Pseudoprogression following neoadjuvant chemoimmunotherapy for lung squamous cell carcinoma mimicking pulmonary metastatic disease on computed tomography: A case report and review of the literature.

Pseudoprogression of malignancy in patients treated with systemic immunotherapy is a well- recognised phenomenon and has also been seen in patients treated with combined chemoimmunotherapy. Neoadjuvant chemoimmunotherapy prior to surgery is a relatively new treatment strategy for the management of many malignancies. We report the case of a patient who was suspected to have primary lung squamous cell carcinoma progression following neoadjuvant chemoimmunotherapy. Tissue histopathology from biopsies demonstrated granulomatous sarcoid-like inflammation rather than progression or metastatic disease. The patient proceeded to have successful surgical clearance of residual tumour. Significantly, failure to suspect granulomatous reactions and pseudoprogression has profound influence on the trajectory of patient care, such as, the potential for patients to miss out on curative surgery. In this case report and review of the literature, we evaluate the role of pseudoprogression and the need for radiologists to be aware of this phenomenon so that they do not mistakenly report new metastases and derail the treatment paradigm for patients with curable malignant conditions.

Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders.

BACKGROUND: Non-infectious (inflammatory) cutaneous granulomatous disorders include cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG). These disorders share macrophage predominant inflammation histologically, but the inflammatory architecture and the pattern of extracellular matrix alteration varies. The underlying molecular explanations for these differences remain unclear. OBJECTIVE: To understand spatial gene expression characteristics in these disorders. METHODS: We performed spatial transcriptomics in cases of CS, GA, NL, and NXG to compare patterns of immune activation and other molecular features in a spatially resolved fashion. RESULTS: CS is characterized by a polarized, spatially organized T helper (Th) 1 predominant response with classical macrophage activation. GA is characterized by a mixed, but spatially organized pattern of Th1 and Th2 polarization with both classical and alternative macrophage activation. NL showed concomitant activation of Th1, Th2, and Th17 immunity with a mixed pattern of macrophage activation. Activation of type 1 immunity was shared among, CS, GA, and NL and included upregulation of IL-32. NXG showed upregulation of CXCR4-CXCL12/14 chemokine signaling and exaggerated alternative macrophage polarization. Histologic alteration of extracellular matrix correlated with hypoxia and glycolysis programs and type 2 immune activation. CONCLUSIONS: Inflammatory cutaneous granulomatous disorders show distinct and spatially organized immune activation that correlate with hallmark histologic changes.

The Use of Steroids to Treat Hypercalcemia Due to Granulomatous Disease From Disseminated Coccidioidomycosis.

The clinical course and treatment of hypercalcemia from a granulomatous disease in the setting of an infectious etiology, namely disseminated coccidioidomycosis, remains incompletely understood. The mechanism and treatment of hypercalcemia have been documented in most granulomatous disorders, with sarcoidosis being the most well-understood so far. We discuss a case of a patient with a recent diagnosis of disseminated coccidioidomycosis who presented with hypercalcemia despite adequate infection control. The treatment course involved combinatorial-calcitonin, low-dose bisphosphonates, and corticosteroids, which led to a favorable outcome.

Neovascular Glaucoma: A Rare Presenting Feature of Vogt-Koyanagi-Harada Syndrome.

Vogt-Koyanagi-Harada syndrome (VKH) is an uncommon multi-system autoimmune inflammatory disorder characterized by bilateral granulomatous panuveitis with serous retinal detachment accompanied by neurological, auditory, and cutaneous manifestations like headache, hearing loss, vitiligo, and poliosis. It has a female preponderance, usually in middle age. We report the case of a 20-year-old male who presented to us with rapidly progressive visual loss accompanying granular panuveitis, complicated cataract, and a mixed mechanism neovascular glaucoma with acute angle closure. He was treated for IOP control and underwent aggressive immunosuppression and, later, bilateral laser iridotomies. It wasn't until one month after the initial presentation that he presented with vitiligo and poliosis of the eyebrows and eyelashes, clinching the diagnosis of VKH syndrome. This case highlights the diagnostic challenge faced due to acute neovascular glaucoma being the initial presenting feature of VKH; hitherto not documented before, although acute angle closure glaucoma or crisis has occasionally been reported at presentation; the classical VKH presentation being an acute posterior segment uveitis or less commonly, a chronic, recurrent panuveitis presenting with/ without complications. This case underlines the importance of considering VKH syndrome in a patient with bilateral granulomatous panuveitis, as dermatological involvement can emerge later in the disease course, by which time vision might have already been compromised significantly.

Description of BCG and Tuberculosis Disease in a Cohort of 79 Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.

NLRP3 inflammasome inhibition decreases Schistosomiasis japonica-induced granulomatous inflammation and fibrosis in BALB/c mice.

To research the role of the NLRP3 inflammasome in Schistosoma japonicum-induced granuloma formation and liver fibrosis. In in vivo tests, BALB/c mice were used. shNLRP3 plasmid based on adeno-associated virus serotype 8 (AAV8-shNLRP3) was injected to block NLRP3 inflammasome via tail vein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected to assess liver injury. H&E staining was used for routine histopathological assessment; Masson's trichrome staining was used to detect fibrous tissues and collagen fibers. Hepatic expression of NLRP3, procaspase-1, bioactive caspase-1, collagen-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and α-smooth muscle actin (α-SMA) were detected by western blot. Serum levels of IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). The inflammatory cell infiltration and hepatic expression of IL-1ß around the granuloma were detected by immunohistochemistry staining. Treatment of S. japonicum infected mice with AAV8-shNLRP3 significantly reduced the hepatic levels of bioactive caspase-1 and IL-1ß, as well as circulating IL-1ß concentrations, while reducing the amounts of myeloperoxidase (MPO) and F4/80 positive cells around the granuloma. Moreover, collagen deposition, TIMP-1, and α-SMA, which are markers of hepatic stellate cell (HSC) activation, were reduced around the liver granuloma. These findings highlight a therapeutic potential of AAV8-shNLRP3 in schistosomiasis cirrhosis.

Bacillus Calmette-Guérin (BCG)-Induced Pneumonitis: A Case Report.

Bladder cancer is the second most common genitourinary (GU) malignancy worldwide. Treatment involves early cystectomy and intravesical Bacillus Calmette-Guérin (BCG), which is effective for T1 high-grade tumors and carcinoma in situ (CIS) but can cause significant side effects, including chemical and bacterial cystitis, hematuria, incontinence, pneumonitis, malaise, fever, and sepsis. We present the case of a 47-year-old male with transitional cell carcinoma (TCC, G3 pTa) treated with transurethral resection of bladder tumor (TURBT) who developed a fever and non-productive cough after BCG injections. Initially discharged, he returned with worsened symptoms. His vital signs showed a fever of 38.2°C, a heart rate of 104 beats per minute (bpm), and a saturation of 93% on room air. Blood tests indicated inflammation and liver dysfunction. Imaging revealed lung micronodularity, and further CT imaging showed bilateral miliary nodules indicative of BCG pneumonitis. MRI ruled out disseminated tuberculosis, identifying a hepatic cyst. Cultures from blood, urine, sputum, and broncho-alveolar lavage were negative, but granulomatous inflammation was confirmed on liver biopsy. The patient was treated with oral glucocorticoids and anti-tuberculosis medications (rifampicin, isoniazid, and ethambutol), and clinical improvement was shown. The patient was discharged, and a follow-up at the respiratory clinic was scheduled. BCG pneumonitis, a severe BCG therapy complication, necessitates early diagnosis and management to reduce morbidity and mortality.

Granulomatous mastitis during pregnancy with sudden onset of gait difficulty and erythema nodosum: A case report and review of the literature.

Granulomatous mastitis (GM), a benign inflammatory disease of the breast, often mimics breast cancer on presentation. We present a case of GM during pregnancy manifesting as a breast mass, sudden onset of plantar pain, and erythema nodosum (EN). A 31-year-old pregnant Japanese woman, gravida 2, para 1, was referred to our hospital with severe plantar pain on both soles, causing difficulty walking. This pain worsened and EN appeared on both lower legs, followed by a left breast mass. Ultrasound findings suggested malignancy; however, aspiration biopsy confirmed GM. Her arthritis and EN resolved 2 days after commencing oral prednisolone and her walking improved. EN with/without arthritis is commonly associated with GM, especially during pregnancy. The described manifestations with a breast mass are suggestive of this diagnosis.

Granulomatous Mastitis: An Autobiographical Case Report.

Granulomatous mastitis (GM) is a rare, benign inflammatory breast disease that predominantly affects women of childbearing age and often mimics breast carcinoma. The diagnosis requires histopathological examination due to nonspecific imaging findings. Treatment includes antibiotics, corticosteroids, and surgery, but no standardized protocols exist. This autobiographical case report describes a 34-year-old woman with a tender breast lump following trauma, initially misdiagnosed as a simple abscess. Despite incision and drainage, she developed erythema nodosum, persistent fever, and arthritis, which responded to corticosteroids. Further investigation, including an ultrasound-guided biopsy and MRI, confirmed GM. Recurrent symptoms were managed with prednisolone and doxycycline, leading to significant improvement. This case report aims to highlight the diagnostic challenges associated with GM, emphasizing the necessity for a detailed histopathological examination to achieve an accurate diagnosis. It also brings attention to the significant emotional impact on patients facing a rare and complex diagnosis. By presenting this case, we aim to highlight the critical importance of a comprehensive and multidisciplinary approach to patient care in managing GM effectively.

A Case of Chronic Granulomatous Disease Masquerading As Tubercular Lymphadenitis in an Infant.

Chronic granulomatous disease (CGD) is a rare inborn error of immunity characterized by recurrent fungal and bacterial infections due to defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. This case report describes an 11-month-old female who was initially diagnosed with tubercular lymphadenitis and presented with fever and bilateral neck swelling. Despite receiving anti-tubercular treatment (ATT) and intravenous antibiotics, the patient experienced recurrent infections and abscesses, prompting further investigation. Laboratory tests revealed normal immunoglobulin levels but abnormal nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) tests, indicating CGD. Genetic analysis (clinical exome by next-generation sequencing) confirmed a novel NCF2 gene mutation associated with autosomal recessive CGD. This patient was treated with prophylactic antibiotics and antifungals and subsequently underwent successful hematopoietic stem cell transplantation (HSCT). This highlights the diagnostic challenges associated with CGD, particularly in tuberculosis-endemic regions such as India, emphasizing the importance of considering primary immunodeficiency disorders in patients with recurrent infections. Early diagnosis and appropriate treatment, including HSCT, can significantly improve patient outcomes. The patient remained infection-free on prophylactic antimicrobials for 1.5 years post-discharge, demonstrating the potential for a favorable prognosis with timely intervention and comprehensive management.

Categories and Profiles of Uveitis in Vogt-Koyanagi-Harada Syndrome With Systemic Correlation: Inferences From a Tertiary Multispecialty Hospital.

Introduction Vogt-Koyanagi-Harada (VKH) syndrome is a granulomatous, autoimmune panuveitis, affecting the eyes, ears, skin, and meninges. It can cause choroiditis and can progress to the retina and optic disc causing visual loss. Imaging using fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and enhanced depth imaging-ocular coherence tomography (EDI-OCT) is required for clinical evaluation and management. Steroids and immunosuppression are the treatment modalities used. Aim The aim of this study is to report the correlation and severity of uveitis in relation to systemic manifestations. Method A retrospective study including 100 patients with VKH syndrome was carried out. They were classified based on clinical manifestations and investigations such as FFA, ICGA, B-scan ultrasonography (USG), and ocular coherence tomography (OCT). Patients were characterized as complete, incomplete, and probable VKH syndrome. Laboratory investigations were performed, and statistical analysis was done. Results Probable VKH syndrome was found to be the most common form of presentation in our study population. Defective vision was the most common complaint among the patients. Extraocular manifestations included tinnitus, vertigo, alopecia, headache, fatigue, and vitiligo and were seen in 33% of the patients. Disc edema and serous retinal detachment were seen in 85% of the patients. Improvement was noted in 25% of the patients with the use of corticosteroids. Conclusion Response to treatment with systemic corticosteroids and immunosuppression in the acute phase of uveitis is better compared to chronic uveitis. The ophthalmologist is usually first consulted in VKH syndrome due to presenting ocular complaints. A multidisciplinary approach is key to providing holistic management.

Surgical Excision of Palisaded Neutrophilic and Granulomatous Dermatitis of the Vulva: A Case Report.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an inflammatory cutaneous disorder of unknown etiology that typically occurs in association with systemic disease. Rheumatoid arthritis and systemic lupus erythematosus are the most common associated diseases. PNGD manifests as skin-colored to erythematous papules and plaques, mainly on the extremities. However, to the best of our knowledge, no cases of PNGD in the vulva have been reported in foreign literature to date. Herein, we report the first case of a 31-year-old female with systemic lupus erythematosus disease who presented multiple plaques and a pigmented, rough, mamillated skin surface affecting the vulva, leading to disfigurement of the vulva and interfering with sexual intercourse due to severe pain, irritation, and frequent infection. Surgical excision of the whole lesion with reconstruction of the vulva was done in two sessions and histologically diagnosed as PNGD.

Central Retinal Artery Occlusion Leading to Diagnosis of Eosinophilic Granulomatous Polyangiitis After Adenovirus Vector COVID-19 Vaccination.

Purpose: To present a case of central retinal artery occlusion (CRAO) leading to the diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) within 1 week of an adenovirus vector COVID-19 vaccination. Methods: A case was reviewed. Results: A 50-year-old man with atopic dermatitis and asthma presented with acute painless vision loss in 1 eye. An examination and imaging findings showed CRAO. Further evaluation found eosinophilia and elevated inflammatory markers. A workup for vasculitis showed elevated cytoplasmic-antineutrophil cytoplasmic antibody, perinuclear-antineutrophil cytoplasmic antibody, myeloperoxidase antibody, rheumatoid factor, and total immunoglobulin E. Skin biopsies were consistent with eosinophilic granulomatosis with polyangiitis. Steroids, cyclophosphamide, and mepolizumab were initiated. At 1 year, the patient's systemic symptoms had improved but his vision had not. Conclusions: Few reports exist of CRAO associated with eosinophilic granulomatosis with polyangiitis, with no other instances related to an adenovirus vector COVID-19 vaccination. Treating a systemic vasculitis early can be vision saving in the fellow eye and prevent systemic life-threatening complications.

Novel insights: crosstalk with non-puerperal mastitis and immunity.

The two primary types of non-puerperal mastitis (NPM) are granulomatous lobular mastitis (GLM) and plasma cell mastitis (PCM). Existing research indicates that immune inflammatory response is considered to be the core of the pathogenesis of GLM and PCM, and both innate and adaptive immune responses play an important role in the pathophysiology of PCM and GLM. However, the regulatory balance between various immune cells in these diseases is still unclear. Consequently, we present a comprehensive summary of the immune-related variables and recent advances in GLM and PCM.

Causes of Oral Granulomatous Disorders: An Update and Narrative Review of the Literature.

Granulomatous diseases include a diverse range of chronic inflammatory disorders with a wide variety of pathologies and clinical characteristics. In particular, the orofacial region can be affected by granulomatous conditions-whether as an isolated disease or as part of a systemic disorder. Regardless of the nature of the disease or its mechanism of development, precise diagnosis can be challenging, as etiopathogenesis may be driven by several causes. These include reactions to foreign bodies, infections, immune dysregulation, proliferative disorders,, medications, illicit drugs, and hereditary disorders. Granulomas can be identified using histopathological assessment but are not pathognomonic of a specific disease, and therefore require correlation between clinical, serological, radiographical, and histopathological findings. The purpose of this review is to provide a summary of the etiopathogenesis, clinical and histopathologic characteristics, and treatment of oral granulomatous disorders.

Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era.

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, underpinning current methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.

Role of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and Gene Xpert.

BACKGROUND: Mediastinal tubercular lymphadenitis is form of extrapulmonary tuberculosis [EPTB]. Clinical presentations are non-specific and diagnosis remains great clinical challenge. Microbiological and or histopathological evidences need to be present in order make diagnosis secure before initiation of anti-tubercular therapy (ATT). Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) provides tissue samples and aids management of this difficult to diagnosed entity. Current study describe role of EUS-FNA and Gene Xpert (GXP) in mediastinal tubercular lymphadenitis. METHODS: Retrospective analysis of 72 patients with mediastinal lymphadenopathy who underwent EUS-FNA were carried out. Linear echoendoscope was used for evaluation mediastinum. EUS echo features of LNs were studied. Twenty two-G needle used was for aspiration tissue sample from pathologic lymph nodes (LNs). FNA samples were analysed by cytology, Acid-Fast Bacilli (AFB) staining and GXP study. All procedures were uneventful without any complications. RESULTS: Forty two patients were diagnosed as tuberculosis (TB) following first EUS-FNA setting. Six patients underwent repeat EUS-FNA procedure following which another 3 were diagnosed as TB while remaining 3 started on empirical ATT based on additional supportive evidences. Forty five patients showed granulomatous inflammation on cytological analysis, AFB positivity noted in 16 (33.33%) patients while GXP in 26 (57.78%) patients. Rifampicin resistance detected in 3 ((6.25%) patients. All patients were followed clinico-radiologically for response to treatment. CONCLUSION: Tuberculous lymphadenitis is the most common cause of mediastinal lymphadenopathy in TB endemic countries. EUS-FNA provides microbiological and histopathological/cytological evidences in this difficult to diagnosed EPTB and thereby avoids empirical ATT.

Radiological response of non-specific granulomatous mastitis to anti-tuberculous treatment: A single centre study in an endemic nation.

BACKGROUND: Tuberculous mastitis (TBM), is an uncommon form of extra-pulmonary tuberculosis. Clinical and radiological overlap of tuberculous mastitis with malignancy and other granulomatous conditions, along with its paucibacillary nature, make it a diagnostic challenge. In our study, we aim to assess the radiological response of microbiologically negative granulomatous mastitis cases to anti-tuberculous treatment (ATT) in an endemic country. METHODS: Eighty-seven cases demonstrating granulomatous lesions on breast biopsy were identified. Of these, 49 patients who were treated with ATT and had at least two serial ultrasound follow-ups were included in our study. Mammogram and ultrasound were used for initial imaging. Subsequently, ultrasound was used for serial follow-up. Mantoux skin test, acid fast staining and histological examination of tissue sample were the other investigations used. RESULTS: Radiologically, on ultrasound, well-circumscribed hypoechoic masses were noted in 18 patients, followed by ill-defined collections with tubular extensions in 15 cases, abscesses in 8, and a focal heterogeneity in 8 patients. Following ATT, 17 patients showed radiological resolution in 4 weeks, 18 of them at 3 months, and nine of them in 6 months. CONCLUSION: Excellent and prompt radiological response to ATT, indicates the need for a high degree of suspicion for tuberculous mastitis (TBM), in endemic countries, even though microbiological tests may turn out negative.

Periocular granulomatous inflammatory lesions mimicking conjunctival melanoma recurrence in the setting of systemic nivolumab treatment.

Purpose: Conjunctival melanoma is a rare neoplasm with high rates of recurrence and metastasis. Traditional management includes surgical excision and cryotherapy, followed by adjuvant therapy as needed. Immune checkpoint inhibitors, including nivolumab, are a targeted treatment option with improved survival rates. However, various immune-related adverse effects have been reported with these drugs. While systemic granulomatous inflammation is a documented systemic side effect, it has rarely been reported in the conjunctiva and ocular adnexa. Observation: A patient with a history of recurrent metastatic conjunctival melanoma presented with both a left sub-conjunctival and upper eyelid lesion after the commencement of treatment with nivolumab. The lesions were excised with a clinical suspicion for metastasis and consisted of noncaseating granulomatous inflammation with no evidence of malignancy on histopathologic examination. Infectious and primary autoimmune etiologies were ruled out. Conclusion and importance: This is a biopsy-proven case of periocular immune checkpoint inhibitor-associated granulomatous inflammation.