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Cancers
Special Issues
Thymic Tumors: From Diagnosis to Treatment
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Thymic Tumors: From Diagnosis to Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 August 2021) | Viewed by 25550

Special Issue Editor

Prof. Dr. Giuseppe Marulli

E-Mail Website
Guest Editor
Thoracic Surgery Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy
Interests: lung cancer; mediastinal diseases; robotic and minimally invasive surgery; surgery of the airway; lung transplantation

Special Issue Information

Dear Colleagues,

Because of the relative rarity of thymic tumors, their diagnosis and subsequent treatment represent a challenging issue for clinicians. The three major subtypes of primary thymic tumors include thymomas, thymic carcinomas, and thymic neuroendocrine tumors, presenting with an incidence far higher for thymomas (2.2 to 2.6/million/y) than for thymic carcinomas (0.3 to 0.6/million/y).

Due to the few series of patients analyzed in the published literature, our knowledge of thymic tumor biology, pathology, and outcomes has increased slowly, particularly in recent years, thanks to large international collaborations leading to the generation of consensus guidelines.

The clinical stage guides the treatment regimen for thymic tumors. Radical thymectomy is the gold standard treatment for thymoma—in particular, completeness of surgical resection and adequate margins are considered the most important prognostic factors, while the use of multimodality treatment is of paramount importance, especially in the case of more advanced tumors. A multidisciplinary approach involving thoracic surgeons, thoracic oncologists, radiologists, pathologists, and radiation oncologists should be the standard of care.

Minimally invasive techniques (VATS or RATS) compared with conventional open approaches give some advantages (shorter hospital stay, quicker recovery, better aesthetic result, etc.). Despite this, the use of MinInvasive approaches in thymic surgery is still controversial because of the supposed higher risk of rupture of the capsule with the consequent spread of tumoral cells, increased risk of local recurrence, and reduced safety margins.

Moreover, no clear guidelines are available regarding lymph node dissection, and data from the majority of studies show that lymph node sampling is not routinely performed during surgeries.

This Special Issue will highlight the current state-of-the-art in thymic tumor management, and future perspectives in diagnostic and therapeutic approaches. 

 

Prof. Dr. Giuseppe Marulli
Guest Editor

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Keywords

  • thymic tumors
  • MinInvasive
  • robotic surgery
  • mediastinal diseases

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Published Papers (9 papers)

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Research

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13 pages, 3353 KiB  
Article
Masaoka-Koga and TNM Staging System in Thymic Epithelial Tumors: Prognostic Comparison and the Role of the Number of Involved Structures
by Marco Chiappetta, Filippo Lococo, Luca Pogliani, Isabella Sperduti, Diomira Tabacco, Emilio Bria, Ettore D’Argento, Mariangela Massaccesi, Luca Boldrini, Elisa Meacci, Venanzio Porziella, Dania Nachira, Maria Teresa Congedo and Stefano Margaritora
Cancers 2021, 13(21), 5254; https://doi.org/10.3390/cancers13215254 - 20 Oct 2021
Cited by 15 | Viewed by 2371
Abstract
Background: The aim of this study was to evaluate the Masaoka–Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 [...] Read more.
Background: The aim of this study was to evaluate the Masaoka–Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka–Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact. Results: Considering the Masaoka–Koga system, 5- and 10-year overall survival (5–10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III (p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5–10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 (p = 0.02), with overlapping T2–T3 curves. Including the number of involved structures, in Masaoka–Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5–10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5–10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement (p = 0.07). Conclusion: The two staging systems present limitations due to overlapping curves in early Masaoka–Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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12 pages, 1508 KiB  
Article
Evaluation of Surgical Therapy in Advanced Thymic Tumors
by Till Markowiak, Mohammed Khalid Afeen Ansari, Reiner Neu, Berthold Schalke, Alexander Marx, Hans-Stefan Hofmann and Michael Ried
Cancers 2021, 13(18), 4516; https://doi.org/10.3390/cancers13184516 - 8 Sep 2021
Cited by 4 | Viewed by 1851
Abstract
A complete resection of thymic tumors is known to be the most important prognostic factor, but it is often difficult to perform, especially in advanced stages. In this study, 73 patients with advanced thymic tumors of UICC stages III and IV who underwent [...] Read more.
A complete resection of thymic tumors is known to be the most important prognostic factor, but it is often difficult to perform, especially in advanced stages. In this study, 73 patients with advanced thymic tumors of UICC stages III and IV who underwent radical resection were examined retrospectively. The primary endpoint was defined as the postoperative resection status. Secondary endpoints included postoperative morbidity, mortality, recurrence/progression-free, and overall survival. In total, 31.5% of patients were assigned to stage IIIa, 9.6% to stage IIIb, 47.9% to stage IVa, and 11% to stage IVb. In stages III a R0 resection was achieved in 53.3% of patients. In stages IV a R0/R1 resection was documented in 76.7% of patients. Surgical revision was necessary in 17.8% of patients. In-hospital mortality was 2.7%. Median recurrence/progression-free interval was 43 months (p = 0.19) with an overall survival of 79 months. The 5-year survival rate was 61.3%, respectively. Median survival after R2 resection was 25 months, significantly shorter than after R0 or R1 resection (115 months; p = 0.004). Advanced thymic tumors can be resected with an acceptable risk of complications and low mortality. In stage III as well as in stage IV the promising survival rates are dependent on the resection-status. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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16 pages, 4741 KiB  
Article
The Rarest of Rare Thymic Lesions: A 10-Year Surgical Pathology Experience
by Fiorella Calabrese, Francesco Fortarezza, Federica Pezzuto, Francesca Lunardi, Giovanni Comacchio, Marta Sbaraglia, Giulia Pasello, Giuseppe Marulli, Angelo Paolo Dei Tos and Federico Rea
Cancers 2021, 13(16), 4056; https://doi.org/10.3390/cancers13164056 - 12 Aug 2021
Cited by 1 | Viewed by 2937
Abstract
The thymus is a specialized primary lymphoid organ located in the midline pre-vascular mediastinum. The organ is the site of various pathological processes, neoplastic and not, whose rarity has not allowed in-depth studies on clinical or histological features of rarest and unusual variants. [...] Read more.
The thymus is a specialized primary lymphoid organ located in the midline pre-vascular mediastinum. The organ is the site of various pathological processes, neoplastic and not, whose rarity has not allowed in-depth studies on clinical or histological features of rarest and unusual variants. Herein, we report a 10-year Padova experience in the surgical pathology of the thymus, focusing on the pathological description of nonneoplastic lesions and rare epithelial and mesenchymal tumors recorded in our database, which comprises over 600 thymectomies. The extrapolated rare cases have been categorized into four groups that included 15 cysts, 18 carcinomas, 5 neuroendocrine tumors, and 2 soft tissue tumors. The cases are described from a clinical and pathological point of view and discussed in dedicated sections with a review of the most important literature. In this case, review series, we aim to update the epidemiology of these rare entities, improve diagnostic awareness, and finally, promote a collaborative network between referral centers. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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12 pages, 1409 KiB  
Article
Vascular Involvement in Thymic Epithelial Tumors: Surgical and Oncological Outcomes
by Giovanni M. Comacchio, Andrea Dell’Amore, Maria Carlotta Marino, Michele Dario Russo, Marco Schiavon, Marco Mammana, Eleonora Faccioli, Giulia Lorenzoni, Dario Gregori, Giulia Pasello, Giuseppe Marulli and Federico Rea
Cancers 2021, 13(13), 3355; https://doi.org/10.3390/cancers13133355 - 4 Jul 2021
Cited by 10 | Viewed by 2102
Abstract
Background: The involvement of mediastinal great vessels is common in advanced stage thymic tumors, which makes their surgical resection challenging. Moreover, the impact of vascular involvement on the oncological prognosis is still unclear. The aim of this study is to investigate the surgical [...] Read more.
Background: The involvement of mediastinal great vessels is common in advanced stage thymic tumors, which makes their surgical resection challenging. Moreover, the impact of vascular involvement on the oncological prognosis is still unclear. The aim of this study is to investigate the surgical and oncological outcomes and the impact of vascular involvement in a population of patients operated for advanced stage thymic tumors. Methods: A retrospective analysis on four hundred and sixty-five patients undergoing resection for advanced stage (Masaoka III–IV) thymic tumors in a single high-volume center was performed. One hundred forty-four patients met the inclusion criteria and were eligible for the study. Patients were divided in two groups according to the presence or absence of vascular involvement. Results: the two groups did not differ for the baseline characteristics and showed comparable surgical outcomes. Vascular involvement was not associated with worse overall survival but with an increased recurrence rate (p = 0.03). Multivariable analysis demonstrated a higher risk of recurrence in patients without R0 resection (HR 0.11, 0.02–0.54, p = 0.006) and with thymic carcinoma (HR 2.27, 1.22–4.24, p = 0.01). Conclusions: resection of thymic tumors with vascular involvement can be performed with optimal surgical results in a high volume center. From the oncological point of view, the involvement of the great vessels seems to be associated with a higher recurrence rate without affecting long-term survival. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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Review

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12 pages, 1087 KiB  
Review
Current Roles of PET/CT in Thymic Epithelial Tumours: Which Evidences and Which Prospects? A Pictorial Review
by Filippo Lococo, Marco Chiappetta, Elizabeth Katherine Anna Triumbari, Jessica Evangelista, Maria Teresa Congedo, Daniele Antonio Pizzuto, Debora Brascia, Giuseppe Marulli, Salvatore Annunziata and Stefano Margaritora
Cancers 2021, 13(23), 6091; https://doi.org/10.3390/cancers13236091 - 3 Dec 2021
Cited by 10 | Viewed by 3762
Abstract
Background: The use of 18F FDG PET/CT scan in thymic epithelial tumours (TET) has been reported in the last two decades, but its application in different clinical settings has not been clearly defined. Methods: We performed a pictorial review of pertinent literature [...] Read more.
Background: The use of 18F FDG PET/CT scan in thymic epithelial tumours (TET) has been reported in the last two decades, but its application in different clinical settings has not been clearly defined. Methods: We performed a pictorial review of pertinent literature to describe different roles and applications of this imaging tool to manage TET patients. Finally, we summarized future prospects and potential innovative applications of PET in these neoplasms. Results: 18FFDG PET/CT scan may be of help to distinguish thymic hyperplasia from thymic epithelial tumours but evidences are almost weak. On the contrary, this imaging tool seems to be very performant to predict the grade of malignancy, to a lesser extent pathological response after induction therapy, Masaoka Koga stage of disease and long-term prognosis. Several other radiotracers have some application in TETs but results are limited and almost controversial. Finally, the future of PET/CT and theranostics in TETs is still to be defined but more detailed analysis of metabolic data (such as texture analysis applied on thymic neoplasms), along with promising preclinical and clinical results from new “stromal PET tracers”, leave us an increasingly optimistic outlook. Conclusions: PET plays different roles in the management of thymic epithelial tumours, and its applications may be of help for physicians in different clinical settings. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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11 pages, 766 KiB  
Review
Difficult Decisions in Minimally Invasive Surgery of the Thymus
by Ankit Dhamija, Jahnavi Kakuturu, J. W. Awori Hayanga and Alper Toker
Cancers 2021, 13(23), 5887; https://doi.org/10.3390/cancers13235887 - 23 Nov 2021
Cited by 3 | Viewed by 1915
Abstract
A minimally invasive resection of thymomas has been accepted as standard of care in the last decade for early stage thymomas. This is somewhat controversial in terms of higher-staged thymomas and myasthenia gravis patients due to the prognostic importance of complete resections and [...] Read more.
A minimally invasive resection of thymomas has been accepted as standard of care in the last decade for early stage thymomas. This is somewhat controversial in terms of higher-staged thymomas and myasthenia gravis patients due to the prognostic importance of complete resections and the indolent characteristics of the disease process. Despite concerted efforts to standardize minimally invasive approaches, there is still controversy as to the extent of excision, approach of surgery, and the platform utilized. In this article, we aim to provide our surgical perspective of thymic resection and a review of the existing literature. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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Graphical abstract

12 pages, 1235 KiB  
Review
Which Is the Best Treatment in Recurrent Thymoma? A Systematic Review and Meta-Analysis
by Marco Chiappetta, Ugo Grossi, Isabella Sperduti, Stefano Margaritora, Giuseppe Marulli, Alfonso Fiorelli, Alberto Sandri, Tetsuya Mizuno, Giacomo Cusumano, Masatsugu Hamaji, Alfredo Cesario and Filippo Lococo
Cancers 2021, 13(7), 1559; https://doi.org/10.3390/cancers13071559 - 29 Mar 2021
Cited by 7 | Viewed by 2938
Abstract
Background: Optimal recurrent thymoma management remains arguable because of limited patient numbers, and relatively late and variable recurrence patterns. Given the absence of high-quality evidence and relatively small study cohorts, we performed a quantitative meta-analysis to determine the outcome of surgical and non-surgical [...] Read more.
Background: Optimal recurrent thymoma management remains arguable because of limited patient numbers, and relatively late and variable recurrence patterns. Given the absence of high-quality evidence and relatively small study cohorts, we performed a quantitative meta-analysis to determine the outcome of surgical and non-surgical approaches assessing the five-year overall survival (5y overall survival (OS)) in patients with recurrent thymoma. Methods: We performed a comprehensive literature search and analysis according to PRISMA guidelines of studies published from 1 January 1980 until 18 June 2020 from PubMed/MEDLINE, EMBASE, and Scopus. We included studies with the cohorts’ superior to 30 patients describing recurrent thymoma treatment, comparing surgical and non-surgical approaches reporting survival data. Results: Literature search revealed 3017 articles. Nine studies met all inclusion criteria and were selected for the meta-analysis. The recurrences were local/regional in 73–98% of cases and multiple in 49–72%. After treatment, 5y OS ranged from 48–77% and 10y OS from 37–51%. The quantitative meta-analysis showed a better outcome comparing surgical vs other treatments. Two studies showed statistically significant risk differences in the 5y OS favoring complete resection. After pooling results of seven studies using the random model, the combined 5y OS risk difference was 0.39, with lower and upper limits of 0.16 and 0.62, respectively (p = 0.001), and a moderate heterogeneity among studies (p = 0.098, I2 = 43.9%). Definitive conclusions could not be drawn regarding the prognostic impact of myasthenia gravis, histology, and patterns of relapse reported in literature. Conclusions: Surgical treatment after thymoma recurrence is associated with a significant better 5y OS; therefore, surgical resection should be preferred in all technically feasible cases. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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Other

Jump to: Research, Review

12 pages, 435 KiB  
Systematic Review
Lymph Nodes Involvement and Lymphadenectomy in Thymic Tumors: Tentative Answers for Unsolved Questions
by Debora Brascia, Angela De Palma, Marcella Schiavone, Giulia De Iaco, Francesca Signore, Teodora Panza, Doroty Sampietro, Gianluca Di Milo, Mariangela Valentini, Salvatore Pisconti and Giuseppe Marulli
Cancers 2021, 13(20), 5085; https://doi.org/10.3390/cancers13205085 - 11 Oct 2021
Cited by 8 | Viewed by 1945
Abstract
Thymic tumors are the most common primary neoplasms of the anterior mediastinum, although, when compared with the entire thoracic malignancies, they are still rare. Few studies addressed the questions about lymph node involvement pattern in thymic neoplasms, about which subgroup of patients would [...] Read more.
Thymic tumors are the most common primary neoplasms of the anterior mediastinum, although, when compared with the entire thoracic malignancies, they are still rare. Few studies addressed the questions about lymph node involvement pattern in thymic neoplasms, about which subgroup of patients would be appropriate candidates for lymph node dissection or about the extent of lymphadenectomy or which lymph nodes should be harvested. The aim of this review is to collect evidence from the literature to help physicians in designing the best surgical procedure when dealing with thymic malignancies. A literature review was performed through PubMed and Scopus in May 2021 to identify any study published in the last 20 years evaluating the frequency and the extent of lymph node dissection for thymic tumors, its impact on prognosis and on postoperative management. Fifteen studies met the inclusion criteria and were included in this review, with a total of 9452 patients with thymic cancers; lymph node metastases were found in 976 (10.3%) patients in total. The current literature is heterogeneous in the classification and reporting of lymph node metastases in thymic carcinoma, and data are hardly comparable. Surgical treatment should be guided by the few literature-based pieces of evidence and by the experience of the physicians. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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11 pages, 4966 KiB  
Commentary
Advancement in Diagnostic Imaging of Thymic Tumors
by Francesco Gentili, Ilaria Monteleone, Francesco Giuseppe Mazzei, Luca Luzzi, Davide Del Roscio, Susanna Guerrini, Luca Volterrani and Maria Antonietta Mazzei
Cancers 2021, 13(14), 3599; https://doi.org/10.3390/cancers13143599 - 18 Jul 2021
Cited by 10 | Viewed by 3962
Abstract
Thymic tumors are rare neoplasms even if they are the most common primary neoplasm of the anterior mediastinum. In the era of advanced imaging modalities, such as functional MRI, dual-energy CT, perfusion CT and radiomics, it is possible to improve characterization of thymic [...] Read more.
Thymic tumors are rare neoplasms even if they are the most common primary neoplasm of the anterior mediastinum. In the era of advanced imaging modalities, such as functional MRI, dual-energy CT, perfusion CT and radiomics, it is possible to improve characterization of thymic epithelial tumors and other mediastinal tumors, assessment of tumor invasion into adjacent structures and detection of secondary lymph nodes and metastases. This review aims to illustrate the actual state of the art in diagnostic imaging of thymic lesions, describing imaging findings of thymoma and differential diagnosis. Full article
(This article belongs to the Special Issue Thymic Tumors: From Diagnosis to Treatment)
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