Granulomatous Infiltrate Research Articles

Role of Multimodality Imaging in Cardiac Sarcoidosis: A Retrospective Single-Center Experience

Background/Objectives: Cardiac sarcoidosis (CS) is a rare entity characterized by granulomatous infiltration of the myocardium, which can lead to myocardial fibrosis, conduction abnormalities, and the development of heart failure, thereby elevating the risk of sudden cardiac death (SCD). While endomyocardial biopsy (EMBx) is regarded as the gold standard for diagnosis, its low sensitivity and inherent procedural risks may limit its practical application. Methods: This study retrospectively explored the role of advanced imaging modalities, specifically cardiovascular magnetic resonance imaging (CMR) and fluorodeoxyglucose positron emission tomography (FDG-PET), in the diagnosis and management of CS within a single center. In this retrospective study, we aimed to assess the utility of advanced imaging modalities in the clinical diagnosis of CS and the monitoring of treatment. Results: A total of 92 patients were identified as having cardiac sarcoidosis, with males constituting 66.3% of the sample and a mean age of 62 years (±11.9). Among these patients, 80 (87%) underwent FDG-PET. Here, the basal inferolateral segment was the most frequently observed segment of the heart with FDG uptake. A total of 77 patients (84%) underwent CMR, with 51 demonstrating late gadolinium enhancement (LGE). The basal inferolateral segment exhibited the highest frequency of LGE (26%). Logistic regression analysis indicated that patients presenting with a combination of LGE, FDG uptake on PET, and a “mismatch pattern” faced a two-fold increase in the risk of experiencing major adverse cardiac events (odds ratio = 2.311, p = 0.077). Conclusions: This study underscores the importance of multimodality imaging as a non-invasive alternative for CS diagnosis and management, reducing reliance on EMBx.

Sarcoid Vasculitis in the Skin: A Clinicopathologic Study of 8 Cases With Various Skin Lesions but the Common Unique Cannonball-like Vessel Destruction by Sarcoid Granulomas.

While the skin is a common target organ for sarcoidosis, cutaneous granulomatous vasculitis is rare among patients with sarcoidosis. Due to the lack of detailed studies on cutaneous sarcoid vasculitis, both dermatologists and pathologists remain unfamiliar with this rare but important vasculitic disorder. We clinicopathologically evaluated eight cases with biopsy-proven cutaneous vasculitis and cutaneous sarcoidosis and analyzed morphologic changes in the process of vasculitis for both small vessels and muscular vessels in detail. The various skin lesions ranged from papulonodular erythema, annular erythema, maculopapular erythema, livedo reticularis-like eruptions, erythema nodosum-like lesions, subcutaneous nodules to ulcerative lesions. The extremities were the most frequently affected sites. Bilateral hilar lymphadenopathy with pulmonary sarcoidosis was the most common extracutaneous comorbidity. Skin-limited sarcoidosis was identified in 3 cases. All cases demonstrated a common histopathologic feature with sarcoid granulomas impinging on the target vessels with resultant vessel destruction. Perivascular infiltration of sarcoid granulomas resulted in compression and destruction of small vessels. In muscular arteries and veins, sarcoid granulomas closely attached to the muscular vessel wall, infiltrated the muscular layers and either occupied or penetrated the vessel walls, eventually invading the vascular lumen and replacing the entire muscular layers. The intimal infiltration of sarcoid granulomas resulted in a marked luminal narrowing. The scarcity of reports on cutaneous sarcoid vasculitis may be due to the overlooking or misinterpretation of vascular destruction caused by sarcoid granuloma infiltration as a feature of sarcoid granuloma masses.

Steroid‐responsive granulomatous mural folliculitis associated with ovine herpesvirus‐2 in a Pygmy goat

AbstractThis case reports a Pygmy goat diagnosed with granulomatous mural folliculitis associated with ovine herpesvirus‐2 infection. Three biopsy samples were collected at different time points throughout the evolution of the disease, which were submitted to histopathology and polymerase chain reaction analyses. Despite the suspected viral aetiology, the goat showed significant clinical improvement with a tapering regimen of immunosuppressive corticosteroids, achieving clinical remission. A progressive reduction in the follicular granulomatous infiltrate and in apoptosis of follicular keratinocytes was observed, while the viral presence persisted. The disease remained controlled with a follow‐up period of 2 years, although a flare occurred after discontinuation of the treatment. The findings suggest that the granulomatous reaction affecting the follicles may be immune‐mediated rather than directly induced by the cytopathic effects of the virus.

Cardiac sarcoidosis: diagnosis and management.

Non-caseating granulomatous infiltration of the myocardium is the hallmark of cardiac sarcoidosis (CS). CS manifests clinically as conduction disturbance, ventricular arrhythmia, sudden cardiac death and/or heart failure with reduced ejection fraction. Other than confirmation through endomyocardial biopsy, a diagnosis of probable CS can be established by histological evidence of systemic sarcoidosis in addition to characteristic clinical or advanced imaging findings. Cardiac Magnetic Resonance imaging (CMR) and 18F-flurodeoxyglycose positron emission tomography (FDG-PET) are imaging modalities indispensable in the diagnosis and monitoring of CS. FDG-PET is the method of choice for identifying the active inflammatory phase of CS and in the monitoring and modifying of immunosuppressive treatment. CMR is better suited for assessing cardiac morphology and function. Both modalities are more effective in detecting CS when used in combination than either is alone. Management of CS is primarily based upon observational data of low quality due to a paucity of randomized controlled trials. Corticosteroid therapy and/or tiered-immunosuppression are the mainstays of treatment in reducing myocardial inflammation. Steroid-sparing agents aim to limit the unfavorable side-effects of a significant steroid burden. Antiarrhythmics and guideline-directed medical therapies are utilized for control of ventricular arrhythmia and left ventricular dysfunction respectively. CS necessitates multidisciplinary care in specialized centers to most effectively diagnose and manage the disease. Additional randomized trials are warranted to further our understanding of medical optimization in CS.

Granulomatous Folliculotropic Secondary Syphilis: An Unusual Histopathological Clue.

Syphilis is a sexually transmitted disease that can present a wide variety of clinical and histopathological manifestations. We present the case of a 75-year-old patient with a persistent maculopapular rash on the trunk and extremities, in which the biopsy showed an exclusively perifollicular granulomatous infiltrate. In the immunohistochemical staining with anti-Treponema pallidum antibodies, spirochetes scattered within the perifollicular inflammatory infiltrate were identified. These findings together with the serological analysis allowed the diagnosis of secondary syphilis. Folliculotropic nonalopecic syphilis is rare, and the pathogenic mechanisms that cause this specific tropism are unknown. On the other hand, granulomatous inflammation is a pattern typically described in tertiary syphilis but also occasionally found in secondary syphilis. We present a case of secondary syphilis with the combination of both histopathological findings, an uncommon constellation for dermatopathologists to consider.

Migrating foreign body granulomas after rupture of a breast implant

AbstractWe present the case of an 80‐year‐old female with a history of bluish streaks and painful lumps on her left arm, initially misdiagnosed as a soft tissue infection. Further investigation revealed granulomatous infiltrates in the arm and a ruptured breast implant. Upon presentation, nodular and painful swelling prompted a new biopsy. Histology and electron spectroscopy confirmed silicone deposits within granulomas. The rupture of the breast implant was identified as the likely source of silicone migration to the arm, possibly exacerbated by a past fall. Treatment challenges included the extensive size of the granuloma, leading to a trial of methotrexate therapy with initial improvement but subsequent discontinuation due to poor tolerance. This case underscores the potential for silicone migration from ruptured breast implants to induce distant granulomatous reactions, necessitating individualised treatment approaches.

Effector CD4+ T-cell subsets in Takayasu arteritis-differences between the peripheral blood and the aorta.

Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of six patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (P = 0.031 and P = 0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (P = 0.016 and P = 0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T-cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rho = -0.610 and rho = -0.463, respectively) and with Th17 cells (rho = -0.365 and rho = -0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet, and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND CARDIAC SARCOIDOSIS: THE GREY ZONE

Abstract Cardiac sarcoidosis (CS) is a rare multisystem disorder characterized by granulomatous infiltration of the myocardium, whose clinical manifestations can be extremely heterogeneus. We report the case of a 47–year–old man with a previous diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVD). In history he had a marked arrhythmic pattern with multiple episodes of sustained ventricular arrhythmias, biventricular disfunction (LVEF 37%, RVEF 32%) and extensive biventricular transmural late–gadolinium enhancement (greater than 50%) at cardiac RMN. At EKG epsilon wave mainly seen in precordial leads. In November 2022 he was implanted with bicameral defibrillator and in March 2023 he underwent ablation procedure for ventricular tachycardia with RF with endo–epicardial approach. In May 2023 he arrived at our Centre for acute decompensated heart failure. At restored hemodynamic stability, screening for the possible inclusion in transplant list was started. Right heart catheterization (RHC) showed low cardiac index with no pulmonary hypertension. Chest CT unexpectedly showed the presence of multiple micronodules with perilymphatic distribution with confluent appearance compatible with pulmonary sarcoidosis. In consideration of this result, the transplant program was temporarily postponed and investigations for possible cardiac involvement of an inflammatory nature were started. 18F–FDG PET–CT showed pulmonary, splenic, lymphonodal and especially cardiac uptake in the mid–distal segment of the lateral wall of the left ventricle and in the inferior–apical site suspicious for inflammatory pathology. Unfortunately, both lymphonodal and cardiac biopsies were inconclusive because of insufficient material. Nevertheless, the clinical scenario satisfied the Japanese criteria for possible CS; therefore, treatment with prednisone 1 mg/kg was started and a 18F–FDG PET–CT was planned after 3 months of steroid therapy. CS can disguise as a phenocopy of arrhythmogenic right ventricular cardiomyopathy because of several common characteristics, especially arrhythmic presentation. Due to these similarities, a careful overall evaluation of each patient with ARVD is mandatory as several transplant centers have reported cases of CS in explanted heart with a pretransplant misdiagnosis of ARVD or dilated cardiomiopathy. Performing a chest CT in all ARVD patients as part of transplant screening may be considered.

Granulomatous Slack Skin With Lung and Esophagus Involvement: A Case Report and Molecular Analysis.

Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.

The First Case of Phaeohyphomycosis Caused by Exophiala xenobiotica in an Immunocompetent Patient in Korea

Phaeohyphomycosis is a rare fungal infection caused by dematiaceous fungi commonly associated with immunocompromised patients. Exophiala (E.) species are linked to phaeohyphomycosis, and in Korea, E. dermatitidis, E. jeanselmei, and E. salmonis were previously isolated from affected patients. Here, we describe a unique instance of phaeohyphomycosis in an immunocompetent patient attributed to E. xenobiotica. A 75-year-old female presented with an asymptomatic erythematous crusted subcutaneous nodule on the dorsum of her left-hand. Her past medical history was negative for immunosuppression or trauma to the affected area. Histopathological examination revealed suppurative granulomatous infiltration, with septate hyphae and spores detected by periodic acid-Schiff staining in the dermis. A fungal culture made from a tissue sample revealed E. xenobiotica, with subsequent confirmation through phylogenetic analyses of the internal transcribed spacer (ITS) and large subunit regions (LSU) of ribosomal ribonucleic acid (rRNA). The patient was diagnosed with phaeohyphomycosis and underwent a 3-week course of terbinafine, followed by 7 weeks of fluconazole. These treatments significantly improved the lesion. To our knowledge, this is the first reported case of phaeohyphomycosis caused by E. xenobiotica in Korea.

Miescher’s cheilitis granulomatosa: a case report

Miescher’s cheilitis granulomatosa (MCG) is a rare idiopathic chronic persistent painless lip swelling with granulomatous infiltrate. It is often associated with orofacial granulomatosis and Melkersson—Rosenthal syndrome. Sometimes cheilitis granulomatosa is attributed to sarcoidosis (Besnier—Boeck—Schaumann disease) without systemic lesions. Although there is a possibility that it is a separate disease. Secondary causes include a reaction in response to infection with Mycobacterium tuberculosis, as well as to the introduction of tissue fillers.The publication presents a clinical case of Miescher’s cheilitis, the probable cause of which were the following infectious agents: long­term untreated caries of many teeth and COVID­19.Patient K., 46 years old, complained of swelling and enlargement of the lower lip, a feeling of numbness and discomfort. She fell ill a week ago. Swelling formed gradually over 6—7 days without disturbing the general condition; the body temperature was within the normal range. The lips were swollen, increased in size, slightly hyperemic, the lower one was turned outwards. The lips had a soft­elastic consistency and were not painful to palpate. Pain, tactile and temperature sensitivity were preserved. Dermoscopy was performed. White­grey, structureless areas forming a reticular pattern were observed on the entire surface of the examined area. The vessels were not clear, full­blooded, visualised in the surrounding skin at a considerable distance from the lip edge. The patient was prescribed systemic and topical corticosteroids, hydroxychloroquine, and hyaluronidase. The oral cavity was sanitised. During the month of treatment, the swelling of the lips gradually decreased. At the control examination in two months, the patient’s lip size decreased by 2—2.5 times. There was no relapse of the disease.Conclusions. In our opinion, Miescher’s cheilitis granulomatosa is a separate type of cheilitis, probably of autoimmune nature, in the implementation of which bacterial and viral infectious agents play an important role (focal infection, caries, maxillary sinusitis, frontitis, etc.). The recovery of our patient after the sanitation of the infection foci and complex anti­inflammatory therapy is a convincing proof.

Differential Upregulation of Th1/Th17-Associated Proteins and PD-L1 in Granulomatous Mycosis Fungoides.

Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.

Drug-induced autoimmune-like liver injury

Drug-induced liver injury (DILI) is arare yet potentially life-threatening disease. Besides intrinsic DILI, which is mainly caused by paracetamol overdosing and which is dose-dependent and predictable, there is idiosyncratic DILI-an unpredictable and dose-independent injury of the liver caused by certain medications that only occurs in aminority of patients taking this drug. The reason why some patients react with DILI towards aspecific drug is still unknown. However, the immune system plays acentral role, which is underlined by the association of certain human leukocyte antigen (HLA) polymorphisms and DILI caused by specific drug classes. Due to the immunological processes that lead to the liver injury in DILI, there are great overlaps regarding laboratory and histological parameters between DILI and autoimmune hepatitis (AIH). Differentiating DILI and AIH can therefore be challenging, especially at the time of presentation. In addition, there are other immunologically mediated DILI phenotypes, in particular the newly defined drug-induced autoimmune-like hepatitis (DI-ALH) and liver injuries caused by checkpoint inhibitors (CPI). DI-ALH is characterized by autoimmune features and good responses towards corticosteroids, with the difference that DI-ALH mostly does not relapse after discontinuation of corticosteroids. CPI-induced liver injury has become more frequent with the rising use of those drugs and is characterized by adistinct histopathological pattern with granulomatous hepatitis and infiltration dominated by cytotoxic Tcells. Similarly, the recently recognized liver injury following vaccinations also shows an autoimmune phenotype; however, in contrast to AIH, cytotoxic Tcells seem to dominate the inflammatory infiltrates in the liver.

Disseminated Tuberculosis Revealed by Conus Medullaris Tuberculoma

A 29-year-old man from Comoros presented with rapidly progressive paraplegia and sexual dysfunction. Magnetic resonance imaging (MRI) showed a contrast-enhanced conus medullaris lesion. Differential diagnoses included tumors, abscesses, and inflammatory diseases. Neurosurgery was delayed to complete examinations. Cerebral MRI showed three abscesses. Body computed tomography scan showed supracentimetric polyadenopathies, pulmonary nodules, prostatic lesion, and enhanced seminal vesicle, with hypermetabolism on positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose scan. Histology of lymph node biopsy showed granulomatous infiltration without acid-fast bacilli, and positive polymerase chain reaction for Mycobacterium tuberculosis. Lymph node culture was positive after 2 months, urine culture after 3 weeks, but cerebrospinal fluid and sputum cultures were negative. A 1-year antituberculosis therapy was initiated, associated with corticosteroids because the patient developed tuberculosis-immune reconstitution syndrome, revealed by the recurrence of neurological symptoms. After 2 months the patient completely recovered and could run. MRI showed stability of the voluminous tuberculoma with decrease of medullary edema. Avoiding surgery in those cases may prevent iatrogenic neurological deterioration.

Clinical analysis of lupus miliaris disseminatus faciei: a cross-sectional study and literature review.

The clinical similarity of lupus miliaris disseminatus faciei (LMDF) and other papular granulomatous facial disorders often makes its correct diagnosis challenging. Diagnosis often requires the assistance of pathological examination, and dermoscopy can be used as an auxiliary and non-invasive examination method, however, the current findings remain incomplete. This study aimed to summarize the clinical, histopathological and dermoscopic features of LMDF in the Chinese Han population and aiming to provide practical significance to correct diagnosis. 109 patients of LMDF were collected in the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University from August 2015 to August 2023. The clinical and histopathological manifestations of all patients, as well as the dermoscopic image features of 44 cases, including background, follicular findings, vessels, and other structures, were summarized and evaluated. The most significant histopathological features of LMDF in 109 cases is epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. The most significant dermoscopic features of LMDF in all 44 cases were orange structureless background (30/44), follicular plug (32/44), follicular white scar-like area (32/44), unspecific linear vessels (24/44), linear vessels with branch (24/44) and white streaks (18/44). Histopathologically, LMDF is characterized by the presence of epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. Dermoscopically, it exhibits a distinctive orange structureless background, follicular plug, follicular white scar-like area, nonspecific linear vessels, linear vessels with branches, and white streaks.

Mycosis Fungoides and Granulomatous Slack Skin: A Single Entity With Distinct Clinical Phenotypes.

Granulomatous cutaneous T-cell lymphoma includes mycosis fungoides with significant granulomatous inflammation (GMF) and granulomatous slack skin (GSS), listed in the WHO classification as a subtype of mycosis fungoides (MFs).1 These overlapping entities have shared clinical and histopathologic features which can present a diagnostic challenge. The dominance of the granulomatous infiltrate and the often sparse lymphocytic infiltrate frequently with minimal cytological atypia are features that distract from the correct diagnosis, even when raised by the clinician. We describe the clinical and histopathologic characteristics of 3 cases of granulomatous cutaneous T-cell lymphoma, illustrate the close clinical and pathologic relationship between GMF and GSS and emphasize the diagnostic difficulties that the granulomatous infiltrate can present. Furthermore, we demonstrate, for the first time, considerable elastolysis in a significant proportion of classical (Alibert-Bazin) MF lesions and therefore postulate that the differences observed between GMF and GSS are one of degree and secondary to their anatomic location rather than reflecting meaningful separate entities.

Abstract 15864: Genetic Findings of Cardiac Sarcoidosis in a Case of Apical Variant Hypertrophic Cardiomyopathy With Recurrent Ventricular Tachyarrhythmias

Background: Genetic sequencing is changing the way physicians practice medicine. Hypertrophic cardiomyopathy (HCM) is one of the most common inheritable cardiac diseases. Sarcoidosis is a multisystem disease involving granulomatous infiltration of the lungs, heart, and other organs thought to be caused by a dysregulated immune system, influenced by genetic factors. Here, we present a case where an individual initially diagnosed with HCM was experiencing frequent episodes of ventricular tachycardia (VT). Further workup, including advanced imaging along with whole genome screening (WGS), revealed an unlikely diagnosis of concurrent cardiac sarcoidosis (CS). Clinical History: A 62-year-old man had ventricular fibrillation with workup notable for an ECG with deeply inverted T-waves, normal coronary angiography, and an echocardiogram and MRI showing apical HCM. An ICD was placed. Six years later, he had VT requiring a shock and was started on sotalol. He has now developed recurrent exercise-induced VT. While VT is seen HCM, the increasing frequency prompted further evaluation. A CT coronary angiogram showed normal coronaries and mediastinal lymphadenopathy. Lymph node biopsy revealed noncaseating granulomas and a PET/CT revealed hypermetabolic basal myocardium meeting HRS criteria for CS. Given minimal apical FDG uptake and a low likelihood that he had CS for 9 years without significant fibrosis, he likely has both HCM and CS. Using WGS, four genetic variants previously described in CS and HCM were identified confirming this diagnosis, HLA-DRB1, HLA-DQA1, ALPK3, and TTN. Discussion: HLA-DRB1 and HLA-DQA1 are both major histocompatibility complexes associated with CS. ALPK3 encodes alpha kinase 3 while TTN encodes titin. Truncating variants of ALPK3 are associated with HCM while pathogenic TTN variants have been described to cause HCM, DCM, and ARVC. This case reflects the potential of WGS in aiding clinicians in confirming an unlikely diagnosis.

Efficacy of photodynamic therapy in an experimental mice tuberculosis model

The objective: to study the efficacy of antimicrobial photodynamic therapy (APDT) using hydroxyaluminum phthalocyanine (Photosens) as a photosensitizer in the experimental model of tuberculosis infection in mice.Subjects and Methods. Balb/cmice were infected with the multiple drug resistant (MDR) strain of M. tuberculosis Beijing BO/W148. APDT with hydroxyaluminum phthalocyanine and red laser light exposure were started on Day 45. A total of 4 sessions of APDT on the projection of both lungs, liver and spleen were performed. On Day 60, the therapeutic eff ect of APDTwas assessed by evaluation of severity of mycobacterial load and specific granulomatous infiltration in the lungs, liver and spleen. The absorption of light energy of laser radiation by the chest and abdominal walls, as well as tissues of lungs, liver and spleen was determined by photometry using afluovisor.Results. The tissues of the experimental animal retain a significant amount of light energy, however, the residual value of light transmission is sufficient to provide a pronounced therapeutic effect which manifests itself as a significant decrease of mycobacterial load and specific inflammatory process in all the studied internal organs.Conclusion. APDT may be an effective tool to treat some forms of tuberculous infection including those caused by M. tuberculosis with MDR.

FRI347 Lymphocytic Hypophysitis In The Setting Of Necrotizing Granulomatous Inflammation

Abstract Disclosure: C. Kelly: None. L. Ghalib: None. Hypophysitis is rare; accounting for 0.24-0.39% of all pituitary diseases. Hypophysitis can be primary or secondary in nature. Granulomatous disease rarely causes pituitary enlargement, but Sarcoidosis and Granulomatosis with Polyangiitis have been documented to cause granulomatous infiltration of the pituitary. This case regards a man with granulomatous infiltration of the pituitary not consistent with either of the aforementioned disease processes. A 40 year old male presented to Urgent Care with headaches and blurry vision. Headaches were unresponsive to analgesics. The patient then presented to his PCP with the same complaints. MRI was then performed which showed a heterogeneously enhancing sellar and suprasellar mass. He was evaluated by Neurosurgery who recommended he undergo endoscopic resection of the pituitary lesion. Preoperative evaluation of pituitary axes were concerning for central hypothyroidism with a TSH of 1.046 uIU/mL (0.550-4.780) and free T4 of 0.76 ng/dL (0.89-1.76),as well as central hypogonadism with a FSH of 0.4 mIU/mL (&amp;lt;18.1), LH of 0.18 mIU/mL (1.5-9.3),and testosterone of 17 ng/dL (87-814). All other axes normal. Resection of the pituitary mass occurred approximately one week later at which time he was evaluated by Endocrinology for the first time. Prior to discharge, the patient was started on levothyroxine, but gonadal replacement was deferred to outpatient setting. Grossly the pituitary mass was concerning for lymphocytic hypophysitis (LH), and thus the patient was discharged on prednisone for empiric therapy. At the time of his endocrinology follow up, his headaches and visual changes had improved, but he was experiencing polydipsia, polyuria, and nocturia. Labs were consistent with Diabetes Insipidus (DI), and he was started on desmopressin. Surgical pathology had returned “acute and chronically inflamed granulation-like tissue associated with necrosis” confirming LH. CT chest was performed to evaluate for secondary causes of granulomatous disease which showed mediastinal lymphadenopathy without parenchymal lung disease. Serologic evaluation was positive for ANA, myeloperoxidase antibody, and SS-B antibody. While attempting to wean his prednisone the patient experienced recurrence of his headaches, which resolved when he returned to higher doses. The patient was evaluated by Pulmonology given the mediastinally mphadenopathy, who recommended bronchoscopy. When specimens from the mediastinal lymph nodes were evaluated by pathology, it was again significant for necrotizing granulomatous disease, but ACE and IL-2 were negative which argued against a diagnosis of sarcoidosis. He was evaluated by Rheumatology who recommended further infectious work upas well as consideration of initiation of a steroid-sparing agent for granulomatous disease. Workup of secondary etiologies for LH is ongoing given the systemic involvement. Presentation: Friday, June 16, 2023

An mTORC1-Dependent Mouse Model for Cardiac Sarcoidosis.

Background Sarcoidosis is an inflammatory, granulomatous disease of unknown cause affecting multiple organs, including the heart. Untreated, unresolved granulomatous inflammation can lead to cardiac fibrosis, arrhythmias, and eventually heart failure. Here we characterize the cardiac phenotype of mice with chronic activation of mammalian target of rapamycin (mTOR) complex 1 signaling in myeloid cells known to cause spontaneous pulmonary sarcoid-like granulomas. Methods and Results The cardiac phenotype of mice with conditional deletion of the tuberous sclerosis 2 (TSC2) gene in CD11c+ cells (TSC2fl/flCD11c-Cre; termed TSC2KO) and controls (TSC2fl/fl) was determined by histological and immunological stains. Transthoracic echocardiography and invasive hemodynamic measurements were performed to assess myocardial function. TSC2KO animals were treated with either everolimus, an mTOR inhibitor, or Bay11-7082, a nuclear factor-kB inhibitor. Activation of mTOR signaling was evaluated on myocardial samples from sudden cardiac death victims with a postmortem diagnosis of cardiac sarcoidosis. Chronic activation of mTORC1 signaling in CD11c+ cells was sufficient to initiate progressive accumulation of granulomatous infiltrates in the heart, which was associated with increased fibrosis, impaired cardiac function, decreased plakoglobin expression, and abnormal connexin 43 distribution, a substrate for life-threatening arrhythmias. Mice treated with the mTOR inhibitor everolimus resolved granulomatous infiltrates, prevented fibrosis, and improved cardiac dysfunction. In line, activation of mTOR signaling in CD68+ macrophages was detected in the hearts of sudden cardiac death victims who suffered from cardiac sarcoidosis. Conclusions To our best knowledge this is the first animal model of cardiac sarcoidosis that recapitulates major pathological hallmarks of human disease. mTOR inhibition may be a therapeutic option for patients with cardiac sarcoidosis.