of the complete surgical resection when possible. Conclusion: Our results highlight the lack of consensual management of TC. The chemotherapy regimen, the second-line chemotherapy and the indications of radiation therapy seem non-consensual and need further studies. Many interrogations remain concerning the management of these tumors according to their histologic grade. The real place of targeted therapy remains to assess and the rare opinions published are based on rare and non-representative cases. Review Article Review of the literature about Thymic Carcinomas Mona Mlika1,2* and Faouzi Mezni1,2 1Department of Pathology, Abderrahman Mami Hospital, University Tunis El Manar, Tunisia 212UR18 Research Unit, Tunis El Manar Faculty, Tunisia Dates: Received: 14 June, 2017; Accepted: 12 July, 2017; Published: 13 July, 2017 *Corresponding author: Mona Mlika, Department of Pathology, Abderrahman Mami Hospital, 2037, Tunis, Tunisia, Tel: 00216 98 53 8862; E-mail:

Symptoms were specifi ed in 728 cases and consisted in chest pain (263 cases) and dyspnea (187 cases). The other symptoms consisted in cough (151 cases), superior vena cava syndrom (57 cases), dysphonia (30 cases), weight loss (11 cases), asthenia (10 cases), fever (11 cases), and para-neoplastic syndrome (28 cases). The tumor was asymptomatic in 107 cases. Physical exam fi ndings were specifi ed in 3 cases and revealed sub-clavicular lymph node in 1 case and right cervical tumefaction in 1 case.
Chest-x-ray fi ndings were specifi ed in 2 cases and consisted in an anterior mediastinal mass situated in the left lung with pleural effusion and nodules in one case and a mediastinal

Discussion and Conclusion
Our study is about thymic carcinomas and present the advantage of studying an important number of series and cases. This study allowed a complete analysis of this pathology with the different aspects (epidemiology, symptoms, biology, microscopy, therapeutic management and prognosis). Our limits consist in the lack of clinical and microscopic fi ndings.
They were differentiated from thymomas by Rosai and Levine in 1978 and were considered as a distinct entity in the WHO classifi cation (1999), which distinguished the group of thymomas (TET de type A et B) and thymic carcinomas (TET de type C) [27][28][29][30][31][32][33][34][35][36][37][38][39]. Thymic carcinomas are observed at any age with a mean age varying between 50 and 60 years . The mean age in our review of the literature achieved 55.32 years with extremes varying between 10 and 89 years. A male predominance was observed in almost all cases .
The advantage of this treatment is refl ected by the improvement of the global survival, the survival without recurrence and without metastases [29,36]. A second line chemotherapy was used in 2 studies according to the protocols ABVD (Adriamycin + Delicum + Bleomycin + Velbemycin). This association was used in non resectable tumors [10,12,21,45,47,50,52,56,59,63,6 8]. The results of this association remain non-consensual because of the few number of patients included in this association. No prospective study has been described in the literature. Adjuvant radiation therapy has been discussed in the literature without a real consensus [91]. It was used in 19% of the cases. After a complete surgical resection, the utility of radiation therapy has been debated in the literature and was reported to have no effect on the global survival or the survival without progression [5,22,56,58]. For low grade tumors, some authors reported the role of radiation therapy following surgical resection in the decrease of loco regional recurrences and secondary localizations [6,9,28,36,54,61,62,66,80,92].
The place of targeted therapy has been assessed in the literature. A high expression of the Epidermal Growth Factor (EGFR) and HER has been reported especially in advanced tumors [29,89]. Moreover, the expression of Kit, assessed by immunohistochemistry, is characteristic of thymic carcinomas.
It has been reported in 2 % of thymomas and 80 % of thymic carcinomas. The expression of Kit was also used as a diagnostic tool of these tumors [39,93] [8,31,67]. Nine studies reported that the staging wasn't a relevant prognostic factor [6,9,19,20,30,46,57,71,74]. These studies reported that the vascular invasion was a bad prognosis factor and that it needs to be integrated in the staging system [46,57,71] [22]. The extension of the surgical resection has also been considered as a prognostic factor especially when associated to a lymph node curettage [8,23]. Adjuvant chemotherapy or radiation therapy have been also reported as a good prognostic factor related to the global survival and the survival without progression. [6,9,28,36,54,61,62,66,80].
Based on our literature review, the diagnosis of thymic carcinoma necessitates a multidisciplinary approach including clinicians, radiologists, pathologists and biologists. This is due to the absence of specifi c microscopic fi ndings despite DOI: http://dx.doi.org/10.17352/aprc.000027 of the utility of some antibodies, especially CD5 and CD117 antibodies in the diagnosis of these tumors. We noticed that the information concerning the diagnostic delay between the biopsy and the issue of the pathology report weren't assessed so we can't have an idea about the diagnostic delay. Even if, the complete surgical resection represents the mainstay treatment, the advantages of the incomplete surgical resection still have to be proved. We noticed the variety of chemotherapy protocols used but noticed that in almost all cases, a platinum-based chemotherapy was used. The impact of targeted therapies wasn't assessed because of the rarity of the reported cases.