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Breast cancer is the most frequent neoplasm in female population. Conversely, thymic epithelial tumors (TETs) are rare diseases, often discovered in late stages. TET patients have a high risk of developing secondary malignancies compared with general population, with an incidence rate from 8 to 31%. We recently observed the synchronous appearance of both these neoplasms in two patients. The first patient, a 60-year-old female, was diagnosed with breast cancer. She underwent quadrantectomy and sentinel axillary lymph node dissection. Pathological diagnosis was invasive breast cancer non special type (NST), G2 pT1 N0, estrogen receptor (ER) 95%, progesterone receptor (PR) 90%, human epidermal growth factor receptor 2 (Her2) negative, Ki67: 30%. Staging work-up (chest X-ray followed by CT scan) discovered a solid mass of 70 mm in the anterior mediastinum, suspect for thymic tumor lesion, that also showed a tracer uptake at FDG scan (SUVmax 10). Patient underwent thymectomy with pathologic diagnosis of thymoma, subtype B2/B3, stage pT1a pN0 (AJCC TNM 8th edition). The second patient, a 62-year-old woman experiencing post-COVID persistent dyspnea, underwent a CT scan and an FDG PET scan. Imaging showed a thoracic lesion suspicious for thymic neoplasm infiltrating the chest wall (tracer uptake SUVmax 6.7) and simultaneously two contrast-enhanced nodules, one in each breast (left breast: 15 mm, SUVmax 2; right breast: 20 mm, SUVmax 2.6). Surgical biopsies were performed in all the 3 lesions. The pathological diagnoses were: (I) non keratinizing squamous cell carcinoma of the thymus; (II) invasive left breast cancer (NST) ER 90 %, PR 30%, Her2 negative, Ki67: 10%; (III) invasive right breast cancer (NST) ER 90%, PR 30%, Her2 positive (3+), Ki67 10%. The presence of synchronous thymic and breast malignancies appears to be very singular and requires personalized treatment strategies. Furthermore, additional studies are needed to understand if TETs and their related immune system dysregulation could increase the risk of secondary tumors, or whether genetic disorders might be responsible for an increased predisposition to develop synchronous malignancies. In both scenarios, future studies should explore the utility of tailoring screening procedures for TET patients.

Mediastinum is a complex anatomic space in which different malignancies can occur, originating from different cell types, such as epithelial thymic, lymphoid, germinal cell and mesenchimal cell. Their diagnosis requires dedicated knowledge and expertise, due to heterogeneous features. Indeed, there is also a frequent overlap between different histologies leading to uncertainty in the diagnostic process. Here, we present an uncommon mediastinal mass challenging in its characterization. A thirty-year-old woman performed thoracic CT scan for dyspnea and persistent cough. Imaging showed a solid mass of 14×11 cm involving the left thorax with mediastinal deviation to the right side. Patient underwent resection en bloc of left endothoracic mass and segmental resection of the left upper lung lobe, and of the 3rd, 4th and 5th ribs. Initial histological examination was suggestive for B3 thymoma/thymic carcinoma due to the positivity for p63, CD99, CD117 and vimentin. Pathological stage pT1b. Patient was then referred to our rare tumor Reference Center. Histological review showed small-medium sized tumor cells. The immunohistochemical panel showed negativity for cytokeratins (CKMNF116, CKAE1/AE3, CK19), as well as PAX8, CD56 NSE and CD117; while CD99 was positive, excluding the diagnosis of thymic/thymoma neoplasms; c-kit and other thymoma related genes resulted negative for mutations at a next generation sequencing (NGS) analysis. On the other hand, the negativity of different types of cytokeratins and the elevated mitotic index associated with the sporadic positivity for p63 was not specific for an epithelial neoplasm. Morphological pattern and positivity for CD99 led to a diagnosis of undifferentiated sarcoma. A third revision, was performed at the National Sarcoma Center and included the assessment of markers for sarcoma cluster differentiation. Tumor cells were characterized by the positivity for CD99 and NKX2.2 consistent with a diagnosis of Ewing’s sarcoma, despite the negativity for ETV4. The evaluation of expert centers was critical to establish a correct diagnosis in this complex case. Taking into account the time lasting from the diagnosis and the aggressiveness of this kind of neoplasm, the patient was candidate for chemo-radiotherapy after a multidisciplinary discussion.

BACKGROUND: Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system with humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients. The aim of our study is evaluating immunization in TET patients, who received both doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. METHODS: Starting from 14 April 2021, we enrolled 50 TET patients (pts), who received COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody serological levels were analysed by chemiluminescent immunoassay (CLIA) at different time-points: T0 (before the first vaccine dose), T1 (1 week after second dose), T2 (4 weeks after second dose), and late monitoring T3, T4, T5, T6 (at 3, 6, 9, 12 months after second dose, respectively). Preliminary data relative to12 pts, collected at T0, T1 and T2, were available for this report. Local ethical committee approved this study and all enrolled patients signed informed consent. RESULTS: Among the 12 patients, 8 were female and 4 males; 9 pts had thymoma and 3 thymic carcinomas; myasthenia gravis (autoimmunity) was diagnosed in one patient, and 4 patients suffered from Good Syndrome (immunodeficiency). None had COVID-19 infection prior to immunization. All 12 pts had received both vaccine doses by the time of this analysis. At baseline, all pts were negative for the serological antibody titers (method range, 3.80–400 AU/mL, positivity for titer >25); at T1, 11 pts (92%) were negative; at T2, 10 pts (84%) remained negative. Interestingly, the only 2 pts with positive titers at T2 were both in remission of disease. CONCLUSIONS: Our preliminary data showed that the majority of TET patients enrolled in this study had no seroconversion after 4 weeks from the second dose of COVID 19 vaccine. Despite preliminary, our data might have important implications for the immunization of TET patients.

Recently, syndrome coronavirus type 2 (SARS-CoV-2) infection outbreak has determined the use of thoracic CT scan for diagnostic purposes, leading to incidental detection of mediastinal masses. However, the differential diagnosis between benign and malignant mediastinal neoplasms could be challenging. Furthermore, in a recent study, thymus hyperplasia was observed significantly more frequently in COVID 19 patients compared to controls. Here, we describe a case series of patients with incidental detection of mediastinal masses after COVID 19 infection. (I) The first patient was a 43-year-old male, who performed a CT scan in December 2020 after COVID infection, showing a hypodense lesion of 48×31 mm in the superior anterior mediastinum. Subsequently, the patient developed dysphagia, difficulty in swallowing and right eye ptosis, thus he underwent FDG-PET scan that revealed an uptake of the tracer with a standardized uptake value (SUVmax) of 6. Therefore, thymectomy by robotic assisted surgery was performed. The histological diagnosis was: “thymoma AB, Stage: pT1 a”. (II) The second patient was a 33-year-old female, who performed in January 2021 high resolution chest CT scan, after COVID infection, due to persistence of breath shortness and fatigue. Imaging detected a mass of about 30 mm in the anterior mediastinal space, although a subsequent FDG-PET scan showed no significant tracer uptake. The patient, who is still symptomatic, is currently in follow up. (III) The third patient, a 36-year-old female, performed in April 2021 a chest CT scan due to persistent respiratory distress syndrome, related to SARS-Cov-2 infection that was contracted during pregnancy. The imaging was performed after delivering and showed a solid wedge-shaped lesion of 26 mm in the thymic loggia. The FDG PET scan carried out in June 2021 showed tracer uptake (SUVmax 2.7) in anterior mediastinal space. The patient was initially candidate to thymectomy, but due to the size reduction of the thymic mass observed on a follow-up CT scan, she was deemed eligible for follow up. In conclusion, our experience suggests that differential diagnosis in young symptomatic patients experiencing mediastinal masses after COVID infection is challenging and requires multidisciplinary expertise.