Search Results (30)

A 27-year-old male presented with chronic diarrhea, bloating, and abdominal pain since age 13. Initially attributed to lactose intolerance, treated with dairy-free diet, symptoms persisted despite negative workup—normal celiac serology, stool studies, and abdominal ultrasound. Recent symptoms included severe diarrhea, fatigue, weakness, 8 kg weight loss, hair loss, elevated IgE and fecal calprotectin. Gastroscopy showed flattened, granular gastric mucosa with focal hyperemia in the antrum and greater curvature. Histology revealed severe chronic inactive H. pylori-negative gastritis with a prominent subepithelial collagen band (verified by Crossmon’s trichrome), confirming collagenous gastritis—a rare entity first described in 1989. The condition has a slight female predominance and bimodal age peaks (adolescence and >60 years). Symptoms are nonspecific, including abdominal pain, diarrhea, weight loss and anemia. Pediatric cases often feature nodular mucosa and anemia; adults more commonly present with watery diarrhea, sometimes linked to collagenous colitis. Diagnosis requires histological features including patchy subepithelial collagen band ≥ 10 μm thick, lymphocytic or eosinophilic infiltration of the lamina propria, epithelial changes and entrapped capillaries. Patterns include atrophic, lymphocytic-like, and eosinophil-rich. Crossmon’s or Masson’s trichrome, Congo red, and tenascin immunohistochemistry aid in proving collagen and excluding amyloidosis. Treatment is mainly symptomatic or with proton pump inhibitors; corticosteroids may be effective in refractory cases. Full article

Extrahepatic cholangiocarcinoma (eCCA) is a highly aggressive malignancy arising from the biliary epithelium, with surgical resection representing the only potentially curative treatment. The predominant periductal infiltrating growth pattern, characterized by subepithelial tumor spread and desmoplastic stromal reaction, severely limits the diagnostic sensitivity of conventional endoscopic sampling techniques, which primarily assess the luminal mucosal surface. This review provides a histomorphology-oriented diagnostic framework for indeterminate extrahepatic biliary strictures, integrating advanced endoscopic technologies with emerging optical diagnostic approaches. ERCP combined with cholangioscopy demonstrates superior sensitivity for perihilar strictures, while EUS-guided tissue acquisition shows higher diagnostic yield in distal cholangiocarcinoma, also providing locoregional staging. Advanced EUS technologies—including elastography, contrast harmonic EUS, and Detective Flow Imaging—further improve characterization of indeterminate strictures by evaluating tissue stiffness, microvascular architecture, and periductal infiltration. Ex vivo fluorescence confocal laser microscopy (FCM) enables real-time microscopic evaluation of biopsy specimens, reducing diagnostic turnaround time and minimizing inadequate sampling. A location-adapted diagnostic algorithm integrating cross-sectional imaging, ERCP, cholangioscopy, and EUS is proposed. An integrated, biology-informed endoscopic approach tailored to tumor location and ductal wall involvement may significantly improve early eCCA detection and guide patient selection for curative treatment. Full article

Autoantibodies targeting α6β4 integrin have been identified in individual patients with mucous membrane pemphigoid (MMP). Reactivity against α6 integrin has been associated with oral lesions, while anti-β4 integrin reactivity has been linked to ocular involvement. However, the pathogenic effects of these antibodies have not been fully elucidated. Here, we investigated the pathogenic potential of anti-α6 and anti-β4 integrin IgG both in vitro and in vivo. Immune complexes of anti-α6 and anti-β4 integrin induced the release of reactive oxygen species from normal human leukocytes and stimulated CXCL2 secretion in cultured murine C5N keratinocytes. In vivo, repeated injections of IgG against a recombinant fragment of β4 integrin into C57BL/6 mice led to palpebral conjunctival swelling and mild oral lesions. The latter was observed following injection of IgG against a recombinant fragment of α6 integrin. Histopathological analysis revealed subepithelial inflammatory infiltrates without evidence of split formation. Direct immunofluorescence microscopy showed linear deposits of IgG at the basement membrane zone in most tissues, whereas C3 deposition was largely absent. This lack of complement activation was corroborated by a complement fixation assay, which confirmed that IgG against α6 and β4 integrin failed to induce C3 deposition in normal murine conjunctivae, buccal mucosa, or skin. Collectively, these findings indicate that IgG autoantibodies against α6 and β4 integrin exhibit pathogenic activity in vitro and induce mild disease in vivo, possibly due in part to relatively inefficient complement activation in this model. Full article

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 antibodies, have significantly improved outcomes in a variety of solid tumors, including urothelial carcinoma. However, their use is frequently associated with immune-related adverse events (irAEs) which frequently affect the skin and mucous membranes. Among these, plasma-cell-rich infiltrates are exceptionally rare. Circumorificial plasmacytosis (COP) is a rare, predominantly reactive condition typically involving mucosal transition zones, with histologic features characterized by dense, polyclonal plasma cell infiltrates and a benign clinical course. Only two case reports have described COP in association with ICI therapy and, to date, transformation or overlap with lymphoproliferative disorders such as marginal zone lymphoma has not been documented. We report the case of an 86-year-old male with urothelial carcinoma who developed a progressive, ulcerated, bleeding lesion of the lower lip during adjuvant nivolumab therapy. Histologic examination revealed a dense subepithelial infiltrate of mature plasma cells and lymphocytes. Direct and indirect immunofluorescence studies were negative, excluding autoimmune blistering disorders. Immunohistochemistry showed a predominance of CD138-positive plasma cells with a moderate kappa light-chain shift, CD19 expression, and absence of CD56, Cyclin-D1, and CD117, arguing against a plasma cell neoplasm. Molecular analysis via multiplex PCR revealed a clonal B-cell population with distinct IgH rearrangements, and some EBV-positive cells were also identified by EBER in situ hybridization. The histopathologic and molecular findings suggested a marginal zone lymphoma-like, plasmacytic proliferation arising in the setting of COP. This case illustrates a rare and diagnostically challenging constellation at the intersection of reactive and clonal B-cell proliferations in the context of ICI therapy. Although the lesion demonstrated features of clonality, the overall low B-cell content, indolent clinical course, and lack of systemic involvement support a reactive, immunodeficiency-associated lymphoproliferation rather than overt lymphoma. This case expands the known spectrum of mucocutaneous irAEs and highlights the need for careful clinicopathologic correlation, including immunophenotyping and molecular diagnostics. Awareness of such rare presentations is essential to avoid overdiagnosis and unnecessary systemic treatment in patients with otherwise indolent lesions. Full article

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus that is associated with long-term morbidity and mortality. Pathomorphological findings of LN are broadly divided into proliferative lupus nephritis (PLN) and membranous lupus nephritis (MLN). PLN is characterized by diffuse global or segmental proliferative glomerulonephritis with significant infiltration of inflammatory cells. Type 1 T-helper (Th1) cells, which predominate under inflammatory conditions, and NETosis, as the process of forming neutrophil extracellular traps (NETs), are key factors in the development of PLN. Meanwhile, MLN is characterized by diffuse membranous nephropathy (MN) with global granular subepithelial immune deposits. MLN patients usually experience massive proteinuria, and occasionally show an unfavorable renal prognosis despite aggressive treatment, similar to PLN patients. Intriguingly, in some instances, MLN patients do not show the general immunoserological characteristics of SLE, such as low serum complement and elevated anti-DNA antibody titers. Several reports have indicated an association between Th2 cell dominance and the development of MLN. Moreover, exostosin 1 (EXT1) and exostosin 2 (EXT2) on the glomerular basement membrane have recently been discovered as novel putative antigens for secondary MN, and have been shown to be up-regulated in patients with MLN. To date, many studies have focused on the dissimilarities between PLN and MLN. However, the reason for two polar morphological forms existing within the same disease is not completely clear. The present review addresses published observations on this topic in addition to providing our assertion regarding characteristic NETosis and glomerular EXT1/EXT2 expressions between PLN and MLN. Full article

Background/Objectives: Plasma cell gingivitis (PCG) is a rare, benign, non-dental-plaque-induced inflammatory condition characterized by dense subepithelial infiltration of polyclonal plasma cells. Due to its nonspecific clinical presentation, PCG represents a diagnostic challenge. This case report aims to describe a clinical case of PCG, highlighting the diagnostic process, histopathological correlation, and therapeutic approach. Methods: A 57-year-old male presented with a polypoid, erythematous, and edematous gingival lesion in the anterior maxillary region, with spontaneous bleeding on probing. Following clinic assessment, an incisional biopsy was performed, alongside complete hematological and inflammatory profiling. Histological and immunohistochemical analyses revealed the presence of an inflammatory infiltrate. Results: Histological evaluation revealed spongiotic squamous epithelium characterized by a dense plasma cell infiltrate with a liquenoid pattern of CD3-positive T and CD20-positive B lymphocytes. A polytypic expression of kappa and lambda light chains was also detected. The patient underwent topical corticosteroid therapy, showing progressive clinical improvement and resolution of symptoms, although minor mucosal involvement persisted. Conclusions: PCG remains a rare and underdiagnosed condition requiring integration of clinical, hematological, and histopathological data for accurate diagnosis. While corticosteroids remain the first-line therapy, emerging treatments, including photobiomodulation, may offer future adjunctive strategies to improve outcomes and reduce recurrence. Full article

Postpartum uterine involution in cattle involves complex morphological and immunological changes essential for restoring uterine health and fertility. This study evaluated endometrial biopsies collected at four postpartum time points to characterize tissue remodeling and immune cell dynamics during involution. Histology revealed intact luminal columnar epithelium in 92.98% of samples, with stable stromal architecture. Stromal edema decreased by Day 7 but increased again by Day 35, while endometrial gland numbers significantly rose at Day 35, suggesting glandular recovery linked to resumed cyclicity. Subepithelial collagen deposition peaked on Day 21, indicating active extracellular matrix remodeling. Immunologically, early postpartum was marked by increased PMNs and macrophages, whereas Day 21 showed peak infiltration of natural killer (NK) cells and T and B lymphocytes, sometimes forming lymphoid aggregates. Manual and automated immune cell quantifications correlated well. These findings demonstrate a dynamic shift from acute neutrophil-dominated inflammation to a lymphocyte-rich environment during uterine involution. This immune modulation may contribute to the earlier diagnosis of subclinical endometritis, typically identified at later stages of postpartum period. Overall, this study provides insight into the temporal immunomorphological events supporting uterine recovery, with potential implications for reproductive management in dairy cattle. Full article

Viral conjunctivitis is a highly contagious ocular condition that significantly impacts patient quality of life and healthcare resources. Despite its self-limiting nature, the condition remains a significant public health concern due to its high transmissibility, prolonged symptoms, and potential complications such as subepithelial infiltrates (SEIs). This review aimed to synthesize and evaluate current management strategies for adenoviral conjunctivitis and provide an evidence-based treatment framework. A systematic literature search of PubMed and the Cochrane Library was conducted, identifying 25 eligible studies published between 2009 and 2024 that focused on clinical interventions including supportive care, antiseptics, corticosteroids, antivirals, and immune modulators. The findings indicate that while supportive therapy and hygiene measures remain central to care, antiseptic agents, specifically povidone–iodine, and topical steroids offer additional benefit in reducing symptom duration and complications. Combination therapies integrating antiseptics, corticosteroids, and immunomodulators show promise for more severe cases, especially those complicated by SEIs. This review proposes an evidence-based comprehensive, multimodal approach management algorithm while highlighting the need for future research in antiviral development and diagnostic innovation to avoid mistreatment and unnecessary antibiotic use. Full article

Purpose: Epidemic keratoconjunctivitis (EKC) is a common viral ocular infection that can lead to persistent subepithelial infiltrates (SEIs), resulting in significant visual impairment and patient discomfort, necessitating effective treatment strategies beyond corticosteroid monotherapy. This study aims to evaluate the efficacy of topical tacrolimus (0.1%) ointment alone versus its combination with prednisolone (1%) drops to provide optimal therapeutic strategies for SEIs secondary to EKC. Methods: This retrospective observational study evaluates 102 eyes of ninety-five individuals. The patients were divided into two groups based on the treatment approach. The first group received tacrolimus ointment alone (n = 34), whereas the second group received a combination of prednisolone drops and tacrolimus ointment (n = 68). Best-corrected visual acuity (BCVA), the corneal subepithelial infiltrate score (CSIS), the subjective symptom score (SSS), and the Fantes corneal haze grading score (FCHGS) were evaluated before treatment and at 1, 3, 6, 9, 12, and 18 months post-treatment. Results: Both groups showed significant improvements in the BCVA, CSIS, SSS, and FCHGS values, with no significant difference between the groups at 18 months (p > 0.05). The combination therapy resulted in a significantly faster treatment response than tacrolimus alone (p < 0.05) in terms of CSIS, SSS, and FCHGS values. An increase in intraocular pressure (IOP) was observed in four patients in the combination treatment group after three months. Conclusions: Topical tacrolimus, both alone and in combination with topical prednisolone, was effective in treating subepithelial infiltrates secondary to EKC. Combination therapy may be applied early for faster recovery; however, close monitoring of IOP is necessary in individuals using topical prednisolone. Full article

Background/Objectives: Symptoms of pudendal nerve neuropathy may overlap with various symptoms of interstitial cystitis (IC). As documented, there is a well-established correlation between the genes involved in ATP metabolism, neuropathy, and IC. ATP-binding cassette (ABC) transporters genes, in fact, are vital for ATP signaling. This study aims to associate the ABCF2 gene with a suspected pudendal nerve neuropathy and IC. Methods: Histological analysis was conducted for diagnosing IC while the genetic variant was identified by whole exome sequencing (WES) Trio and confirmed through Sanger. Results: We report a patient with IC, confirmed by histological examination, presenting with a suspected bladder and pudendal nerve neuropathy, though not analytically confirmed. Histological analysis revealed urothelial detachment caused by a dense subepithelial lymphocytic infiltrate, predominantly composed of mast cells, which serve as key diagnostic markers for interstitial cystitis (IC). WES analysis identified the heterozygous genetic variant c.1253T>G p.Phe418Cys within ABCF2 gene, precisely in its functional domain which actively operates in the hydrolysis of ATP energizing various biological systems. As reported, this gene displays high expression patterns in bladder tissue. The variant, absent in the healthy brother, was inherited from the father which presents mosaicism. The in silico prediction analyses classified this variant as pathogenic, identifying potential alterations in the protein structure. Conclusions: Although the precise role of ABCF2 should be supported by further studies, we hypothesize that its disruption might impair ATP metabolism, likely altering the nociceptive response and leading to the patient’s neuropathy. Further analyses are imperative to validate this research, for laying the groundwork for a specific therapy targeting the genetic dysregulation involved in this condition. Full article

We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression. Full article

Background: Nasal polyps (NPs) represent the end-stage manifestation of chronic rhinosinusitis (CRS), a relatively common pathological condition encountered in all ages of life. Methodology: The aim of our study was to evaluate the histological features and inflammatory cellular components of NPs in a retrospective cohort (143 cases) of pediatric, adult and elderly populations in order to discuss the possible morphological age-related differences statistically documented. Results: In the pediatric group, the inflammatory infiltrate presented many eosinophils mixed with lymphocytes, while in the adult population, lymphocytes and plasma cells were mainly evident, frequently with a perivascular distribution or with the formation of subepithelial lymphoid nodules. In the elderly population, inflammation was less evident and was associated with cavernous-like angecthatic structures with thrombotic stratification. Nearly all morphological findings exhibited statistically significant values among differently aged subgroups. Conclusions: Our results support the presence of histological specificities of NPs at different ages of life, providing new insight into the etiopathogenesis of NPs. The future role of biological therapies, mainly in cases refractory to already available standard medical and surgical treatments, may be analyzed by a prospective study using a larger cohort with a long-term evaluation also in relation to a possible relapse. Full article

Vesicovaginal fistula is a cause of deterioration in the quality of life. It is a communication between the bladder and vagina resulting in the uncontrollable leakage of urine through the vagina. Recently, regenerative methods have been used more frequently, and platelet-rich plasma is one of these methods. The functional properties of platelet-rich plasma are based on the synthesis and secretion of multiple growth factors released after platelet activation. The aim of this study was to investigate how platelet-rich plasma influences the condition of the tissue and the healing ability of the urothelium, vaginal epithelium and tissues surrounding the fistulous canal. The study included eight patients who had undergone the Latzko procedure aimed at closing the vesicovaginal fistula. Samples were collected during primary surgery without platelet-rich plasma and after failed surgery, during a second attempt. The specimens were subjected to histological and immunohistochemical evaluation. The histology demonstrated that in platelet-rich plasma patients, greater vascularization and wider subepithelial mucosa layering was observed. Inflammatory infiltration in the subepithelial layer was increased in platelet-rich plasma patients. No localization differences in growth factor proteins were found in either group, but in platelet-rich plasma-patients, the reactions were stronger. It can be concluded that the use of platelet-rich plasma improves the morphological structure of the injected tissues. Full article

Lupus nephritis (LN) is one of the most severe complications in patients with systemic lupus erythematosus (SLE). Traditionally, LN is regarded as an immune complex (IC) deposition disease led by dsDNA–anti-dsDNA-complement interactions in the subendothelial and/or subepithelial basement membrane of glomeruli to cause inflammation. The activated complements in the IC act as chemoattractants to chemically attract both innate and adaptive immune cells to the kidney tissues, causing inflammatory reactions. However, recent investigations have unveiled that not only the infiltrating immune-related cells, but resident kidney cells, including glomerular mesangial cells, podocytes, macrophage-like cells, tubular epithelial cells and endothelial cells, may also actively participate in the inflammatory and immunological reactions in the kidney. Furthermore, the adaptive immune cells that are infiltrated are genetically restricted to autoimmune predilection. The autoantibodies commonly found in SLE, including anti-dsDNA, are cross-reacting with not only a broad spectrum of chromatin substances, but also extracellular matrix components, including α-actinin, annexin II, laminin, collagen III and IV, and heparan sulfate proteoglycan. Besides, the glycosylation on the Fab portion of IgG anti-dsDNA antibodies can also affect the pathogenic properties of the autoantibodies in that α-2,6-sialylation alleviates, whereas fucosylation aggravates their nephritogenic activity. Some of the coexisting autoantibodies, including anti-cardiolipin, anti-C1q, anti-ribosomal P autoantibodies, may also enhance the pathogenic role of anti-dsDNA antibodies. In clinical practice, the identification of useful biomarkers for diagnosing, monitoring, and following up on LN is quite important for its treatments. The development of a more specific therapeutic strategy to target the pathogenic factors of LN is also critical. We will discuss these issues in detail in the present article. Full article

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma. Full article