Utility of new FDG-PET/CT guidelines for diagnosing cardiac sarcoidosis in patients with implanted cardiac pacemakers for atrioventricular block.

Diagnosing cardiac sarcoidosis (CS), especially in isolated cases, is challenging, particularly due to the limitations of endomyocardial biopsy, leading to potential undiagnosed cases in pacemaker-implanted patients. This study aims to provide real world findings to support new guideline for CS using 18F-fluoro-deoxyglucose positron-emission tomography computed tomography (FDG-PET/CT) which give a definite diagnosis of isolated CS (iCS) without histological findings. We examined consecutive patients with cardiac pacemakers for atrioventricular block (AV-b) attending our outpatient pacemaker clinic. The patients underwent periodical follow-up echocardiography and were divided into two groups according to echocardiographic findings: those with suspected CS and those without suspected CS. Patients suspected of having nonischemic cardiomyopathy underwent FDG-PET/CT for CS diagnosis. We investigated the utility of the new guideline for CS using FDG-PET/CT. Among the 272 patients enrolled, 97 patients were implanted with cardiac pacemakers for AV-b. Twenty-two patients were suspected of having CS during a median observation period of 5.4 years after pacemaker implantation. Of these, one did not consent, and nine of 21 cases (43%) were diagnosed with definite CS according to the new guidelines. Five of these nine patients were diagnosed with iCS using FDG-PET/CT. The number of patients diagnosed with definite CS using the new guidelines tended to be approximately 2.3 times that of the conventional criteria (p = 0.074). Three of the nine patients underwent steroid treatment. The composite outcome, comprising all-cause death, heart failure hospitalization, and a substantial reduction in left ventricular ejection fraction, were significantly lower in patients receiving steroid treatment compared to those without steroid treatment (p = 0.048). The utilization of FDG-PET/CT in accordance with the new guidelines facilitates the diagnosis of CS, including iCS, resulting in approximately 2.3 times as many diagnoses of CS compared to the conventional criteria. This guideline has the potential to support the early identification of iCS and may contribute to enhancing patient clinical outcomes.

Microblading reaction as a manifestation of systemic sarcoidosis: two case reports and a review of the literature.

BACKGROUND: Sarcoidosis is a multisystemic disease characterized by granulomatous inflammation. Sarcoidosis often poses a diagnostic challenge owing to its nonspecific or mild clinical features. In 20-35% of cases, sarcoidosis initially presents on skin. However, skin lesions commonly mimic dermatological conditions. Therefore, it is important to not underestimate the skin manifestations and perform histopathological examinations to make a timely diagnosis. CASE PRESENTATION: We present two cases of 33-year-old Caucasian female patients with orange-red macules and plaques that developed in the eyebrow area 1 and 6 years after microblading, respectively. Histopathological examination confirmed a diagnosis of sarcoidosis. The lymph nodes and lungs were also affected in both patients. CONCLUSION: Our two reports suggest that an esthetic procedure involving dermal or subcutaneous injection of foreign materials can trigger the development of cutaneous and systemic sarcoidosis. However, this relationship has not been described yet. Physicians should, therefore, be aware of this complication to properly evaluate and treat such patients in a timely manner.

Uncommon diagnosis of multinodular goiter - isolated extrapulmonary manifestation of sarcoidosis in thyroid gland (scientific case reports).

AIM: By means of the scientific description of two uncommon cases who underwent. surgical resection of multinodous goiter and following histopathological investigation revealing isolated extrapulmonary manifestation of sarcoidosis, this uncommon diagnosis including symptomatology, clinical findings, diagnostic and therapeutic management is to be illustrated. CASE DESCRIPTIONS: Diagnostics: Scintigraphy of the thyroid gland with a left-thyroid cold node; ultrasound-guided puncture (cytological investigation, non-suspicious). THERAPY: Elective thyroidectomy with no macroscopic anomalies und no abnormal aspects with regard to surgical tactic and technique. Histopathological investigation: Complete resection specimen of the thyroid gland with granulomatous inflammation consistent with sarcoidosis. CLINICAL COURSE: Uneventful with no further manifestations of sarcoidosis in the following diagnostics. DIAGNOSTICS: Ultrasound, inhomogeneous node (37×30×35 mm) of the right thyroideal gland with echo-poor parts and peripheral vascularization; scintigraphy showing marginally compensated unifocal autonomy of the thyroid gland (laboratory parameters, increased serum level of thyroglobulin [632 ng/mL]). THERAPY: Planned right hemithyroidectomy with confirmed nodous structure of thyroid parenchyma, without suspicious lymph nodes. Histopathological investigation: 33-mm follicular, nodular, encapsulated structure of thyroid parenchyma (diagnosed as follicular adenoma); 2nd opinion: low-grade differentiated carcinoma of thyroid gland with angioinfiltrating growth and granulomatous inflammation of sarcoidosis type. Procedural intent: After tumor-board consultation, completing thyroidectomy was performed within a 5-weeks interval (pT2 pN0[0/1] V1 L0 G3 R0) with subsequent ablating radio'active iodine therapy; 18 F-FDG-PET-CT (several atypical infiltrates within the right upper lobe of the lung) and bronchoscopy with no detection of further manifestation of sarcoidosis. CONCLUSION: Sarcoidosis is considered a rare granulomatous multi-locular, systemic disease of not completely known etiopathogenesis with substantial heterogeneity. In most cases, it is associated with the lung, but which can become manifest in various organs. Frequently, extrapulmonary manifestations are usually detected as histological findings by coincidence, which require further investigation to find out additional manifestations as well as to exclude florid infection or other granulomatous processes (clarifying competently differential diagnosis). Therapy is only indicated in symptomatic organ manifestations, taking into account the high rate of spontaneous healing and possible side effects.

Transbronchial lymph node forceps biopsy as a novel tool in diagnosis of mediastinal lymphadenopathy: a pilot study.

BACKGROUND: Differential diagnosis of mediastinal lymphadenopathy is an issue of debate. Lymph nodes may be enlarged due to a variety of inflammatory, infectious, or malignant reasons. Therefore, obtaining samples from the affected nodes is crucial for the diagnosis. Usually, these patients are subjected to TBNA (EBUS or conventional) or mediastinoscopy if TBNA is not conclusive. This study evaluated the safety and feasibility of this new technique of transbronchial forceps biopsy for the diagnosis of mediastinal lymphadenopathy. METHODS: The study included 18 patients with confirmed mediastinal lymphadenopathy who were admitted in Chest Department, Cairo University in the period from December 2019 to December 2020. All patients were subjected to flexible bronchoscopy with conventional transbronchial needle aspiration (C-TBNA) and transbronchial forceps biopsy (LN-TBFB) from the enlarged mediastinal lymph node in the same procedure. RESULTS: we found the technique of LN-TBFB safe with no serious complications. We were able to reach a diagnosis in 7/7 (100%) cases of sarcoidosis, 6/7 (85.7%) cases of malignant lymph nodes. We had three cases where the histopathology showed hyperactive follicular hyperplasia, and a single case of tuberculous lymphadenitis. C-TBNA was diagnostic in 71.4% of sarcoidosis cases, 42.9% of malignant cases, but failed to diagnose the one patient with tuberculous lymphadenitis. CONCLUSION: Lymph node transbronchial forceps biopsy (LN-TBFB) was found to be safe and effective in the diagnosis of mediastinal lymphadenopathy. We strongly advocate the use of this minimally invasive technique for diagnosing pathologically enlarged mediastinal lymph nodes, as a last step before mediastinoscopy.

Diagnosis of Pulmonary Sarcoidosis.

Diagnosis of sarcoidosis depends on a compatible clinical and imaging presentation, histologic finding of non-necrotizing granulomatous inflammation, and exclusion of alternative causes of granulomatous diseases. This study has reviewed the diagnostic algorithms and approaches of sarcoidosis.

Role of Bronchoscopy in Diagnosis of Sarcoidosis.

Sarcoidosis is a multisystem inflammatory disorder with unclear etiology and can often pose a diagnostic challenge. A tissue diagnosis is often necessary to illustrate the non-caseating granulomas on histopathology. This review aims to synthesize current evidence related to tissue diagnosis of sarcoidosis using various bronchoscopic techniques. We start by discussing standard bronchoscopic techniques which have remained the cornerstone of diagnostic workup such as bronchoalveolar lavage (BAL), endobronchial biopsy (EBB), conventional transbronchial needle aspiration (cTBNA) and transbronchial lung biopsy (TBLB) followed by newer modalities that incorporate real-time image guidance using endobronchial and endoscopic ultrasound. Although BAL, EBB, and TBLB have been employed as a diagnostic tool for several decades, their sensitivity and diagnostic yield is inferior to ultrasound-based endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). More recently, convincing evidence has also emerged to support the diagnostic accuracy and tissue yield of transbronchial lung cryobiopsy which will also be discussed in this review. These advances in bronchoscopic equipment and techniques over the last 2 decades have made it possible to obtain tissue samples using minimally invasive techniques thus avoiding invasive open lung biopsy and the risks that inherently follow. Up-to-date knowledge of these modalities is imperative for ensuring evidence-based medicine and improving patient-centric outcomes.

Neurosarcoidosis and Neurologic Complications of Sarcoidosis Treatment.

Sarcoidosis is an immune-mediated multisystem granulomatous disorder. Neurosarcoidosis (NS) accounts for 5% to 35% of cases. The diagnostic evaluation of NS can be a clinical challenge. Gadolinium-enhanced magnetic resonance imaging (MRI) is the gold standard to evaluate central nervous system NS. In almost all cases treatment is warranted. Although glucocorticoids remain the first-line therapy in patients with sarcoidosis, in NS timely initiation of second- or third-line treatment is strongly recommended. Of these, tumor necrosis factor-alpha inhibitors are the most promising. However, the treatment itself may be responsible for/associated with developing neurologic symptoms mimicking NS. Thus, it is important to consider the possibility of drug-induced neurologic symptoms in sarcoidosis.

Cutaneous Sarcoidosis.

Sarcoidosis is a multisystem disease that most commonly affects the lungs, lymphatic system, eyes, and skin but any organ may be involved. Cutaneous sarcoidosis most commonly presents as pink-red to red-brown papules and plaques that commonly affect the head and neck. With the skin being readily accessible for evaluation and biopsy, when sarcoidosis is suspected, dermatologic evaluation may be helpful for establishing a definitive diagnosis. Treatment strategy depends on the severity and distribution of skin lesions and should incorporate patient preference and treatment considerations for other organs that may be involved.

Sarcoidosis associated with Trastuzumab in a young female with carcinoma of breast.

Trastuzumab is a humanized monoclonal antibody against human epidermal growth factor, useful in breast cancer. It is well tolerated but sometimes may associate with significant adverse effects. Sarcoidosis is a granulomatous disease involving multiple organs with poorly understood aetiology. Mediastinal lymphadenopathy is the most common presenting feature of Sarcoidosis. Reported cases of Sarcoidosis associated with Trastuzumab are quite less in number. High degree of suspicion of the above is thought of in a scenario of malignancy patients receiving chemotherapy. Newly appearing FDG avid lymph node in PET scan may give first impression of metastasis and treatment failure or infection. However correct diagnosis is a must (differentiating metastasis, treatment failure or infection) to provide correct treatment and avoid side effects of inappropriate therapies. Correct diagnosis also helps in appropriate prognostication and unnecessary stoppage of Trastuzumab. Here we are describing Sarcoidosis associated with Trastuzumab in a patient with breast cancer.

Imaging Features of Pediatric Sarcoidosis.

Sarcoidosis is a granulomatous inflammatory disease of uncertain cause. It occurs most commonly in young and middle-aged adults and less frequently in children; therefore, few data on pediatric sarcoidosis exist in the literature. The diagnosis and management of sarcoidosis remain challenging because of diverse and often nonspecific clinical and imaging findings. In addition, the clinical picture varies widely by age. Prepubertal and adolescent patients often present with adult-like pulmonary disease; however, early-onset sarcoidosis is typically characterized by the triad of arthritis, uveitis, and skin rash. Sarcoidosis is mostly a diagnosis of exclusion made by demonstrating noncaseating granulomas at histopathologic examination in patients with compatible clinical and radiologic findings. Although sarcoidosis often affects the lungs and thoracic lymph nodes, it can involve almost any organ in the body. The most common radiologic manifestation is pulmonary involvement, characterized by mediastinal and bilateral symmetric hilar lymphadenopathies with perilymphatic micronodules. Abdominal involvement is also common in children and often manifests as hepatomegaly, splenomegaly, and abdominal lymph node enlargement. Although neurosarcoidosis and cardiac sarcoidosis are rare, imaging is essential to the diagnosis of central nervous system and cardiac involvement because of the risky biopsy procedure and its low diagnostic yield due to focal involvement. Being familiar with the spectrum of imaging findings of sarcoidosis may aid in appropriate diagnosis and management. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis.

Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2-positive (TREM2-positive) macrophages expressing angiotensin-converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1,6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis.

Vitreous Humor Proteomic Profile in Patients With Vitreoretinal Lymphoma.

Purpose: Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Methods: Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. Results: In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. Conclusions: This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.

Spatial Transcriptomics Reveals Signatures of Histopathological Changes in Muscular Sarcoidosis.

Sarcoidosis is a multisystemic disease characterized by non-caseating granuloma infiltrating various organs. The form with symptomatic muscular involvement is called muscular sarcoidosis. The impact of immune cells composing the granuloma on the skeletal muscle is misunderstood. Here, we investigated the granuloma-skeletal muscle interactions through spatial transcriptomics on two patients affected by muscular sarcoidosis. Five major transcriptomic clusters corresponding to perigranuloma, granuloma, and three successive muscle tissue areas (proximal, intermediate, and distal) around the granuloma were identified. Analyses revealed upregulated pathways in the granuloma corresponding to the activation of T-lymphocytes and monocytes/macrophages cytokines, the upregulation of extracellular matrix signatures, and the induction of the TGF-ß signaling in the perigranuloma. A comparison between the proximal and distal muscles to the granuloma revealed an inverse correlation between the distance to the granuloma and the upregulation of cellular response to interferon-γ/α, TNF-α, IL-1,4,6, fibroblast proliferation, epithelial to mesenchymal cell transition, and the downregulation of muscle gene expression. These data shed light on the intercommunications between granulomas and the muscle tissue and provide pathophysiological mechanisms by showing that granuloma immune cells have a direct impact on proximal muscle tissue by promoting its progressive replacement by fibrosis via the expression of pro-inflammatory and profibrosing signatures. These data could possibly explain the evolution towards a state of disability for some patients.

Unnecessary orchiectomy due to atypical sarcoidosis manifesting as a unilateral scrotal mass: a case report and literature review.

Sarcoidosis is a disease characterised primarily by lung tissue involvement. Extrapulmonary involvement, particularly in the genitourinary tract, is extremely rare, particularly when it comes to primary disease detection in this location. The gold standard in establishing a definitive diagnosis of sarcoidosis is a combination of the clinical picture, the results of imaging methods, and histopathological examination from the biopsy taken (thus ruling out other causes of granulomatous inflammation). However, it is common for the biopsy to be infeasible or for the patient to refuse such an examination, resulting in the neglect of this critical verification. We introduce the case of a young 29-year-old man of Czech nationality who had been complaining for some time about non-specific pain above the pubic bone and in the lower abdomen, which was combined with a painless enlargement of the right half of the scrotum. Due to suspected malignancy, it was, after considering clinical, imaging, and laboratory findings, decided to perform a radical orchiectomy as a treatment option. The histological examination revealed that it was not cancer, but rather a rare genitourinary form of extrapulmonary sarcoidosis. In this case, radical resection had been, therefore, unnecessary. We also present a review of the literature on published extrapulmonary, genitourinary, and testicular sarcoidosis cases. All the above demonstrates the importance of considering a possible atypical sarcoidosis manifestation and histological confirmation before pursuing radical solutions.

Great mimicker: definite isolated cardiac sarcoidosis masquerading as hypertrophic cardiomyopathy.

A healthy man in his 50s was hospitalised after presenting with chest pain and dyspnoea. An echocardiogram revealed asymmetrical septal hypertrophy, leading to a diagnosis of hypertrophic cardiomyopathy. Due to progressive conduction abnormalities during his hospitalisation, further evaluation was performed. Cardiac MRI revealed dense late gadolinium enhancement of the septum in the area of hypertrophy. Additionally, fluorodeoxyglucose-positron emission tomography demonstrated increased uptake within the same region, suggestive of active inflammation. Subsequent endomyocardial biopsy showed non-caseating granulomatous inflammation, consistent with cardiac sarcoidosis. Treatment with prednisone and methotrexate was initiated, and an implantable cardioverter-defibrillator was placed following thorough risk stratification. This case highlights the importance of multimodality imaging and the pursuit of a tissue diagnosis in the evaluation of cardiomyopathy.

Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos / Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients

La afectación cardíaca en la sarcoidosis ha sido descrita tanto en presencia de síntomas como en su ausencia. Este trabajo ayuda a comprender la sarcoidosis y su presentación clínico-morfológica. Presentamos dos pacientes jóvenes (37 y 27años), con muerte súbita, a quienes se les realizó la autopsia completa con estudio toxicológico. El hombre de 37años presentaba una sarcoidosis pulmonar generalizada, en ganglios mediastínicos y granulomas sarcoideos intramiocárdicos en el ventrículo izquierdo, que producían un espesor de pared de 14mm. Esto derivó en una miocardiopatía dilatada secundaria que debutó como muerte súbita. El segundo caso, un varón de 27años, presentaba sarcoidosis con importante afectación pulmonar y mediastínica. La presencia de granulomas en el tabique cardíaco sobre un fondo fibrótico podría ser el origen de un mecanismo arritmogénico de muerte súbita. La autopsia clásica y el examen del sistema de conducción cardíaco son cruciales en la muerte súbita.(AU)

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.(AU)

[Transbronchial cryobiopsy for mediastinal lesions: a pilot study]. / Transbronkhial'naya kriobiopsiya limfouzlov i novoobrazovanii sredosteniya: pilotnoe issledovanie.

OBJECTIVE: To describe a novel transbronchial cryobiopsy technique for mediastinal lesions after initial ultrasound assessment and EBUS-TBNA. MATERIAL AND METHODS: Transbronchial cryobiopsy (TBCB) was performed in 35 patients with suspicious mediastinal lesions between November 2020 and September 2022. Age of patients ranged from 22 to 75 years (median 50 [39; 62]). Men-to-women ratio was 13:22. RESULTS: According to morphological data, patients with sarcoidosis (n=13), NSCLC (n=7) and metastases of other tumors (n=3) prevailed. There were patients with B-cell lymphoma (n=1), Castleman disease (n=1) and small cell lung cancer (n=2). Among 15 biopsies for immunohistochemical examination, samples were sufficient for final morphological conclusion in 11 (73.3%) cases (95% CI 48.5-89.1). In 4 (11.4%) cases (95% CI 4.5-26), examination was uninformative. Repeated biopsy was performed in 2 cases, and sarcoidosis of thoracic lymph nodes was confirmed. Sensitivity, specificity and accuracy of transbronchial cryobiopsy were 93.3, 100 and 94%, respectively. There were no clinically significant complications. In one case, chest X-ray revealed pneumomediastinum without need for additional treatment. CONCLUSION: Transbronchial mediastinal cryobiopsy is a perspective method for diagnosis of mediastinal neoplasms. Apparently, this approach may be advisable in patients with suspected sarcoidosis or lymphoproliferative diseases.