Preeclamptic nephropathy -- an endothelial lesion. A morphological study with a review of the literature.

OBJECTIVE: We investigated wether an endothelial lesion, postulated in pathogenesis of preeclampsia (PE) in general, is also pathogenetically relevant in the characteristic renal lesions of PE, presenting as special glomerular alterations, designated as "preeclamptic nephropathy". STUDY DESIGN: Renal biopsies of 90 women with PE were analyzed by light microscopy (LM), immunohistology (IH) and electron microscopy (EM). Corresponding with clinical data clinicomorphological correlations were performed. RESULTS: In IH and EM the altered glomeruli demonstrate an endothelial lesion. Consecutive morphological reactions could be revealed by EM, allowing a subdivision in different stages of disease. The late stage indicates the reversibility of these renal lesions. Close correlations were found between clinical and morphological data. Focal glomerulosclerosis presents a hyperperfusion lesion, developing only facultatively in PE as a result of hyperfiltration. CONCLUSION: In preeclamptic nephropathy the first morphological substrate of renal changes with the key to pathogenesis presents itself as an endothelial lesion. This results in a disturbance of glomerular basement membrane permeability and in an imbalance of different mediator systems, with dominance of vasoconstrictive reactions but also coagulative-, reparation-, and proliferation-processes, leading to the characteristic glomerular alterations of preeclamptic nephropathy.

High-sensitivity diagnosis of AA amyloidosis using Congo red and immunohistochemistry detects missed amyloid deposits.

Biopsy diagnosis of early amyloid-A (AA) amyloidosis has often been difficult. Examination of 57 consecutive biopsy specimens from 42 patients with inflammatory pediatric diseases permitted comparison of the precision of biopsy amyloid diagnosis in six different laboratories (labs), which applied the following methods: Congo red alone (four unspecialized labs combined as Lab 1), Congo red and electron microscopy (Lab 2), or Congo red and immunohistochemistry using monoclonal antibodies (Lab 3). Lab 3 reexamined the diagnoses made by Lab 1 and Lab 2. Of the 42 patients, 17 patients with 32 biopsies were selected for this study based on the presence of amyloid in at least one biopsy. Whereas massive or no amyloid was concordantly recognized by all labs in 18 biopsies from nine patients, discordance was demonstrated in 14 biopsies from eight patients. Comparison of Labs 1-3 revealed amyloid in 12 rectal and 18 renal biopsies evaluated by Lab 3, whereas Lab 2 missed amyloid in two of 18 renal biopsies and Lab 1 missed amyloid in 11 of 12 rectal biopsies. Most amyloid was missed when only minute amounts of amyloid were present. Had our technique (Lab 3) been available at the time of biopsy, amyloid could have been diagnosed years earlier, thereby sparing the patient further biopsies and allowing initiation of earlier treatment before organ damage could occur.

Incidental finding of a hepatic lesion: differential diagnostic problems for fibrolamellar hepatic carcinoma.

We report the case of a 39-yr-old female with a liver lesion that was incidentally detected by ultrasound. Examination of biopsy specimens revealed focal nodular hyperplasia. A metastatic tumor in the right os ilium developed in the following weeks and showed specific uptake of 99mTc-hepatic 2,6-dimethyliminodiacetic acid (HIDA), suggesting metastasis from a differentiated hepatocellular carcinoma. The final pathologic diagnosis was multifocal, solid and glandular hepatocellular carcinoma, partly differentiated as fibrolamellar carcinoma, and an osseous metastasis from the differentiated hepatocellular carcinoma.

Primary systemic amyloidosis leading to advanced renal and cardiac involvement in a 30-year old man.

The case of a 30-year-old man with primary systemic amyloidosis is reported. Three months prior to admission the patient developed fever, night sweats, dyspnea, and bilateral ankle swelling. Recurrent left-sided pleural effusion led to further investigation when massive proteinuria with free monoclonal lambda chains in the urine became evident. Abdominal subcutaneous fat aspiration and renal biopsy confirmed the diagnosis of amyloidosis. Bone marrow biopsy and bone scan did not reveal multiple myeloma. Echocardiography showed a sparkling texture of the interventricular septum. Pulsed-wave Doppler recording of the left ventricular inflow profile showed the pattern of advanced cardiac amyloidosis consistent with markedly impaired diastolic heart function. Electrocardiogram-gated magnetic resonance imaging was carried out for noninvasive evaluation of cardiac function. The patient was started on repeated courses of melphalan, prednisone, and colchicine therapy. Despite increasing deterioration of renal function the therapy was tolerated quite well, and the patient is still alive 10 months after initial diagnosis. Although very rare in this age, primary systemic amyloidosis should be considered as a cause of pleural effusion, proteinuria, and congestive heart failure and should lead to further investigation.

[Nephropathy in pregnancy--an endothelial lesion?]. / Schwangerschaftsnephropathie--eine Endothelläsion?

Morphological examination of renal biopsies from 90 women with preeclampsia (PE), assessment of the clinical data and clinicomorphological correlations produced the following results: 1. By light-microscopy the renal lesions in PE imitate a picture of glomerulonephritis of mesangial type with different degrees of severity. 2. Morphometric investigations confirmed the impression gained by light-microscopy of swelling of endothelial cells and podocytes as well as endocapillary cell proliferation and enlargement of the glomeruli. 3. The immunohistological findings are non-specific and argue against immune complex deposition, but are suggestive of insudative processes. In addition immunohistological investigations of fibronectin and factor VIII-associated antigen reveal a pathogenetic relevant alteration of endothelial cell. 4. Electronmicroscopy is the most valid diagnostic method allowing subdivision of the quantitative different lesions in various degrees of severity. Furthermore the use of this method allows elucidation of the dynamics of the underlying disease process, which progresses through successive stages i.e. early, fully developed and late stage, supporting the reversibility of these glomerular lesions. 5. Close correlations are found between the clinical parameters and morphological findings in nephropathy in pregnancy-induced hypertension. The hypertension, proteinuria and nephrotic syndrome, which characterize the clinical picture, correlate with the severity of the glomerular lesions and the further course of the disease. Moreover, hypertension also correlates with mesangial and subendothelial deposits and with focal segmental hyalinosis and sclerosis, occurring in some cases. The focal segmental hyalinosis and sclerosis should be regarded as hyperperfusion-lesions indicating benign nephrosclerosis and developing only facultatively in PE. 6. The first morphological substrate of nephropathy in pregnancy-induced hypertension with the key to pathogenesis present itself as endothelial lesion, possibly caused by oxygen free radicals, lipid-peroxides or hyperfusion. In result of the endothelial lesion an imbalance of the different mediator systems i.e. thromboxane-prostacyclin, endothelin-EDRF with dominance of vasoconstrictive reactions would be effective. Thus the following induction of coagulative, vasoconstrictive and proliferative processes results in the characteristic glomerular lesions in PE.

Esthesioneuroblastoma. A case report.

Esthesioneuroblastoma (ENB) is a rare neuroectodermal tumor originating from the olfactory mucosa and therefore usually arising from the nasopharynx. A case in which the diagnosis was made in connection with the extraction of a tooth is reported. Manifestation in the dento-alveolar region is unusual for this tumor. The case presented is also unusual in that the classic symptoms of ENB were not present. Diagnosis, classification, and therapy are described with a brief review of the literature.

[Oral leukoplakias--a histopathological and retrospective study]. / Orale Leukoplakien--eine histopathologische und retrospektive Studie.

In a retrospective study 85 patients of our department with clinical oral leukoplakia occurring between 1980 and 1985 were checked histologically and reclassified. Compared to other studies and unusual high malignant transformation rate (14.1%) was found which seemed to be depended on the high rate of radiated patients. Four of twelve patients were healed due to early diagnosis and radical surgery performed consecutively. Using these data as a basis the different courses and therapies are demonstrated.

[The melanotic neuroectodermal tumor of childhood. Tumor identification with immunohistochemical methods. A case report]. / Der melanotische neuroektodermale Tumor des Kindesalters. Tumoridentifikation mit immunhistochemischen Methoden. Ein Fallbericht.

The authors report a case of a melanotic neuroectodermal tumor of infancy occurring in the maxilla of a 6-month-old female infant. The tumor displayed a biphasic cellular pattern with small neuroblast-like cells and large melanocytic cells showing a highly characteristic immunophenotype. Both tumor cell types immunostained for neuron specific enolase (NSE) and vimentin. The melanocytoid cells reacted additionally with the anti-keratin antibody Kl 1 and with HMB 45, an antibody specific for melanocytic antigens. The melanotic neuroectodermal tumor of infancy usually runs a benign course, however, local recurrence and metastasis may occur. The course of the disease cannot be predicted from morphological findings.

[Diagnosis and therapy of aggressive fibromatosis (extra-abdominal desmoid) in the head and neck area]. / Diagnostik und Therapie der aggressiven Fibromatose (extraabdominal desmoid) im Kopf-Hals-Bereich.

Desmoid tumours (extraabdominal desmoids, aggressive fibromatosis) are rare connective tissue tumours, that grow infiltratively and destructively. The analysis of the course of disease in three patients suffering from desmoid tumours in the head and neck region (regio submandibularis, regio parotidea, parapharyngeal space) confirmed the data in literature that painless swelling and dysfunction are the first non-specific signs of the disease. Morphologically reactive fibromatosis and fibrosarcoma should be considered (amongst others) in differential diagnosis. CT and MR scans are useful in determining the extent of the tumours and help to distinguish the tumour from nerves, vessels and bone. Surgery is the therapy of choice in the head and neck region. Primary surgery was performed in our patients. Due to recurrences two of our patients have been operated on several times including major plastic reconstructive surgery. One patient died three and a half years after primary treatment due to sarcomatous degeneration. A large parapharyngeal recurrence was successfully reduced by percutaneous radiation therapy in our second patient. Follow-up of our third patient was NAD 15 months after resection of a large parapharyngeal/mediastinal process including blocking of two cervical vertebrae. Summing up, desmoid tumours are rare connective tissue tumours in the head and neck region with a destructive biological behaviour similar to malignant tumours and a high recurrence rate. Surgery is the treatment of choice. In recurrences or if the tumour is not properly resectable, radiation must be considered, whereas the chemotherapeutical approach is not yet well established.

[Ameloblastomas in the growth period--aspects of differential diagnosis and therapy]. / Ameloblastome im Wachstumsalter--differentialdiagnostische und therapeutische Aspekte.

This paper is focussed on problems associated with the histological evaluation of odontogenic tissues in the growth period. It is particularly parts of the dental lamina or harmless odontogenic tumors (e.g. ameloblastic fibromas) that can be mistaken for ameloblastomas. Since these false diagnoses may occur in growing patients, radical resections for treatment of ameloblastomas should only be performed after a second histological evaluation and when typical intraosseous lesions are present.

[Membranoproliferative glomerulonephritis in non-Hodgkin's lymphoma nad myeloproliferative syndrome--a causal relationship?]. / Membranoproliferative Glomerulonephritis bei Non-Hodgkin-Lymphomen und myeloproliferativem Syndrom--eine kausale Beziehung?

A pathogenetic relationship is postulated for the development of membranoproliferative glomerulonephritis type I in non-Hodgkin's lymphoma (B-cell lymphoma of low-grade malignancy) and myeloproliferative syndrome, which we have observed in eight patients. This hypothesis is supported by the fact that chronic lymphatic leukaemia and immunocytoma are often associated with immunodysregulative phenomena, and by the immunohistological and ultrastructural findings in the kidney, especially the frequent electron-microscopic finding of cryoglobulins, which results in the membranoproliferative type of immune-complex glomerulonephritis, an expression of a disturbance in immune balance. The pathogenetic mechanism may involve cryoglobulins themselves as immune complexes; it is also possible that monoclonal cryoglobulins combine with an antigen to form immune complexes or lead to in situ formation of immune complexes. In addition, other immune complexes, for example with endogenous tumour-associated antigens and exogenous antigens (e.g. hepatitis antigens), may be involved in the pathogenesis.

IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients.

This study is concerned with the correlation between tubulointerstitial changes (interstitial fibrosis, acute renal failure, and interstitial fibrosis with acute renal failure), glomerular changes (focal and segmental lesions, hyperperfusion lesions), vascular changes, clinical data at the time of biopsy (serum creatinine concentration, creatinine clearance, hematuria, proteinuria, and hypertension) and first symptoms (hematuria, proteinuria and hypertension) and the kidney survival rate in 239 patients with IgA nephritis without nephrotic syndrome. The morphological and clinical parameters were subjected to multivariate analysis in order to examine their significance with regard to the prognosis. The interstitial fibrosis was proven to be the most important morphological parameter, and the most important clinical parameters were the serum creatinine concentration and the creatinine clearance.

Long-term prognosis of chronic idiopathic membranous glomerulonephritis. An analysis of 334 cases with particular regard to tubulo-interstitial changes.

A retrospective long-term study (average follow-up time 5.2 years) of 334 patients with idiopathic membranous glomerulonephritis (MGN) was carried out with the following results: 1) MGN was found to have a relatively good prognosis when all cases were considered together: 5-year kidney survival rate (KSR) -88%, and 10-year KSR -77%. 2) Univariate survivorship analysis showed the following morphological and clinical parameters to be associated with an increased risk of terminal renal insufficiency or death from renal disease: a) tubulo-interstitial changes; b) glomerular stage III as opposed to stages I and II; c) elevation of serum creatinine concentration at the time of the biopsy; d) arterial hypertension at the time of the biopsy. 3) Multivariate analysis showed that only tubulo-interstitial changes (interstitial fibrosis and/or acute renal failure) found at the time of the biopsy and their clinical correlate, serum creatinine concentration, were significant and therefore of definite prognostic importance. 4) Unsystematic therapy with steroids and/or cytostatic agents does not improve the long-term prognosis of MGN. 5) The cause of disease in the tubulo-interstitial system in MGN is discussed. Interstitial fibrosis is considered to develop possibly as a consequence of unresorbed interstitial edema which can develop during an episode of acute renal failure. Coexisting T-cell-mediated disease in the region of the intertubular capillaries is also considered as a possible factor in the development of interstitial fibrosis.

[Clinical pathology of the glomerulus--from phenomenon to entity. The mesangial lesion]. / Klinische Pathologie des Glomerulus--vom Phänomen zur Entität. Die mesangiale Läsion.

The numerous findings discussed lead to the following conclusions: 1. The mesangial lesions, which may take a wide range of different forms, can be classified into two groups according to whether an underlying immunological pathomechanism is involved. Those that result from such a pathomechanism represent various types of glomerulonephritis. 2. Amongst these immunologically-mediated glomerulonephritides mesangioproliferative glomerulonephritis (and, of this group, IgA nephritis) is the most common. Membranoproliferative glomerulonephritis is the most severe of these diseases. Either may be idiopathic or secondary, or may occur in association with systemic disease. 3. The number of macrophages in the mesangial lesions in glomerulonephritis correlates with the severity of the glomerulonephritis, the localization of the immune complex deposits and the degree of proteinuria. If the immune complex deposits extend out of the mesangium into the subendothelial space, the number of macrophages is higher, the structural changes are more marked, and proteinuria is more severe. 4. Various pathomechanisms and nosologic entities can lead to mesangial lesions of the type seen in mesangioproliferative glomerulonephritis or membranoproliferative glomerulonephritis. On the other hand, the same entity may be associated with mesangial lesions of different severity, and consequently the prognosis varies. Differential diagnosis of the mesangial lesions, which represent heterogeneous nosologic entities, requires the use of light microscopic, immunohistochemical, and electron microscopic techniques. Exact diagnosis is necessary because of the differences in prognosis. 5. The course and prognosis of mesangial lesions are determined by immunological and nonimmunological factors. Long-term studies have demonstrated that prognostically relevant information can already be gained at the time of biopsy by the assessment of certain morphological features (e.g., immunohistological findings, severity of glomerulonephritis, the presence of focal/segmental lesions) and clinical parameters (e.g., proteinuria, hematuria, hypertension, and serum creatinine concentration). The decisive predictor of an unfavorable prognosis is the presence of interstitial fibrosis.