Formation Of Epithelioid Granulomas Research Articles

Pathomorphological characteristics of tuberculous placenta and its clinical implication

BackgroundThe study of pathologic diagnosis of placental TB is rare. The aim of this study is analyzing the pathomorphological characteristics of tuberculosis (TB) placenta during pregnancy and its clinical significance.MethodsNineteen cases of placental tissue specimens during pregnancy were collected from June 2015 to February 2022 at Shanghai Public Health Clinical Center, the only inpatient center for pregnant women with TB in Shanghai, China. Hematoxylin-eosin staining, acid-fast staining, and molecular testing were applied to analyze them comprehensively in combination with clinical information.ResultsAmong the 19 cases, 7 cases caused intrauterine stillbirth, 3 cases received artificial abortion required by the pregnant woman, the other 9 cases received standard delivery and the infants survived, however, 3 of them were low-weight preterm infants, and another 1 case suffered mild intrauterine asphyxia. The 9 surviving infants were followed-up, of which 3 cases got congenital TB. For pathological characteristics of placental tissues under light microscopy, there were 3 cases of epithelioid granuloma formation, 13 cases of acute fetal membranitis, 4 cases of caseous necrosis, 7 cases of inflammatory necrosis, 10 cases of coagulative necrosis, and 6 cases with small focal calcifications. All placental tissues were positive for acid-fast staining and polymerase chain reaction (PCR). Molecular pathological diagnosis showed that 18 cases were positive for Mycobacterium tuberculosis, with 1 case not having received examination.ConclusionsCombining acid-fast staining and molecular pathological testing is helpful for accurately diagnosing placental TB.

DESKRIPSI PERBEDAAN SITOLOGI NON GRANULOMA LIMFADENITIS TUBERKULOSIS PADA PASIEN HIV AIDS : STUDI KASUS

ABSTRACT
 Introduction: HIV AIDS is a disease with CD4 as the main target and frequently accompanied by lymphadenopathy symptoms. Most lymphadenopathy is caused by tuberculosis. The prevalence of limphadenitis in HIV TB is 40-80%. Cytological features of TB lymphadenitis in HIV AIDS and non-HIV have differences and associated with lower CD4 counts.Case: Male, 58 years old with complaints of right and left neck mass since 1 month. It was enlarged since 1 week, not accompanied by pain and injury. Patient also complained fever, night sweats, weight loss, white spots in the mouth. On physical examination, found right neck mass of 7x6 cm and left of 5x4 cm, flat surface elastic solid mass, difficult to move, no tenderness and inflammation. VCT result of three methods was reactive, absolute CD4 cell count 81.8 cells/UL and 6.13 log copies/mL viral load. Cytology result was hypocellular smears containing large necrotic areas with lymphocyte cells, histiocytes, PMN without signs of malignancy, conclusion: TB lymphadenitis. Patients received anti TB category one and ARV 2 weeks after TB treatment.
 Discussion: Lymphadenopathy symptoms in HIV AIDS from many etiologies are almost same so a cytological examination is needed. In TB lymphadenitis cytology, there are 3 groups of typical features are granuloma, granuloma with necrosis and only necrosis then it was confirmed ZN staining (smear bacilli). In HIV AIDS is more found necrosis without granuloma except CD4>100. This is because T cell function which is important in the formation of epithelioid granuloma is decreased. At an advanced stage with CD4 decreases, there is no epithelioid cell formation but rather foamy macrophage formation.Conclusion: HIV AIDS patient with CD4 81.8 and cervical tuberculosis lymphadenitis has different cytological features with large necrotic areas without granulomas.
 

Association Between Obesity and Sarcoidosis: A Systematic Review and Meta-analysis

<i>Background</i>: Sarcoidosis is a systemic inflammatory disease characterized by epithelioid granuloma formation in various organs. The etiology of sarcoidosis is unknown. Several studies report an increased risk of sarcoidosis in obese patients. The purpose of this study is to conduct a systematic review to assess the risk of sarcoidosis in obese or overweight patients, and to provide a population-based estimate of the risk of sarcoidosis in obese and overweight individuals. <i>Methods</i>: Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA) guidelines, we conducted a comprehensive search of studies (Randomized control trial (RCT), cohort or case-control) studies that estimated the risk of sarcoidosis with body mass index (BMI) between 2009-2019 using keywords and MESH terms related to obesity and sarcoidosis. The search was conducted in MEDLINE, EBSCO, and CINAHL. Three independent investigators reviewed each article and assessed for bias. Data was extracted from each study that met inclusion criteria. Quantitative analysis was performed using Review Manager 5.3 software. <i>Results</i>: An initial search yielded 77 potential articles; 73 articles did not meet inclusion criteria and 4 were included in the final analysis. The pooled risk estimate for the incidence of sarcoidosis in obese and overweight individuals was 1.68 [95% confidence interval 1.5-1.87] with a significant statistical heterogeneity, I² of 92%. <i>Conclusion</i>: From our systematic review, obese and overweight individuals have a 68% (RR 1.68, 95% CI 1.50 to 1.87) increased risk of developing sarcoidosis in comparison with normal or underweight individuals. More studies are needed to further evaluate the role of obesity in the etiopathogenesis of sarcoidosis.

Diagnosis of Mycobacterium abscessus/chelonae complex cutaneous infection: Correlation of tissue culture and skin biopsy.

Mycobacterium abscessus and M. chelonae belong to the rapid-growing nontuberculous mycobacteria (NTM) group, which are defined by their ability to form visible colonies on agar within 7 days of subculture. Cutaneous infections by this complex show a heterogeneous clinical presentation with varied histopathologic findings. However, the presence of vacuoles in many specimens has been reported as a specific histologic finding. Herein, we correlate the histopathology of patients with tissue-culture positive M. abscessus/M. chelonae complex in order to identify features that may prompt a rapid categorization of the infectious etiology. The cohort includes 33 skin punch biopsy specimens from 28 patients who had associated positive tissue cultures. The most frequent clinical presentation was a single or multiple nodule. Twenty-seven specimens (81.81%) were found to have vacuoles. The observation of certain histologic features (ie, polymorphonuclear microabscesses and epithelioid granuloma formation) should raise the possibility of infection by NTM. In addition to these findings, we believe the presence of vacuoles in the dermal and subcutaneous inflammation should raise suspicion for NTM.

The clinical analysis of pulmonary lymphoepithelioma-like carcinoma with epithelioid granuloma: Fourteen cases and literature review.

e20545 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer associated with Epstein-bar virus (EBV) infection. Even less reported were those with Epithelioid granuloma (EG) and were frequently misdiagnosed. Current study aimed at investigating the clinical presentation, pathological characteristics and treatments of PLELC complicated with EG to improve our understanding of this disease. Methods: Data was collected from January 2013 to December 2017. A total of 105 patients were diagnosed as PLELC, in which 14 patients were with EG. Their clinical features, pathological characteristics and treatment were analyzed. Results: The 14 patients with EG (13.3%) in our group were followed-up 15 months (10-31 months).The median age was 48.5 year-old (38-67 year-old) and 85.7% were under the age of 60, meanwhile females had a slightly higher proportion than males (1.8:1). Most patients were at early stage (71.4%) with nonspecific manifestations such as cough, expectoration and lack of rich-lewis phenomenon. EG were often located in tumor or beside the tumor (71.4%), others were located in lymph node. It was all negative in specific stain of pathology and all positive in situ hybridization of EBV-encoded RNA (EBER). In our study, two patients received palliative chemotherapy with the duration of progression-free survival in 8 and 10 months, respectively. Twelve patients underwent surgical resection including ten with adjuvant or neo-adjuvant chemotherapy. Three patients had disease relapsed in 8, 13 and 25 months after surgery, respectively. None of them had tuberculosis occurring, progression or relapse, even if anti-tuberculosis therapy were not taken. Conclusions: PLELC complicated with EG, a rare phenomenon, was lack of rich-lewis phenomenon and specific clinical characteristic compared with those without EG. The formation of EG may be caused by immunological hypersensitivity to tumor cell or EBV infection instead of tuberculosis. It was important for us to make an exact pathological diagnosis, and attention should be paid to obtain samples by biopsy and make differential diagnosis. PLELC complicated with EG could receive multimodality therapy such as chemotherapy and surgery. However, anti-tuberculosis therapy was not necessary.

Corynebacterium kroppenstedtii in granulomatous mastitis: Analysis of formalin-fixed, paraffin-embedded biopsy specimens by immunostaining using low-specificity bacterial antisera and real-time polymerase chain reaction.

Granulomatous mastitis (GM) is a rare inflammatory disease of the post-lactation breast, clinically mimicking breast cancer. GM is microscopically characterized by formation of epithelioid granulomas and abscess (suppurative granulomas) with lipid droplet-centered inflammation. Corynebacterium kroppenstedtii (Ck) is known as a causative bacterium of GM, and identification of Ck infection within the lesion should thus be essential for confirming the diagnosis. In the present study, we analyzed formalin-fixed, paraffin-embedded (FFPE) biopsy specimens of a total of 18 GM lesions with immunostaining and real-time PCR for Ck genome. Widely cross-reactive rabbit antisera against Bacillus Calmette-Guerin (BCG), Bacillus cereus, Treponema pallidum and Escherichia coli were chosen. With real-time PCR, Ck genome was demonstrated in 7 of 18 GM lesions. Immunohistochemically, the low-specificity antisera reacted with the cytoplasm of phagocytes and/or granuloma-engulfed lipid droplets in 12 of 18 GM lesions. Antigenic positivity was observed in the following order: BCG > B. cereus > T. pallidum > E. coli. Real-time PCR using DNA extracted from FFPE sections was useful but not consistent for identifying the Ck genome in GM, while immunostaining using cross-reactive antisera against four kinds of bacteria was not Ck-specific but was applicable to visualizing bacterial infection within the GM lesions.

12歳で大量腹水を認め、腹腔鏡検査で診断された結核性腹膜炎の1症例

A 12-year-old girl had complained of abdominal pain for 1 month. She visited a local clinic because of fever over 38°C. The fever continued despite administration of antibiotics, and she was referred to the Department of Pediatrics at our hospital, which in turn referred her to the Department of Gynecology because she had massive ascites. No abnormal findings were detected in the uterus or ovaries by ultrasonography. Enhanced computed tomography revealed massive ascites, peritoneal thickening, many small nodules in the omentum, and bilateral pleural effusion. Serum CA125 level was remarkably elevated (1,538 U/ml). In addition, adenosine deaminase levels in ascetic fluid were elevated (136 U/l). Cytological examination of the ascites showed many neutrophils but no malignant cells. Laparoscopic examination was performed for diagnosis, which revealed diffused miliary white modules in the whole abdomen. Peritoneal biopsy was performed, and pathological examination showed formation of epithelioid granuloma with partial necrosis. The clinical diagnosis was tuberculous peritonitis.

Pathologic basis of pyogenic, nonpyogenic, and other spondylitis and discitis.

Pyogenic spondylitis and discitis are usually seen following a recent infection or surgery. A septic embolus causes an infarcted area within the bone. Pyogenic spondylitis is characterized by edema, vascular leakage, and supportive inflammatory reaction characterized with polymorphonuclear leukocytes. In tuberculosis of the spine, active lesions are characterized by formation of epithelioid granulomas with central caseating necrosis. Mycobacterium tuberculosis can be shown by histochemical stains for acid-fast bacteria or by immunochemistry. In brucella spondylitis, microgranulomatous proliferation composed of histiocytes containing numerous bacilli without caseating necrosis is characteristic. Brucella melitensis can be shown on histochemical Gram stain.

Immunodeficiency and disseminated mycobacterial infection associated with homozygous nonsense mutation of IKKβ

A, Genealogical tree for the kindred. Arrow highlights index case. Asterisks denote family members who died within the first 2 months of life with febrile illnesses. B, Histology showing granuloma in skin by hematoxylin and eosin staining.

Mycosis Fungoides With Unusual Granulomatous Pulmonary Manifestations

Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, with the lungs being the most common site of extranodal involvement. Our patient is a 65 year old woman who was diagnosed with mycosis fungoides and presented with lung parenchymal infiltrates shortly thereafter. Histological examination of the lung lesion revealed an atypical small lymphocytic infiltration along with prominent granulomas and focal angiocentric lesions. Flow cytometry studies confirmed pulmonary involvement by mycosis fungoides. Granulomatous inflammation has been described earlier within the cutaneous infiltrates of mycosis fungoides. However, the presence of granulomas in the lungs involved by mycosis fungoides has only been described in one previous case report. We are reporting the second case of pulmonary involvement by mycosis fungoides with very unusual histologic features including the formation of epithelioid granulomas and angiocentric lesions, supported by flow cytometry studies.

A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials

BackgroundThe most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures.ResultsCarbon black particles (Printex 90) and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs). Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm2) of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1) as well as profibrotic (M2) phenotypic markers.ConclusionsInduction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model offers a time- and cost-effective platform to evaluate the potential of engineered high aspect ratio nanomaterials, including carbon nanotubes, nanofibers, nanorods and metallic nanowires, to induce granulomas following inhalation.

Gastrointestinal: Rectal sarcoidosis due to paralytic ileus resembling adult‐onset Hirschsprung disease

A 37-year-old woman was referred to our hospital with refractory paralytic ileus. Previous abdominal CT scans from two months previously were normal, but the oral contrast medium remained in the bowel when the test was repeated. No organic obstruction of the small intestine was found by gastrograffin small bowel study. We tentatively diagnosed chronic idiopathic intestinal pseudo-obstruction (CIIP). However, gastroduodenal manometry revealed heterogeneous phase III activity from the second to third parts of the duodenum (visceral myopathy type), which made CIIP unlikely. Colonoscopy revealed no organic obstruction of the colon but there was rectal dilatation and extensive retention of stools. Biopsy specimens from the terminal ileum, ascending colon and the rectum were normal with no inflammation or dysplasia. Because of the finding of rectal dilation and weak colonic contraction a barium enema was performed for suspected adult-onset Hirschsprung disease. This revealed narrowing of the distal rectum (Fig. 1 arrow). Rectal manometry showed that the patient had no reflex contraction of the rectum despite anal dilatation with a balloon at 30 mmHg. These findings were compatible with Hirschsprung disease. To confirm the diagnosis, biopsy of all layers of the rectal wall was performed. Histological examination revealed numerous epithelioid cell granulomas (Fig. 2) involving the peripheral nerves and nerve plexuses of the muscular and the submucosal layers. Hyperplasia of acetylcholinesterase-positive fibers was not found in the lamina propria. Therefore, she was diagnosed as having rectal sarcoidosis with secondary paralytic ileus. There was no hilar lymphadenopathy, granular changes, or opacification on chest X-ray and CT scan. Angiotensin-converting enzyme, a marker of sarcoidosis, was normal at 10.5 (8.3–21.4) IU/L, but serum soluble IL-2receptor antibody was very high at 1,901 (135–483) pg/ml. Tuberculin skin test was negative (0 × 0/6 × 6 mm). Bronchoscopy revealed a mucosal reticular network that was compatible with sarcoidosis. The CD4/CD8 cell ratio was high (4.76) in the bronchial lavage fluid, but no granulomas were detected by transbronchial lung biopsy. We treated her for neurosarcoidosis with prednisolone at 60 mg/day. Her symptoms improved gradually, and she was discharged on oral prednisolone (30 mg/day). At that time, the mucosal reticular network had resolved on bronchoscopy. Narrow rectum (arrow) on barium enema with proximal recto-sigmoid dilatation. Epithelioid cell granulomas involving preipheral nerves and nerve plexuses of the muscular and submucosal layers (HE stain, magnification × 20). Sarcoidosis is a systemic disease that causes the formation of epithelioid granulomas. The incidence of symptomatic bowel obstruction due to sarcoidosis is 0.6%. However, all previous reported cases of bowel obstruction were from mechanical obstruction caused by sarcoid granulomas. A Pubmed search using the key words ‘sarcoidosis’ and ‘paralytic ileus’ from 1949 to 2009 did not reveal any previous publications on paralytic ileus induced by intramuscular sarcoid granulomas resembling adult-onset Hirschsprung disease. Contributed by

Importance of the major Fli C antigenic site of Salmonella enteritidis as a subunit vaccine antigen

Our previous study indicated that the antibody against the major antigenic site of SE Fli C (g.m. region) is characteristically produced after the application of SE bacterin, however, the antibody is not produced in chickens after SE infection. In the present study, we determined histologically if the major antigenic site could be a candidate antigen for SE subunit vaccine. When Layermune SE, a commercial SE bacterin, was injected subcutaneously into the shoulder region as a positive control, the following histological changes were observed: formation of epithelioid granuloma with epithelioid cells and multinuclear giant cells surrounding necrotic sites and oil cysts (Indicator 1); a perivascular accumulation of lymphocytes near the granulation tissue (Indicator 2); peripheral fibroplasia encapsulating the granulation tissue (Indicator 3). On the other hand, at the injection site from the incomplete Freund adjuvant as a negative control antigen, there was only hyperplasia of the connective tissues around oil cysts. By using these indicators, the histological changes induced by injection of major antigenic site (SEp9) of Fli C, Fli C, and SE somatic antigen were evaluated. Histological changes after the injection with SEp9 demonstrated Indicators 2 and 3. The injection with SE Fli C demonstrated all three indicators. Contrarily, de-flagellated SE antigen injection induced only Indicator 3. The present results suggest that the antigen g.m. site of SE Fli C (SEp9) may play an important role as a subunit vaccine not only for including continuous immunological reaction in SE infection in chickens but also for antigen presentation.

Histological grading patterns in patients of cutaneous leishmaniasis.

To determine the histological grading patterns in a cohort of hospitalized patients of cutaneous leishmaniasis. Case series. The study was conducted at PNS Shifa Hospital, Karachi, from May 2004 to June 2006. One hundred patients of Cutaneous Leishmaniasis (CL), admitted in dermatology wards at PNS Shifa Hospital, Karachi, were examined. Only admitted patients of all ages and both sexes were included in the study. Patients of CL, who had received or were receiving systemic treatment were excluded. The lesions having marked secondary bacterial infection were also excluded. Initial diagnosis was clinical. History of being to an endemic area supported the diagnosis. The lesions were divided in two groups. Early, with duration less than 03 months and late, with duration between 3 and 12 months. The clinical lesions were noted as nodules, plaques, ulcers, crusted ulcers, lupoid lesions and plaques with scarring. Three types of skin smears (slit skin smear, saline aspirate smear and dab smear) were taken and examined with Giemsa stain. Cultures were performed on Nicolle-Novy-MacNeal (NNN) culture medium from Defense Scientific and Technology Organization (DESTO) Lab., Pakistan. Incisional skin biopsies were done. The biopsy specimens were examined by hemotoxylin and eosin stain (H & E stain). The number of Leishmania Tropica (LT) bodies was graded according to modified Ridley's parasitic index 1983. Clinical features were correlated with the histological patterns. Five histological patterns were identified in current study: 1) diffuse dermal infiltration without necrosis, 2) patchy dermal infiltration, 3) diffuse dermal infiltration with necrosis, 4) early reactive granuloma formation and 5) established epithelioid granuloma formation. LT bodies were identified in 75% of cases. Epidermal features were non-specific. The early lesions presented with diffuse infiltrate and late lesions showed granuloma formation. Five distinct types of histological patterns of CL have been recognized in this study. The early lesions presented with diffuse infiltrate and late lesions showed granuloma formation but the mixed patterns were also seen. The yield of LT bodies is much higher with histopathology as compared to skin smears and hence is most diagnostic.

Peripheral T‐Cell Lymphoma with Secondary Epithelioid Granulomatous Cutaneous Involvement: A Clinicopathologic Study of Four Cases

Epithelioid granuloma formation has rarely been observed in specific cutaneous lesions from T-cell lymphomas other than those of mycosis fungoides/Sézary syndrome (MF/SS). Three patients diagnosed with nodal and/or extranodal (tonsillar) non-Hodgkin's peripheral T-cell lymphoma (PTCL) and one patient with angioimmunoblastic T-cell lymphoma (AILD), developed specific cutaneous involvement showing prominent epithelioid cell and/or granulomatous inflammation. The original diagnostic lesions had no granulomatous features. In addition to a specific lymphomatous infiltrate, prominent dermal and/or subcutaneous granulomatous infiltrates were observed. Sarcoid-like granulomas were observed in two patients (one of them presented a granuloma annulare-like pattern in early lesions), granulomatous panniculitis was noted in one patient and in one patient with AILD, masses of epithelioid cells were noted. The clinicopathological features of cutaneous involvement by PTCL showing a florid epithelioid and/or granulomatous cell reaction are reviewed. Various histopathological patterns can be observed. The diagnostic difficulties of these cases are stressed.

Secondary Syphilis Presenting as Cutaneous T‐Cell Lymphoma in an HIV‐Positive Patient

We present the case of an HIV‐positive 38‐year‐old Caucasian male with a history of fevers, chills, and disseminated nonpruritic erythematous papules that began on his abdomen. An initial skin biopsy revealed a lymphohistiocytic infiltrate at the dermoepidermal junction, exocytosis of atypical lymphocytes, and minimal spongiosis. Immunohistochemistry showed increased CD8‐positive cells but only scattered CD30‐positive cells. PCR analysis demonstrated T‐cell receptor gamma gene rearrangement. RPR, blood and tissue cultures were all negative. The patient was thought to have a cytotoxic cutaneous T‐cell lymphoma. Over time, the lesions progressed to the palms and soles and the patient remained febrile. Repeat biopsy demonstrated a lichenoid interface dermatitis with a superficial and deep perivascular, interstitial, and periadnexal lymphohistiocytic infiltrate and the formation of epithelioid granulomas throughout the dermis. The epidermis showed blurring of the dermoepidermal junction, spongiosis, and exocytosis of lymphocytes and neutrophils. Few spirochetes were demonstrated by Steiner stain. Repeat RPR and FTA‐Abs serologies were positive. The patient was diagnosed with late secondary syphilis and was successfully treated with benzathine penicillin. This case demonstrates that atypical lymphoid infiltrates can simulate mycosis fungoides in an HIV‐positive patient with secondary syphilis and also reiterates that syphilis is a great mimicker of other entities.

A Clinicopathologic Case Report of Inflammatory Pseudotumors Involving the Conjunctiva and Lung

Inflammatory pseudotumors are characterized histopathologically by aggregates of inflammatory lymphocytes, plasma cells, neutrophils, and fibroblasts. We report a rare case of inflammatory pseudotumor involving both the conjunctiva and lung. A 58-year-old man with a 6-year history of pulmonary inflammatory pseudotumor was referred to our hospital for evaluation of conjunctival swelling in the left eye and bilateral iritis. The subconjunctival tumor enlarged slowly, but regressed spontaneously. After partial resection of the subconjunctival and lung tumors, the presence was confirmed of aggregates of chronic inflammatory cells (lymphocytes, plasma cells, neutrophils, fibroblasts) without noncaseating epithelioid granuloma formation. Gene rearrangement testing ruled out malignancy. The patient was treated with oral corticosteroids for fever and primary biliary hepatic cirrhosis. Iritis signs subsided slightly in response to corticosteroids, but persisted. The temporal subconjunctival pseudotumor resolved without recurrence. This case was compatible histopathologically with inflammatory pseudotumor, and is a rare case of simultaneous occurrence in the lung and conjunctiva.

Osteopontin is involved in the formation of epithelioid granuloma and bile duct injury in primary biliary cirrhosis.

Recently, it was shown that osteopontin (OPN) is involved as a chemoattractant cytokine in the recruitment of macrophages and T lymphocytes in the granulomas of diverse etiologies and also plays an important role in the production of autoantibodies and development of autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by immune-mediated bile duct damage with frequent epithelioid granulomas. In this study, the expression of OPN was immunohistochemically examined in 25 PBC and 52 control livers. Epithelioid cells within granuloma in PBC expressed OPN variably. These cells were also positive for CD68, suggesting their histiocyte/macrophage lineage. In addition, strong expression of OPN was seen in the cytoplasm of mononuclear cells infiltrating around granulomas and also damaged bile ducts in PBC. The number of such positive mononuclear cells and the ratio of OPN-positive cells/total infiltrating cells in portal tracts were higher in PBC than in controls. The majority of these OPN-positive cells were found to be IgG- or IgM-producing plasma cells. These suggest that in PBC, OPN is an important immune molecule in portal tracts, and contributes to the recruitment of mononuclear cells into epithelioid granuloma and also participates in bile duct injury via B-cell differentiation and plasma cell expansion.

Growth factor-expressing mast cells accumulate at the thyroid tissue-regenerative site of subacute thyroiditis.

The localization and biological roles of the multifunctional cell type mast cells remain unclear in subacute thyroiditis that is characterized by both epithelioid granuloma formation and thyroid tissue repair. We examined their immunolocalization with tryptase of a mast cell marker, using the biopsy specimens from 12 cases. In the epithelioid granuloma, no mast cells were detected in any of the cases, although a small number of them (4.6 +/- 2.4) were seen at the fibrous stroma around the granuloma in all cases. By contrast, in all cases, increased mast cells (28 +/- 7.2) localized at the thyroid tissue-regenerative site where both thyroid folliculogenesis and angiogenesis take place. To elucidate possible roles of mast cells in the disease, we also examined their immunoexpressions of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF), which affect thyroid folliculogenesis and angiogenesis. In all 12 cases, mast cells displayed all of these growth factors in a manner not specific to the infiltrating site. The data suggest that growth factor-expressing mast cells may play crucial roles in the thyroid tissue repair of subacute thyroiditis, modulating thyroid folliculogenesis and angiogenesis; and that the multifunctionality of the cells may be partly dependent on their expressions of various growth factors.

Covalent binding of proteins to grafted plastic surfaces suitable for immunoassays. II. Picograms of IgE detected in BAL fluid in sarcoidosis

An ELISA is described for the quantitation of minute amounts of human IgE using microtiter strips which were surface modified according to a procedure previously described. This ELISA used an IgG fraction of a rabbit polyclonal anti-IgE antibody coupled to the carboxylated surface, which prior to coupling had been preactivated with a water soluble carbodiimide. A biotinylated affinity purified rabbit anti-IgE antibody was used together with streptavidin conjugated alkaline phosphatase and biotinylated enzyme for the detection of bound analyte. Sarcoidosis is a systemic disorder of as yet unknown cause with epithelioid granuloma formation in the lung as a prominent feature. With the bronchoalveolar lavage technique, epithelial lining fluid was obtained and analyzed for IgE content since differences of immunoglobulin concentration in bronchoalveolar lavage fluid (BALF) may reflect disease activity. Our modified ELISA system was used for measuring IgE in BALF from healthy controls and sarcoid patients. The assay using modified strips demonstrated a considerably improved sensitivity compared to the use of physical adsorption of first antibody to untreated strips. The detection limit of the improved assay was approximately 3 pg IgE/sample (100 μl). Quantitative recovery of IgE was demonstrated within the measuring range (51.2–12 500 pg IgE/ml) and more than 40% (23/54) of the sarcoid patients showed values above the lowest standard concentration (51.2 pg/ml). In contrast, none of the healthy controls (0/22) had detectable IgE as defined by the detection limit of the assay.