Primary Thymic Tumors Research Articles

Outcome of Robotic Assisted Resection of Large Primary Thymic Tumors: A Single High Volume Institutional Experience

Outcome of Robotic Assisted Resection of Large Primary Thymic Tumors: A Single High Volume Institutional Experience

Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases.

Insulinoma-associated protein 1 (INSM1) immunohistochemistry has been established as a sensitive and reliable immunohistochemical marker for detecting neuroendocrine differentiation in tumors across various organ systems. However, this marker has not been adequately investigated in primary thymic neuroendocrine tumors. We have studied a series of 27 cases of primary neuroendocrine carcinomas of the thymus, including 3 typical carcinoids, 18 atypical carcinoids, 4 large cell neuroendocrine carcinomas, and 2 small cell carcinomas. Immunostaining on whole tissue sections for INSM-1 was evaluated. Results of immunostaining for chromogranin and synaptophysin were also evaluated. 26/27 tumors (96%) demonstrated nuclear positivity for INSM1. 18 tumors (67%) showed strong and diffuse nuclear staining (3 +), 3 tumors (11%) moderate (2 +) nuclear staining, and 5 tumors (19%) showed weak (1 +) nuclear staining. The average percentage of tumor cells positive for INSM1 was 76%. Only one tumor, a small cell carcinoma, was negative. All tumors were positive for synaptophysin, and 26/27 (96%) were positive for chromogranin A. This study confirms that INSM1 immunohistochemistry is a sensitive marker of neuroendocrine differentiation in primary thymic neuroendocrine neoplasms and demonstrates similar performance characteristics compared to other organ systems. The nuclear staining with this marker offers the advantage of eliminating some of the ambiguity in the interpretation sometimes encountered with other markers. An added advantage is the consistent staining across the entire spectrum of neuroendocrine tumors of this organ.

Primary glomus tumor of the thymus in a 66-year-old patient

We report a unique case of a 66-year-old man who was incidentally identified to have a mass in the thymus region by computerized tomography scan. CT revealed a well-defined 1.6 × 1 × 0.9 cm thymus mass with moderate uniform enhancement. Thoracoscopic thymectomy was performed, and the pathological diagnosis was primary glomus tumor of the thymus. There were no atypia or malignant histological features, and no primary tumors in other sites. To our knowledge, this is the first case of primary thymic glomus tumor reported in the literature.

Imaging and Histopathological Features Of Primary Thymic Neuroendocrine Tumor.

To investigate CT, MRI, and PET/CT features with histopathological findings of primary thymic neuroendocrine tumor. All 9 cases with pathologically proven primary thymic neuroendocrine tumors were reviewed retrospectively. Among them, 7 underwent enhanced CT, 1 with MRI (enhanced) and another with PET/CT scan. Multiple characters were examined, including tumor location, contour, CT attenuation, enhancement pattern, involvement of surrounding structure and lymphadenopathy. Among 9 patients studied, 7 (77%) masses were located in the anterior superior mediastinum, 1 in the anterior superior-middle mediastinum, and 1 in the anterior and middle mediastinum. The maximum diameter (longitudinal) ranged from 4.2 to 23 cm (mean ± standard deviation, 9.5 cm ± 2.8). Four masses had irregular, 3 had lobulated, and 2 had smooth contours, while 8 masses had clear margins and 1 had an ill-defined margin. Six masses showed heterogeneous attenuation with necrotic/cystic component (n=5), calcification (n=2) and hemorrhage(n=1), and 3 showed homogeneous attenuation on the non-enhanced image. After contrast administration, 8 masses showed heterogeneous attenuation, and 1 showed homogeneous attenuation with tumor vessels visible in 4 masses. Among all, 8 masses showed strong enhancement, and 1 showed moderate enhancement in comparison to muscles in the anterior thoracic wall on enhanced images. Involvement of adjacent mediastinal structures was observed in 5 cases. Immunohistochemical analysis showed that the tumor cells were positive for CgA, Syn, CK, CD56 and EMA. Primary NETs are large masses located anterior superior mediastinum, irregular in contour, showing heterogeneous attenuation with necrotic/cystic component and strong heterogeneous enhancement with tumor vessels, compressing local mediastinal structures. In addition, immunohistochemical examination is required in such a diagnosis.

CT and MRI features in 22 cases of primary malignant thymic germ cell tumours

To analyse the computed tomography (CT) and magnetic resonance imaging (MRI) features of malignant thymic germ cell tumours (GCTs), in order to improve the accuracy of diagnosis of these tumours. Twenty-two patients (20 men, two women; age, 28±8.64 years) with malignant thymic GCTs confirmed at histopathology were enrolled retrospectively, and their CT and MRI findings were analysed. According to the CT findings, malignant thymic GCTs usually manifest as a bulky mass that typically grows to both sides of the midline (20/22, 90.9%), with irregular shape (15/22, 68.2%), lobulation (12/22, 50%), ill-defined margin (9/22, 40.9%), and incomplete capsule (21/22, 95.5%). Twenty masses revealed heterogeneous density with multifocal necrosis or cystic change in 19 (86.4%). Most cases (16/18, 88.9%) showed mild to moderate enhancement, and the branch-like vessel was found in 14 (14/18, 77.8%) cases. The minimum apparent diffusion coefficient (ADCmin) and mean apparent diffusion coefficient (ADCmean) values in 14 patients were (1.13±0.45) and (1.37±0.49)×10-3 mm2/s, respectively. Compared with CT findings, the incidences of an incomplete capsule, heterogeneous signal, and necrotic or cystic change on MRI images occurred in all patients with malignant thymic GCT. In addition, peritumoural oedema was found in all 14 (100%) cases. MRI is superior to CT in showing incomplete capsule, peritumoural oedema, heterogeneous signal, and necrotic or cystic change of GCTs. Branch-like enhancement and multifocal necrosis may help the diagnosis of malignant thymic GCTs.

Post-Operative Outcomes Associated With Open Versus Robotic Thymectomy: A Propensity Matched Analysis

To compare post-operative outcomes associated with thymectomy performed using either open or robotic approaches. Retrospective cohort study from a single-center prospective registry consisting of patients undergoing thymectomy between 2000 and 2020. Patients were grouped according to surgical approach (open vs robotic). A propensity-score matching analysis was performed in a 2:1 open to robotic ratio, and surgical outcomes were evaluated. We analyzed 234 thymectomies (155 open; 79 robotic). Myasthenia gravis was present in 23.2% and 32.9% (P=0.249) in the open and in the robotic group, respectively. All covariates were balanced in the matched groups (open n=114; robotic n =5 9), except lesion size. The robotic approach was significantly associated with shorter surgical time (median 95 vs 65 minutes, P < 0.001), lesser clinical (21.1% vs 6.8%, P=0.016) and surgical (11.4% vs 1.7%, P=0.036) complications during the same hospitalization, less Clavien-Dindo grade 2 or higher complication rates (28.1 vs 15.3%, P=0.048), chest tube duration (median: 3 vs 0 days, P < 0.001) and in-hospital length of stay (median: 5 vs 0 days, P < 0.001). Bleeding (P=0.214), ICU length of stay (P=0.167), reoperation rate (open, 1.8% vs robotic 0%), 90-day mortality (P=0.341) and readmission rate post discharge (P=0.277) were similar between the groups. In the matched population with primary thymic epithelial tumors, the completeness of resection rate was similar (open, 92.1% vs robotic 96.8%, P=0.66.). Robotic thymectomy is associated with improved post-operative outcomes when compared to open thymectomy, without compromising the goals of oncologic surgery. Longer follow-up is needed to ensure oncologic equivalence.

Thymic epithelial tumors: Do we know all the prognostic factors?

BackgroundThymic epithelial tumors constitute a morphologically and clinically diverse group of rare neoplasm of the anterior mediastinum.MethodsHere, we present an analysis of 188 patients diagnosed with primary thymic tumors between 1995 and 2015. The prognostic value of selected clinical and morphological factors was assessed in relation to overall survival and recurrence‐free survival.ResultsThe risk of recurrence increased significantly in thymic carcinoma diagnosis (P = 0.0036), co‐occurrence of other diseases, and weight loss (P = 0.0012 and 0.0348, respectively). Multivariate analysis showed that the most important independent risk factor for disease recurrence was clinical stage IV (P = 0.0036). A total of 63 patients (33.5%) died. In the univariate analysis, the following factors were considered as independent prognostic factors for overall survival: clinical stage (P < 0.0001), histological type (P < 0.0001), lymph node involvement (P < 0.001), WHO performance status 2 (P < 0.0001), anemia (Hb <9.5 g/dL; P = 0.0002), leucocytosis (>12.5 G/L; P = 0.0011), LDH level (>185 U/L; P < 0.0001), concomitant diseases (P = 0.0012) and weight loss (P < 0.0001).The strongest independent risk factor for death was stage IV disease (P < 0.001).ConclusionsThe results confirmed a fairly good prognosis for patients with thymic epithelial tumors. Clinical stage was the most important prognostic factor, but, some additional clinical factors may also have prognostic value.

Evaluation of the prognostic value of surgery and postoperative radiotherapy for patients with thymic neuroendocrine tumors: A propensity-matched study based on the SEER database.

BackgroundThe prognostic value of surgery and postoperative radiotherapy (PORT) for primary thymic neuroendocrine tumors (TNETs) was estimated using the SEER database.MethodsThis retrospective study used SEER data of TNET patients between 1998 and 2015. Propensity score matching (PSM) was performed according to whether surgery was performed. The prognostic effects on overall survival (OS) and cancer‐specific survival (CSS) were evaluated using multivariate Cox regression.ResultsA total of 3947 patients were included: 293 (7.4%) TNET, 2788 (70.6%) thymoma, and 866 (21.9%) thymic carcinoma. Compared to other subtypes, TNET patients were younger, included a larger proportion of men, had a well or moderately differentiated histological grade, higher disease stage at diagnosis, and were more likely to have regional lymph node metastasis. The median OS and CSS for TNET were 82.9 (95% confidence interval 74.3–91.4) and 101.9 (95% confidence interval 91.9–111.8) months, respectively, significantly shorter than for thymomas. In the matched cohort of TNET patients, multivariate analysis of OS and CSS revealed a significantly poorer prognosis in the non‐surgery group (P < 0.001). Compared to total/radical resection, TNET patients who underwent debulking resection had significantly inferior outcomes (P < 0.05). Postoperative radiotherapy favorably impacted OS and CSS in Masaoka–Koga stage III–IV TNET patients; this OS impact was also observed in stage IIB patients.ConclusionTNETs are extremely rare with relatively dismal outcomes. This analysis revealed the role of complete surgical resection and the favorable effect of postoperative radiotherapy in specific TNET subgroups.

AB040. PS02.04: DOTATATE PET/CT in thymic atypical carcinoid tumor with secondary ACTH-dependent Cushing’s syndrome

: Neuroendocrine thymic tumors represent the least common type of primary thymic tumor with a prevalence of 2–5%. We present a case of locally advanced thymic atypical carcinoid tumor diagnosed incidentally while investigating progressive Cushing’s syndrome. CT scan demonstrated a large 2.9 cm exophytic thyroid nodule and a 2.0 cm anterior mediastinal mass. Biopsy of the thyroid nodule demonstrated benign thyroid tissue, and Octreotide scan revealed avid uptake in the right thyroid lobe with minimal uptake in the thymic tumor. 68-Gallium DOTATATE PET-CT scan showed intense uptake in the thyroid gland followed by a moderate amount of activity in the anterior mediastinal mass. The patient underwent a median sternotomy and radical thymectomy with en bloc resection of the left innominate vein and primary repair of the superior vena cava. On further evaluation, the presumed thyroid nodule appeared contiguous with the thymic lesion and separate from the thyroid. Final pathology demonstrated a poorly differentiated 4.4 cm atypical carcinoid tumor with nine positive lymph nodes. On the third postoperative day, the serum cortisol level precipitously decreased to a level of 6.8 µg/dL. This case highlights the challenges surrounding the diagnosis of hormonally active thymic carcinoids, and demonstrates the utility of 68-Gallium DOTATATE PET scan in localizing somatostatin-positive neuroendocrine tumors, and surgical planning.

Clinicopathologic analysis of 3 patients with metaplastic thymoma

Objective To investigate the clinicopathologic characteristics of metaplastic thymoma. Methods The histological features and immunophenotype of three cases with metaplastic thymoma were studied, and the literatures were reviewed. Results There were 2 females and 1 male of 3 patients with 45, 52 and 40 years old, respectively. All tumors were characterized by a biphasic pattern composed of epithelial components and spindle cells. The epithelial areas consisted of anastomosing cords and islands or broad trabeculae of cohesive neoplasia cells. Some epithelial cells showed mild cytologic atypia, the presence of prominent nuclear grooves or pseudoinclusion body, and very low mitotic activity. The cells appeared bland and a fine nuclear chromatin pattern, and the mitoses were not found. The epithelial cells were diffusely and strongly positive for AE1/AE3. The spindle cells were diffusely positive for Vimentin. The Ki-67 fraction was low (< 5 %) in both components. Conclusions Metaplastic thymoma is a rare primary thymic epithelial tumor, and its biologic behavior is likely benign or lowly malignant process. Occasionally, the tumor invades adjacent tissue or recurrence. With complete tumor resection, the patients have good prognosis. The diagnosis of metaplastic thymoma mainly relies on its morphologic features and immunohistochemical profiles. Key words: Metaplasia; Thymoma; Immunohistochemically

Morvan Syndrome: A Case Report With Patient Narrative and Video.

A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management.

Potential Role of Adjuvant Radiation Therapy in Cervical Thymic Neoplasm Involving Thyroid Gland or Neck.

PurposeThe purpose of this study is to assess the clinicopathologic features, treatment outcomes, and role of adjuvant radiation therapy (RT) in cervical thymic neoplasm involving the thyroid gland or neck.Materials and MethodsThe medical and pathologic records of eight patients with cervical thymic neoplasm were reviewed retrospectively. All patients underwent surgical resection, including thyroidectomy or mass excision. Adjuvant RT was added in five patients with adverse clinicopathologic features. The radiation doses ranged from 54 Gy/27 fractions to 66 Gy/30 fractions delivered to the primary tumor bed and pathologically involved regional lymphatics using a 3-dimensional conformal technique.ResultsEight cases of cervical thymic neoplasm included three patients with carcinoma showing thymus-like differentiation (CASTLE) and five with ectopic cervical thymoma. The histologic subtypes of ectopic cervical thymoma patients were World Health Organization (WHO) type B3 thymoma in one, WHO type B1 thymoma in two, WHO type AB thymoma in one, and metaplastic thymoma in one, respectively. The median age was 57 years (range, 40 to 76 years). Five patients received adjuvant RT: three with CASTLE; one with WHO type B3; and one with WHO type AB with local invasiveness. After a median follow-up period of 49 months (range, 11 to 203 months), no recurrence had been observed, regardless of adjuvant RT.ConclusionAdjuvant RT after surgical resection might be worthwhile in patients with CASTLE and ectopic cervical thymoma with WHO type B2-C and/or extraparenchymal extension, as similarly indicated for primary thymic epithelial tumors. A longer follow-up period may be needed in order to validate this strategy.

Primary neuroendocrine tumors of the thymus: Clinical review of 22 cases.

Primary neuroendocrine tumors of the thymus are rare mediastinum tumors, which present a distinct type of tumor, which exhibit morpholgical and biological neuroendorcine features including the production of numerous biogenic amines. The aim of the present study was to evaluate factors influencing long-term survival in patients with primary neuroendocrine tumors of the thymus. A total of 22 patients exhibiting primary thymic neuroendocrine tumors, who were treated at the Zhejiang Cancer Hospital (Hangzhou, China), between 1995 and 2012 were reviewed. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model was used for multivariate analysis. The overall five-year survival rate was 45.5% and the median survival time was 59 months in all of the patients. Histological grade (P<0.001), Masaoka-Koga stage (P=0.003) and surgical resection status (P=0.004) were identified to be associated with patient survival time. Furthermore, multivariate analysis identified that the histological grade was an independent prognostic factor, which was applicable to all patients (P=0.009). Therefore, the histological grade and Masaoka-Koga stage, as well as surgical resection status present three prognostic factors in patients exhibiting primary thymic neuroendocrine tumors.

Imaging of a Case of Metaplastic Thymoma on 18F-FDG PET/CT

Metaplastic thymoma is a rare primary thymic epithelial tumor. This report presents the 18F-FDG PET/CT appearance of a metaplastic thymoma developed in a 61-year-old female patient. The FDG uptake of the mediastinal mass showed a high maximum SUV, thus suggesting the possibility of thymic cancer. Surgical resection was performed for both a definitive diagnosis and treatment of the mediastinal tumor. A histological examination of the resected specimen revealed metaplastic thymoma. Although rare, thymoma should be carefully considered in the differential diagnosis in cases of mediastinal masses presenting with highly positive findings on 18F-FDG PET/CT to avoid any inappropriate patient management.

Immunohistochemical analysis of thymic carcinoma focusing on the possibility of molecular targeted and hormonal therapies

Thymic carcinoma is a rare mediastinal malignant tumor, and in many patients, the tumor is detected in an inoperable advanced stage. Even when chemotherapy is administered to such patients, the patients show a poor response. We investigated new biomarkers of therapeutic molecular targets. This study included 44 patients diagnosed and treated for primary thymic epithelial tumors at Showa University Northern Yokohama Hospital, Showa University Hospital, and Showa University Fujigaoka Hospital from 2003 to 2011. We investigated new biomarkers of therapeutic molecular targets, such as the peroxisome proliferator-activated receptor γ (PPARγ), insulin-like growth factor 1 receptor (IGF1R), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), human epidermal growth factor type 2 (HER2)/neu, CD44, and L-type amino acid transporter 1 (LAT1), in thymic tumors. Immunohistochemical analysis showed that the PPARγ positivity rate in thymic carcinoma was 32 %, which was significantly higher than that in thymoma (4 %). The IGF1R positivity rate in thymic carcinoma was 73 %, which was significantly higher than that in thymoma (27 %). Therefore, by examining the expressions of PPARγ and IGF1R, it would be possible to identify therapy-responsive patients and to improve results of thymic carcinoma treatment.

Single Thymic Gland Metastasis From Resected Non-small-cell Lung Cancer

Primary thymic tumors are rare, but secondary ones are exceptionally uncommon. We report the case of a single metastasis within the thymic gland from a lung adenocarcinoma that had been completely resected 3 years before. There was high diagnostic doubt because the thymic lesion was not associated with the recurrence of the paraneoplastic syndrome or the increased CEA levels described at the moment of the treatment of the primary tumor. The lesion was diagnosed and treated at the same time by transcervical thymectomy. At the 1-year follow-up, the patient is alive and disease-free.

Metástasis exclusivas en el timo de un cáncer de pulmón no microcítico resecado

Primary thymic tumors are rare, but secondary ones are exceptionally uncommon. We report the case of a single metastasis within the thymic gland from a lung adenocarcinoma that had been completely resected 3 years before. There was high diagnostic doubt because the thymic lesion was not associated with the recurrence of the paraneoplastic syndrome or the increased CEA levels described at the moment of the treatment of the primary tumor. The lesion was diagnosed and treated at the same time by transcervical thymectomy. At the one-year follow-up, the patient is alive and disease-free.

Metaplastic Thymoma of the Mediastinum

Metaplastic thymoma is a rare primary thymic epithelial tumor, and its biologic behavior is uncertain. We report 7 cases of metaplastic thymoma. The spindle components of the tumor seemed to be undergoing epithelial-mesenchymal transition, which is characterized by the loss of E-cadherin expression. Epstein-Barr virus seemed not to have an etiologic role in metaplastic thymoma. No gross genetic alterations were found by using comparative genomic hybridization. The patients were alive and well in follow-up ranging from 11 to 172 months (mean, 81.7 months). The findings suggest that metaplastic thymoma has a benign clinical course. Unless the histomorphologic findings show malignant features, surgical excision alone is recommended.

Tumours and tumour‐like conditions of the thymus other than thymoma; a practical approach

Masses within the thymus and mediastinum are frequently biopsied to establish a diagnosis. The specimens sent for histopathological analysis are typically small (needle) biopsy specimens on which the pathologist is challenged to provide a classifying diagnosis. Despite the fact that the pathology of the anterior mediastinum is predominantly centred on the thymus and it thus might be expected that the range of possible diagnoses is limited, the list of disease entities is in fact extensive, encompassing hyperplastic conditions and both benign and malignant neoplasms. In addition to primary thymic epithelial tumours, a number of less common diseases typical for this location may be encountered, including extragonadal germ cell tumours, lymphomas, soft tissue tumours and a number of conditions which may simulate a tumour, such as cysts and inflammatory conditions. In this review, the disease entities that may be encountered in biopsy material from anterior mediastinal/thymic processes are discussed and an approach to tackle the differential diagnosis is provided.

Clinical influence of 18F‐fluorodeoxyglucose positron emission tomography on the management of primary tumours of the thymus

The objective of the current study was to evaluate the effect of PET on the management of primary tumours of the thymus. Patients with a primary tumour of the thymus who underwent PET were identified from a prospective database. Forty-three PET scans were carried out on 26 patients with primary thymic tumours. Sensitivity, specificity and accuracy were 79, 100 and 85%, respectively. Conventional imaging and PET findings were discordant in 10 cases (23%). PET appropriately changed patient management in three (7.0%) cases based on accurate results that differed from pre-PET imaging. Most PET scans carried out (88%) did not influence clinical management. Patient comorbidities, limited treatment options and already planned surgery are factors that may hinder the effect of PET in the setting of thymic tumours. The potential for false-negative results, probably because of a combination of low-fluorodeoxyglucose avidity and small volume residual disease, needs to be considered in management planning. However, the positive predictive value of PET is high and enables appropriate modification of management in a small, but potentially important subset of patients.