Diagnostic value of fine-needle aspiration biopsy of thyroid nodules in children and adolescents.

From 1971 to 2001, 188 fine-needle aspiration biopsies (FNAB) of the thyroid gland were performed in 169 children and adolescents with thyroid nodules. In 65.4% the results of FNAB were classified as benign. In 13.8% FNAB was considered insufficient for diagnosis, due to the absence or small number of cells. The results of FNAB were classified as suspicious or malignant in 17.6% (n = 33). Surgery was performed in 118 patients (69.8%) and the results of cytological evaluation and histopathology were compared. The accuracy of FNAB was 77.2%, specificity 63.6%, and sensitivity 78.9%, which is less than reported for adults. Histopathological evaluation showed 13 malignant tumors. In two of the 13 malignancies, FNAB was inadequate because of a lack of thyroid cells. Of the remaining 11 malignancies, seven were detected by FNAB but four of these were classified as benign. Because of the lower accuracy of FNAB, we suggest a more aggressive diagnostic and therapeutic approach in children and adolescents than for adults.

[Facioscapulohumeral muscle dystrophy and heart disease]. / Fazioskapulohumerale Muskeldystrophie mit Herzbeteiligung.

Cardiac involvement is well known in a number of skeletomuscular diseases but not in facio-scapulohumeral muscular dystrophy (FSHD). We report on a 71 year old woman with progressive cardiac insufficiency in FSHD, which was also confirmed by molecular analysis in one of the two daughters affected by the disease. Autopsy of the deceased patient showed the typical changes in skeletal muscles including focal inflammatory infiltrates in the diaphragm and, in addition, cardiac muscular involvement. The histological changes resembled those seen in primary cardiomyopathy despite the normal muscle mass volume. Both clinically and morphologically, the cardiac disease was the cause of death in this patient with FSHD.

[Formation of desmoids in postoperative lumbar scars--a case report]. / Desmoidbildung in postoperativer lumbaler Narbe -- kasuistischer Beitrag.

Desmoids are tumours of the connective tissue cells with aggressive growth. Frequent recurrences of these tumours have often been described. Genetic and endocrine factors as well as local tissue biomechanics are thought to be responsible for the pathogenesis. This case report should contribute to the discussion about possible pathogenetic factors.

[Neuropathological findings after cardiac surgery-retrospective study over 6 years]. / Neuropathologische Befunde nach herzchirurgischen Operationen. Retrospektive über 6 Jahre.

Neuropathological studies may contribute to the discovery of central nervous system complications after heart surgery and thus help to reduce the incidence of postoperative neurological or cognitive disturbances. We examined the brains of 262 such patients operated for coronary bypass, valve replacement, or heart transplantation. Circulatory disturbances (macro- and microhemorrhages, infarcts, subarachnoid hemorrhages, and hypoxemic brain damage) were present in 128 cases (49%), as the cause of death in 33 cases (12.6%). The infarcts were caused by local arteriosclerosis of brain arteries, arterial emboli originating from the operative sites or myocardial infarctions, or by fat emboli, foreign body emboli or megakaryocytic capillary emboli in rare cases. Inflammatory disturbances were present in 17 cases and consisted of fungal or bacterial septicopyemic changes (12) or of glial nodules (5) as the substrate of a viral or autoimmunencephalitis (Bickerstaff). An incidental finding was Alzheimer's disease in 37 cases (14% of the material) of elderly patients, often associated with cerebral amyloid angiopathy but not as cause of death or cause of macroscopic brain hemorrhage. Since we have conducted an autopsy study, there is a limitation to transfer the documented changes to the total group of post-cardiac surgery patients with neurologic and cognitive deficits. Contrary to some previous reports, histologically overt microembolic phenomena do not seem to play a major role in our material. On the other hand, careful scrutiny revealed non-fatal white matter microhemorrhages of varying frequency in the different groups, especially after valve operations. These as well as the occasional glial nodules, after resorption and microscarring, could well be the cause of slight neurologic and cognitive impairments.

Glucose monitoring with long-term subcutaneous microdialysis in neonates.

BACKGROUND: Microdialysis is a new approach for continuous monitoring of small molecules in the extracellular space, and hypoglycemia is a common problem in neonatal intensive care. The objective of this study was to evaluate subcutaneous microdialysis for long-term glucose monitoring in neonatal intensive care. We determined the relative recovery of the microdialysis system in vitro and in vivo, the stability of the relative recovery in vivo during long-term microdialysis, and the correlation between blood and dialysate concentrations of glucose and urea. Furthermore, we evaluated the sensitivity and specificy of subcutaneous microdialysis for the diagnosis of hypoglycemia. PATIENT AND METHODS: Thirteen infants (10 neonates) with gestational ages of 30.2 to 45.6 weeks were investigated by microdialysis of subcutaneous adipose tissue and blood sampling. Subcutaneous microdialysis was performed for a median (range) duration of 9 (4-16) days. RESULTS: The application was safe, even in extremely low birth weight infants (<1000 g) with scanty subcutaneous adipose tissue. The mean +/- standard deviation of the relative recovery in vitro was 101 +/- 3% for glucose and 100 +/- 2% for urea. Using urea as the internal standard, the mean relative recovery in vivo was 96.4 +/- 12.7% at the beginning and remained constant up to 16 days. The correlation between microdialysate and blood was significant for glucose (r = 0.88) and urea (r = 0.98). Subcutaneous microdialysis allowed the detection of asymptomatic hypoglycemias. The diagnostic sensitivity of a dialysate glucose

[Unifocal autonomy and carcinoma of the thyroid gland]. / Unifokale Autonomie und Karzinom der Schilddrüse.

Two cases operated upon with the clinical diagnosis of unifocal autonomous functioning thyroid nodules (AFTN) are reported where the histological diagnosis revealed a well differentiated thyroid carcinoma (follicular, papillary) without metastasis. The pathogenesis of differentiated thyroid carcinomas in cases of AFTN may be coincident. Alternatively it may evolve from thyroid epithelial cells of the hot nodule, resulting in a "hot" well differentiated thyroid carcinoma. These cases show that under the clinical diagnosis of AFTN a differentiated thyroid carcinoma can be hidden occasionally.

[A comparative study of cytological and histological studies of the thyroid gland]. / Vergleichende Untersuchung zytologischer und histologischer Befunde der Schilddrüse.

We compare the results of fine-needle aspiration cytology of the thyroid gland with postoperative histological findings in 533 patients with thyroidectomy operated on between 1987 and 1994. The classification of the cytological preparations followed the proposal of Weiss and Pilz [35] with the groups 0-IV. In group 0 the most frequent findings were cystic changes in multinodular goitre or malpuncture, respectively. The groups I and II contained cases with multinodular goitre, thyroiditis and follicular adenomas, but 4 carcinomas too. The group III comprised particularly follicular adenomas and carcinomas (8 cases). Both cases in group IV were carcinomas. In group III (cytologic group with suspicious findings) there were 65 cases with false positive results of the cytologic investigation resulting in a specificity of 86.4%. 4 out of 14 thyroid carcinomas could not be detected by cytologic preparations corresponding to a sensitivity of 71.4% for carcinomas. The false negative rate for thyroid carcinomas in group II was caused by regression areas in the center of the tumors (3 cases) as well as one microcarcinoma. Preoperative fine-needle aspiration cytology of the thyroid gland reduces the number of patients operated on for multinodular goitre or cold nodules especially in cases suspicious of carcinoma.

Inflammatory and immunological parameters in children with haemolytic uremic syndrome (HUS) and gastroenteritis-pathophysiological and diagnostic clues.

The objective of this study was to identify parameters indicating a risk for developing typical haemolytic uremic syndrome (D+HUS) during the prodromal phase of diarrhea caused by enterohaemorrhagic Escherichia coli (EHEC). Forty-eight children were studied prospectively with regard to inflammatory serum factors on admission to hospital. Ten patients developed D+HUS (group I), 15 suffered from viral-gastroenteritis (group IIa) and 23 from other types of bacterial gastroenteritis (group IIb). Mean levels of IL-8 tended to be elevated in group I compared to groups IIa and IIb. Neopterin and IL-10 levels particularly were significantly decreased in HUS in comparison to both gastroenteritis groups. Low IL-10 levels indicate a substantial disregulation of the immune response in HUS, as IL-10 downregulates the pro-inflammatory response and suppresses pro-coagulant activity in experimental endotoxemia. Our results suggest low neopterin, high IL-8 and especially low IL-10 levels are indicators of a high risk for developing HUS.

Malignant schwannoma and late-onset form of neurofibromatosis (NF-VII type) in a patient with skeletal manifestations.

INTRODUCTION: Von Recklinghausen's neurofibromatosis is known to occur with markedly variable expressivity. Nevertheless, cases that do not feature characteristic findings are uncommon. CASE: We report an extremely rare, sporadic case of neurofibromatosis, exclusively represented in the skeleton of a 49-year-old woman. The late onset of the disease and the absence of common diagnostic criteria permit us to classify it as neurofibromatosis type VII. Additionally, the disease was complicated by early malignant transformation of a thoracic neurinoma, which was removed by a wide local resection. Two years after surgery, the patient developed local recurrence and liver metastases. She died a few months later despite aggressive chemotherapy.

Increased thyroid epithelial cell proliferation in toxic thyroid nodules.

Most toxic thyroid nodules (TTN) result from clonal expansion of a single cell caused by a somatic mutation in the thyrotropin (TSH) receptor, the Gsalpha protein, or yet unknown proteins. Expanding a single cell into a TTN with thousands of cells suggests a prolonged increase in proliferation compared to nonaffected surrounding cells. To test this hypothesis, we evaluated cell proliferation in TTN. Tissue from 20 TTN and their surrounding normal thyroid tissue was studied for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 epitope as markers for cell proliferation. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. Nineteen samples were evaluated for PCNA immunohistochemistry. In 16 TTN, a significant (p< or =0.05%) up to 3-fold increase in the labeling index for PCNA was detectable. In only 3 toxic nodules (2 without a detectable TSH receptor or Gsalpha protein mutation), we found no significant difference in the labeling index compared to the surrounding tissue. Because labeling for KI-67 was much lower, only 16 toxic thyroid nodules were quantified. Twelve of these showed significantly (p< or =0.05%) increased labeling indices. The increase of the labeling index for both markers was similar for histologically defined adenoma versus adenomatous nodule or nodules with or without TSH receptor mutation or clonal versus polyclonal origin of toxic nodules studied. These findings are evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most TTNs, independent of their histopathological or molecular characteristics. Although increased proliferation in many TTNs is very likely the result of TSH receptor mutations, the cause of increased proliferation in TTN without a mutation is unknown.

[Tumor genesis and prognostic factors in colorectal carcinoma with special consideration of tumor localization]. / Kausale Genese und Prognosefaktoren des Kolonkarzinoms unter besonderer Berücksichtigung der Lokalisation des Tumors.

The rising incidence of colorectal carcinoma, particularly in the industrial nations of Europe and USA, directs the attention to the aetiological factors of these tumors: nutrition, the association with colorectal adenoma, familiarly genetic disorders as familiar adenomatous polyposis and hereditary non polyposis colorectal cancer. Some aspects of molecular biology are discussed. Furthermore, right and left part of the colon (divided by the Cannon-Boehm point) and the neoplasms of these sections of the colon are different in embryology, function and morphology. The cancers of the right colon develop without polypoid changes, those of the left part in majority via the adenoma-carcinoma sequence. It is possible to demonstrate differences between these two localizations in the DNA-content (diploid tumors on the right side), in the lost of allels (especially distal tumors), in proliferation activity (lower in right side tumors) and in the expression of oncofetal antigens. Besides, there are some histological differences between neoplasms of the right and left colon (production of mucin, "Crohns like lymphoid reaction" histological grading). In our own material of 262 patients with resected colon carcinoma we have investigated the distribution of carcinoma in the right and left colon, furthermore the T-classification, histological grading and the proportion of mucinous carcinoma in the different tumor localizations.

[Morphologic findings in fetuses and placentas of late abortion in the 2nd trimester]. / Morphologische Befunde an Feten und Nachgeburten von Spätaborten des II. Trimenons.

To investigate possible causes of abortion (and intrauterine foetal death) we reviewed clinical and morphological data of foetuses and placentas morphologically from 830 spontaneous abortions seen during a 12 years period (1978-1989) at the Institute of Pathology, University of Leipzig, and the Pathological Institute of Hoyerswerda. Our review showed that definite and possible causes of foetal death and abortion could be classified as placental, foetal maternal, and clinical. Placental changes, which included infection of the foetal membranes, disturbances of the uteroplacental circulation (abruptio placentae with bleeding) and placental dysmaturity, were the most important causes and accounted for 73.8% of the cases. Foetal causes mainly comprised multiple twin pregnancies and foetal malformations. In 20 cases (2.4%) we found malformations as a cause of foetal death and consecutive abortion. Overall, malformations were found in 7.5% of the cases examined. Maternal and obstetric complications of pregnancy were less frequent. In 16.5% of our cases, the cause of the abortion or intrauterine death remained obscure. However, since 1989, genetic analysis and prenatal diagnostic procedures have improved, bringing a greater knowledge on the spectrum and aetiology of possible developmental disorders in the foetus. This should reduce the number of unexplained abortions.

Cerebral manifestation of Wilson's disease successfully treated with liver transplantation.

The main indication for orthotopic liver transplantation (OLTx) in Wilson's disease (WD) is severe hepatic decompensation. Our 15-year-old patient is the second case to date in whom OLTx was performed because of neurologic manifestations resulting from WD. His initial condition involving recurrent headaches, tremor, and athetoid hand movements progressively deteriorated during therapy with D-penicillamine, zinc sulfate, and trientine until he was severely dysarthric, unable to walk, and bedridden. After OLTx, his neurologic condition became almost normal.

[Preoperative ECG in routine preoperative assessment of children]. / Das präoperative EKG als Routineuntersuchung bei Kindern.

OBJECTIVE: The aim of this study is to examine whether a routine preoperative ECG is necessary in children to assess the risks in anaesthesia and surgery. METHODS: We examined the records of 3030 children anaesthetized in our hospital in 1990 and compared records of complications with preoperative ECGs. We also evaluated questionnaires on this subject which we had sent to 51 large pediatric hospitals in Germany in 1991. RESULTS: During 3030 anaesthetic procedures there were 93 complications, 67 of which were not of cardiac origin. Of the 26 cardiac complications only 4 needed therapy (AV-Block 2 degrees, fall in blood pressure). Preoperative ECGs were recorded in 180 cases: 152 were normal, 8 showed harmless deviations from normal and 16 were recorded because of known cardiac defects. None of the 180 children developed complications during anaesthesia. Our questionnaire was returned completed carefully by 36 of the 51 hospitals. In most hospitals a preoperative ECG is only recorded when heart disease is known or suspected. CONCLUSION: Routine preoperative ECGs are unnecessary in children unless there are clinical symptoms of heart diseases or heart disease is suspected.

[Genesis and importance so-called inflammatory infiltration of the placenta. II. Immunohistochemical findings]. / Zur Genese und Bedeutung der sogenannten Asphyxieinfiltrate der Plazenta. II. Immunhistochemische Befunde.

We investigated the morphologically distinct forms of inflammatory infiltration of the placenta both histologically and immunohistologically (n = 24). Our material included cases of membraneous inflammation (chorioamnionitis), inflammatory infiltration of arteries in the chorionic membrane, basal and intervillous placentitis. NACE staining was used to detect myeloid cells and monoclonal antibodies (LCA, CD3, CD8, CD20, CD68). To detect lymphoid and macrophageal cells we also measured the proliferation activity with MiB 1. In cases of chorioamnionitis and subchorial demarcation and in the arteries of the chorionic membranes the main inflammatory cell is the myeloid cell (most often the mature neutrophil granulocyte). T-lymphocytes were only occasionally found. In cases of intervillous placentitis, on the other hand, lymphocytic infiltration predominates, consisting of T-lymphocytes which are mostly CD8 negative, and some monocytes and macrophages. Basal inflammation in the demarcation zone was characterized by T-lymphocytes. We interpret this as indicating basal demarcation. According to our histological and immunohistological observations, "asphyxial infiltrates" are abortive forms of a placental (bacteriological) inflammation, possibly infective in origin. We do not consider asphyxial infiltration to be a separate entity with its own causal pathogenesis.

[Genesis and significance of so-called asphyxial infiltrates in the placenta. I. Histologic results]. / Zur Genese und Bedeutung der sogenannten Asphyxieinfiltrate der Plazenta. I. Histologische Befunde.

The conventional conception of the cause and formal pathogenesis of so-called "asphyxial infiltrates" of the placenta is presented. Morphological examples are given. Our study included 561 newborn cases. Eighty two cases (14.6%) had such cell infiltrates, and there were 6 cases with phlegmoneous inflammation of the fetal membranes. These morphological findings correlated with the following clinical characteristics: term of birth, weight classes of newborns, Clifford-signs, clinical risks with respect to hypertension, the course of pregnancy and particularly the risk of inflammation. Additional correlates were the clinical statement of hypoxia and acidosis in newborns. We discovered relationships between these cell infiltrates and the Clifford-signs, and to some clinical risks (especially those for inflammation), but not to hypoxia and acidosis of the newborn. Our results show, that there are no relations between the conventional "Asphyxial infiltrates" of the placenta and the hypoxia and acidosis observed in newborns.

[Primary malignant melanoma of the esophagus]. / Das primäre maligne Melanom des Osophagus.

Primary malignant melanoma of the esophagus is extremely rare. Less than 200 cases have been published worldwide up to now. We report a case of a 65-years old male suffering from dysphagia for four months. The endoscopy showed a polypoidal tumor of black colour in the distal part of the esophagus. The histological diagnosis of the initial biopsy specimen was melanoma. Partial esophagectomy and lymph node sampling were performed. The resected specimen showed a polypoid tumor with black pigmentation of 8 x 5 x 3 centimeter. Histopathology revealed a primary malignant melanoma of the esophagus stage pT2 pN1 M0 and grading three. The patient died 8 months after resection from general metastatic disease. Age, sex, symptoms, duration of symptoms and time of survival are similar as described in former cases.

[Pathogenesis of hypotrophic and eutrophic preterm deliveries --a morphologic study of 212 cases]. / Zur Genese hypotroph-prätermer und eutroph-prätermer Geburten--eine morphologische Untersuchung von 212 Fällen.

The exact pathogenesis of prematurity and intrauterine growth retardation (IUGR) is still obscure in detail. Histological examination of placental tissue may be helpful. In a retro- and prospective study we examined 212 placentas including eutroph-term (n = 80 as controls), hypotroph-term (n = 68), eutroph-preterm (n = 53) and hypotroph-preterm (n = 11) deliveries, respectively. Placentas of the control group showed a significant higher weight, a higher utero-placental diameter and a smaller thickness. We observed villous dysmaturity in a significant higher frequency in risk groups, compared with controls (70-80% vs. 15%). Retarded villous maturity occurred in 38.2% in the hypotroph-term group and in 36.4% in the hypotroph-preterm group, respectively. Placentas of eutroph-preterm deliveries showed a prematurity of the villous tree in 47.2% Our own results and data from literature suggest, that the majority of prematurity and IUGR is not caused by placental dysmaturity itself. Fetal hypotrophy is sometimes caused by inadequate adaptation of the placental tissue due to a virtual slowly appeared disturbance, probably in the uterine maternal blood flow. After the adaptation of placental tissue the organ is able to secure the fetal nutrition supply. A second "hit", e.g. inflammation of the chorion may lead to prematurity. If the compensation of the dysbalance between fetal nutrition-supply and placental capacity is impossible the birth of a premature fetus, mostly dysmature, takes place.