Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

Activity of Antioxidant Enzymes in the Regional Blood Flow during Pelvic Venous Disorders in Women.

Activity of some antioxidant enzymes (superoxide dismutase, catalase, and glutathionedependent enzymes), as well as the level of LPO products in the region regional blood flow (collateral branches of the main trunks of ovarian veins) in women with pelvic venous disorders were studied. A compensatory increase in activity of superoxide dismutase, catalase, and glutathione peroxidase during stage I of the disease was found; during stage II, superoxide dismutase activity decreased and glutathione peroxidase increased, while during stage III, pronounced decrease in activities of all studied enzymes was observed. The level of lipid peroxidation products in the regional blood flow increased as the disease progressed, with maximum values in the third stage.

Guidance for diagnosing autoimmune pancreatitis with biopsy tissues.

The biopsy-based diagnosis of autoimmune pancreatitis (AIP) is difficult but is becoming imperative for pathologists due to the increased amount of endoscopic ultrasound-guided biopsy tissue. To cope with this challenge, we propose guidance for the biopsy diagnosis of type 1 AIP. This guidance is for pathologists and comprises three main parts. The first part includes basic issues on tissue acquisition, staining, and final diagnosis, and is intended for gastroenterologists as well. The second part is a practical guide for diagnosing type 1 AIP based on the AIP clinical diagnostic criteria 2018. Inconsistent histological findings, tips for evaluating IgG4 immunostaining and key histological features including the ductal lesion and others are explained. Storiform fibrosis and obliterative phlebitis are diagnostic hallmarks but are sometimes equivocal. Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Examples of each are provided. The third part describes the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC), focusing on histological features of acinar-ductal metaplasia in AIP, which is an important mimicker of PDAC. This guidance will help standardize pathology reports of pancreatic biopsies for diagnosing type 1 AIP.

Efficacy and limitations of the histological diagnosis of type 1 autoimmune pancreatitis with endoscopic ultrasound-guided fine needle biopsy with large tissue amounts.

OBJECTIVES: We examined the efficacy and limitations of acquiring large specimens by endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for diagnosing type 1 autoimmune pancreatitis (AIP). METHODS: Patients from 12 institutions with non-neoplastic diseases or pancreatic ductal adenocarcinoma (PDAC) with large EUS-FNB specimens were investigated. Slides stained with hematoxylin-eosin, elastic, IgG4, and IgG stains were evaluated. The IgG4- and IgG-positive cell numbers were counted in three foci. The diagnoses were based on the Japan Pancreas Society 2011 (JPS 2011) criteria and the International Consensus Diagnostic Criteria (ICDC). RESULTS: We analyzed 85 non-neoplastic (definite type 1 AIP in 73/85 based on the ICDC) cases and 64 PDAC cases. IgG4-positive cells were numerous (>10 in 85.9%), and the IgG4/IgG ratios were high (>40% in 81.2%). Plasma cell crushing by an artifact caused unsuccessful immunostaining, notably in smaller samples. Tissue lengths were an important factor for the presence of storiform fibrosis and obliterative phlebitis, but storiform fibrosis was equivocal even in large tissues. A definite or possible histological diagnosis was achieved in 45.9% (39/85) and 41.2% (35/85), respectively, and contributed to the definite final diagnosis of type 1 AIP in 33.3% (ICDC) and 55.6% (JPS 2011) in cases with segmental/focal lesions. In the PDAC group, >10 IgG4-positive cells was rare (2/58), but elastic stains revealed fibrous venous occlusions in 10.3% (6/58). CONCLUSIONS: EUS-FNB with large tissue amounts was useful for diagnosing type 1 AIP, notably by facilitating successful IgG4 immunostaining, but definite diagnosis may not be achieved even in cases with large specimens.

Pathological characteristics and diagnosis of IgG4-related disease.

IgG4-related disease (IgG4-RD) has been accepted as a distinct entity in various fields. It is being increasingly diagnosed and treated in routine practice. However, difficulties are still associated with the diagnostic process. Serum IgG4 elevations and imaging studies are useful, but not entirely diagnostic for this condition. Therefore, a pathological examination still plays an important role. Three characteristic microscopic changes are dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. IgG4 immunostaining reveals many IgG4-positive plasma cells and an IgG4/IgG-positive cell ratio of more than 40%. In addition to the number and ratio of IgG4-positive plasma cells, the diffuse distribution of positive plasma cells needs to be confirmed because IgG4-positive plasma cells may focally aggregate in many other conditions. In small biopsy samples, it is important to recognize not only characteristic findings, but also microscopic changes that are unlikely to occur in IgG4-RD because the identification of the latter findings leads to the exclusion of this condition. Another challenging field regards the diagnosis of long-standing disease. Along with disease progression, inflammatory infiltrate decreases, while storiform fibrosis and obliterative phlebitis are suspected to persistently exist. Therefore, the recognition of the latter two findings will be a diagnostic clue. Given the general suspicion that IgG4-RD has recently been over-diagnosed, precise tissue examinations based on the proposed standards and close clinicopathological correlations are crucial.

Enterocolic lymphocytic phlebitis with marked myointimal hyperplasia and perivenous concentric fibrosis.

Enterocolic lymphocytic phlebitis (ELP) is a rare enteropathy characterized by lymphocytic phlebitis of the mesenteric veins without arteritis. Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare disease similar to ELP, characterized by myointimal hyperplasia that constricts the lumen of veins, causing mucosal injury. A 62-year-old man with chief complaint of abdominal pain was treated by partial resection of the ileum after 3 months of conservative therapy. The pathologic diagnosis was ELP with prominent myointimal hyperplasia. Histologically, the lesion consisted of lymphocytic infiltration into the vein accompanied by prominent myointimal hyperplasia and perivenous concentric fibrosis, which are characteristics shared by ELP and IMHMV. The observations in this case suggest that some of ELP and IMHMV may belong to the same disease spectrum. Furthermore, perivascular concentric fibrosis was a remarkable observation that may contribute to differential diagnosis between ELP and "true" IMHMV.

Caracterización histológica y clínica de pacientes con enfermedad relacionada con inmunoglobulina G4 en un centro de alta complejidad en Cali, Colombia / Histological and clinical characteristics of cases of immunoglobulin G4-related disease in a tertiary hospital, in Cali, Colombia

Introducción: La enfermedad relacionada con inmunoglobulina G4 (IgG4) ha sido reconocida durante la última década. Es una condición fibroinflamatoria con capacidad de comprometer casi cualquier órgano. El diagnóstico requiere la confirmación histológica, clínica y paraclínica. En Colombia, este es el estudio con mayor número de casos. Objetivo: Describir las características clínicas e histopatológicas de los pacientes diagnosticados con enfermedad relacionada con IgG4 en la Fundación Valle del Lili. Métodos: Estudio observacional descriptivo retrospectivo. Se revisaron los registros clínicos y patológicos de pacientes a quienes se les diagnosticó enfermedad relacionada con IgG4 en la institución. Se utilizó estadística descriptiva. Resultados: Entre 2013 y 2016 se diagnosticaron 16 pacientes. La mediana de edad fue 44 años, rango intercuartílico 30-58 y 10 (62,5%) fueron mujeres. La presentación clínica más común fue la asociación de masa+síntomas constitucionales+síntomas relacionados con el sitio de localización 43,8% (n=7). No hubo predominancia por algún órgano. En la histopatología todos presentaron infiltrado linfoplasmocitario y fibrosis estoriforme, el 75% flebitis obliterante; en todos los casos se evidenció≥10 células/CAP de IgG4+ y el 81% tuvieron una razón de IgG4+/IgG+>50%. Conclusión: Dada la baja sospecha y el amplio espectro clínico, se cree que existe un subdiagnóstico de la enfermedad. De acuerdo a nuestros hallazgos se recomienda que ante la presencia de infiltrado linfoplasmocitario, fibrosis estoriforme o flebitis obliterante en la evaluación histológica, se solicite inmunohistoquímica para IgG e IgG4, cuya positividad deberá ser correlacionada con estudios complementarios para la confirmación diagnóstica

Introduction: Immunoglobulin G4 (IgG4)-related disease has been described in the last decade. It is a fibro-inflammatory condition capable of affecting almost every organ and diagnosis requires both clinical and paraclinical confirmation. We present the largest study to date in Colombia. Objective: To describe the clinical and histopathological characteristics of patients diagnosed with IgG4-related disease at the Fundación Valle del Lili. Methods: Observational-descriptive retrospective study. The clinical and pathological records of patients diagnosed with IgG4-related disease at the Fundación Valle del Lili were reviewed and a descriptive statistical analysis made. Results: From 2013-2016, 16 patients were diagnosed. Median age was 44 years (RIC 30-58) and 10 (62.5%) were women. The most common clinical presentation was a combination of a tumefactive mass, constitutional symptoms and site-related symptoms (43.8%) (n=7). No preference for any organ was seen. Histopathology revealed all cases had dense lymphoplasmacytic infiltrate and storiform-type fibrosis; 75% also had obliterative phlebitis. In all cases≥10 cells/HPF of IgG4+ were found and 81% had a ratio of IgG4+/IgG+>50%. Conclusion: IgG4-related disease appears to be underdiagnosed, probably due to its broad clinical spectrum as well as a low index of awareness among clinicians. We recommend that, when dense lymphoplasmacytic infiltrates, storiform-type fibrosis or obliterative phlebitis are found, immunohistochemistry for IgG and IgG4should be requested. Positive results then must be correlated with complementary studies to confirm the disease

Severe Phlebitis Accompanying Vascular Rejection Type Acute T Cell-Mediated Rejection in Renal Transplantation.

PURPOSE: Renal transplant patients with vascular rejection type acute T cell-mediated rejection (ATCMR) grade II have a poor prognosis. Vascular lesions in those cases are thought to randomly occur, thus we searched for a novel pathological marker related to vascular rejection in kidney transplantation. METHODS: We determined pathological characteristics in 14 ATCMR grade II patients treated during an acute phase from 2004 to 2013. We then examined whether those findings appeared in transplant kidney biopsy specimens, except for cases of vascular rejection, in patients examined from 2010 to 2014. RESULTS: In 9 of the 14 ATCMR grade II patients, phlebitis was accompanied by inflammatory cells that formed polypoid projections in the venous lumen and partial disappearance of vascular endothelium. Further investigation showed those inflammatory cells to be T cells and macrophages. Histological findings revealed coexisting phlebitis in 2 of 13 patients with ATCMR grade I, 3 of 24 with borderline changes, and none with normal findings. Phlebitis occurred at a significantly greater rate than the other findings in cases of vascular rejection (P < .05). However, there was no significant difference in regard to graft survival between patients with and without phlebitis (P = .1829). CONCLUSION: Our results suggest severe phlebitis as a novel finding associated with the pathology of vascular rejection in patients with a renal allograft.

[Histological and clinical characteristics of cases of immunoglobulin G4-related disease in a tertiary hospital, in Cali, Colombia]. / Caracterización histológica y clínica de pacientes con enfermedad relacionada con inmunoglobulina G4 en un centro de alta complejidad en Cali, Colombia.

INTRODUCTION: Immunoglobulin G4 (IgG4)-related disease has been described in the last decade. It is a fibro-inflammatory condition capable of affecting almost every organ and diagnosis requires both clinical and paraclinical confirmation. We present the largest study to date in Colombia. OBJECTIVE: To describe the clinical and histopathological characteristics of patients diagnosed with IgG4-related disease at the Fundación Valle del Lili. METHODS: Observational-descriptive retrospective study. The clinical and pathological records of patients diagnosed with IgG4-related disease at the Fundación Valle del Lili were reviewed and a descriptive statistical analysis made. RESULTS: From 2013-2016, 16 patients were diagnosed. Median age was 44 years (RIC 30-58) and 10 (62.5%) were women. The most common clinical presentation was a combination of a tumefactive mass, constitutional symptoms and site-related symptoms (43.8%) (n=7). No preference for any organ was seen. Histopathology revealed all cases had dense lymphoplasmacytic infiltrate and storiform-type fibrosis; 75% also had obliterative phlebitis. In all cases≥10 cells/HPF of IgG4+ were found and 81% had a ratio of IgG4+/IgG+>50%. CONCLUSION: IgG4-related disease appears to be underdiagnosed, probably due to its broad clinical spectrum as well as a low index of awareness among clinicians. We recommend that, when dense lymphoplasmacytic infiltrates, storiform-type fibrosis or obliterative phlebitis are found, immunohistochemistry for IgG and IgG4should be requested. Positive results then must be correlated with complementary studies to confirm the disease.

Evidence and role of phlebitis and lipid infiltration in the onset and pathogenesis of Wooden Breast Disease in modern broiler chickens.

Wooden Breast Disease (WBD), a myopathy that frequently affects modern broiler chickens, is a disorder that has been associated with significant economic losses in the poultry industry. To examine tissue changes associated with the onset and early pathogenesis of this disorder, a time-series experiment was conducted using chickens from a high-breast-muscle-yield, purebred commercial broiler line. Birds were raised for up to seven weeks, with a subset of birds sampled weekly. Breast muscle tissues were extracted at necropsy and processed for analysis by light microscopy and transmission electron microscopy. Histologic presentation indicated localized phlebitis with lipogranulomas in Week 1, focal single-myofibril degeneration in Week 2 preceding an inflammatory response that started in Week 3. Lesions in Week 4 were characterized by multifocal to diffuse muscle fibre degeneration, necrosis, interstitial oedema accompanied by increased lipid and inflammatory cell infiltration. Lesions in Weeks 5-7 revealed diffuse muscle degeneration, necrosis, fibrosis and fatty infiltration with lipogranulomas. Ultrastructural examination showed myofibrillar splitting and degeneration, irregular, displaced and degenerated Z-lines, mitochondrial degeneration and interstitial fibrosis with dense regular collagen fibres. This study, therefore, demonstrates that WBD exhibits an earlier onset in modern broilers than when detectable by clinical examination. Further, this study shows that the disease assumes a progressive course with acute vasculitis, lipid deposition and myodegeneration occurring in the earlier stages, followed by a chronic fibrotic phase.

[IgG4 immunohistochemistry in Riedle thyroiditis].

Objective: To observe the histopathological changes and immunohistochemical expression of IgG4 in Riedle thyroiditis (RT) and to study the relationship between RT and IgG4-related diseases (IgG4-RD). Methods: A total of 5 RT patients were collected from the Department of Pathology, Peking Union Medical College Hospital during April 2012 to August 2014. The clinical and immunohistochemical features were analyzed in the 5 patients. Histopathologic analysis was performed on hematoxylin and eosin-stained sections. Results: There were one male and four female patients, aged 52 to 78 years (median 59 years). Five cases were characterized by multiple nodules of thyroid, which increased year by year. All patients were found to have surrounding tissue compression symptoms and signs. Two female patients were found to have hypothyroidism. The serum concentration of IgG was elevated in 2 cases, and the serum concentration of IgG was not tested before operation in the remaining patients. By ultrasound, all presented as low echo or medium low echo. Strong echo occasionally appeared in hypoechoic nodules. Microscopically, fibrous tissue hyperplasia was infiltrated with varying numbers of lymphocytes and plasma cells. The occlusion of phlebitis was found in 4 cases and eosinophils were found in 3 cases. IgG4 counts and IgG4/IgG ratios in 5 cases were 20/HPF, 16%; 60/HPF, 82%; 22/HPF, 28%; 400/HPF, 266% and 33/HPF, 71%, respectively. Conclusions: With the similar pathological manifestations between RT and IgG4-RD, immunohistochemical staining shows that the number of IgG4 positive plasma cells and IgG4/IgG ratio of RT are increased in varying degrees. Some cases meet the diagnostic criteria of IgG4-RD, and speculate that some cases of RT belong to IgG4-RD.

Segmental colitis caused by idiopathic myointimal hyperplasia of mesenteric veins.

Diseases causing colonic ischemia may be mistaken with other causes of segmental colitis such as inflammatory bowel disease, especially in young patients. The authors present the case of a 47-year-old male with severe proctosigmoiditis. Assessment excluded infectious causes, thrombophilia and systemic vasculitis. The initial histological specimen was suggestive of inflammatory bowel disease and therapy was initiated with intravenous steroids and, at day 5, infliximab, with no response. The patient was proposed for surgery. Pathological examination of the surgical specimen revealed an idiopathic myointimal hyperplasia of mesenteric veins, a rare entity exhibiting necrotizing phlebitis with rapid progression to segmental necrosis in the rectosigmoid colon. In this paper the authors discuss the differential diagnosis of proctosigmoiditis in young ages and the approach to this exceptionally rare ischemic entity.

Central nervous system granulomastous phlebitis with limited extracranial involvement of the heart and lungs: An autopsy case.

Primary angiitis of the central nervous system is a rare condition, usually with an insidious onset. There is a wide variety of histological types (granulomatous, lymphocytic or necrotizing vasculitis) and types of vessel involved (arteries, veins or both). Most cases are idiopathic. We describe a first case of idiopathic granulomatous central nervous system phlebitis with additional limited involvement of the heart and lung, exclusively affecting small and medium sized veins in a 22-year-old woman, presenting as a sub acute headache. The reasons for this peculiar limitation of inflammation to the veins and the involvement of the heart and lungs are unknown.

[Expression of IgG4 in Rosai-Dorfman disease and its significance].

OBJECTIVE: To study the prevalence of IgG4-positive plasma cells in Rosai-Dorfman disease and to assess the association between Rosai-Dorfman disease and IgG4-related sclerosing disease (IgG4-SD). METHODS: The clinicopathologic features of 12 tissue samples of Rosai-Dorfman disease (11 extranodal and one nodal) from nine patients were reviewed. The degree of fibrosis and occlusive phlebitis was studied by HE staining. The expression of IgG4 and IgG in plasma cells were studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system. RESULTS: Nine tissue samples showed different degree of fibrosis (four tissue samples were mild, one tissue sample was moderate and four tissue samples were severe) and two tissue samples showed occlusive phlebitis in the lesional tissue. Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (> 50 per high-power field) in four tissue samples, moderate infiltration (30 to 50 per high-power field) in two tissue samples, mild (10 to 29 per high-power field) in three cases and negative infiltration (< 10 per high-power field) in three tissue samples (P < 0.01). Three tissue samples fulfilled the diagnostic criteria of IgG4-SD (> 50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including one tissue sample each of Rosai-Dorfman disease in the left facial skin, above the left eye socket, and in the right parotid. CONCLUSIONS: Some cases of Rosai-Dorfman disease fulfill the diagnostic criteria and show the histologic features of IgG4-SD. They may represent members of the IgG4-SD spectrum. The detection of IgG4-positive plasma cells in the lesional tissues of Rosai-Dorfman disease may have clinical pathological significance.

MANAGEMENT OF OMPHALOPHLEBITIS AND UMBILICAL HERNIA IN THREE NEONATAL GIRAFFE (GIRAFFA CAMELOPARDALIS).

Umbilical disorders, including omphalophlebitis, omphaloarteritis, external umbilical abscesses, urachal abscesses, patent urachus, and umbilical hernias, represent a significant challenge to the health and well-being of a neonate. The three neonatal giraffe (Giraffa camelopardalis) in this report were evaluated for umbilical swellings. Two developed omphalophlebitis, and one had an uncomplicated umbilical hernia. Omphalophlebitis is an inflammation and/or infection of the umbilical vein. Giraffe calves with a failure of passive transfer may be predisposed and should be thoroughly evaluated for the condition. Umbilical hernias result from a failure of the umbilical ring to close after parturition or from malformation of the umbilical ring during embryogenesis. These problems were surgically corrected for all three individuals, although one died due to postsurgical complications. The risks involved include anesthetic complications, surgical dehiscence, and maternal rejection. Early detection and surgical intervention are recommended for the correction of omphalophlebitis and umbilical hernias in neonatal giraffe.