Blau syndrome (BS), is an autoinflammatory granulomatosis disease characterized by a distinct triad of skin, joint, and eye disorders similar to those of sarcoidosis, but the lung involvement frequently observed in sarcoidosis are rare. Granulomas from patients with BS displayed a distinct morphology indicating an exuberant chronic inflammatory response. Patients with BS may have granulomatous lung lesions, which require early diagnosis. To determine whether therapeutic intervention is needed for lung lesions, examining transbronchial lung cryobiopsy specimens and accumulating cases of BS with lung involvement could be contributed to improving BS management in the future.

Granuloma annulare (GA) is an idiopathic condition characterized by granulomatous inflammation in the skin. Prior studies have suggested that GA develops from various triggers, leading to a complex interplay involving innate and adaptive immunity, tissue remodeling, and fibrosis. Macrophages are the major immune cells comprising GA granulomas; however, the molecular drivers and inflammatory signaling cascade behind macrophage activation are poorly understood. Histologically, GA exhibits both palisaded and interstitial patterns on histology; however, the molecular composition of GA at the spatial level remains unexplored. GA is a condition without Food and Drug Administration-approved therapies despite the significant impact of GA on QOL. Spatial transcriptomics is a valuable tool for profiling localized, genome-wide gene expression changes across tissues, with emerging applications in clinical medicine. To improve our understanding of the spatially localized gene expression patterns underlying GA, we profiled the spatial gene expression landscape from 6 patients with GA. Our findings revealed mixed T helper 1 and T helper 2 signals comprising the GA microenvironment and spatially distinct M1 and M2 macrophage polarization characteristics. IFN-γ and TNF signals emerged as important regulators of GA granulomatous inflammation, and IL-32 emerged as a key driver of granulomatous inflammation. Overall, our spatial transcriptomics data indicate that GA exhibits mixed immune and macrophage polarization.

Lung cancer screening with low-dose computed tomography (LDCT) can significantly improve survival rates with early detection. With the increased amount of imaging studies being performed for screening, there are more incidental lesions found. Malignancy and pulmonary infections are two of the major differentials when a lesion is found on CT. Neither a CT scan nor a positron emission tomography can reliably differentiate between malignancy and infectious lesions. Here, we present an unexpected case of multiple nodules detected on LDCT that was performed for lung cancer screening and the workup that was done to lead to a diagnosis.

Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients against developing active tuberculosis, suggesting that these drugs could help the host to control the pathogen at the initial stages of the disease. This work studies the effect of fluvastatin on the early response of healthy peripheral blood mononuclear cells (PBMCs) to inactivated Mycobacterium tuberculosis (Mtb) H37Ra. We found that in fluvastatin-treated PBMCs, most monocytes/macrophages became foamy cells that overproduced NLRP3 inflammasome components in the absence of immune stimulation, evidencing important cholesterol metabolism/immunity connections. When both fluvastatin-treated and untreated PBMCs were exposed to Mtb H37Ra, a small subset of macrophages captured large amounts of bacilli and died, concentrating the bacteria in necrotic areas. In fluvastatin-untreated cultures, most of the remaining macrophages became epithelioid cells that isolated these areas of cell death in granulomatous structures that barely produced IFNγ. By contrast, in fluvastatin-treated cultures, foamy macrophages surrounded the accumulated bacteria, degraded them, markedly activated caspase-1 and elicited a potent IFNγ/cytotoxic response. In rabbits immunized with the same bacteria, fluvastatin increased the tuberculin test response. We conclude that statins may enhance macrophage efficacy to control Mtb, with the help of adaptive immunity, offering a promising tool in the design of alternative therapies to fight tuberculosis.

BACKGROUND: Mesotherapy is a popular cosmetic procedure for localized delivery of substances. However, due to the lack of standardized processes, there are potential risks of adverse reactions. Granulomas formation is one of the chronic reactions which impose significant physical and mental burdens on patients.
OBJECTIVE: The aim of this analysis is to evaluate the safety and feasibility of combining intense pulsed light (IPL) with intralesional corticosteroids for treating noninfectious granulomas after mesotherapy.
METHODS: This retrospective observational case series included patients who suffer from noninfectious granulomas after mesotherapy and received combination of IPL and intralesional corticosteroids treatment between October 2021 and December 2022 at Peking University Shenzhen Hospital, Shenzhen, China. The process and effect were analyzed and summarized.
RESULTS: Among the seven patients, five expressed extreme satisfaction with the efficacy, while two was slightly satisfied. The physicians believed that all patients had shown significant improvement. No adverse reactions or recurrences were observed during follow-up.
CONCLUSIONS: Based on this analysis, the application of the combined treatment in patients suffering from noninfectious granuloma due to mesotherapy demonstrates good clinical efficacy and safety, making it worth considering as a treatment option.

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Contracturing granulomatous myositis is a rare myopathy in which patients present with flexion contractures of the upper limbs in addition to slowly progressive muscle weakness and pain. Whether it represents a distinct nosological entity remains a point of discussion. We present a patient with isolated granulomatous disease of the muscle that responded very well to intravenous immunoglobulins after treatment failure of corticosteroids and methotrexate.

OBJECTIVE: The appendix, although considered a vestigial organ, is of considerable clinical importance because acute appendicitis is a common medical problem. There are also other disease processes involving the appendix. The appendix is among the first specimens that the pathologist (and surgeon) cuts one\'s teeth on. Thus, there may be a tendency to underestimate the clinically and prognostically significant appendiceal pathologies.
METHODS: We provide a vade mecum of the pathologic features of a wide range of nonneoplastic appendiceal pathologies, with an emphasis on developing a practical approach to grossing, microscopy, and reporting-all with clinical and therapeutic implications. Much of this is based on literature on MEDLINE with reference to years 2008 to 2023, as well as on personal experiences and interpretations.
RESULTS: The appendix can harbor a myriad of nonneoplastic pathologies, including infections, inflammations of varying etiologies (including interval appendectomy), endometriosis, diverticulosis, and so on. Chronic appendicitis, Crohn disease, and clinical audit are recurring themes while COVID-19 is a new entity.
CONCLUSIONS: Most importantly, all pathologists should appreciate that the appendix is not as \"routine\" a specimen as one would want to believe.

According to the World Health Organization (WHO), around 1 million children worldwide are diagnosed with tuberculosis each year. The Bacillus Calmette-Guérin (BCG) vaccine has been used around the world for over 100 years. The complications of the BCG vaccination can occur in about 0,06% of children and include local or systemic adverse reactions. Due to the close analogy between the vaccine strain and other species of the Mycobacterium tuberculosis complex (MTBC), molecular methods are recommended for differential diagnosis of Vaccine adverse events (VAE) after BCG. The ability to quickly and specifically identify BCG is important in view of different treatment regimens. The aim of the study was to assess the usefulness of genetic testing for Mycobacterium bovis BCG in the paraffin-embedded specimens\' methods. We describe two cases of VAE in immune-compromised children presenting with osteoarticular changes that had been clinically suspected of tuberculosis and led to molecular identification through GeneXpert, GenoType MTBC, and Spoligotyping. Results: Mycobacterium bovis BCG was detected in osteoarticular changes embedded in paraffin block of two patients. Conclusion: Genetic tests using paraffin-embedded materials allow for quick identification and differential diagnosis of patients with Tuberculosis and VAE after BCG. This is an important issue, especially in cases where the tissue has only been submitted for histopathological examination without microbiological diagnostics for tuberculosis.

Inborn errors of immunity (IEIs) are a heterogeneous group of diverse clinical and genetic phenotypes that have an estimated combined prevalence as high as 1/1000. Increased risk of frequent, severe, or opportunistic infections is a common feature of IEIs, but there are also diverse immune-mediated, non-infective complications that are associated with significant morbidity and mortality. As patient survival increases, these are becoming more apparent within the liver. Hepatic involvement of IEIs may not only manifest as infections, but also nodular regenerative hyperplasia, granulomatous disease, autoimmune hepatitis and malignancy. As therapeutic options for patients are expanding, with both pharmaceutical treatments as well as haematopoietic stem cell transplant (HSCT), iatrogenic liver injury is increasingly common and important to identify. This review article summarises the spectrum of hepatic complications seen in IEIs, and highlights the challenges of management within this patient cohort, where immunosuppression is poorly tolerated. Early recognition and prompt diagnosis of potential hepatic complications is therefore crucial in ensuring potentially reversible causes are treated, but significant uncertainty remains regarding best practice for many features of immune dysregulation with limited high-quality evidence.