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Sarcoidosis is an immune-mediated inflammatory disorder with unknown aetiology that is marked by non-caseating granulomas in affected organs. Pulmonary sarcoidosis is the most common manifestation, but gastrointestinal involvement, particularly in the small bowel, is exceedingly rare. While symptom-driven treatment guidelines that are steroid based are well established for pulmonary and few extrapulmonary manifestations (ie, cardiac, neurologic, renal), gastrointestinal sarcoidosis treatment is largely extrapolation with optimal management under investigation. Additionally, few works document small bowel obstruction related to small bowel sarcoidosis. We present a case of short-interval recurrent small bowel obstruction in a man in his sixties that revealed newly diagnosed sarcoidosis with suspected small bowel involvement who never underwent steroid therapy. The patient exhibited gastrointestinal symptoms, despite asymptomatic pulmonary disease and a course of prednisone may have reduced his risk of recurrence. We also review suggested gastrointestinal sarcoidosis treatment and surveillance guidelines with focus on the small bowel.

While gastrointestinal (GI) tuberculosis (TB) accounts for 1%–3% of all TB cases worldwide, TB of the stomach is extremely rare and accounts for 1%–2% of all GI TB. Little is known about this entity, and most data are obtained from case reports. We report a case of a woman in her 60s who presented with a 2-week history of generalised weakness, fatigue and shivering, with severe loss of appetite on background history of dyspepsia and significant weight loss for the preceding 2 years. Upper endoscopy revealed a large gastric ulcer. Biopsy and histopathology revealed caseating granulomas with numerous acid-fast bacilli detected with Ziehl-Neelsen stain. She was diagnosed with gastric TB. Subsequently, she was also diagnosed with pulmonary, adrenal and colonic involvement.

Xanthogranulomatous salpingo-oophoritis (XGSO) is an exceptionally rare entity. Its clinical manifestations and imaging modalities can mimic benign and malignant adnexal diseases, making it difficult to diagnose. Here we report a case of XGSO in a young woman who was operated with suspicion of a borderline ovarian tumour. Preoperative diagnosis of XGSO should be considered to avoid radical surgical treatment, especially in young patients.

We present a unique case of biopsy-proven necrotising sarcoidosis involving the central nervous system in a man in his 40s. The patient presented with a 2-week history of right-sided headache and diplopia. He had right trochlear and abducens nerve palsy, sensory blunting over V1 and V2 segment of right trigeminal sensory nerve and right sensory neural hearing loss. A contrast-enhanced MRI revealed an enhancing dural-based mass lesion in the petroclival area suggestive of probable meningioma. Surgical resection was attempted and intraoperative consultation with frozen section revealed granulomata. So, the lesion was biopsied and surgical intervention was terminated. A diagnosis of necrotising neurosarcoidosis was confirmed on histopathology. He was treated with steroids after excluding other causes of intracranial necrotising granulomas like tuberculosis and he clinically responded favourably. We report one of the very few case reports of histologically proven necrotising sarcoidosis involving the central nervous system mimicking petroclival meningioma.

Tuberculosis (TB) is one of the greatest masqueraders in medical practice and can have manifestations involving any organ or organ systems of the body. The presentation of disseminated TB can range from typical features like fever, weight loss and fatigue to protean manifestations. We share the case of an elderly man who presented to us with weight loss, anaemia, weakness and lymphadenopathy involving thoracic and intraabdominal locations. Work up of anaemia revealed features of Coombs-positive autoimmune haemolytic anaemia (AIHA) and evaluation of weakness showed laboratory results consistent with adrenal insufficiency. Biopsy of the abdominal lymphnode yielded caseating granulomas with CB-NAAT positivity forMycobacterium tuberculosis. Anti-TB chemotherapy with short-term replacement dose of systemic steroids corrected the haemolysis, anaemia and addisonian crisis. The case alerts clinicians regarding the uncommon association of TB with Coombs positive AIHA and adds one more aetiology to the pathogenesis of anaemia in TB. Furthermore, the occurrence of AIHA and hypoadrenalism in the same patient with TB is exceedingly rare and has not been reported.

Made available in DSpace on 2022-10-10T13:56:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-06-06. Added 1 bitstream(s) on 2022-10-10T15:39:51Z : No. of bitstreams: 1 S1519-69842024000100325.pdf: 683252 bytes, checksum: 60c423322185e736c29136f6cb27ce89 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) A infecção por micobactérias não tuberculosas é uma das doenças bacterianas crônicas mais comuns em peixes ornamentais de aquário e parece estar diretamente relacionada a práticas de manejo estressantes. Além disso, também representa potencial zoonótico. Aqui, apresentamos o isolamento e a caracterização de micobactérias não tuberculosas de peixes-anjo de água doce doentes (Pterophyllum scalare) em São Paulo, Brasil. Foram avaliadas nove fêmeas reprodutoras descartadas com sinais de doença. Os peixes exibiam letargia, perda de apetite, caquexia, úlceras cutâneas e exoftalmia. Na necropsia, quatro peixes apresentaram granulomas macroscópicos no baço. Mycobacterium chelonae, M. fortuitum, M. gordonae, M. intracellulare e M. peregrinum foram isolados e identificados por análise de restrição por PCR de hsp65. A análise histopatológica revelou lesões microscópicas compatíveis com micobacteriose, e o bacilo de Mycobacterium foi observado pela coloração de Ziehl-Neelsen. Notavelmente, todas as espécies de Mycobacterium identificadas neste estudo já foram relatadas em pacientes humanos; portanto, animais doentes podem ser uma fonte de infecção para pessoas que manipulam peixes e aquários. Nontuberculous mycobacteria infection is one of the most common chronic bacterial diseases in ornamental aquarium fish and appears to be directly related to stressful husbandry practices. Furthermore, it also represents zoonotic potential. Here we present the isolation and characterization of non-tuberculous mycobacteria from diseased freshwater angelfish (Pterophyllum scalare) in São Paulo, Brazil. Nine discarded breeding females with signs of disease were evaluated. The fish exhibited lethargy, loss of appetite, cachexia, skin ulcers, and exophthalmia. At necropsy, four fishes presented macroscopic granulomas in the spleen. Mycobacterium chelonae, M. fortuitum, M. gordonae, M. intracellulare and M. peregrinum were isolated and identified by hsp65 PCR restriction analysis. Histopathological analysis revealed microscopic lesions compatible with mycobacteriosis, and Mycobacterium bacillus were observed by Ziehl-Neelsen stain. Notably, all Mycobacterium species identified in this study have already been reported in human patients; therefore, diseased animals may be a source of infection for people who handle fish and aquariums. Universidade de São Paulo, Departamento de Medicina Veterinária Preventiva e Saúde Animal Universidade Estadual Paulista (UNESP), Instituto de Biotecnologia Universidade Estadual Paulista (UNESP), Instituto de Biotecnologia CAPES: 001 CAPES: 1808006 CNPq: 154900/2018-4 CNPq: 310736/2018-8

BACKGROUND The search for aesthetic non-surgical procedures is growing. The use of polymethylmethacrylate (PMMA) as a filling material in the nose represents one of the many options among these aesthetic procedures. Its use, however, can lead to complications. The treatment of these complications is often challenging. METHODS We performed a retrospective clinical analysis of the medical records of patients undergoing treatment of PMMA granulomas of the nose at a private clinic from January, 2015, to January, 2021. A short-pulsed neodymium-YAG (Nd:YAG) laser was applied intranasally or directly by cutaneous incision in the granulomas. Laser-tissue interaction heats the alloplastic material, fragments the product and creates cleavage paths, thereby facilitating the removal of PMMA, either by intercartilaginous removal or aspiration. RESULTS Twenty-seven patients were included in the study. All had a history of PMMA injection in the nose. All patients were treated with an intralesional pulsed 1064nm Nd:YAG laser. The material removed after laser-tissue interaction was sent for histopathological examination; this showed the presence of microparticles of exogenous material compatible with PMMA. The partial removal of the alloplastic material was shown to be effective in all cases. One patient developed a small blister in the nasal dorsum. Follow-up ranged from six to 47 months. CONCLUSIONS The use of intralesional Nd:YAG laser for the treatment of PMMA granulomas on the nose proved to be an effective and safe procedure with improvement of nasal shape, without compromising respiratory function. This technical option represents yet another alternative in the treatment of PMMA granuloma complications. J Drugs Dermatol. 2021;20(11): 1161-1166. doi:10.36849/JDD.6550.

A patient in California, USA, with rare and usually fatal Balamuthia mandrillaris granulomatous amebic encephalitis survived after receiving treatment with a regimen that included the repurposed drug nitroxoline. Nitroxoline, which is a quinolone typically used to treat urinary tract infections, was identified in a screen for drugs with amebicidal activity against Balamuthia.

We present the pathology of monkeys naturally infected with Mycobacterium tuberculosis complex from five different colonies in Rio de Janeiro, Brazil. On the basis of gross and histopathological findings, the lesions were classified into chronic-active, extrapulmonary, early-activation or latent-reactivation stages. Typical granulomatous pneumonia was seen in 46.6% of cases (six rhesus monkeys [Macaca mulatta] and one Uta Hick's bearded saki [Chiropotes utahickae]). The absence of pulmonary granulomas did not preclude a diagnosis of tuberculosis (TB): classical granulomatous pneumonia was observed in the chronic-active and latent-reactivation stages but not in the extrapulmonary and early-activation stages. The early-activation stage was characterized by interstitial pneumonia with a predominance of foamy macrophages and molecular and immunohistochemical evidence of M. tuberculosis complex infection. TB should be considered as a cause of interstitial pneumonia in New World Monkeys. We recommend the use of immunohistochemistry and molecular analysis for diagnosis of TB, even when typical macroscopic or histological changes are not observed.

Inflammatory granulomas (neurocysticercosis [NCC] and tuberculomas) are important causes of seizures in children and adults in the developing world. Although several studies have explored seizure characteristics individually in patients with either NCC or tuberculoma, none has compared the seizure recurrence rate between them. This study included patients aged 5 to 18 years with viable parenchymal NCC or tuberculomas who had completed regular follow-up of at least 12 months at a tertiary institute in India. Their baseline seizure and electroencephalographic characteristics, antiseizure medications (ASMs), and breakthrough seizure rates at 12, 24, and 52 weeks were noted. A total of 103 and 54 patients with active NCC and tuberculomas respectively were included. The number of patients who had at least one breakthrough seizure at 12, 24, and 52 weeks in both groups was comparable (P = 0.32, 0.27, and 0.13), and the vast majority were controlled on monotherapy (98% cases in each group). The proportion of patients who required an increase in the dose or change of ASMs or polytherapy, the proportion of children who had status epilepticus at or before 12 months, abnormal electroencephalogram at 12 months, and calcified and active granuloma in neuroimaging at 12 months were also comparable between the two groups (P > 0.05 for all). The number of patients who had ASM-related adverse events and discontinued ASM due to serious adverse events was comparable between both groups, except for hepatotoxicity in the tuberculoma group. The predictors for breakthrough seizures that were found to be statistically significant in the NCC group were the presence of perilesional edema in the baseline magnetic resonance imaging (P = 0.02) and more than five active granulomas (P = 0.01); predictors in the tuberculoma group were the presence of severe perilesional edema causing midline shift in the baseline magnetic resonance imaging (P = 0.01) and more than five active granulomas (P = 0.04). The recurrence rates of breakthrough seizures over the next 12 months in newly detected cases of active NCC and tuberculomas were comparable.

Papulonecrotic tuberculid (PNT) is an uncommon form of id eruption, which occurs in association with tuberculosis infections in patients with a high degree of immunity and allergic sensitivity to mycobacterial organisms. It commonly presents as recurrent crops of papulonecrotic lesions that crust or ulcerate, and heal with atrophic varioliform scars over time. The differential diagnoses of PTN are wide and varying. Tuberculin test is usually strongly positive. Histology shows tuberculoid histology with endarteritis and thrombosis of dermal blood vessels. One of the hallmarks of PNT is its prompt response to antituberculous therapy. The purpose of this article is to increase awareness of this condition among dermatologists.

Background Female genital tuberculosis (FGTB) causes infertility in a significant number of females. The immunological impact of tuberculosis on endometrium in infertile females has not been studied before. The present study was designed to evaluate markers related to infiltrating immune cells and implantation in endometrial aspiration from infertile females and correlate with conventional tests and polymerase chain reaction (PCR) for tuberculosis (TB). Methods It was a prospective cohort study with 385 patients out of which IHC was done in 306 over a period of 3 years from 2013 to 2016 in a tertiary care hospital. Women with infertility, 20–35 years of age, without history of pulmonary TB or intake of antitubercular therapy were included. Endometrial samples were subjected to PCR for TB along with microbiological and histological examination for TB. Immunohistochemistry for CD45, CD3, CD20, CD4, CD8, CD68, CD138, Interferon gamma, Interleukin 10 (IL-10) and implantation markers MUC1 and Notch 1 were done on the endometrial samples along with 25 control subjects. Results Conventional tests for tuberculosis like staining for acid fast bacilli (AFB), granuloma on histology or culture positivity were seen in 2.61% (6/306; 1.96% had granulomas, 1/306; 0.32% was AFB positive, 2/306; 0.6% were liquid culture positive). PCR was positive in 190/306 (62.09%). CD3, CD20, CD45, CD68, CD4, CD8 and CD 138 expressing infiltrating cells were not significantly related to PCR positive cases. Interferon gamma expressing lymphocytes were significantly higher (38.94%) in PCR positive endometria compared to 26.72% in the PCR negative (p = 0.04). Notch −1 expression correlated significantly with the occurrence of pregnancy. A trend towards high intensity expression of Notch1 was seen in PCR negative cases. MUC-1 expression did not correlate with pregnancy although interferon gamma expression was significantly related to low intensity MUC1 expression. Conclusions Immunohistochemical markers are not reliable tests in diagnosis of FGTB. Notch 1 expression though showing correlation with pregnancy has to be further evaluated with a panel of other implantation markers. Study funding Indian Council of Medical Research, New Delhi, India.

The lesion resulting from the interaction between Mycobacterium and the host immune response is the tuberculous granuloma. Tuberculous granulomas, except in incipient stages, are partially or totally encapsulated by connective tissue. The aim of this study was to assess the immunoexpression of the extracellular matrix proteins fibronectin, collagen III, and collagen I in granulomas caused by Mycobacterium caprae in goats (Capra aegagrus hircus) to understand capsule development at different granuloma stages. For this purpose, a retrospective study of 56 samples of tuberculous granulomas in lung (n = 30) and mediastinal lymph node (n = 26) from 17 goats naturally infected with M. caprae in stages I (n = 15), II (n = 14) and III (n = 27) was carried out. Fibronectin immunoreaction was extracellular, fibrillar-reticular in the center of stage I, II and III granulomas and peripheral in stages II and III granulomas. Collagen III immunoexpression was extracellular and fibrillar in the center of stages I, II and III tuberculous granulomas in lung and mediastinal lymph node, and progressive expression was observed in the periphery of stages II and III granulomas. Finally, collagen I immunoexpression was extracellular and fibrillar, showing a progressive loss of central expression and an increase in peripheral expression in stage III granulomas compared to stage I granulomas. Immunoexpression of these extracellular matrix proteins could help understand fibrogenesis and dating in tuberculous granuloma in both animal models and humans.

This paper aimed to present a clinical case presenting an unusual periapical radiolucent lesion, its approach and treatment, and as an element of differential diagnosis in periapical pathology. Foreign body granuloma (FBG) is a tissue reaction that is triggered by the deposit of a foreign material affecting the skin and internal organs that the immune system tries to delimit and, if possible, eliminate. FBG may constitute a complication of a surgical procedure or a new pathology for the patient, which precedes an iatrogenic event causing diagnostic difficulties. This study presented an unusual periapical radiolucent lesion in a male patient with a periapical radiolucent area found in panoramic radiography; the lesion was enucleated, histopathologically confirming an FBG, which was the result of a biomaterial used in surgery for nasal polyps and deviated septum performed years before. This case shows us a very unusual presentation of an FBG within the maxillary bone after surgery for nasal polyps and deviated septum. The appropriate use of the available imaging tools and histopathological study and interpretation is emphasized, to be able to carry out a successful long-term treatment with the lowest chances of recurrence. In addition, an interdisciplinary approach is very important, which leads us to the comprehensive treatment of the patient. The proper use of diagnostic and imaging methods that we currently have, as well as knowledge of differential diagnoses, is essential to successfully diagnose and treat injuries in the maxillofacial area. El objetivo de este artículo es exponer un caso clínico con presentación de una lesión radiolúcida periapical inusual, su abordaje y tratamiento, así como su propuesta de elemento de diagnóstico diferencial en patologías periapicales. El granuloma de cuerpo extraño (GCE) es una reacción tisular desencadenada por el depósito de un material extraño que afecta a la piel y a los órganos internos y que el sistema inmunitario trata de delimitar y, si es posible, eliminar. El FBG puede constituir una complicación de una intervención quirúrgica o una patología nueva para el paciente, que precede a un evento iatrogénico causando dificultades de diagnóstico. En este estudio se presenta una lesión radiolúcida periapical inusual en un paciente varón con un área radiolúcida periapical encontrada en la radiografía panorámica; la lesión fue enucleada, confirmando histopatológicamente un FBG, que era el resultado de un biomaterial utilizado en la cirugía de pólipos nasales y tabique desviado realizada años antes. Este caso nos muestra una presentación muy inusual de un FBG dentro del hueso maxilar tras una cirugía de pólipos nasales y desviación de tabique. Se enfatiza el uso adecuado de las herramientas de imagen disponibles y el estudio e interpretación histopatológica, para poder llevar a cabo un tratamiento exitoso a largo plazo con las menores posibilidades de recurrencia. Además, es muy importante el enfoque interdisciplinario, que nos lleva al tratamiento integral del paciente. El uso adecuado de los métodos diagnósticos y de imagen que tenemos en la actualidad, así como el conocimiento de los diagnósticos diferenciales, es fundamental para diagnosticar y tratar con éxito las lesiones en el área maxilofacial.

The use of vitamin E for Facial rejuvenation is a dangerous practice and is associated with potential local, and sometimes systemic and life-threatening complications. Clinicians should be aware of complications induced by the injection of illegal products for tissue augmentation. Also, regulatory organizations should monitor illegal beauty centers and enact restrictive laws.Herein, we report a case of liquid vitamin E injection for cosmetic facial rejuvenation and development of facial persistent erythema and induration, treated with oral prednisolone, azathioprine, and minocycline. Also, we review the reported cases of vitamin E injection for cosmetic facial rejuvenation.Lipogranuloma is one of those complications of vitamin E injection for cosmetic rejuvenation. It mostly represents inflammation, edema, erythema, and tenderness. Since there was no standard treatment for this complication, the management of these patients is challenging. Patients who have undergone cosmetic interventions in illegal institutions are more likely to develop such complications including medical and psychological problems. Clinicians should be aware of these complications for the best diagnosis and treatment.

BRAF-inhibitors have emerged as a promising targeted therapy for malignancies with BRAF mutations, particularly metastatic melanoma. However, granulomatous reactions including sarcoidosis and sarcoid-like-reactions have been reported as a consequence of BRAF-inhibition. It is important to adequately characterise these granulomatous reactions including cutaneous manifestations and systemic involvement, in order to guide investigations and management. A literature review was conducted to characterise the spectrum of granulomatous reactions associated with BRAF-inhibitors - identifying 55 reactions affecting 51 patients, with 37 reactions limited to cutaneous involvement. Further, possible correlation with cancer response, mechanisms of granuloma formation, as well as a proposed workup and management approach for these granulomatous reactions are presented.

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. We searched the records of the California Animal Health and Food Safety Laboratory from 1990 through 2020 for cases of coccidioidomycosis in horses. The selection criteria for these cases were: 1) live-born horses submitted for autopsy, and 2) a diagnosis of coccidioidomycosis was established, regardless of cause of death. During that time, 19,054 horses were received, and 26 cases (0.14%) of coccidioidomycosis were diagnosed in horses, of which 19 (73%) cases had pneumonia and/or pleuritis with or without lesions in other organs, and 7 (27%) cases had lesions only in organs other than the lungs (nasal mucosa, spleen, thoracic lymph nodes, heart, pericardial sac, liver, kidney, mediastinum, and/or mesentery). Pneumonia was diagnosed as the cause of death in 1,838 (9.64%) of the horses received; Coccidioides spp. was the cause of pneumonia in 19 (1.0%) of these animals. Horses have been reported to have low susceptibility to coccidioidomycosis, and the severity and chronicity of the disease can be variable. Lesions in our cases consisted of multifocal-to-coalescing pyogranulomas with intralesional fungal spherules. Coccidioidomycosis must be considered a differential diagnosis in cases of persistent cough, chronic weight loss, fever, and cases with a travel history to, or living in, a region considered endemic for coccidioidomycosis. Coccidioides spp. infection should also be considered when pyogranulomatous inflammation is found within lung, spleen, nasal mucosa, and lymph nodes of horses.

Background: The testes are the male reproductive glands and the homolog of the ovary in females performing critical functions. Pathologic conditions could arise from the testes and blunt or completely obliterate these functions leading to clinically overt or covert sequelae. The aim of this research is to study the pattern of histologically diagnosed testicular disease in relation to clinical features at the Jos University Teaching Hospital between January 2012 and December 31st, 2021. Methodology: This study is a retrospective analysis of all cases of testicular biopsies. All histologically diagnosed testicular lesions were identified from the departmental records and clinical data obtained further from the patients’ folder at the Medical Records Department. Results: Four hundred and thirty (430) biopsies were seen, of which 304 (70.7%) were orchidectomy specimens. The commonest histological diagnosis was testicular atrophy accounting for 328(76.3%) cases. Testicular torsion is followed by 42(9.8%) cases. Together, inflammatory conditions accounted for 36(8.4%) cases out of which granulomatous inflammation made up 52.3% of cases. There were 16(3.7%) neoplastic conditions all of which were malignant, out of which 6(37.5%) were seminomas. The age range, mean, median and modal age was 1-90 years, 53.4 +21.3years, 60 years and 70 years respectively. Prostatic carcinoma therapy in the form of bilateral orchidectomy was the major indication for surgery. Conclusion: The majority of testicular lesions in our locality are atrophies and most of these lesions are obtained as orchidectomies for therapy of prostatic cancer.

Intraocular tuberculosis has protean clinical manifestations and remains an important etiological differential for uveitis in an endemic region. A 27-year-old male presented with visual acuity of counting fingers close to face in right (OD) and 20/25 in left eye (OS). Examination revealed a choroidal granuloma in OS and healed serpiginous-like choroiditis in OD. Antitubercular therapy was started with systemic corticosteroids. Granuloma resolved completely; however, the patient presented with neuroretinitis and posterior scleritis, as first and second recurrence, respectively, within a oneyear period. These were managed with systemic corticosteroids and immunosuppressive therapy was added, after second recurrence. The patient responded well and maintains remission. This case presented a clinical challenge with distinct recurrence patterns of tubercular posterior uveitis in the same eye, which has not been reported before. Successful management entailed use of antitubercular therapy, corticosteroids, and immunosuppressive therapy in a step-ladder approach, resulting in preservation of vision and achieving long-term remission.

Los quistes y granulomas periapicales están entre las lesiones más prevalentes. Sin embargo, hay circunstancias en las que se reúnen los patrones clínicos y radiográficos y, en consecuencia se presenta la necesidad de llevar a cabo un análisis histopatológico para un buen diagnóstico. Objetivo: determinar las características radiográficas e histopatológicas de las lesiones periapicales persistentes de pacientes sometidos a cirugías perirradiculares efectuadas en el posgrado de Endodoncia de la Universidad Santo Tomas sede Bogotá, durante un periodo de 6 meses. Método: estudio tipo reporte de casos, por medio de un muestreo por conveniencia, se aceptaron pacientes atendidos por residentes del postgrado de endodoncia de la sede Bogotá, que se encontraban dentro de la ventana de observación, muestras tomadas de las cirugías perirradiculares realizadas durante el segundo semestre del 2022. Se le indicó a cada uno de los pacientes la necesidad de retirar la lesión por medio de cirugía, y adicionalmente el tejido extraído se le realizaría un análisis histológico. Una vez el paciente confirmó que entiende el procedimiento se continuó a la firma del consentimiento informado. Resultados: la muestra estuvo compuesta por 10 pacientes, con una distribución por género de 3 hombres y 7 mujeres, con edades comprendidas entre 27 y 67 años y una edad media de 46,7 años. Se totalizaron 10 lesiones periapicales. Para cada paciente, se realizó la evaluación clínica, radiográfica y un diagnóstico presuntivo. Una vez realizada la cirugía, las muestras fueron enviadas al laboratorio para su análisis, se informó el hallazgo de cuatro granulomas y seis quistes. Conclusiones: para evitar la aparición de este tipo de lesiones, es necesario realizar un muy buen tratamiento endodóntico siguiendo las directrices específicas para cada caso tratado. Periapical cysts and granulomas are among the most prevalent lesions. However, there are circumstances in which the clinical and radiographic patterns meet and, consequently, the need to carry out a histopathological analysis for a good diagnosis. Objective: To determine the radiographic and histopathological characteristics of the persistent periapical lesions of patients undergoing perirradicular surgeries performed in the Endodontics graduate program of the Santo Tomas University, Bogotá, during a period of 6 months. Method: Case report type study, by means of convenience sampling, patients attended by residents of the endodontics postgraduate course of the Bogotá campus, who were within the observation window, samples taken from perirradicular surgeries performed during the study, were accepted. Each of the patients was told the need to remove the lesion by means of surgery, and additionally the extracted tissue would undergo a histological analysis. Once the patient confirmed that he/she understood the procedure, the informed consent was signed. Results: The sample consisted of 10 patients, with a gender distribution of 3 men and 7 women, with ages between 27 and 67 years and a mean age of 46.7 years. There were a total of 10 periapical lesions. For each patient, clinical and radiographic evaluation and a presumptive diagnosis were made. Once the surgery was performed, the samples were sent to the laboratory for analysis, the finding of four granulomas and six cysts was reported. Conclusions: To avoid the appearance of this type of injury, it is necessary to carry out a very good endodontic treatment following the specific guidelines for each case treated. Especialista en Endodoncia http://www.ustabuca.edu.co/ustabmanga/presentacion Especialización

Schistosoma mansoni eggs retained in host tissues induce innate cytokine release, contributing to the induction of Type-2 immune responses and granuloma formation, important to restrain cytotoxic antigens, but leading to fibrosis. Interleukin(IL)-33 participates in experimental models of inflammation and chemically induced fibrosis, but its role in S. mansoni-induced fibrosis is still unknown. To explore the role of the IL-33/suppressor of the tumorigenicity 2 (ST2) pathway, serum and liver cytokine levels, liver histopathology, and collagen deposition were comparatively evaluated in S. mansoni-infected wild-type (WT) and IL-33-receptor knockout (ST2−/−) BALB/c mice. Our data show similar egg counts and hydroxyproline in the livers of infected WT and ST2−/− mice; however, the extracellular matrix in ST2−/− granulomas was loose and disorganised. Pro-fibrotic cytokines, such as IL-13 and IL-17, and the tissue-repairing IL-22 were significantly lower in ST2−/− mice, especially in chronic schistosomiasis. ST2−/− mice also showed decreased α-smooth muscle actin (α-SMA) expression in granuloma cells, in addition to reduced Col III and Col VI mRNA levels and reticular fibres. Therefore, IL-33/ST2 signalling is essential for tissue repairing and myofibroblast activation during S. mansoni infection. Its disruption results in inappropriate granuloma organisation, partly due to the reduced type III and VI collagen and reticular fibre formation.

An 8-y-old Labrador Retriever dog had mild ataxia of the hindlimbs 4 mo after lumbosacral dorsal laminectomy for intervertebral disk disease. Ataxia of the hindlimbs gradually worsened over the next 6 y. On autopsy, gross lesions were not recognized in the spinal cord. Histopathology revealed an intradural extraparenchymal cholesterol granuloma in the cauda equina associated with remnant nerve roots. Nerves associated with the cholesterol granuloma had axonal degeneration, myelin vacuolation, and edema. In those foci, macrophages were increased in number between nerve fibers. Immunohistochemistry for neurofilament protein and Luxol fast blue staining highlighted the presence of remnant axons and myelin sheaths within the granuloma. Inflammatory cell infiltrates in the granuloma were mainly macrophages and CD3- or CD20-immunopositive T or B lymphocytes, respectively. We conclude that the cholesterol granuloma likely formed subsequent to degenerative neuropathy in the cauda equina.

Sarcoidosis is a granulomatous disorder. Rarely, malignancy is accompanied by a granulomatous reaction. This retrospective study addressed whether cancer can masquerade as sarcoidosis.TriNetX identified 1029 newly diagnosed cases of sarcoidosis between October 2015 and September 2020, of whom 50 had a subsequent diagnosis of malignancy.In 36 cases, the malignancy was unrelated to sarcoidosis. In 7 cases, the diagnosis of sarcoidosis delayed the eventual cancer diagnosis by a range of 1 month to 2 years. In 7 cases, the subsequent diagnosis of cancer might have been related to the therapy for sarcoid.Cancer masquerading as sarcoidosis is very rare occurring in 7 (0.7%) of our 1029 cases. In no case was lung cancer masquerading as sarcoidosis. Searching for occult malignancy in patients with a known diagnosis of sarcoidosis is rarely indicated.

BioCen-128 is a new active pharmaceutical ingredient composed of a specific bovine thymic fraction of a polypeptide nature. Positive results of similar thymus extracts have been shown to be effective in delaying the processes associated with aging, immunosenescence and Alzheimer's disease (AD), where the inflammation plays an important role. Because of the anti-inflammatory potential of BioCen-128, the aim of this study was to evaluate the granuloma model induced by a cotton wool implantation and the model induced by intracerebroventricular (ICV) administration of streptozotocin (STZ).The experiment was carried out using male OF-1Mice administered BioCen-128 in via the IP route at 5, 10 and 20 mg/kg of corporal weigh showed a decrease in the wet and dry weights of the granuloma, providing evidence of a systemic anti-inflammatory effect. In the ICV model of STZ, the administration of BioCen-128 improved cognitive function.These responses suggested an anti-neuroinflammatory effect explainable by the action of thymosin β4 and thymosin alfa proteins. The results suggested that BioCen-128 could be used in the prevention and treatment of some diseases, for example AD, where neuroinflammation is one of the biological events that take place.

Abstract: Sarcoidosis is a worldwide inflammatory disorder of unknown etiology that is characterized by the formation of non-caseating immune granulomas in involved organs, most commonly in the lungs and eyes. Although clinical manifestations of sarcoidosis depend on the organs involved, the most common symptoms include fatigue, fever, weight loss, eye pain, dyspnea, and chest pain. Sarcoidosis usually undergoes spontaneous regression, yet its chronic form progressively threatens the involved organs through the induction of fibrotic damage. Despite decades of medical research, the etiology of sarcoidosis still remains unclear. Nevertheless, a combination of contributors, including genetic factors, environmental exposures, and microbial agents, is believed to trigger the inflammatory state observed in this disease. Furthermore, a highly polarized Th1 and Th17 response with diminished immunomodulatory mechanisms constitute the most significant immunological event associated with this disorder. Indeed, sarcoid granulomas, which consist of highly activated antigen-presenting cells (APCs) and lymphocytes, maintain a robust specialized niche to facilitate antigen presentation and exaggerated immune responses. Both the unknown etiology and multisystem nature of the disease have hampered the development of specific therapeutics and definitive diagnostic assays for sarcoidosis. Consequently, its diagnosis and treatment still represent a challenging task for clinicians. In this article, we aim to summarize contemporary findings of sarcoidosis and its etiology, pathogenesis, and treatment.

PurposeAlpha-melanocyte stimulating hormone (α-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of α-MSH on normal bronchial epithelial cells are largely unknown, especially in the context of in vitro sarcoidosis models.MethodsWe evaluated the anti-inflammatory effects of α-MSH on two different in vitro sarcoidosis models (lung-on-membrane model; LOMM and three-dimensional biochip pulmonary sarcoidosis model; 3D-BSGM) generated from NBECs and an in vivo sarcoidosis mouse model.ResultsTreatment with α-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with α-MSH also significantly decreased macrophages and cytotoxic T-cells counts in a sarcoidosis mice model.ConclusionOur results confirm the direct role of type I IFNs in the pathogenesis of sarcoid lung granulomas and highlight α-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis.Graphical Abstract

Sarcoidosis is a variable, multisystem granulomatous disease, which can affect many organs including the lungs, lymph nodes, and eyes. It is difficult to differentiate sarcoidosis and tuberculosis because of their similar clinical and pathological features.This study aimed to describe a sarcoidosis case with typical ocular and systemic manifestations combined with suspected tuberculosis infection.A 30-year-old Chinese man, initially diagnosed with tuberculosis, presented with typical ocular sarcoidosis during antituberculosis therapy. The ocular surface, anterior chamber, anterior chamber angle, ciliary body, vitreous, optic disc, and lacrimal gland of the patient all exhibited manifestations of sarcoidosis, although optic disc involvement has rarely been reported. Typical ocular sarcoidosis manifestations and positive responses to corticosteroid therapy of the patient helped us reach the diagnosis of systemic sarcoidosis. The patient was followed up for 48 months and showed significant improvement of miliary nodules and lymph nodes in both lungs. However, the appearance of uveitis in the right eye persisted because of nonadherence to steroid treatment.This case shows the importance of ophthalmic evaluation in the diagnosis and management of sarcoidosis and supports a possible role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis.

The final stage of spine neoplasm diagnostics is histological examination. In order to obtain the tissue from neoplasm punction biopsy is used.Objective: to assess the efficacy of punctional biopsy with further pathohistological examination in patients with neoplasm in thoracic and lumbar spine.Methods: we analyzed 259 case histories of patients with pathological spine changes.Results: punction biopsy was made in 238 patients (89 %). In 30 (11 %) patients it was no effective because of the large amount of obtained material, in 27 (10 %) pathohistological diagnosis was not established. Pepeated biopsy was made in these cases. As a result at primary and secondary biopsies the diagnosis was confirmed in 95.5 %.Conclusions: punctional biopsy with pathohystological examination is integral part of diagnostic process at spine neoplasm. It allows to obtain enough material for studying (inspite of the dense of tissues) to decrease the risks of contamination of surrounded tissues. Such minimalinvasive method gives possibility to use it in patients with comorbidities. Most of primary spine cancer is represented by myeloma and malignant lymphoma. Episodic were cases of hondrosarcoma, osteosarcoma and fibrosarcoma, when the lesion was spread on one or two vertebrae. Most frequent non malignant lesions were haemangioma and eosino­philic granuloma. Metastatic disease were revealed in 74 (28 %) of patients and often appeared in cases of low grade cancer and adenocarcinoma., Заключительным этапом диагностики опухолевых заболеваний позвоночника является гистологическое исследование. Для получения ткани из очага поражения используют пункционную биопсию.Цель: оценить эффективность пункционной биопсии (с последующим патогистологическим исследованием) у пациентов с новообразованиями в грудном и поясничном отделах позвоночника.Методы: проанализировано 259 историй болезни пациентов с патологическими изменениями в позвоночнике.Результаты: пункционная биопсия выполнена всем больным. При этом у 30 (11 %) человек она оказалась неэффективной из-за небольшого количества полученного материала, а у 27 (10 %) не установлен патогистологический диагноз. Этим 57 (21 %) пациентам проведена повторная биопсия очага поражения. В результате первичной и вторичной биопсии у 95,5 % обследованных патоморфологически диагноз подтвержден.Выводы: пункционная биопсия с последующим патогистологическим исследованием является неотъемлемым этапом диагностического процесса при новообразованиях позвоночника. Она позволяет получить достаточное количество материала (независимо от плотности ткани) для изучения и уменьшить риск контаминации окружающих тканей. Малоинвазивность метода дает возможность использовать его у пациентов с тяжелыми сопутствующими соматическими патологиями. Большинство злокачествен­ных первичных поражений позвоночника представлены плазмоклеточной миеломой (миеломной болезнью) и злокачественной лимфомой; одиночными были случаи хондросаркомы, остеосаркомы и фибросаркомы, когда очаг поражения распространялся на один или два позвонка. Наиболее часто обнаружены такие доброкачественные поражения позвоночника, как гемангиома и эозинофильная гранулема. Метастатические изменения в позвоночнике выявлены у 74 (28 %) пациентов и чаще всего развивались в случае низкодифференцированного рака и аденокарциномы., Заключним етапом діагностики пухлинних захворювань хребта є гістологічне дослідження. Для отримання тканини з вогнища ураження використовують пункційну біопсію.Мета: оцінити ефективність пункційної біопсії (з подальшим патогістологічним дослідженням) у пацієнтів із новоутвореннями в грудному та поперековому відділах хребта.Методи: проаналізовано 259 історій хвороби пацієнтів із патологічними змінами в хребті.Результати: пункційну біопсію виконано всім хворим. При цьому в 30 (11 %) осіб вона виявилася неефективною через невелику кількість отриманого матеріалу, а у 27 (10 %) не встановлено патогістологічний діагноз. Цим 57 (21 %) пацієнтам проведено повторну біопсію вогнища ураження. У результаті первинної та вторинної біопсії у 95,5 % обстежених патоморфологічно діагноз підтверджений.Висновки: пункційна біопсія з наступним патогістологічним дослідженням є невід’ємним етапом діагностичного процесу в разі новоутворень хребта. Вона дозволяє отримати достатню кількість матеріалу (незалежно від щільності тканини) для вивчення та зменшити ризик контамінації прилеглих тканин. Малоінвазивність методу дає можливість використовувати його в пацієнтів із важкими супутніми соматичними патологіями. Більшість злоякісних первинних уражень хребта представлені плазмоклітинною мієломою (мієломною хворобою) і злоякісною лімфомою; поодинокими були випадки хондросаркоми, остеосаркоми та фібросаркоми, коли вогнище ураження поширювалося на один або два хребця. Найчастіше визначали такі доброякісні ураження хребта, як гемангіома й еозинофільна гранульома. Метастатичні зміни в хребті виявлено в 74 (28 %) пацієнтів і найчастіше розвивалися в разі низькодиференційованого раку й аденокарциноми.

The ESX-1 type VII secretion system is required for virulence of pathogenic mycobacteria, including Mycobacterium tuberculosis. ESX-1 interacts with infected macrophages, but its potential roles in regulating other host cells and immunopathology have remained largely unexplored. The conserved ESX-1 type VII secretion system is a major virulence determinant of pathogenic mycobacteria, including Mycobacterium tuberculosis and Mycobacterium marinum. ESX-1 is known to interact with infected macrophages, but its potential roles in regulating other host cells and immunopathology have remained largely unexplored. Using a murine M. marinum infection model, we identify neutrophils and Ly6C(+)MHCII(+) monocytes as the main cellular reservoirs for the bacteria. We show that ESX-1 promotes intragranuloma accumulation of neutrophils and that neutrophils have a previously unrecognized required role in executing ESX-1-mediated pathology. To explore if ESX-1 also regulates the function of recruited neutrophils, we performed a single-cell RNA-sequencing analysis that indicated that ESX-1 drives newly recruited uninfected neutrophils into an inflammatory phenotype via an extrinsic mechanism. In contrast, monocytes restricted the accumulation of neutrophils and immunopathology, demonstrating a major host-protective function for monocytes specifically by suppressing ESX-1-dependent neutrophilic inflammation. Inducible nitric oxide synthase (iNOS) activity was required for the suppressive mechanism, and we identified Ly6C(+)MHCII(+) monocytes as the main iNOS-expressing cell type in the infected tissue. These results suggest that ESX-1 mediates immunopathology by promoting neutrophil accumulation and phenotypic differentiation in the infected tissue, and they demonstrate an antagonistic interplay between monocytes and neutrophils by which monocytes suppress host-detrimental neutrophilic inflammation.IMPORTANCE The ESX-1 type VII secretion system is required for virulence of pathogenic mycobacteria, including Mycobacterium tuberculosis. ESX-1 interacts with infected macrophages, but its potential roles in regulating other host cells and immunopathology have remained largely unexplored. We demonstrate that ESX-1 promotes immunopathology by driving intragranuloma accumulation of neutrophils, which upon arrival adopt an inflammatory phenotype in an ESX-1-dependent manner. In contrast, monocytes limited the accumulation of neutrophils and neutrophil-mediated pathology via an iNOS-dependent mechanism, suggesting a major host-protective function for monocytes specifically by restricting ESX-1-dependent neutrophilic inflammation. These findings provide insight into how ESX-1 promotes disease, and they reveal an antagonistic functional relationship between monocytes and neutrophils that might regulate immunopathology not only in mycobacterial infection but also in other infections as well as in inflammatory conditions and cancer.

Since their discovery nearly 40 years ago, B-1 cells have continued to challenge the boundaries between innate and adaptive immunity, as well as myeloid and lymphoid functions. This B-cell subset ensures early immunity in neonates before the development of conventional B (B-2) cells and respond to immune injuries throughout life. B-1 cells are multifaceted and serve as natural- and induced-antibody-producing cells, phagocytic cells, antigen-presenting cells, and anti-/pro-inflammatory cytokine-releasing cells. This review retraces the origin of B-1 cells and their different roles in homeostatic and infectious conditions before focusing on pollutants comprising contact-sensitivity-inducing chemicals, endocrine disruptors, aryl hydrocarbon receptor (AHR) ligands, and reactive particles.

Schistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus Schistosoma sp., which affects over 230 million people worldwide, causing 200,000 deaths annually. There is no vaccine or new drugs available, which represents a worrying aspect, since there is loss of sensitivity of the parasite to the medication recommended by the World Health Organization, Praziquantel. The present study evaluated the effects of the recombinant enzymes of S. mansoni Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT), Purine Nucleoside Phosphorylase (PNP) and the MIX of both enzymes in the immunotherapy of schistosomiasis in murine model. These enzymes are part of the purine salvage pathway, the only metabolic pathway present in the parasite for this purpose, being essential for the synthesis of DNA and RNA. Female mice of Swiss and BALB/c strains were infected with cercariae and treated, intraperitoneally, with three doses of 100 µg of enzymes. After the immunotherapy, the eggs and adult worms were counted in the feces; the number of eosinophils from the fluid in the peritoneal cavity and peripheral blood was observed; and the quantification of the cytokine IL-4 and the production of antibodies IgE was analyzed. The evaluation of the number of granulomas and collagen deposition via histological slides of the liver was performed. The results demonstrate that immunotherapy with the enzyme HGPRT seems to stimulate the production of IL-4 and promoted a significant reduction of granulomas in the liver in treated animals. The treatment with the enzyme PNP and the MIX was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine, to reduce the number of eggs in the feces and to negatively modulate the number of eosinophils. Therefore, immunotherapy with the recombinant enzymes of S. mansoni HGPRT and PNP might contribute to the control and reduction of the pathophysiological aspects of schistosomiasis, helping to decrease the morbidity associated with the infection in murine model.

Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb) are pathogens responsible for millions of new infections each year; together, they cause high morbidity and mortality worldwide. In addition, late-stage HIV infection increases the risk of developing tuberculosis (TB) by a factor of 20 in latently infected people, and even patients with controlled HIV infection on antiretroviral therapy (ART) have a fourfold increased risk of developing TB. Conversely, Mtb infection exacerbates HIV pathogenesis and increases the rate of AIDS progression. In this review, we discuss this reciprocal amplification of HIV/Mtb coinfection and how they influence each other's pathogenesis. Elucidating the infectious cofactors that impact on pathogenesis may open doors for the design of new potential therapeutic strategies to control disease progression, especially in contexts where vaccines or the sterile clearance of pathogens are not effectively available.

To investigate choroidal granulomas visualized by indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in response to treatment.Ten eyes of eight patients with tubercular, sarcoid, or Vogt-Koyanagi-Harada-associated choroidal granulomas were evaluated in this multicentric study. All patients underwent ICGA and OCTA at baseline, 1, and 3 months after treatment onset. Granulomas were identified as hypofluorescent lesions on intermediate ICGA phases. Late ICGA behavior and OCTA visualization were assessed.On baseline intermediate ICGA, 222 choroidal granulomas were detected. Overall, 174/222 granulomas were detected on baseline OCTA images. At 1 month, 28% of lesions were healed and 48 late ICGA hyperfluorescent lesions were identified. At 3 months, 63% of baseline lesions were healed, with 33 persistent late hyperfluorescent lesions. Optical coherence tomography angiography sensitivity was reduced at 1 and 3 months compared with baseline. Some flow-voids detected on OCTA at 1 and 3 months did not correspond to any visible lesion on ICGA.Different healing behaviors of choroidal granulomas were identified combining ICGA and OCTA analysis. Late ICGA hyper-fluorescent lesions may be the consequence of a possible fibrotic shift. Structural changes in the choroid may persist after active granulomas resolution resulting in persistent flow voids on OCTA.

A 10 yr old female spayed Pomeranian presented with a history of dyspnea and coughing and was diagnosed with a cranial mediastinal mass presumed to be a thymoma. Surgical removal was elected and occurred without intraoperative complications. Histopathology revealed the lesion to be a cholesterol granuloma. The patient developed a brief period of increased respiratory difficulty 3 days postoperatively. Thoracic radiographs showed mild pleural effusion and the patient improved with supportive care. Five months postoperatively, repeat thoracic radiographs revealed no evidence of recurrence or respiratory pathology. This case report describes a cholesterol granuloma in a unique location and reviews the pathogenesis/pathophysiology of this type of mass.

Background/Aims: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. Methods: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. Results: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%.Conclusions: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

Necrotizing and non-necrotizing epithelioid granulomatous chronic inflammation is the usual recognizable histopathologic presentation of mycobacterial infections. In immunosuppressed patients, atypical histomorphologic patterns may occur. Rare and diagnostically challenging manifestations of nontubercular mycobacterial infections in transplant and Human Immunodeficiency Virus (HIV)-infected patients include mycobacterial spindle cell pseudotumor and suppurative lesions. Lesions composed of nodular spindle cell proliferation mimicking inflammatory, histiocytoid and spindle cell tumors, and similarly suppurative lesions simulating abscesses have been mostly reported in association with nontuberculous mycobacterial infections mainly in nodal and various extranodal sites. Similar lesions related to Mycobacterium tuberculosis that involve serosal membranes are unusual and diagnostically challenging. Our aim is to report mycobacterial spindle cell pseudotumor-associated pericarditis, suppurative abscess-forming pleuritis, and cholesterol pleuritis due to tuberculosis in three HIV-infected young adult males. Initially, we confused the mycobacterial spindle cell pseudotumor for Kaposi sarcoma, the suppurative pleuritis for bacterial and fungal empyema, and the cholesterol pleuritis with rheumatoid arthritis. A prior knowledge of the immune status of our patients helped us confirm our final correct diagnosis of mycobacterial infection by performing Ziehl-Neelsen special stain. Polymerase chain reaction detected Mycobacterium tuberculosis in respiratory samples. Utilization of acid-fast special stains in all HIV-patients regardless of the histopathologic appearances, and the application of an appropriate panel of immunomarkers should help pathologists reach the correct diagnosis and avoid pitfalls. Without prior clinical knowledge, pathologists should raise this possibility in young patients with such unusual manifestations, because correct pathologic recognition is clinically important for the appropriate management of these vulnerable patients.

While patients presenting with clinical signs and symptoms of acute appendicitis (AA) often receive surgical intervention shortly after presentation, certain patients may instead receive non-operative management initially, with appendectomy later. The histology of such interval appendicitis (IA) has only been described in small series. Also, we have noticed a recent increase in the incidence of IA specimens at our institution.We identified appendectomy specimens in our department during 2018 with available haematoxylin and eosin slides and electronic clinical data, and evaluated multiple histological findings. Cases were then divided into AA and IA, based on clinical history (AA if the patient presented to the hospital within 1 week of symptom onset and underwent appendectomy within 48 h; IA if appendectomy was delayed at least 1 week). Changes between groups were compared. The cohort included 165 cases (125 AA, 40 IA). Findings significantly more common in AA included mucosal acute inflammation, mural acute inflammation and acute serositis. Findings significantly more common in IA included Crohn-like mural inflammation, mural fibrosis, goblet cell hyperplasia, granulomas, xanthogranulomatous inflammation, haemosiderin-laden macrophages and granulation tissue. The rate of IA in 2018 (24%) was noticeably higher than in previous years.Acute inflammatory changes are more common in AA but can remain present in IA. Mural fibrosis, serosal adhesions, haemosiderin-laden macrophages and granulation tissue suggest IA. Granulomas and xanthogranulomatous inflammation can also be seen in IA, and Crohn-like mural inflammation is not uncommon. These histological patterns can guide signout and prevent diagnostic errors, particularly when clinical information is unavailable.

Peripancreatic tuberculous lymphadenopathy can mimic pancreatic cancer on imaging. There have only a few reports on varices from portal vein obstruction due to abdominal tuberculous lymphadenopathy. Iatrogenic disseminated tuberculosis is also rare. Herein, we present a rare case of peripancreatic tuberculous lymphadenopathy with ruptured duodenal varices due to portal vein obstruction. The patient presented to our hospital with hematemesis. Computed tomography revealed a peripancreatic mass. Duodenal varices rupture from portal vein obstruction due to pancreatic cancer were initially suspected. The patient underwent portal vein stenting for portal vein obstruction and endoscopic ultrasound-guided fine-needle aspiration for diagnosis, which revealed granulomas indicative of tuberculosis. The patient was discharged once because fine-needle aspiration did not lead to a definitive diagnosis of tuberculosis. Subsequently, he developed disseminated tuberculosis. Peripancreatic tuberculous lymphadenopathy can cause ectopic varices with portal vein obstruction. Tuberculosis should also be included in the differential diagnosis in the case of portal vein obstruction, to facilitate early treatment and avoid unnecessary surgery. Furthermore, fine-needle aspiration or portal vein stenting for tuberculous lesions can cause disseminated tuberculosis. Since a diagnosis might not be made until after several fine-needle aspirations have been conducted, careful follow-up is necessary after the procedure for such lesions.

A 50-year-old man was admitted to our hospital with the complaints of fever and general malaise. He had no history of human immunodeficiency virus (HIV) infection or treatment with immunosuppressive agents. We performed renal biopsy to investigate possible acute kidney injury. Pathological findings showed inflammatory cell infiltration, including granulomatous lesions in the interstitium. We diagnosed the patient with acute granulomatous tubulointerstitial nephritis. We initiated prednisolone (PSL) 40 mg/day (0.6 mg/kg), in combination with isoniazid for a latent tuberculosis infection, because of positive results in interferon-γ release assays. The patient's fever and malaise promptly disappeared, and his renal function improved. After the patient had been discharged, Mycobacterium intracellulare grew in cultures of his renal tissue and urine. We gradually reduced the dose of PSL; we initiated combination therapy with ethambutol, clarithromycin, and rifampin. After 2 years of follow-up, the patient continued treatment for chronic kidney disease; it has since enabled him to avoid renal replacement therapy. This report describes a rare instance of nontuberculous mycobacteria-associated tubulointerstitial nephritis in a patient without a history of HIV infection or organ transplantation. In differential diagnosis of granulomatous tubulointerstitial nephritis, clinicians should consider drugs, sarcoidosis, tubulointerstitial nephritis and uveitis syndrome, vasculitis, and infections (e.g., involving mycobacteria). Prompt microbiological examinations, especially of urine or biopsy cultures, are vital for diagnosis.

The purpose of the study is to assess the etiology detection ability of Metagenomic Next-Generation Sequencing (mNGS) on formalin fixation and paraffin embedding (FFPE) tissue from postoperative biopsy specimens.We prospectively enrolled specimens from patients undergone surgery biopsy due to undefinite diagnosis and pathologically indicated granulomatous lesions. FFPE tissues were tested by mNGS and histopathology. The etiology detection rate of mNGS was calculated and compared with histopathology..Among the 69 cases eventually included, 41 (59.42%) were diagnosed with infectious granuloma. The overall fungi and mycobacteria etiology detection rates of mNGS in granuloma lesions was 87.80% (36/41). The mNGS increased the detection rate by 68.29% (28/41) compared with histopathology, the difference was statistically significant (χ2 = 28.97,The mNGS could accurately and quickly detect fungi and mycobacteria in FFPE specimens from postoperative granuloma specimens and identify the pathogens to the species level.China Clinical Trial Registry ChiCTR2000035464.

Objectives Despite the clear benefits of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in mitigating the impact of the coronavirus disease 2019 pandemic, there are emerging reports of postvaccination myocarditis, the majority of which are diagnosed based on the clinical and radiologic findings without biopsy confirmation. We report a case of biopsy-confirmed lymphohistiocytic myocarditis after Moderna mRNA-1273 vaccination. Methods We describe a case of a previously healthy 45-year-old woman who had palpitations, exercise intolerance, and syncope 1 week after her first mRNA-1273 vaccine dose. Laboratory tests and cardiac imaging were compatible with myocarditis. Given her unusual clinical presentation, an endomyocardial biopsy was performed to exclude other potential etiologies. Results The endomyocardial biopsy specimen showed patchy endocardial and intramyocardial lymphohistiocytic infiltrates with scattered eosinophils and focal myocyte injury. CD3 and CD68 immunostains confirmed the lymphocytic and histiocytic nature of the infiltrate, respectively. A focal histiocytic collection suggestive of an ill-defined granuloma was present. The histologic and immunohistochemical findings of a lymphohistiocytic myocarditis were highly suggestive of a postvaccination hypersensitivity reaction. Conclusions Myocarditis following SARS-CoV-2 vaccination is a rare adverse event. The findings of a lymphohistiocytic myocarditis with scattered eosinophils and a possible ill-defined granuloma are highly suggestive of a hypersensitivity reaction. The mechanism by which this inflammation occurs remains uncertain. Despite our findings, the benefits of SARS-CoV-2 vaccination far outweigh the risks.

Summary Objective Vocal process granuloma (VPG) has a varied treatment success rate and may frustrate patients and physicians due to poor outcomes. There is still a lack of standard protocols to manage VPG. This study aimed to review the efficiency of a standardized low-dose laryngeal electromyographic (LEMG)-guided botulinum toxin A (BTA) injection in intractable vocal granulomas. Methods Twenty-four patients with intractable VPG were recruited. All patients underwent percutaneous LEMG-guided BTA injection on the thyroarytenoid-lateral cricoarytenoid muscle complex in an office setting. The injecting dose was standardized to 1 U in 0.1 mL normal saline at a time. We evaluated the treatment effect by measuring the lesion size with serial laryngoscope evaluations. Results The postinjection follow-up time varied from 3 to 23 months. Twenty-one patients (87.5%) experienced complete regression of the granuloma over 1–7 months (median 3 months). No major adverse effects were noted during the follow-up period. Conclusion For recalcitrant VPG, LEMG-guided low-dose BTA injection has the potential to be a safe, efficient, and effective treatment.

The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation.Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records. We analyzed the trends of these parameters according to the year and season of diagnosis.654 patients were included in the study. The number of incident CD cases increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR 2.53, p = 0.02), had more perianal diseases (OR: 2.30, p 0.0001) and more granulomas (OR: 1.61, p = 0.003), but fewer eosinophils (OR: 0.35, p 0.0001) and less chronic lymphoplasmacytic infiltrate (OR: 0.56, p = 0.008) as compared to the 2009-2014 cohort. There was fewer CD diagnosis during winter. Patients diagnosed in the fall had lower PCDAIs, less failure to thrive and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall.The clinical and histological phenotype of CD has changed over time and there are important seasonal trends in the frequency and severity on disease behavior suggesting possible disease triggers.

Some cases of patients with IgA nephropathy diagnosed via kidney biopsy and antineutrophil cytoplasmic antibody (ANCA) positivity have been reported. This article describes a case series comprising patients with IgA nephropathy and ANCA positivity seen at a medical center in the city of São Paulo, Brazil, from 1996 to 2016. A total of 111 patients underwent diagnostic kidney biopsies for IgA nephropathy. Five were ANCA-positive at the time of diagnosis; their mean age was 45 ± 15.3 years and they were predominantly females with a mean proteinuria of 2.2 ± 0.9 g/day and a median serum creatinine level of 2.5 (2.0 - 8,6) mg/dL; all had hematuria. Four of the five were cANCA-positive (80%); all had normal serum C3 and C4 levels; and 80% were positive for ANA. One case presented an association with infection, but no associations were found with medication. One patient had granuloma and another had a collapsing lesion. This article describes the cases of five ANCA-positive patients (with predominantly cANCA positivity) submitted to diagnostic kidney biopsies for IgA nephropathy; one patient had a collapsing lesion, but progressed well. Resumo Alguns casos clínicos de biópsia renal diagnóstica de nefropatia por IgA em pacientes com títulos séricos positivos de anticorpo anticitoplasma de neutrófilos (ANCA) vêm sendo publicados. Descreve-se uma série de casos de nefropatia por IgA com ANCA positivo de centro único da cidade de São Paulo, Brasil, no período de 1996 a 2016. No período estudado, houve 111 pacientes com biópsia renal com diagnóstico de nefropatia por IgA; destes, 5 tinham ANCA positivo ao diagnóstico com média de idade de 45 ± 15,3 anos, predominando o sexo feminino, com média de proteinúria de 2,2 ± 0,9 g/dia, hematúria presente em 100% dos casos e mediana de creatinina sérica de 2,5 (2,0 - 8,6) mg/dL. O cANCA foi o padrão mais encontrado, em 4 dos 5 casos (80%), com os níveis séricos das frações de complemento C3 e C4 normais em todos e FAN positivo em 80% dos casos. Houve associação com infecções em um caso, mas sem associação com medicações. À microscopia óptica, um dos pacientes tinha granuloma e outro, lesão colapsante. Em resumo, descreve-se cinco casos de pacientes com biopsia renal diagnóstica de nefropatia por IgA com ANCA sérico positivo predominando cANCA, destacando um paciente desse grupo com microscopia óptica com lesão colapsante que, apesar disso, teve boa evolução.