Long-standing laryngeal rhinoscleroma with rare Mikulicz cells.

Rationale: The Sarcoidosis Diagnostic Score (SDS) has been established to quantitate the clinical features consistent with sarcoidosis in a monocentric study. Objectives: We aimed to confirm the diagnostic value of SDS in a large, multicontinental study and to assess the utility of SDS in differentiating sarcoidosis from alternative diagnoses, including infectious and noninfectious granulomatous diseases. Methods: We included patients with biopsy-confirmed sarcoidosis at nine centers across the world. Patients without sarcoidosis seen at the same sites served as control patients. Using a modified World Association of Sarcoidosis and Other Granulomatous Disorders organ assessment instrument, we scored all patients for the presence of granuloma on biopsy, highly probable symptoms, and least probable symptoms for each area. Two sarcoidosis scores were generated: SDS Biopsy (with biopsy) and SDS Clinical (without biopsy). SDS Clinical and Biopsy were calculated for all patients. We calculated and compared the area under the curve (AUC) for SDS Clinical and Biopsy according to different diagnosis scenarios. Results: A total of 1,041 patients with sarcoidosis and 1,035 without sarcoidosis were included. The results for SDS Clinical (AUC, 0.888; 95% confidence interval [CI], 0.874-0.902) and SDS Biopsy (AUC, 0.979; 95% CI, 0.973-0.985) according to AUC were good to excellent for differentiating sarcoidosis from alternative diagnosis. SDS Clinical was less discriminatory in males (P = 0.01) and in high tuberculosis prevalence centers (P < 0.001). However, SDS Clinical (AUC, 0.684; 95% CI, 0.602-0.766) and SDS Biopsy (AUC, 0.754; 95% CI, 0.673-0.835) were not sufficiently discriminative for noninfectious granulomatous diseases, but both SDSs could differentiate sarcoidosis from infectious granulomatous diseases. Algorithms were proposed for the SDS Clinical and SDS Biopsy to assist the clinician in the diagnostic process, and cutoff values were proposed for the SDS Clinical and SDS Biopsy, allowing the diagnosis of sarcoidosis to be safely confirmed or rejected in most cases except for noninfectious granulomatous disease. Conclusions: This multicontinental study confirms that both SDS Clinical and SDS Biopsy have good to excellent performance in discriminating sarcoidosis from alternative diagnoses. Differences in the AUC were seen for high tuberculosis prevalence versus low tuberculosis prevalence centers and for males versus females. Both SDSs had good discriminatory function for infectious granulomatous disease but failed in cases of noninfectious granulomatous disease such as berylliosis.

Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzyme-linked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor-α) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1β was expressed in greatest (10–100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P=0.05, r=0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P=0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P=0.05 and P=0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1β overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients.

Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue.

Spontaneous early exposure is a complication that could account for significant interference during the early healing phase of dental implants. Spontaneous perforations of the mucosa covering implants have been classified according to the degree of implant exposure from 0 (no perforation) to IV (complete exposure). In this study, the characteristics of the epithelium and connective tissue of clinically non-perforated mucosa over submerged implants are histologically and histomorphometrically evaluated. Ten randomly selected tissue disks of intact (Class [Cl]-0) mucosa covering submerged implants were removed using a biopsy punch. Identical mucosal punch specimens were obtained from edentulous sites treated by non-submerged (1-stage) implants for use as controls. Specimens were histopathologically examined. The epithelial width and inflammatory infiltrate adjacent to the epithelium were histomorphometrically measured and the data statistically analyzed. Non-perforated mucosa covering the submerged implants (Cl-0) was characterized by an inflammatory fibro-epithelial hyperplasia. In 70% of Cl-0 hematoxylin and eosin-stained sections, there was mineralized material in the connective tissue, mostly sequestra. The epithelial width was 1.5 times higher (0.553 +/- 0.187 mm) when compared to controls (0.345 +/- 0.129 mm; P <0.0001). Concomitantly, the chronic inflammatory infiltrate was almost double in Cl-0 specimens (1,411 +/- 617 cell/mm2) when compared to controls (833 +/- 275 cells/mm2; P<0.001). A positive correlation between the linear combination of the epithelial width and the linear combination of the inflammatory cell concentration was found in both groups: Cl-0: r = 0.669, P= 0.0001; control: r = 0.541, P= 0.005. Different factors may result in the formation of spontaneous early perforation, most of which are associated with mechanical trauma to the mucosa or tension in the tissue flaps covering the implants. Bone debris produced during the osteotomy could act as an additional predisposing factor; these are sequestrated and accompanied by chronic inflammatory cell infiltration as well as epithelial-covering reaction. Since this study focused only on specimens from intact mucosa, until further investigation of this phenomenon in spontaneously perforated sites is conducted, no conclusions on the role of these histopathological findings can be made.

Chronic inflammatory infiltrate (CII) might be involved in prostate cancer (PCA) and benign hyperplasia (BPH); however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years) and PSA (ug/l); moreover, CII+, glandular atrophy (GA+), glandular hyperplasia (GH+), prostate Intraepithelial neoplasm (PIN+), atypical small acinar cell proliferation (ASAP+) and PCA positive cores (P+) were evaluated as categorical and continuous (proportion of positive cores). Associations of CII+ and PCA risk were assessed by statistical methods. In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8) resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P &lt; 0.0001; OR = 0.26) and HGPCA (P = 0.0005; OR = 0.05). Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in PCA carcinogenesis remains controversial and needs further research.

Pythiosis is a granulomatous infectious disease caused by the oomycete Pythium insidiosum. In Brazil, there are a considerable number of studies on that disease in dogs mainly from the state of Rio Grande do Sul. Given the unfamiliarity of the affectation in dogs from other locations, such as the Northeast, its description in native animals from federal units of this latter region becomes essential. In this sense, this study aimed to register the first case of canine pythiosis found in the city of Mossoró, Rio Grande do Norte (RN), Brazil. A two-year-old mixed breed female dog was referred to the Veterinary Hospital of the Rural Federal University of the Semi-Arid (Mossoró, RN, Brazil). Physical examination showed swelling in the anal mucocutaneous junction. During rectal palpation, lumen stenosis was detected. Laboratory screening tests were requested, but due to nonspecific results, performing incisional biopsy of the anal lesion was decided. Fragments were sent for histopathological analysis, being used special histochemical staining. Accordingly, a case of pythiosis was found. Pharmacotherapy was applied with itraconazole and terbinafine hydrochloride prescription. After three months and twelve days of treatment, complete remission of the lesions occurred. One should consider pythiosis in native dogs from the city of Mossoró, RN. Adoption of diagnosis appropriate methods is essential for early disease identification, with a positive impact on therapeutic decisions.

Recent technologic advances have significantly enhanced the role of imaging in the detection, characterization, and management of infectious diseases involving the liver. In addition, imaging-guided percutaneous drainage has greatly improved the clinical treatment of patients with focal liver abscess. Infectious liver diseases can be accurately evaluated with ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging. Characteristic changes in US echogenicity, CT attenuation, or MR imaging signal intensity and typical enhancement patterns can contribute to the diagnosis of specific infectious diseases, including abscesses, parasitic diseases, fungal diseases, granulomatous diseases, viral hepatitis, and other less common infections. CT is particularly helpful in revealing the presence of calcifications and gas and in detailing the enhancement pattern. The multiplanar capability of MR imaging and its sensitivity to small differences in tissue composition increase its specificity for certain hepatic infections, including hydatid cyst and candidiasis. Radiologic findings may be sufficient to obviate aspiration or histologic examination, although in most instances they are less specific. Nevertheless, imaging findings taken together with appropriate clinical information may provide the most likely diagnosis, even if biopsy is sometimes required for confirmation.

This is a comprehensive overview of current trends in the prevalence, clinical presentation, diagnostic challenges and management of granulomatous disorders involving the nose and paranasal sinuses in low- and middle-income countries. Emphasis is placed on infective aetiologies contributing to granulomatous diseases and the emerging innovations in the diagnosis and management of these conditions. Granulomatous inflammations represent a distinctive spectrum of conditions arising from infectious, autoimmune, neoplastic, and chemical exposures. The prevalence of these disorders varies globally, with infectious aetiologies being more common in subtropical regions and autoimmune inflammatory conditions predominating in Western countries. Notably, the global burden of certain infectious granulomatous diseases is declining due to improved awareness, socio-economic conditions, and enhanced access to healthcare.However, the incidence of invasive fungal mucormycosis has risen sharply following the COVID-19 pandemic, particularly in the Indian subcontinent. Contributing factors include diabetes mellitus, excessive use of high-dose corticosteroids, and environmental influences. Early diagnosis, along with aggressive surgical debridement and antifungal therapy, remains critical for successful management. Otolaryngologists must be aware of granulomatous conditions affecting the nose and paranasal sinuses, given their potential to cause significant morbidity if left untreated. Timely diagnosis relies on clinical suspicion supported by blood tests, imaging, and histopathology for effective intervention.

Coronary Ostial Stenosis in a Young Patient

BackgroundCutaneous leishmaniasis is distributed worldwide, including Brazil. Its several clinical forms need to be distinguished from other dermatoses. Clinical similarities and lack of a gold standard diagnostic tool make leishmaniasis-like lesions a challenging diagnosis.Objectives.To report the final diagnosis of patients primarily suspected of having American tegumentary leishmaniasis (ATL).Methods.A retrospective cross-sectional study was conducted on the basis of medical records of 437 patients with clinical suspicion of ATL, registered in electronic hospital system between 1980 and 2013. Demographic, clinical, and laboratory data were compiled.Results.Analysis of 86 cases (19.7%) registered as ATL in one of the hypothesis revealed a different final diagnosis; 55 (63.9%) and 31 cases (36.1%) had skin and mucosal lesions, respectively. In 58 cases (67.4%), the requested PCR did not identify Leishmania sp. In 28 cases (32.5%), biopsies established the diagnosis and confirmed tumors, mycobacteriosis, and subcutaneous or systemic mycosis. Overall, 27% of the cases had inflammatory etiology, mainly nasal nonspecific inflammatory processes; 27% had infectious etiology, especially paracoccidioidomycosis and leprosy; 20% had neoplastic etiology, mainly basal and squamous cell carcinoma; 15% had miscellaneous etiology, including neuropathic ulcer, traumatic ulcers, idiopathic ulcer; 11% missed the follow-up.Study limitationsSome cases had no final diagnosis due to loss of follow-up.Conclusion.ATL can be confused with several differential diagnoses, especially inflammatory and infectious granulomatous diseases as well as non-melanoma skin cancers. Clinicians working in tropical areas should be aware of the main differential diagnosis of leishmaniasis-like lesions.

Dear Editor, Clofazimine is a weakly basic antibiotic licensed by the Food and Drug Administration to treat leprosy and multidrug-resistant tuberculosis. After a long course of treatment, clofazimine precipitates and bioaccumulates widely throughout the body to create crystal-like drug inclusions. The most prevalent side effect of clofazimine is thought to be skin pigmentation, which is thought to be caused by the drug’s red hue [1]. A 52-year-old female diagnosed with borderline lepromatous Hansen’s disease presented with brownish hyperpigmentation on the face (Fig. 1a) and forearm (Fig. 2a) for 2 months. She was started on multibacillary multidrug therapy of oral rifampicin, clofazimine, and dapsone 8 months ago. After obtaining the patient’s consent, histopathology from the affected patch on the forearm was done, which revealed perivascular lymphohistiocytic infiltration and fine and coarse brown granular pigment within macrophages (Fig. 3). Dermoscopic examination of the face (Fig. 1b) revealed perifollicular hypopigmentation with an orange hue, as well as an accentuation of the pseudoreticular pattern. The forearm (Fig. 2b) showed skin furrow sparing with accentuation of reticular brown pigment, diffuse homogeneous background brown pigmentation, an orange hue, and a honeycomb pattern. The patient was diagnosed with clofazimine-induced hyperpigmentation.Figure 1: (a) Hyperpigmentation on the face. (b) Dermoscopy of the face (Dermlite, DL5, ×10, polarized mode) demonstrates perifollicular hypopigmentation with an orange hue and accentuation of the pseudoreticular pattern.Figure 2: (a) Hyperpigmentation on the forearm. (b) Dermoscopy of the forearm (Dermlite, DL5, ×10, polarized mode) demonstrates skin furrow sparing with accentuation of reticular brown pigment, diffuse homogeneous background brown pigmentation, an orange hue, and a honeycomb pattern.Figure 3: Histopathology shows perivascular lymphohistiocytic infiltration and fine and coarse brown granular pigment within macrophages (H and E, ×40).Leprosy is an infectious granulomatous disease which, on dermoscopy, reveals the presence of structureless orange to yellowish patches that can be dispersed in a diffuse or localized pattern. The drug clofazimine is a lipophilic phenazine antibiotic that is weakly basic and frequently induces reddish-pink discoloration of the skin [2]. The features of dermoscopic examination of clofazimine-induced hyperpigmentation show a honeycomb pattern with yellowish-white globules interspersed along a black background [3]. Differential diagnosis includes other granulomatous conditions like cutaneous leishmaniasis, sarcoidosis, lupus vulgaris, and lichen planus pigmentosus [4]. Dermoscopy of the lesions allows us to distinguish between drug-induced hyperpigmentation and lepra reactions and facilitates assessment of patient compliance with treatment. Acknowledgements Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Introduction: The testes are immune privileged organs but they are subjected to acute and chronic inflammations that can impair spermatogenesis. Spermatogonial stem cells are less sensitive to injury, capable of self-renewal, and act as a reservoir that can restart impaired spermatogenesis. Objective: To study the association of chronic testicular inflammatory infiltration with an area of complete spermatogenesis in testicular biopsies of men with non-obstructive azoospermia (NOA). Design: Retrospective study. Patients and methods: Review of 109 archived Bouin fixed, paraffin embedded and hematoxylin and eosin stained open testicular biopsies of azoospermic men. Main outcome measure: The absence/presence (focal/widespread) of chronic interstitial inflammatory infiltration and absence/presence of late spermatids. Results: Obstructive picture was found in 25 (22.9%) whereas non-obstructive patterns were found in 84 (77.1%) of the reviewed biopsies. Focal interstitial lymphocytic infiltration (ILI) was found in 9 (36%) obstructive biopsies whereas in non-obstructive patterns 32 (38.1%) had focal and 27 (32.1%) had wide spread ILI. In NOA late spermatids were present in 32 (38.1%) biopsies. Finding late spermatids was significantly highest when the infiltrate was focal and significantly lowest when the infiltrate was wide spread. Conclusion: In NOA, the possibility of finding an area of complete focal spermatogenesis in the open testicular biopsy is significantly highest when there is a focal type of ILI, but the possibility is significantly lowest when the infiltrate is widespread. This may guide the clinical testicular sperm extraction (TESE) procedure.

_DEAR EDITOR,_ Eumycetoma is a chronic, granulomatous infectious disease which is characterized by the formation of large subcutaneous masses and the production of grains. The most common causative agent is the fungus Madurella mycetomatis. Treatment for eumycetoma is disappointing. It needs a combination of antifungal therapy and surgery. The current antifungal agent used for treating eumycetoma is itraconazole (ITZ), because in 2013 the use of ketoconazole was restricted. Unfortunately with this treatment recurrent infections are common and for many patients amputation is unavoidable. Therefore more potent drugs and model systems for mycetoma to predict treatment efficacy are urgently needed. Here we used a previously developed eumycetoma mouse model to determine if there is a correlation between the in vitro activity and the in vivo efficacy of ITZ and amphotericin B (AMB), representing two different classes of antifungal agents to which M. mycetomatis is susceptible. [...]

Activity of lysozyme and adenosine deaminase in patients with pulmonary tuberculosis

Tuberculosis is a chronic, granulomatous infectious disease caused by Mycobacterium tuberculosis. Multidrug resistance is a chronic problem associated with treatment of tuberculosis where a substantial proportion of tuberculosis cases reported in India are multi-drug resistant. Poor patient compliance plays a major role in development of resistance. The main objective of the study was to monitor the events associated with ATT in pulmonary and extrapulmonary tuberculosis patients and to achieve better patient outcomes by regular monitoring. This was a prospective observational study which analysed patients diagnosed with pulmonary and extra-pulmonary kochs’, attending inpatient and out-patient departments as well as registered under the RNTCP at Dr. B.R Ambedkar Medical College and Hospital for a period of 1 year for any events associated with ATT. Routine investigations which are carried out by the patient at the treatment initiation and whenever required were monitored. A total of 175 patients were monitored in the study out of which majority were males. Most patients were category 1 patients. More than one-third of the patient population reported an adverse event. Most ADRs were related to the GI system, followed by Skin Allergy. Most of the events (72%) were patient reported during physician visit while 26% were reported on investigation. The study found that ADRs has led to medication incompliance which leads them to discontinue the medication for a short duration. Close monitoring of these events from the treatment initiation should be emphasized to prevent medication in adherence. It is suggested that the establishment of pharmacovigilance programs in DOTS centres is essential.