PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results from a Cohort of 1157 Primary Neuroendocrine Neoplasms.

As neuroendocrine tumors (NETs) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathologic assessment. Because a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensitive and specific markers are required to improve diagnostic certainty. We investigated the expression of the transcription factor Pituitary Homeobox 2 (PITX2) in a large-scale cohort of 909 NET and 248 neuroendocrine carcinomas (NEC) according to the immunoreactive score (IRS) and correlated PITX2 expression groups with general tumor groups and primary localization. PITX2 expression (all expression groups) was highly sensitive (98.1%) for midgut-derived NET, but not perfectly specific, as non-midgut NET (especially pulmonary/duodenal) were quite frequently weak or moderately positive. The specificity rose to 99.5% for a midgut origin of NET if only a strong PITX2 expression was considered, which was found in only 0.5% (one pancreatic/one pulmonary) of non-midgut NET. In metastases of midgut-derived NET, PITX2 was expressed in all cases (87.5% strong, 12.5% moderate), whereas CDX2 was negative or only weakly expressed in 31.3% of the metastases. In NEC, a fraction of cases (14%) showed a weak or moderate PITX2 expression, which was not associated with a specific tumor localization. Our study independently validates PITX2 as a very sensitive and specific immunohistochemical marker of midgut-derived NET in a very large collective of neuroendocrine neoplasms. Therefore, our data argue toward implementation into diagnostic panels applied for NET as a firstline midgut marker.

Reduction of volume loss after left atrial injury by balloon occlusion-an experimental study.

Background: Advanced-stage lung cancers sometimes require an extensive surgical approach. There is a risk of severe bleeding due to injury to the cardiac atria. Due to the fact that in most cases the surgical planning does not involve the expertise of a heart surgeon or the availability of a heart lung machine, only rapid effective action can avert this life-threatening complication. Methods: In an experimental study of porcine heart-lung packs, three different methods were used to investigate the most effective way of controlling mass hemorrhage due to left atrial injury. In order to obtain a realistic model, the heart-lung packet was connected to a heart-lung machine after appropriate preparation and perfused with volume support. The damage control to the left atrial injury was either performed by manual compression, surgical clamping or balloon catheter occlusion. Results: In addition to manual compression and clamping, the use of a balloon catheter inserted into the atrial lesion was found to be the most effective method. The blood loss of 41.88±7.53 mL (vs. 105.00±31.74 and 106.00±50.67 mL) proved to be the lowest value. Conclusions: For extensive resections of lung carcinoma, balloon catheters of different sizes should be kept ready to rapidly control massive blood loss due to injury of the cardiac atria.

NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections.

Lower respiratory tract infections caused by Streptococcus pneumoniae (Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial cellular response to Spn infection on a transcriptomic, proteomic and metabolic level. We found the NAD+ salvage pathway to be dysregulated upon infection in a cell line model, primary human lung tissue and in vivo in rodents, leading to a reduced production of NAD+. Knockdown of NAD+ salvage enzymes (NAMPT, NMNAT1) increased bacterial replication. NAD+ treatment of Spn inhibited its growth while growth of other respiratory pathogens improved. Boosting NAD+ production increased NAD+ levels in immortalized and primary cells and decreased bacterial replication upon infection. NAD+ treatment of Spn dysregulated the bacterial metabolism and reduced intrabacterial ATP. Enhancing the bacterial ATP metabolism abolished the antibacterial effect of NAD+. Thus, we identified the NAD+ salvage pathway as an antibacterial pathway in Spn infections, predicting an antibacterial mechanism of NAD+.

T4 Lung Carcinoma with Infiltration of the Thoracic Aorta: Indication and Surgical Procedure.

Lung carcinomas infiltrate the aorta mostly on the left side and are altogether rare. As an initial step, complete staging is performed and the results are evaluated in an interdisciplinary tumor board. If the patient's general condition including cardiopulmonary reserves is sufficient, and if there is neither distant metastasis nor an N2 situation, surgical resection may be indicated. The option for neoadjuvant chemotherapy should always be taken into consideration. Depending on the anatomic tumor location, partial lung resection and resection of the affected aortic wall are performed employing a cardiopulmonary bypass. The resected aortic wall is replaced by a vascular prosthesis. In recent years, this proven procedure has partly been replaced by an alternative one, avoiding extracorporeal circulation. An endoaortic stent is implanted in the affected area followed by partial lung resection and resection of the diseased aortic wall. This new procedure has significantly reduced perioperative mortality and morbidity. With proper patient selection, long-term survival can be improved even in this complex malignoma.

Continuous intraoperative neuromonitoring of the recurrent laryngeal nerve during lung operations.

Background: The recurrent laryngeal nerve (RLN), especially on the left side, is particularly vulnerable during lung operations. Therefore, continuous intraoperative neuromonitoring (cIONM) would be desirable. With the use of a double-lumen tube (DLT) for single-lung ventilation, there is some uncertainty where the recording electrode should be positioned. The aim of this study was to assess the feasibility of this technique and to predict the ideal position of a single recording electrode. Methods: Patients scheduled to undergo left thoracotomy due to pulmonary pathologies, two adhesive electrodes were affixed consecutively above the proximal cuff of the DLT prior to intubation for a precise location of the recording from the vocal cords. Following thoracotomy, the vagus nerve alongside the aortic arch was exposed. A continuous stimulation probe (Saxophone® electrode, Dr. Langer Medical, Waldkirch, Germany) was placed around the nerve. The signals of the respective electrode were recorded and analyzed with regard to previously defined limits of positive signaling. Results: Strong signals with an amplitude of at least 165 µV were recorded in 18 of 20 patients. In these patients 100% of the signals were recorded via the distally located electrode. An additional signal was recorded via the proximal electrode in four patients. cIONM was found to be a safe and reproducible technique. Conclusions: The described technique enables the use of cIONM of the RLN throughout the entire course of the surgical procedure.

Prospective randomized study on the efficacy of three-dimensional reconstructions of bronchovascular structures on preoperative chest CT scan in patients who are candidates for pulmonary segmentectomy surgery: the PATCHES (Prospective rAndomized sTudy efficaCy of tHree-dimensional rEconstructions Segmentecomy) study protocol.

INTRODUCTION: Pulmonary segmentectomy, when combined with hilar and mediastinal lymphadenectomy, is currently considered the gold standard treatment for early-stage lung tumors (NSCLC) smaller than 2 cm in diameter. The preoperative planning for segmentectomies usually includes a contrast-enhanced CT with 2D reconstructions (axial, coronary, and sagittal). Recent technological advances allow 3D (volume rendering) reconstructions of preoperative CT scans, intended to improve the surgeon's understanding of the segmental anatomy. The study aims to investigate the added value of 3D reconstruction in enhancing the surgeon's understanding of anatomical structures, thus facilitating surgical planning and improving oncological outcomes. METHODS AND ANALYSIS: This is a prospective, randomized, controlled study. Patients will be randomized into two groups: 1. Group 2D: the preoperative workup for these patients will consist of a contrast-enhanced chest CT with two-dimensional (2D) reconstructions (axial, coronary, and sagittal); 2. Group 3D: the preoperative workup for these patients will consist of a contrast-enhanced chest CT with two-dimensional (2D) reconstructions (axial, coronary, and sagittal) and a 3D reconstruction (volume rendering) of the same chest CT employing dedicated software. The primary endpoints will be negative margin (R0) resection rate, resection margin (staple line-to-tumor distance), and thoracotomy conversions. We will use Fisher's exact test for binary outcomes and Mann-Whitney U test for continuous outcomes. For subgroup analyses, we will use regression. Multivariable analyses will be based on logistic regression for binary outcomes and linear regression for continuous outcomes. ETHICS AND DISSEMINATION: The protocol and the model informed consent forms have been reviewed and approved by the ethics committee (N.: 1-2023) concerning scientific content and compliance with applicable research and human subject regulations. A Subcommittee on Publications was established to review all publications and report its recommendations to the steering committee. The anonymized participant-level dataset and statistical code for generating the results will not be publicly available. TRIAL REGISTRATION: The protocol was registered at ClinicalTrials.gov (ID: NCT05716815; Prospective rAndomized sTudy efficaCy tHree-dimensional rEconstructions Segmentectomy - Full-Text View - ClinicalTrials.gov). Jan 19, 2023.

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial.

BACKGROUND: Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes. METHODS: In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration. RESULTS: In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation. CONCLUSION: During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation. REGISTRATION OF CLINICAL TRIAL: DRKS-ID DRKS00014788 (www.drks.de).

Urgent Pneumonectomy as a Result of an Endoleak Type III-A Late Complication after Aortic Stent Implantation.

We report on an octogenarian, who was hospitalized with acute hemoptysis. Computed tomography angiography revealed a monstrously large thrombosed aortic aneurysm in the left thoracic cavity, completely displacing the lung. Eighteen years ago, the patient had suffered traumatic rupture of the descending aorta loco typico. Surgical exploration revealed a large calcified aneurysmal sac, which had perforated into the left lung. Pneumonectomy was performed, and hemoptysis did not reoccur.

Endoscopic Lung Volume Reduction with One-Way Valves in Patients with Severe Chronic Obstructive Pulmonary Disease with Hypercapnia.

BACKGROUND: Robust clinical evidence on the efficacy and safety of endoscopic lung volume reduction (ELVR) with one-way valves in patients with severe lung emphysema with chronic hypercapnic respiratory failure is lacking. OBJECTIVE: The aim of this study was to compare patient characteristics, clinical outcome measures, and incidences of adverse events between patients with severe COPD undergoing ELVR with one-way valves and with either a partial pressure of carbon dioxide (pCO2) of ≤45 mm Hg or with pCO2 >45 mm Hg. METHODS: This was a multicentre prospective study of patients with severe lung disease who were evaluated based on lung function, exercise capacity (6-min walk test [6-MWT]), and quality-of-life tests. RESULTS: Patients with pCO2 ≤45 mm Hg (n = 157) and pCO2 >45 mm Hg (n = 40) showed similar baseline characteristics. Patients with pCO2 ≤45 mm Hg demonstrated a significant increase in forced expiratory volume in 1 s (p < 0.001), a significant decrease in residual volume (RV) (p < 0.001), and significant improvements in the quality of life and 6-MWT at the 3-month follow-up. Patients with pCO2 >45 mm Hg had significant improvements in RV only (p < 0.05). There was a significant decrease in pCO2 between baseline and follow-up in hypercapnic patients, relative to the decrease in patients with pCO2 ≤45 mm Hg (p = 0.008). Patients who were more hypercapnic at baseline showed a greater reduction in pCO2 after valve placement (r = -0.38, p < 0.001). Pneumothorax was the most common adverse event in both groups. CONCLUSIONS: ELVR with one-way valves seems clinically beneficial with a remarkably good safety profile for patients with chronic hypercapnic respiratory failure.

Initial Airtightness of the Lung Parenchyma After Transection of the Interlobar Fissure - Monopolar Cutter, Stapler Versus Nd: YAG Laser.

INTRODUCTION: Every lobectomy requires the transection of the interlobar fissure. Resection surfaces must be airtight in order to avoid leakage and infection. Using an ex vivo model based on porcine lung, we compared three techniques with respect to initial airtightness at different inspiratory pressures. MATERIALS AND METHODS: In the first technique (group 1), we transected the interlobar fissure with a monopolar cutter and overstitched the edges of the resection area with a monofilament thread. In the second technique (group 2), the interlobar fissure was cut with a stapling device. In the third technique (group 3), the interlobar fissure was cut using a laser fibre connected to an Nd: YAG laser. The resection areas were not overstitched; 15 transections were performed in each group. RESULTS: In group 1, three parenchymatous bridges leaked starting at a pressure of 25 mbar. In the other two groups, all preparations were airtight at this pressure. If the ventilation pressure was increased up to 40 mbar, all seams in group 1 were leaky at a pressure of 35 mbar. Four staple seams were airtight at a pressure of 40 mbar. In group 3, 11 preparations (73.3 %) were airtight up to a pressure of 40 mbar. CONCLUSIONS: Based on our results, the use of an Nd: YAG laser is suitable for the transection of the interlobar fissure. In effect, this technique compares well with the other techniques examined.

Detection of the Lateral Thermal Spread during Bipolar Vessel Sealing in an Ex Vivo Model-Preliminary Results.

Background: As an unwanted side effect, lateral thermal expansion in bipolar tissue sealing may lead to collateral tissue damage. Materials and Methods: Our investigations were carried out on an ex vivo model of porcine carotid arteries. Lateral thermal expansion was measured and a calculated index, based on thermographic recording and histologic examination, was designed to describe the risk of tissue damage. Results: For instrument 1, the mean extent of the critical zone > 50 °C was 2315 ± 509.2 µm above and 1700 ± 331.3 µm below the branches. The width of the necrosis zone was 412.5 ± 79.0 µm above and 426.7 ± 100.7µm below the branches. For instrument 2, the mean extent of the zone > 50 °C was 2032 ± 592.4 µm above and 1182 ± 386.9 µm below the branches. The width of the necrosis zone was 642.6 ± 158.2 µm above and 645.3 ± 111.9 µm below the branches. Our risk index indicated a low risk of damage for instrument 1 and a moderate to high risk for instrument 2. Conclusion: Thermography is a suitable method to estimate lateral heat propagation, and a validated risk index may lead to improved surgical handling.

A Delphi Consensus report from the "Prolonged Air Leak: A Survey" study group on prevention and management of postoperative air leaks after minimally invasive anatomical resections.

OBJECTIVES: This study reports the results of an international expert consensus process evaluating the assessment of intraoperative air leaks (IAL) and treatment of postoperative prolonged air leaks (PAL) utilizing a Delphi process, with the aim of helping standardization and improving practice. METHODS: A panel of 45 questions was developed and submitted to an international working group of experts in minimally invasive lung cancer surgery. Modified Delphi methodology was used to review responses, including 3 rounds of voting. The consensus was defined a priori as >50% agreement among the experts. Clinical practice standards were graded as recommended or highly recommended if 50-74% or >75% of the experts reached an agreement, respectively. RESULTS: A total of 32 experts from 18 countries completed the questionnaires in all 3 rounds. Respondents agreed that PAL are defined as >5 days and that current risk models are rarely used. The consensus was reached in 33/45 issues (73.3%). IAL were classified as mild (<100 ml/min; 81%), moderate (100-400 ml/min; 71%) and severe (>400 ml/min; 74%). If mild IAL are detected, 68% do not treat; if moderate, consensus was not; if severe, 90% favoured treatment. CONCLUSIONS: This expert consensus working group reached an agreement on the majority of issues regarding the detection and management of IAL and PAL. In the absence of prospective, randomized evidence supporting most of these clinical decisions, this document may serve as a guideline to reduce practice variation.

The Value of Contrast-Enhanced Ultrasound (CEUS) in the Detection of Perfusion Disturbances in Abdominal Wall Hernias Compared with Surgical and Histological Assessment.

Purpose: This study aimed to evaluate the value of contrast-enhanced ultrasound (CEUS) in the evaluation of perfusion disturbance in irreducible abdominal wall hernias (AWHs). Methods: From 2006 to 2018, 50 patients with an irreducible AWH were examined using B-mode ultrasound (B-US) and CEUS. The ultrasound findings were correlated with subsequent surgical and histological results. The presence of non-enhanced areas (NEAs) in hernia contents on CEUS and the presence of non-perfused areas (NPAs) on surgical and histological evaluation were analyzed retrospectively. Results: On CEUS, 13/50 hernia contents (26.0%) revealed NEAs during complete CEUS examination and 37/50 (74.0%) revealed no NEAs during CEUS examination. On surgical and histological evaluation, NPAs in hernia contents were identified in 11/13 cases (93.3%) with NEAs on CEUS. CEUS was found to have a sensitivity of 100.0%, a specificity of 94.9%, a positive predictive value of 84.6%, and a negative predictive value of 100.0% for the identification of perfusion disturbance in AWHs. Conclusions: The findings of this study demonstrate that using CEUS as an imaging method may be helpful for evaluating the perfusion of hernia contents in incarcerated AWHs. On CEUS, the presence of NEAs may suggest perfusion disturbance in hernia contents.

Determination of initial airtightness after anatomical laser segmentectomy in an ex vivo model.

If a pulmonary pathology can be removed by anatomical segmentectomy, the need for lobectomy is obviated. The procedure is considered oncologically equivalent and saves healthy lung tissue. In every segmentectomy, lung parenchyma must be transected in the intersegmental plane. Using an ex vivo model based on porcine lung, three transection techniques (monopolar cutter + suture, stapler, and Nd:YAG laser) are to be compared with respect to their initial airtightness. At an inspiratory ventilation pressure of 25 mbar, all three preparations were airtight. Upon further increase in ventilation pressure up to 40 mbar, the laser group performed best in terms of airtightness. Since thanks to its use of a laser fibre, this technique is particularly suitable for minimally invasive surgery; it should be further evaluated clinically for this indication in the future.

Intraoperative Computed Tomography-Based Navigation with Augmented Reality for Lateral Approaches to the Spine.

Background. Lateral approaches to the spine have gained increased popularity due to enabling minimally invasive access to the spine, less blood loss, decreased operative time, and less postoperative pain. The objective of the study was to analyze the use of intraoperative computed tomography with navigation and the implementation of augmented reality in facilitating a lateral approach to the spine. Methods. We prospectively analyzed all patients who underwent surgery with a lateral approach to the spine from September 2016 to January 2021 using intraoperative CT applying a 32-slice movable CT scanner, which was used for automatic navigation registration. Sixteen patients, with a median age of 64.3 years, were operated on using a lateral approach to the thoracic and lumbar spine and using intraoperative CT with navigation. Indications included a herniated disc (six patients), tumors (seven), instability following the fracture of the thoracic or lumbar vertebra (two), and spondylodiscitis (one). Results. Automatic registration, applying intraoperative CT, resulted in high accuracy (target registration error: 0.84 ± 0.10 mm). The effective radiation dose of the registration CT scans was 6.16 ± 3.91 mSv. In seven patients, a control iCT scan was performed for resection and implant control, with an ED of 4.51 ± 2.48 mSv. Augmented reality (AR) was used to support surgery in 11 cases, by visualizing the tumor outline, pedicle screws, herniated discs, and surrounding structures. Of the 16 patients, corpectomy was performed in six patients with the implantation of an expandable cage, and one patient underwent discectomy using the XLIF technique. One patient experienced perioperative complications. One patient died in the early postoperative course due to severe cardiorespiratory failure. Ten patients had improved and five had unchanged neurological status at the 3-month follow up. Conclusions. Intraoperative computed tomography with navigation facilitates the application of lateral approaches to the spine for a variety of indications, including fusion procedures, tumor resection, and herniated disc surgery.

The impact of primary tumor location on prognosis after colorectal lung metastasectomy.

PURPOSE: Currently, right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (REC) are typically seen as different tumor entities. It is unknown if this subdivision by primary tumor location has an influence on the survival of patients with colorectal pulmonary metastasectomy (PM). METHODS: We retrospectively analyzed our prospective database of 233 patients operated on for colorectal lung metastases between 1999 and 2014. Differences in the patient characteristics and the primary tumor and metastatic tumor burden were analyzed using χ2-tests. The long-term survival after PM of the three groups was analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: In total, PM was performed for 37 patients with RCC, 57 patients with LCC, and 139 patients with REC. Patients with LCC were significantly more likely to have UICC stage IV primary tumor (44.2% LCC vs. 37.5% RCC vs. 22.8% REC, p = 0.012) and significantly more likely to have a history of additional liver metastases (45.6% LCC vs. 32.4% RCC vs. 27.3% REC, p = 0.046). The 5-year survival rates after PM for patients with RCC, LCC, and REC were 47, 66, and 39%, respectively (p = 0.001). The median survival times of patients with RCC, LCC, and REC were 55 months (95% CI: 42.2-66.8), 108 months (95% CI: 52.7-163.3), and 44 months (95% CI: 50.4-63.6), respectively. CONCLUSIONS: This study demonstrated a prognostic impact of the primary tumor localization in patients undergoing PM for colorectal lung metastases. Nevertheless, long-term survival was achievable in all groups.

[General Overview of Mediastinal Tumours: Classification, Approaches, Biopsy]. / Allgemeine Übersicht zu Mediastinaltumoren: Einteilung, Zugangswege, Biopsie.

Mediastinal tumours can be a real challenge in terms of diagnostic testing and therapy. One reason for this is that there is a wide range of different tumour types. Even when the tumour is large, many of the affected patients are completely asymptomatic at the time of diagnosis. As a rule, specific types of tumours can be assessed with regard to spatial allocation to a mediastinal compartment. However, if possible, diagnosis should be confirmed via puncture or a biopsy. Various methods are available. Choosing the optimal access route for surgical removal of a mediastinal tumour is an important issue. It must be planned on the basis of the tumour's spatial location, size and extent in imaging. This is the best possible option for low-risk and complete removal of any mediastinal tumour.

Videolaryngoscopy versus direct laryngoscopy for double-lumen endotracheal tube intubation in thoracic surgery - a randomised controlled clinical trial.

BACKGROUND: Double-lumen tube (DLT) intubation is necessary for thoracic surgery and other operations with the need for lung separation. However, DLT insertion is complex and might result in airway trauma. A new videolaryngoscopy (GVL) with a thin blade might improve the intubation time and reduce complexity as well as iatrogenic airway complications compared to conventional direct laryngoscopy (DL) for DLT intubation. METHODS: A randomised, controlled trial was conducted in 70 patients undergoing elective thoracic surgery using DLT for lung separation. Primary endpoint was time to successful intubation. The secondary endpoints of this study were number of intubation attempts, the assessment of difficulty, any complications during DLT intubation and the incidence of objective trauma of the oropharynx and supraglottic space and intubation-related subjective symptoms. RESULTS: 65 patients were included (DL group [n  =  31], GVL group [n  =  34]). Median intubation time (25th-75th percentiles) in GVL group was 93 s (63-160) versus 74 (58-94) in DL group [p = 0.044]. GVL resulted in significantly improved visualisation of the larynx (Cormack and Lehane grade of 1 in GVL group was 97% vs. 74% in DL Group [p = 0.008]). Endoscopic examinations revealed significant differences in GVL group compared to DL group showing less red-blooded vocal cord [p = 0.004], vocal cord haematoma [p = 0.022] and vocal cord haemorrhage [p = 0.002]. No significant differences regarding the postoperative subjective symptoms of airway were found. CONCLUSIONS: Videolaryngoscopy using the GlideScope®-Titanium shortly prolongs DLT intubation duration compared to direct laryngoscopy but improves the view. Objective intubation trauma but not subjective complaints are reduced. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020978, retrospectively registered on 09. March 2020.

Thymoma-Associated Paraneoplastic Autoimmune Multiorgan Syndrome-From Pemphigus to Lichenoid Dermatitis.

Introduction: Paraneoplastic autoimmune multi-organ syndrome (PAMS) is a rare clinical condition characterized by variable and heterogeneous clinical phenotypes in the presence of neoplasias which largely depend on the activation of humoral and cellular immune responses. Clinically, these patients present with a spectrum of antibody-driven pemphigus-like lesions to graft-vs.-host-disease-like exanthemas with a lichenoid inflammatory infiltrate in the skin. PAMS is occasionally associated with thymoma, in which altered immune surveillance eventually leads to multiorgan autoimmunity which often includes variable cutaneous symptoms. This disorder is associated with a profound disturbance of peripheral immune tolerance against human autoantigens. Objectives: We here present a patient with relapsing thymoma who developed PAMS with several cutaneous and extracutaneous autoimmune disorders. Materials: Peripheral blood mononuclear cells (PBMC), sera, and lesional skin biopsies were obtained at different clinical disease stages. Peripheral T cell subsets were characterized phenotypically and the cytokine profile of the peripheral blood T cellular response against distinct epidermal and dermal autoantigens of the skin was analyzed by ELISpot assay. Serological screening was performed by ELISA and immunoblot analysis. Skin biopsies were subjected to immunohistochemical analysis of distinct T cell subsets. Thymoma tissue was analyzed for the presence of T regulatory cells and compared with adult thymus and indolent thymoma. Results and Conclusions: In the present case, thymoma was the cause of the observed multi-organ autoimmune syndromes as its recurrence and surgical removal was associated with the relapse and regression of the cutaneous symptoms, respectively. Initially, the patient presented with two autoimmune disorders with Th2/Th1 imbalance, myasthenia gravis (MG) and pemphigus foliaceus (PF), which regressed upon immunosuppressive treatment. Months later, the patient developed a lichenoid exanthema with a Th1-dominated skin infiltrate. Further clinical evaluation revealed the recurrence of the thymoma and the lichenoid exanthema gradually regressed upon thymectomy. Our contention that T cell recognition against distinct cutaneous autoantigens, such as desmoglein 1 (Dsg1), shifted from a Th2 to a Th1-dominated immune response could not be fully substantiated as the patient was on a stringent immunosuppressive treatment regimen. We could only observe a decrease of the initially present serum IgG autoantibodies against Dsg1. Phenotypic analysis of the associated thymoma showed a lower number of T regulatory cells compared to adult thymus and indolent thymoma, suggesting that impaired thymus-derived immune surveillance had a direct impact on the outcome of the observed cutaneous autoimmune disorders.