Crystal induced arthropathies-a comparative study of 40 patients with apatite rheumatism, chondrocalcinosis and primary synovial chondromatosis.

Introduction: Apatite rheumatism (AR), chondrocalcinosis (Ch-C), and primary synovial chondromatosis (prSynCh) are regarded as distinct clinical entities. The introduction of the non-staining technique by Bély and Apáthy (2013) opened a new era in the microscopic diagnosis of crystal induced diseases, allowing the analysis of MSU (monosodium urate monohydrate) HA (calcium hydroxyapatite), CPPD (calcium pyrophosphate dihydrate) crystals, cholesterol, crystalline liquid lipid droplets, and other crystals in unstained sections of conventionally proceeded (aqueous formaldehyde fixed, paraffin-embedded) tissue samples. The aim of this study was to describe the characteristic histology of crystal deposits in AR, Ch-C, and prSynCh with traditional stains and histochemical reactions comparing with unstained tissue sections according to Bély and Apáthy (2013). Patients and methods: Tissue samples of 4 with apatite rheumatism (Milwaukee syndrome), 16 with chondrocalcinosis, and 20 with clinically diagnosed primary synovial chondromatosis were analyzed. Results and conclusion: Apatite rheumatism, chondrocalcinosis, and primary synovial chondromatosis are related metabolic disorders with HA and CPPD depositions. The authors assume that AR and Ch-C are different stages of the same metabolic disorder, which differ from prSynCh in amorphous mineral production, furthermore in the production of chondroid, osteoid and/or bone. prSynCh is a defective variant of HA and CPPD induced metabolic disorders with reduced mineralization capabilities, where the deficient mineralization is replaced by chondroid and/or bone formation. The non-staining technique of Bély and Apáthy proved to be a much more effective method for the demonstration of crystals in metabolic diseases than conventional stains and histochemical reactions.

Adult hemangioma of the pancreas: difficult diagnosis of a rare disease.

Adult pancreatic hemangiomas are rare. We report a new case and review the literature. Pancreatic hemangiomas do not produce specific symptoms, so diagnosis is not easy. Computed tomography is often misleading, since pancreatic hemangiomas behave differently from liver hemangiomas, which are more frequently seen. Instead of showing arterial peripheral nodular enhancement followed by centripetal filling they take up the contrast material more slowly and the filling is usually inhomogeneous, which may give the impression of a cystic tumor. The reason for this may be that the microscopic structure of the pancreatic hemangioma is different from that of the liver. It partly consists of thin-walled sinusoids which do not communicate with the circulation of the patient. Since no malignant cases have been published to date, surgical resection might be avoided if the diagnosis can be firmly established.

[Conceptual and hypothetical contributions to the pathogenesis of enteritis regionalis (Crohn's disease)]. / Gondolatok és hipotézis az emberi enteritis regionalis (Crohn-betegség) patogeneziséhez.

Crohn's disease (CD) is a multifactorial disorder. The aim of this study was to clarify the pathogenesis of CD by analyzing the clinical data of patients treated at our institute in the last ten years. The authors observed several clinical, pathological and submicroscopic features of Crohn's disease which are characteristic of Selye's concept of stress. The authors propose the hypothesis that CD is initiated by some non-specific chronic stressors which impede cellular homeostasis in the early phase of the disease. Accordingly, extrinsic factors alter the permeability of the very sensitive surface- and intracellular dynamic "liquid" lipoprotein membranes. The primary cell-membrane damage leads to the development of erosions and ulcers which become gateways for intramural penetration of pathogenic microbes from the bowel flora. Thus the changes of the terminal ileum do not represent the initial, but presumably a later stage of the disease. Histological and ultrastructural abnormalities of membrane-structures were found in patients with CD, suggesting, that extra-intestinal manifestations of CD may be explained by these membrane-structural changes in the cells of the neuroendocrine system. Namely, the wall of small blood vessels, the myelinated nerves and some parts of the retina are also rich in such membranes. Several data in the literature indicate that premature birth, damage of embryo and fetus are more frequent in mothers with CD, and these damages are associated with the deleterious effect of glucocorticoids.

Recurrent pancreatic arteritis and vasculogenic relapsing pancreatitis in rheumatoid arthritis - a retrospective clinicopathologic and immunohistochemical study of 161 autopsy patients.

The aim of this study was to determine: the prevalence, and histological characteristics of vasculitis in the pancreas, and to follow the formal pathogenesis of multifocal pancreatitis due to arteritis and/or arteriolitis (multifocal vasculogenic pancreatitis). A randomized autopsy population of 161 in-patients with rheumatoid arthritis (RA) was studied. Systemic vasculitis (SV) complicated RA in 36 (22.36%) of 161 cases; tissue samples of pancreas were available for histologic evaluation in 28 patients. Pancreatitis and vasculitis were characterized histologically and immunohistochemically. Vasculogenic, multifocal pancreatitis was not recognized clinically. Vasculitis of the pancreatic arterioles and small arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischaemia and to regressive changes in the pancreas. This vasculogenic process is more or less widespread and multifocal, depending on the number of involved vessels and is followed by reactive inflammation, depending on the stages of the pathological process. Because of the recurrent nature of vasculitis with time these regressive changes accumulate within the pancreas and may contribute to an unexpected circulatory failure and sudden death of the patient. Vasculogenic microinfarcts in the pancreas may be clinically characterized by unexplained recurrent abdominal symptoms and spontaneous remissions which insidiously may lead to metabolic failure resistant to therapy.

[Lethal complications and associated diseases of rheumatoid arthritis--a retrospective clinicopathologic study of 234 autopsy patients]. / Szövodmények és társult megbetegedések rheumatoid arthritisben--234 elhunyt beteg patológiai és klinikai adatainak retrospektív elemzése.

OBJECTIVE: Complications and/or associated diseases in rheumatoid arthritis can present atypical clinical manifestations which may lead to an incorrect or delayed diagnosis. The aim of this study was to determine: (1) the complications of rheumatoid arthritis, the accompanying diseases, and the mortality of these, (2) the clinically missed diagnoses of complications and/or associated diseases, (3) the possible links between coexistent complications of rheumatoid arthritis and/or diseases associated with it, furthermore the possible role of these in the mortality of rheumatoid arthritis patients. METHODS: Between 1970 and 1999 10,860 patients died at the National Institute of Rheumatology, and among them 234 with rheumatoid arthritis (diagnosed clinically according to the criteria of the American College of Rheumatology). The associated and basic disease, complication(s), and causes of death were determined on the basis of clinical records and in each case the autopsy findings were confirmed by a review of extensive histological material (50-100 tissue blocks from each patient). RESULTS: The complications of rheumatoid arthritis led to death in 152 (65%) of 234 patients. The complications of RA were clinically recognized in 109 (46.6%, 71.7 rel%) and missed in 43 (18.4% 28.3 rel%) of 152 patients. More than two thirds of lethal complications related to rheumatoid arthritis were diagnosed clinically. The remaining 82 (35%) of 234 rheumatoid arthritis patients died of associated diseases; the cause of death was clinically recognized in 78 (33.3%, 95.1 rel%) of 82 cases. There was a significant and positive correlation (1) between vasculitis and cardiac insufficiency (chi2 = 6.37, p <0.01), vasculitis and tuberculosis (chi2 = 4.18, p <0.04), or miliary tuberculosis (chi2 = 3.86, p <0.04); (2) between tuberculosis and miliary tuberculosis (chi2 = 54.84, p <0.001); and (3) between septic infection and purulent arthritis (chi2 = 97.04, p <0.001). There was a significant and inverse correlation between atherosclerosis and vasculitis (chi2 = 5.10, p <0.02), atherosclerosis and amyloidosis (chi2 = 14.58, p <0.001), or atherosclerosis and septic infection (chi2 = 3.81, p <0.05). There was a significant and inverse correlation between atherosclerosis and lethal cases of vasculitis (chi2 = 9.31, p <0.002), of amyloidosis (chi2 = 6.82, p <0.009), of sepsis (chi2 = 3.81, p <0.05) furthermore, between atherosclerosis with lethal outcome (n = 60 of 106) and vasculitis (chi2 = 12.06, p <0.001), or amyloidosis (chi2 = 13.22, p<0.002), or sepsis (chi2 = 10.82, p <0.001), or purulent arthritis (chi2 = 4.18, p <0.04). CONCLUSION: The most important life threatening complications of rheumatoid arthritis (vasculitis, AA amyloidosis and sepsis) are present and lead to death with higher probability in the younger age group (without atherosclerosis), while in older patients who have atherosclerosis these represent a lower risk of death.

Sensitivity and specificity of Congo red staining according to Romhányi. Comparison with Puchtler's or Bennhold's methods.

The sensitivity and specificity of various Congo red staining methods is very important in the diagnosis of amyloidosis. When using a less sensitive staining method, some true positive cases of amyloidosis remain undetected. A more highly specific method potentially detects more cases and reveals amyloidosis in an earlier stage of deposition. In this paper, the Congo red staining method according to Romhányi is discussed in comparison with Puchtler's and Bennhold's methods. Using Romhányi's technique, there is no alcoholic differentiation, and thus no dye molecules are washed off the amyloid filaments. The binding of the oriented dye molecules is optimal for polarization microscopy. With this method, the polar hydrophilic mounting medium, gum Arabic is used. Mounted in this carbohydrate-containing, hydrophilic medium, the Congo red molecules are oriented parallel to the surface of the amyloid filaments and the sign is linear positive, corresponding to an additive character of topo-optical staining reactions. Otherwise, the Congo red molecules are oriented perpendicular to the surface of collagen, reducing the intensity of birefringence and even inducing an inversion of the original sign of the collagen birefringence. With alcoholic differentiation, Congo red dye molecules are extracted and this decreases the birefringence of amyloid deposits, i.e. minimal amyloid deposits may be missed. Using the apolar hydrophobic mounting medium, Canada balsam, an axis-parallel arrangement of Congo red dye molecules on the surface of collagen fibers and amyloid will occur, resulting in an additive topo-optical reaction with a green polarization color and a false positive diagnosis of amyloidosis ("phantom amyloidosis").

Electron microscopic characteristics of beta2-microglobulin amyloid deposits in long-term haemodialysis.

The electron microscopic features of beta2-microglobulin amyloid, deposited in the synovial membrane, are presented and discussed. The patient, a 69-year-old woman underwent chronic hemodialysis for 3 years. Because of constant pain and destructive arthropathy, endoprosthesis of the hip joints were implanted. Extra- and intracellular filamentous-fibrillar amyloid deposits have been demonstrated in ultrathin sections. The extracellular amyloid deposits showed a loose, filamentous or fibrillar structure at the periphery and a dense central core. The loose, filamentous structure may represent an early stage of fresh, newly deposited beta2-microglobulin amyloid, while the condensed and fragmented amyloid filaments may be an advanced "mature" stage of amyloid deposition.

[Ultrastructural findings in the liver due to long-term retinol (isotretinoin) treatment. Significance of the perisinusoidal (Ito) cells]. / Retinoid (isotretionin) tartós kezelés mellékhatásait feltáró ultrastrukturális elváltozások a májban.

A twenty year old, foreign-born sportsman visited the Out-patient Clinic of our Hospital with complaints of progressive arthralgia, hepatomegaly and increasingly abnormal liver function tests of six months duration. Tests for virus hepatitis were negative, alcohol abuse or drug addiction could be excluded. An open needle biopsy of the liver was performed and the tissue was examined with the light and electron microscope. On routine light microscopy no abnormality was recognized. Electron microscopic examination revealed changes characteristic of vitamin A toxicity: hyperplasia of the perisinusoidal (Ito) cells with evidence of their activation and transformation, increased storage of lipids and vitamin A, perisinusoidal fibrosis, damage of the sinusoidal wall, partial necrosis in hepatocytes and an increased number of lysosomes, megalysosomes and smooth endoplasmic reticulum (SER), the signs of cholestasis as well as an increased number of Kupffer cells in the lobules etc. Histochemical examination showed a high content of vitamin A in the transitional (Ito) cells and in hepatocytes. These data led to further questioning of the patient who disclosed that he had acne conglobata which had been treated with Isotretionin, 20 mg/day, for more than half a year. After the therapy was stopped, the symptoms of polyarthralgia improved and after a few months they ceased entirely, however, the laboratory data returned to normal only after a long period of time. This case indicates that electron microscopic examination of the liver biopsy may play an important role in the recognition of vitamin A intoxication. It also illustrates that symptoms of joint disease may be caused by long-term retinoid treatment. The authors have presented the latest clinical and experimental data concerning the changes in the liver, joints and skeleton caused by retinoid intoxication.

Ultrastructural identification of primary tumor site from bone metastases.

The value of electron microscopy is demonstrated by ultrastructural identification of primary tumor site from bone metastases in 2 patients.