Six cases of microscopic polyarteritis exhibiting acute interstitial pneumonia

Out of 21 autopsy cases of microscopic polyarteritis (MPA), six cases that died of acute respiratory failure are described. All of these six cases exhibited pauci-immune necrotizing glomerulonephritis. Of these six cases, systemic vasculitis and respiratory failure occurred almost simultaneously in two, whereas respiratory failure developed when vasculitis recurred in the other four. Pathologically, pulmonary changes were diffuse and almost uniform in each case. Interstitial inflammatory cells (alveolitis), hyaline membrane, restructuring, and fibrosis were observed. The degrees of these changes differed from case to case; four cases showed predominantly exudative changes and two cases exhibited proliferative or organizing ones. Clinical and pathological features were consistent with acute interstitial pneumonia (Alp). lmmunofluorescent and ultrastructural studies did not suggest deposition of immune complexes at the lesions of alveolitis. An etiologic agent could not be identified in these cases. Some lung lesions inciuding pulmonary hemorrhage have been described in association with MPA; however, cases such as those presented here have rarely been reported. It was considered that AIP could be one of the pulmonary disorders in MPA. Furthermore, the possible pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in the evolution of present lung lesion is discussed. Although ANCA were not examined in the present cases, these antibodies should be investigated in future cases.     

Familial canine dermatomyositis. Initial characterization of the cutaneous and muscular lesions

Familial canine dermatomyositis is a recently identified disease of collie dogs that resembles human juvenile dermatomyositis. The lesions in the skin and muscles obtained by biopsy from two litters of dogs were characterized for the purpose of determining the similarity of the lesions to those of human dermatomyositis. The cutaneous lesions began between 7 and 11 weeks of age and were present on the face, lips, ears, and skin over bony prominences of the limbs, feet, sternum, and tip of the tail. Histologically the cutaneous lesions frequently consisted of vesicles, pustules, and ulcers on the lips, face, and ears. Neutrophils, lymphocytes, mast cells, and macrophages were present throughout the dermis. Neutrophils and lymphocytes were also present in and around vessels. Between 13 and 19 weeks of age generalized muscle atrophy was noted. The muscle lesions consisted of interstitial lymphocyte, plasma cell, macrophage, and neutrophil accumulation; myofiber degeneration, regeneration, and atrophy; and fibrosis. Perivascular neutrophils, lymphocytes, and plasma cells were also seen. Histologically, the lesions resembled those present in human juvenile dermatomyositis; and these observations, coupled with clinical, immunologic, and clinical pathologic observations presented elsewhere, suggest that familial canine dermatomyositis is an appropriate and potentially useful model for human juvenile dermatomyositis.     

General Pathology Of Kawasaki Disease

Systemic pathological alterations were studied in thirty-seven autopsied patients with Kawasaki disease. Systemic vasculitis was the most characteristic pathological finding and was present in all the patients. In addition to the vasculitis, there was a high incidence of inflammatory lesions in various organs and tissues: in the heart, endocarditis, myocarditis, and pericarditis; in the digestive system, stomatitis, sialoduct-adenitis, catarrhal enteritis, hepatitis, cholangitis, pancreatitis, and pancreas ductitis; in the respiratory system, bronchitis and segmental interstitial pneumonia; in the urinary system, focal interstitial nephritis, cystitis, and prostatitis; in the nervous system, aseptic leptomeningitis, choriomeningitis, ganglionitis, and neuritis; in the hematopoietic system, lymphadenitis, splenitis, and thymitis. Dermatitis, panniculitis or myositis were also observed in some patients. Therefore, Kawasaki disease is a systemic inflammatory disease which mainly affects the cardiovascular system. These systemic inflammatory lesions are considered to correspond to the variegated clinical manifestaitions. The relationship between Kawasaki disease and infantile polyarteritis nodosa (IPN) were discussed, based on the clinicopathological characteristics.     

Pulmonary function tests at different stages of toxic oil syndrome

The toxic oil syndrome is a new multisystemic disease, caused by ingestion of adulterated olive oil; this oil had a part of rapeseed oil, which was denatured with aniline for industrial use, and then re-refined. It is estimated that 20,000 people were more or less affected, the mortality being 1.7%. There is no clear pathogenetic mechanism, but the most probable is the generation of free radicals, caused by anilides. The clinical picture began with fever, acute interstitial pneumonia, pruritus, exanthems, myalgias and eosinophilia. The main pathological findings were generalized endothelial lesions, septal oedema, mild inflammatory mononuclear infiltrates and hydropic degeneration of type I and II pneumocytes with desquamation of type I. The pneumonic syndrome had a favourable evolution, except in 5% of the patients who went into acute respiratory distress and suffered an important mortality. In 10% of the patients, a moderate hypoxaemia remained with normal chest film; in these cases, a transbronchial biopsy showed more severe endothelial lesions and, in some of these patients, it was possible to find clinical signs of pulmonary hypertension, which was moderate and did not improve with oxygen or vasoactive agents. The neurological symptomatology was progressive, leading to very severe muscular atrophy and, in some cases, to alveolar hypoventilation. The neuromyopathy, as the other clinical manifestations, improved slowly during the following months. A year after the onset, a pulmonary restriction with a low transfer factor of CO remained, and some patients had residual neuromyopathy and severe scleroderma-like lesions of the skin. (ABSTRACT TRUNCATED AT 250 WORDS)     

Anatomo-pathologic findings in 25 autopsy cases of AIDS

Pathologic findings in 25 autopsies of AIDS. The common and severe changes of the central nervous system, lungs, adrenals, heart, kidneys and gonads are reviewed in a series of autopsies of AIDS. In the brain, HIV infection induces directly inflammatory infiltrates including the typical multinucleated giant cells described by Sharer. In addition, primary lymphomas are seen as well as reactive and inflammatory lesions that are caused by opportunistic infections, such as those of poliomavirus, Cytomegalovirus and Toxoplasma gondii. In the lung, interstitial inflammation prevails, which may be related to direct HIV infection and include rare multinucleated giant cells like the ones described by Sharer. Opportunistic infections are often associated, and are commonly sustained by Cytomegalovirus and Pneumocystis carinii. A peculiar findings is the evolution from septal inflammation to fine fibrosis and hyaline degeneration, either focal or diffuse. We believe that the severe respiratory insufficiency that is commonly seen in the advanced stages of AIDS could be related to the interstitial damage. In the adrenal gland, the most common change is Cytomegalovirus infection affecting both the cortex and the medulla, and inducing massive necrosis in the cortex with little or no reaction. Again, adrenal involvement should be related to adrenal functional insufficiency, which may be over-looked clinically because of the preponderant lesions of other sites. In the heart, myocarditis is often discrete, and may be complicated by perivascular fibrosis and rare foci of myocytolysis; in some cases primary lymphomas may also develop. In the kidney, several histological lesions are found, including glomerular damage with segmental necrosis, cortical areas of hyporeactive necrosis, and mild interstitial inflammation. In the gonads, the changes are partly induced by drug abuse, and consist of atrophy with secondary hypoplasia of the germ cells and interstitial fibrosis. In conclusion, the most important abnormalities consist of opportunistic infections, hyporeactive necrosis, fibrotic evolution of the inflammatory infiltrates and neoplasias (Kaposi's sarcoma and lymphomas). In this work, the changes of the lymphoid organs are only mentioned, for they have been widely reviewed elsewhere.     

Evaluation of histological criteria for bullous pemphigoid. Correlation with antigens recognized by immunoblotting of anti-epidermal autoantibodies

The aim of this study was to evaluate the histological findings observed in patients with bullous pemphigoid in whom the diagnosis of bullous pemphigoid could be confirmed by direct immunofluorescence and immunoblot serum analysis. Seven histological criteria were considered for selection of skin biopsy specimens: 1) cleavage of dermal epidermal junction; 2) migration of eosinophils along dermal epidermal junction; 3) presence of intra epidermal eosinophils (with or without associated spongiosis); 4) absence of keratinocyte necrosis; 5) absence of acantholysis; 6) absence of dermal fibrosis; 7) absence of vasculitis. Depending on the number of criteria observed the histological picture was considered as: highly suggestive, suggestive or poorly suggestive of bullous pemphigoid. The histological picture was considered as highly suggestive in 50% of cases, suggestive or poorly suggestive in 37% and 13% of cases respectively. Migration of eosinophils along dermal epidermal junction was observed in 23 biopsy specimens (50%). Histological findings considered as poorly suggestive of bullous pemphigoid consisted of a prurigo-like or an eczematous-like or a drug induced-like picture or no specific cutaneous erosions. An histological picture highly suggestive of bullous pemphigoid was observed in 67% of patients whose serum contained anti-BPAG2 antibodies and in only 36% patients of without anti-BPAG2 antibodies (p=0,04). On the contrary, only one bullous pemphigoid patient (4%) with circulating anti-BPAG2 antibodies had a histological picture poorly suggestive of bullous pemphigoid. These findings are in accordance with the pathogenic properties of anti-BPAG2 antibodies demonstrated in animal models. This study showed that: 1) typical histological findings of bullous pemphigoid are only observed in 50% of skin biopsy specimens. 2) The diagnosis of bullous pemphigoid should be considered in elderly patients even when a poorly specific prurigo-like or eczematous-like histological picture is observed. Moreover, it underlines the usefulness of direct immunofluorescence of skin biopsy specimens and indirect immunofluorescence and immunoblot analysis of serum in such atypical cases of bullous pemphigoid.     

Pathological findings in South American fur seal pups (Arctocephalus australis gracilis) found dead at Guafo Island, Chile

During four breeding seasons (2004-2008), 78 necropsy examinations were performed on South American fur seal pups (Arctocephalus australis gracilis) found dead on Guafo Island, southern Chile (43°36'S, 74°43'W). Tissue samples from 65 pups were examined microscopically. The primary causes of death were enteritis with microscopical lesions of bacteraemia (28.2%), starvation (23.1%), drowning (21.8%), trauma (19.2%) and stillbirth (2.6%). Those pups with enteritis and microscopical lesions of bacteraemia had haemorrhagic enteritis (100%), interstitial pneumonia (86%), periportal hepatitis (73%) and vasculitis (18%). The pups that died from starvation had atrophy of hepatocytes (61%) and cholestasis (61%). The pups that drowned had bronchoalveolar oedema (65%) and foreign bodies in the airways (65%). In animals that died from trauma, the main lesions were skull fractures (67%). This range of pathological findings is within what would be expected in a healthy otariid breeding colony.     

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.     

Fibrosis with emphysema

Wright J L, Tazelaar H D & Churg A (2011) Histopathology  58 , 517–524
Fibrosis with emphysema The concept of fibrosis with emphysema is confused by the existence of two very different clinical/pathological scenarios: first, cases in which a diffuse fibrosing interstitial pneumonia, most commonly usual interstitial pneumonia (UIP), occurs in a patient with emphysema. This combination is largely of clinical interest because of its effects on pulmonary function and pulmonary hypertension, but can produce unusual appearances in surgical lung biopsies when the fibrotic areas are wrapped around emphysematous spaces. However, the underlying morphology of emphysema and UIP or other interstitial lung disease remains unchanged. Radiological consultation is often helpful to show that the patient has both lesions; secondly, cases in which there is localized fibrosis that is part of emphysema, or related to respiratory bronchiolitis, or both. These lesions have been called ‘respiratory bronchiolitis’ (RB), ‘respiratory bronchiolitis–interstitial lung disease’ (RB‐ILD), ‘airspace enlargement with fibrosis’, ‘RB‐ILD with fibrosis’ and ‘clinically occult interstitial fibrosis in smokers’, but are probably all the same entity. Such changes are associated only rarely with the physiological or radiological features of an interstitial lung disease. Care should be taken when describing these lesions in biopsies so as not to give the impression that a diffuse interstitial lung disease is present.     

Results of surgery for aortic regurgitation due to aortic valve prolapse

The clinical, hemodynamic and pathological findings of 13 patients with aortic regurgitation due to aortic valve prolapse caused by advanced myxomatous degeneration were evaluated. Eleven patients showed a favorable outcome with no complications resulting from surgery. One patient died from aortic dissection, and another died suddenly from an unknown cause. Five patients had mitral valve prolapse as a complication. Ten patients (77%) had a long-standing history of hypertension. Twelve patients (92%) were male. None of the patients had the stigmata of Marfan's syndrome. All patients had marked myxomatous degeneration of the aortic valves without any inflammatory changes. Two patients showed microcalcification; 7 demonstrated moderate fibrosis. Five patients showed severe fragility of the cusps which appeared redundant, gelatinous and softened by degenerative changes. Myxomatous degeneration of the aortic valve is not rare, and, in fact, it may be one of the most common pathologic and clinical entities associated with pure aortic insufficiency.     

Rheumatoid arthritis with diffuse pulmonary rheumatoid nodules

Rheumatoid nodules in dermal or subcutaneous tissues, while indicative of rheumatoid arthritis, are very rare. It is even less common to identify these rheumatoid nodules by biopsy as well as in autopsy materials from lung tissue. These nodules may be single or multiple, which seldom cause respiratory symptoms. Here, a patient with diffuse pulmonary rheumatoid nodules and interstitial fibrosis throughout both lungs, is described. The patient, with articular symptoms and seropositivity, exhibited a rapid clinical course and died of respiratory failure 3 months after the appearance of dyspnea. Chest radiography indicated interstitial pneumonitis with bilateral diffuse peripheral shadows. At autopsy, numerous rheumatoid nodules and interstitial fibrosis had destroyed both lungs, such that no residual normal pulmonary tissue remained. It is believed that this was an extremely rare case exhibiting large numbers of rheumatoid nodules throughout the lungs. Findings with this patient indicate that, in patients with rheumatoid arthritis, clinical interstitial pneumonitis confirmed radiologically does not exclude the existence of rheumatoid lung nodules.     

The ultrastructure of human tubulo-interstitial fibrosis

Tubulo-interstitial fibrosis, comprising tubular atrophy, infiltration by inflammatory cells, accumulation of extracellular matrix, and proliferation of mesenchymal cells in the interstitium, is a major characteristic of most progressive chronic renal diseases leading to end-stage renal failure, regardless of cause. All of the ultrastructural characteristics of tubulo-interstitial fibrosis can correlate with clinically defined features of chronic renal dysfunction. The present review illustrates ultrastructural features, emphasising some novel findings, in tubulo-interstitial fibrosis, including widespread expression of actin filaments, fatty degeneration of tubular epithelial cells, presence of cilia, and infiltration of leukocytes into the tubular lumen. The hypothesised development of interstitial myofibroblasts from tubular epithelial cells, and the relationship between tubule injury and capillary abnormality are also discussed.     

A possible autoimmune parathyroiditis following ozone inhalation. II. A histopathologic, ultrastructural, and immunofluorescent study.

Histologic, ultrastructural, and immunofluorescent changes in the parathyroid glands of rabbits have been studied after 48 hours of ozone inhalation at a dosage of 0.75 ppm. The frequent changes observed included hyperplastic parathyroiditis followed by capillary proliferation and leukocytic infiltration. The progressive cytologic events consisted of the presence of eosinophilic leukocytes, reticuloendothelial and lymphocytic infiltration, disaggregation of the parenchyma, and interstitial edema. The ultrastructural changes consisted of degeneration of nuclei, atrophy of the mitochondria, dilatation and atrophy of the endoplasmic reticulum of the chief cells of the parathyroid gland, proliferation of the venous limb of the capillary network, and the prominent interstitial elements. The immunofluorescent techniques revealed positive immunologic response. These data suggest that ozone inhalation perhaps triggers an immune reaction which causes inflammatory injury to the parathyroid gland. The possibility that the modified functional chemical groups of the parathyroid gland act as autoantigen is discussed.     

Interstitial haemosiderin in the lungs of sudden infant death syndrome: A histological hallmark of ‘near-miss’ episodes?

The occurrence of multiple intrathoracic petechial haemorrhages in sudden infant death syndrome is well-documented and undisputed. We describe a study of 24 consecutive sudden infant deaths in which Perls' method for staining of iron in lung sections has been employed in addition to standard post-mortem procedures. Haemosiderin-containing macrophages have been demonstrated in 13 infants in subpleural and interstitial lung tissue in the absence of local fresh interstitial haemorrhage; ten of these infants had no evidence of respiratory tract inflammation and died mainly between one and three months of age. Eleven babies without haemosiderin showed evidence of inflammatory lesions and were predominantly four months or older at death. The demonstration of previous haemorrhagic foci in babies showing no other pathological abnormality may represent a histological hallmark of previous 'near-miss' episodes of hypoxaemia from whatever cause.     

Interstitial mycosis fungoid: a rare variant of mycosis fungoids. Two cases

Mycosis fungoids can present with various clinical and histological features, with only a few of them being recognized as distinct entities in the current WHO and EORTC classifications. Histologically, mycosis fungoids (MF) usually show a superficial perivascular or band-like lymphocytic infiltrate with epidermotropism. We here report two cases of a rare histological variant of MF, called interstitial in the literature. Our first patient, a 71-year-old male, had a previously diagnosed MF, which clinically evolved towards nodules, showing histologically an interstitial lymphocytic infiltrate without epidermotropism and without large cell transformation. The second patient was a 64-year-old female with widespread plaques and nodules. Histologically, a dense dermal interstitial infiltrate was observed, with foci of epidermotropism, without large cell transformation. At relapse after treatment, she presented with plaques, papules and nodules, histologically showing a slight interstitial lymphocytic infiltrate that resembled granuloma annulare or inflammatory morphea. In both patients, clinical aspect suggested MF and a dominant T-cell clone was found in lesional skin. Nodules in MF are not always the hallmark of large cell transformation, but may correspond to unusual interstitial lesions. Diagnosis of such rare variant may be difficult and requires a good clinical pathological correlation together with the search for foci of epidermotropism on skin biopsy and for a dominant cutaneous T-cell clone.     

严重急性呼吸综合征3例尸检病理分析

目的 探讨严重急性呼吸综合征(SARS)患者的病变的病理形态特点及与临床表现的相关性。方法 对3例SARS死亡病例进行尸体解剖,光镜观察各脏器的病理变化,并与临床表现进行联系。结果 肉眼突出的病理改变为双肺的弥漫性出血,镜下为肺泡的急性渗出性、出血性和纤维素性炎症,肺泡毛细血管充血,一些毛细血管内微血栓形成。肺泡壁增厚,单个核细胞浸润,肺泡上皮损伤脱落,肺泡腔内渗出物伴透明膜形成。部分肺泡腔内有纤维素样物质及红细胞,少数肺内支气管动脉内血栓栓塞。淋巴结及脾脏等出血坏死,淋巴细胞衰减。其他实质脏器如肝、心、肾、胰腺等呈非特异性改变,如水样变性,脂肪变性、间质细胞增生等以及3例老年患者此次人院前存在的基础病变。结论 SARS具有其病理形态特点,患者的肺部严重病变及免疫器官的损伤引起相应的临床表现并导致患者死亡。     

Diagnosis of chronic atrophic gastritis by morphometric image analysis. A new method to overcome the confounding effect of the inflammatory infiltrate

The risk of gastric cancer increases with the severity of gastric mucosal atrophy. Atrophy is a 'loss of properly specialized glands'. These glands may be substituted by metaplastic cells and by interstitial fibrosis, or displaced by an inflammatory infiltrate. Agreement among pathologists for the diagnosis of atrophy is poor (kappacoefficient < 0.4), probably because inflammatory infiltrate can confound the identification of gland loss. The aim of this study was to evaluate interstitial fibrosis by image analysis, and thereby overcoming the confounding effect of the inflammatory infiltrate. Gastric biopsies of 40 controls (20 children and 20 adults) and 111 patients with chronic atrophic gastritis were examined. Patients underwent another biopsy a year later. Gastric sections were examined by conventional histology (updated Sydney system) and image analysis to detect collagen and non-collagen fibres. There were no significant intra- or inter-operator differences in the evaluation by image analysis of fibre content in either controls or patients. In both controls and patients, the mean percentage of collagen fibres was lower in the gastric body (9%) than in the antrum (10%). In the antrum it was 14%, 17% and 20% in patients with mild, moderate and severe atrophy, respectively. A year later, histology showed that the grade of atrophy had decreased in 42%, probably due to the regression of inflammation, and increased in 10% of cases, but interstitial fibrosis (expressed as collagen fibre content) was practically unchanged. The use of image analysis of gastric biopsies appears to be a reliable method with which to measure interstitial fibrosis, even in the presence of an inflammatory infiltrate. This study highlights the difference between 'real gastric atrophy', where glands are replaced by collagen fibres, and 'apparent gastric atrophy', where glands are displaced by an inflammatory infiltrate.     

SARS-CoV-2, COVID-19, skin and immunology – What do we know so far?

The pandemic condition coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2-positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial, and maculopapular eruptions and livedo, necrosis, and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors, and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical, and histologic features of virus- and drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.     

Adult respiratory distress syndrome—a review

Adult respiratory distress syndrome (ARDS) represents a common pathway of damage to the lungs by a wide variety of different agents. The important aetiological factors and mechanisms of lung injury are considered. Electron microscopic features as well as light microscopy are described. Factors that may modify the pathological picture are discussed. Probably the most important of these is oxygen. This gas is said to produce interstitial pulmonary fibrosis but this concept is once again questioned.     

Kalziphylaxie

Calciphylaxis is a rare disease which has been increasingly reported in recent decades and has consequently shifted into the focus of clinical and scientific research. The clinical picture is characterized by extensive ischemic ulcerations of the skin and subcutis. Histologically, the small vessels in these lesions show prominent calcifications. Due to the extensive areas of ulceration and necrosis as well as frequently present comorbidities, patients with calciphylaxis are prone to infection and sepsis. In this work, we describe the case of a female kidney-transplant patient with vasculitis who, despite good graft function, developed a fulminant calciphylaxis of both thighs 4 years post transplantation and died of septic complications. The differential diagnoses as well as clinical procedures are described in detail in the case history. In the discussion, we give an overview of the current state of knowledge regarding the etiopathogenesis, risk factors, diagnostic measures and clinical management of calciphylaxis.